Didier Dumur Supelec Christian Cave U. PSud resp. Master Pharma

Transcription

1 Réunion du Groupe de travail en Sciences du Vivant COMPTE RENDU REUNION DU 14 mai 2013 Participants Excusés Michel-Ange Amorim U. Paris-Sud, STAPS Christian Auclair ENS Cachan Jacques Bittoun U. Paris-Sud, animation groupe Julie Bernauer INRIA Claude Boucheix INSERM Serge Bobin Doyen Médecine U. PSud Thierry Doré AgroParisTech Pierre Capy U. Paris-Sud Elisabeth Dufour- FCS, Dir. déléguée à la formation Elli Chatzopoulou INSERM Gergam Didier Dumur Supelec Christian Cave U. PSud resp. Master Pharma Jean-Marc Grognet CEA Claude Chappert CNRS, DG FCS Patricio Leboeuf FCS, Dir. délégué à la recherche Anne Collignon U. Paris-Sud Jane Lecomte U. Paris-Sud Bruno Colombo UEVE, resp. Master SGO Marianne Lefort INRA, animation groupe François Cottin UEVE, resp. Dpt STAPS Loïc Lepiniec INRA Hervé Daniel U. Paris-Sud Anne Mantel U. Paris-Sud Jean-François Delfraissy INSERM Bernard Mignotte UVSQ Vivienne Fardeau CEA, INSTN remplacée par A.Hammadi (présent) Bertrand Ney AgroParisTech Sylvain Fisson UEVE, Dir. Dépt Biologie Marc Pallardy U. Paris-Sud Anne Flury-Herard CEA remplacée par R. Trebossen (présente) Pascale Pottier AgroParisTech Jacques Grassi INSERM Laurent Theodore U. Paris-Sud Hervé Guéguen Supelec Bertrand Thirion INRIA Akli Hammadi CEA Régine Trebossen CEA Marc Humbert U. Paris-Sud Loïc Josseran UVSQ Secrétariat Marc Lavielle INRIA Marie-Noëlle Descamps INRA Pierre Legrain Polytechnique Thierry Meinnel CNRS Christelle Monville U. Evry Val d Essonne Gérald Peyroche ENS Cachan Dominique Porquet Doyen Pharma U. Paris-Sud Bruno Robert CEA, Représentant CAC Claire Rogel-Gaillard INRA Tarek Sharshar UVSQ L ordre du jour de la réunion porte sur 1 : 1. La validation du compte rendu de la réunion du 16 avril 2. Les départements (P. Leboeuf) : Validation du texte Comité de pilotage «SdV» Mise en place d un groupe des directeurs de la «recherche» AAP du PSAMS : résultats AAP 2013/2015 et modalités/calendrier AAP Chaires Idex 1 En annexe, sont reprises les présentations de Patricio Leboeuf (partie 1 «Départements») et d Elisabeth Dufour-Gergam (partie 2 «schools») Page 1/6

2 Avancement structuration des départements 3. Les Schools : Suite de la réunion du 30/04 avec les responsables «enseignement» Gouvernance des schools et des mentions Bourses M1/M2 internationales Avancement des travaux dans les schools A, B et C 4. Formation doctorale 1. Validation du compte rendu de la réunion du 16 avril Le groupe valide le compte rendu du 16/04/ Les départements Validation du texte «comité de pilotage Sciences du Vivant» Les éléments mentionnés lors de la réunion précédente ont fait l objet d une retranscription dans le texte soumis pour avis ce jour (voir doc annexe). Il s agit notamment de l accompagnement de la réflexion et des travaux du CoPil via des regards extérieurs portés par : - le sénat académique, grâce à une interaction régulière avec le CoPil, - un conseil scientifique et stratégique de département, consultatif, pouvant rassembler des personnalités académiques et des représentants du monde socio-économique ; ce conseil sera mis en place lorsque le département aura un peu progressé dans ses travaux et pourra le saisir sur l analyse de quelques dossiers. Les participants valident le texte tel qu il est rédigé ; celui-ci sera transmis au ComIdex pour avis. Patricio Leboeuf ajoute que les autres départements sont en phase d élaboration de textes de présentation ; il souhaite que les unités puissent rapidement se positionner dans les départements, avec la possibilité que certaines puissent émarger sur plusieurs d entre eux. Le groupe souhaite attirer l attention du Comidex sur deux points : (1) il est important d obtenir le pavage d ensemble des départements (et leurs périmètres respectifs) avant de solliciter les unités à se positionner ; (2) il est essentiel, pour la recherche finalisée que les chercheurs et enseignantschercheurs de certaines unités puissent contribuer aux dynamiques scientifiques de plusieurs départements (cas des maths et des SESG, par exemple). Groupe de travail des directeurs de la «recherche» Ce groupe, rassemblant les responsables «recherche» des 23 établissements partenaires, a vocation à se réunir périodiquement 2 afin de discuter des différentes actions liées à la partie «recherche» de l Idex. La 2 ème réunion est organisée le 17 mai prochain, elle traitera des départements, des Chaires d Excellence et des appels à projets. 2 Depuis, il a été décidé : une réunion le 3 ème vendredi de chaque mois Page 2/6

3 Les appels à projets (AAP) du PSAMS L AAP2013/2015 couvrant la période probatoire est la première action-recherche mise en place par l Idex. Cet appel est voué à faire émerger des projets ambitieux inter-établissements, projets figurant dans le «document B» de l Idex. Pour mémoire le budget total consacré aux deux AAP est de l ordre de 15 millions d uros (9 millions pour l AAP 2013/2015 et 6 millions pour le suivant, ). Les critères et modalités de gestion du premier AAP ainsi que les projets concernés, sont rappelés dans la présentation ppt jointe. Parmi les 14 projets présentés, sept ont été retenus dont quatre touchant aux sciences du vivant. Ils seront lancés immédiatement, avec un financement attribué à la hauteur des demandes. Projets sélectionnés : ALIAS (Aliments, Alimentation et Santé), BIG (biologie intégrative), IMSV (Institut de modélisation des systèmes vivants), NeuroSaclay (Neuro sciences), ISIS 3 (Interactions Science-Innovation-Société), ISN (Société Numérique), NanoDesign (plateforme de développement et de valorisation des résultats de la recherche). Quelques autres projets bénéficient de soutiens budgétaires plus symboliques, permettant d accompagner les dynamiques de réseau initiées dans le cadre de l AAP. Tous les projets présentés pour cet AAP sont donnés en annexe ; en effet, le groupe a souhaité pouvoir les consulter, de façon à susciter d éventuelles interactions avec certains d entre eux. La FCS souhaite qu un comité de pilotage soit mis en place pour chaque projet retenu. Elle reçoit actuellement chacun des porteurs de projet pour préciser le processus de gestion et de suivi de leurs travaux, tout en explicitant les critiques des experts du jury. Le lancement de l AAP est prévu rapidement dans l optique d un démarrage des projets début Les critères seraient similaires à ceux utilisés pour le premier appel. Toutefois, l appel sera ouvert à toutes les équipes, contrairement au précédent. Le calendrier prévisionnel : Lancement : mi-juin Clôture : 16 septembre Pré-sélection en ComIdex : 25 septembre Les Chaires d Excellence Conformément au document Idex, dans le cadre de la politique RH, il devrait être mis en place dix chaires durant la période probatoire (450 k chacune). Le montage de dossiers doit donc être rapidement mis en œuvre. Celui-ci devrait être fait selon des critères explicites et transparents, à travers des appels d offres, sans pour autant occulter la possibilité de montages plus opportunistes. Les Chaires pourraient être couplées au volant de postes (10%) pour lesquels les établissements s étaient engagés à une réflexion collective au profit de la stratégie de l Idex. La FCS envisage de privilégier l accueil de jeunes seniors, moins exigeants au plan financier que les plus âgés à très forte notoriété et plus aptes à rester en France à l issue du projet de chaire. L idée est d attirer ces jeunes 3 Ce projet dispose d un budget CNRS complémentaire pour un «PEPS de site CNRS/Paris-Saclay» Page 3/6

4 sur des postes statutaires mais en leur créant un environnement favorable (doc, post-doc, soutien à l équipement et au fonctionnement) et, éventuellement, en les dotant d une prime complémentaire du salaire de base. Des remarques sont formulées : Mener une réflexion approfondie en amont avec les établissements pour identifier chaque année ceux qui seraient en mesure d accueillir les Chaires. Elaborer un appel à projet clair et transparent pour permettre un montage souple compte tenu des expériences de chacun. Avancement de la structuration des départements A partir des chiffres figurant sur le compte rendu de la commission électorale du sénat académique la taille indicative des départements est reprise ci-dessous. L état d avancement des textes de présentation est également mentionné. Département Effectifs Document préliminaire disponible Sciences de la Vie 1800 (+1000 réponses tardives?) Oui Phys des Ondes & de la Matière 750 Oui Phys des deux Infinis & des Origines 750 Oui Chimie 480 Oui Terre, Océan, Atmosphères, Planètes 210 Oui Math 370 Oui SHS 780 En cours Electrical & Optical Engineering 450 Oui Mechanical Engineering 500 Oui Sci & Tech de l Info. & de la Com Oui Pour la FCS, Patricio Leboeuf souhaite qu à titre indicatif soit fourni le taux d implication des laboratoires dans le(s) département(s) afin d obtenir une idée de la répartition des chercheurs dans les grands champs disciplinaires. Toutefois, il est rappelé l importance de ne pas imposer de modèle exclusif à l une ou l autre des communautés, notamment pour ce qui a trait aux dynamiques des communautés thématiques (médicaments/santé ; agriculture, alimentation, environnement ; STIC ; etc.). La structuration doit pouvoir intégrer de la redondance, de façon à promouvoir toutes les passerelles utiles entre communautés. 3. Les schools Informations générales et calendrier La réunion des animateurs des groupes de travail, du 30 avril, avait pour objet la présentation de l état d avancement des travaux, la diffusion et l échange d informations pertinentes. La liste des schools telles que présentées lors du séminaire FCS du 3 avril est reprise en annexe dans la présentation d Elisabeth Dufour-Gergam. Les intitulés ne sont toutefois pas encore stabilisés. Pour qu au 15 octobre, la FCS puisse déposer la présentation du projet d ossature de l offre globale «Masters Paris-Saclay» (mentions + parcours), il est demandé aux animateurs des schools de fournir des éléments approximatifs sur le programme pédagogique et l implication potentielle des établissements dans la réalisation de celui-ci. Ces éléments devront être affinés d ici septembre, pour pouvoir être présentés aux CEVU des différents établissements d enseignement supérieur concernés. Page 4/6

5 Au niveau de la nomenclature des mentions (cf. liste diffusée mais non finalisée), certaines mentions disciplinaires s y retrouvent mais d autres plus thématiques, sont en difficulté. De ce fait : - certaines mentions aux intitulés «libres» ne pourront apparaître que sous forme de parcours d une mention plus générique (la visibilité du parcours sera primordiale) ; - pour d autres, la transformation en parcours autonome dans un parcours plus disciplinaire aurait peu de sens ; dans ce cas, la défense de certains intitulés auprès du MESR pourrait être faite par la FCS, en vue de compléter la nomenclature nationale. Les difficultés et propositions éventuelles de nouveaux intitulés sont donc à faire remonter auprès de la FCS, d ici la fin mai Gouvernance des schools et des mentions En préalable à une réflexion au sujet de la gouvernance, Elisabeth Dufour-Gergam présente un schéma permettant de situer les différentes missions des schools (voir ppt), depuis la vision stratégique jusqu aux éléments plus opérationnels de suivi de la mise en œuvre des formations. Dans ce contexte, elle souhaite d abord que soit bien prise la mesure de ce qu implique la disparition des spécialités par rapport au fonctionnement antérieur des masters. C est pourquoi elle souhaite mettre en place un groupe de travail très opérationnel sur les aspects formation, en s appuyant sur des représentants des établissements d enseignement supérieur. Le groupe insiste néanmoins sur l intérêt d associer aussi des représentants des organismes de recherche, intéressés aussi par ces questions, de façon à stimuler très en amont des formes d interaction innovantes entre formation et recherche, dans le projet d ensemble. Bourses M1/M2 internationales Prochainement un appel pour les TP innovants sera lancé ainsi qu un appel pour les bourses d excellence M2 pour les étudiants disposant d un projet de thèse. La prochaine vague de l appel fermée au 31 mai jury le 19 juin. Le groupe demande une communication large des AAP, au delà des responsables de Masters ou des relations internationales des établissements d ES, de façon à toucher aussi les directeurs d unités, en contact avec de nombreux étudiants et de nombreux collègues universitaires internationaux. Avancement des travaux de la School A Le périmètre de la school est en cours de stabilisation. La prochaine réunion se tiendra le 29 mai afin de travailler sur des propositions plus structurées. Les discussions sont actuellement menées : Les mentions «physique et imagerie médicale» ne se retrouvent pas dans la nomenclature proposée ; Les mentions «sciences de la vision et ergonomie» et «sciences cliniques et paramédicales» pourraient se rapprocher. Les mentions de «biomathématiques et biostatistiques» de PSud, d une part, et de «bioinformatique, génomique et statistiques» d Evry, d autre part, n ont pas de référent dans la nomenclature. Un rapprochement est envisagé avec la volonté qu un intitulé pertinent leur soit associé dans la nouvelle nomenclature. Page 5/6

6 Deux mentions, «Nanobiotechnologies - Nanobiomatériaux» et «Biologie intégrative des adaptations à l exercice pour la santé et la performance (BIAESP)» pourraient également être rattachées à d autres schools : la première dans la mention «matériaux» de la school Basic Sciences, la seconde dans la school C STAPS. Avancement des travaux de la School B Pour la school B, l intitulé est à redéfinir, car les mots «agriculture» et «société» avaient provoqué des réactions. La restriction de la nomenclature des mentions pose un vrai problème. Parmi les intitulés de mentions à considérer : Ecologie Agro sciences Biologie intégrative Le cas de l alimentation et des bioproduits, reste à traiter pour l insérer de façon visible dans la school. Les prochaines réunions sont programmées les 29 mai, 7 et 24 juin prochains. Avancement des travaux de la School C Le groupe aurait souhaité maintenir une lisibilité de deux mentions («Sciences du Mouvement Humain» pour les 5 parcours à dominante Sciences du Vivant, et «Sport et Sciences de la Société» pour les deux parcours liés au management et politiques publiques du sport) alors qu il n y en a qu une seule prévue pour les STAPS dans la nouvelle nomenclature. Toutefois, des discussions sont en cours entre la C3D (Conférence Des Directeurs et Doyens STAPS), le CNU 74 (STAPS) et la DGESIP afin d envisager plusieurs Mentions. La position commune C3D/CNU est la création d une mention généraliste «STAPS» (pour les filières liées à l ergonomie sportive, et les M2R généralistes) et de trois mentions spécifiques : - STAPS APA-S (Activités Physiques Adaptées et Santé) - STAPS ES (Entraînement Sportif) - STAPS MS (Management Sportif) Si la Mention STAPS APA-S est validée par la DGESIP, cela permettra d y intégrer les parcours «Handicap neurologique» (UVSQ, Garches) et «VHMA» (Université Paris-Sud et Paris Descartes). 5. Formation doctorale Cette question n a pas été abordée faute de temps. 6. Questions diverses La prochaine réunion aura lieu mercredi 12 juin 2013, à 9h30, à l INRA de Jouy en Josas, bâtiment 156, salle de réunion du 2 ème étage. Page 6/6

7 Proposition de cre ation d un Comite de pilotage pour animer le de partement Sciences du Vivant de la future UP-Sa Préliminaire : Ce texte a été rédigé pour répondre aux engagements pris dans le cadre de l IDEX. Il a été travaillé par le groupe «Sciences du vivant» mis en place par la FCS puis validé par ce dernier lors de sa réunion de janvier. Telles que sont aujourd hui identifiées ses missions et sa composition, il a vocation à alimenter la réflexion sur les départements de l UP-Sa, préfigurant celui qui pourrait regrouper la communauté des sciences du vivant. Introduction L ambition de l IDEX Paris Saclay (IPS) en Recherche dans le domaine des Sciences du Vivant est décrite dans le document soumis en réponse à l appel à projets pour la phase de sélection (pp ). Il s agit de répondre «au grand défi que constitue la compréhension et la maîtrise du vivant, depuis l avancée des connaissances jusqu aux enjeux sociétaux [en privilégiant] les approches pluridisciplinaires» au meilleur niveau. Un certain nombre de projets sont mis en avant. Certains ont été proposés aux appels à projets LabEx et, pour partie d entre eux, sélectionnés. D autres sont à l état de réflexions préliminaires. La création du Comité de pilotage pour les Sciences du Vivant 1 (CoPil-SdV) est une des actions prévues par l IDEX pour faciliter la réalisation de cette ambition. Dans cette perspective, il a notamment pour fonction d accompagner les projets transversaux, aussi bien ceux déjà identifiés que ceux qu il contribuera à faire émerger. Par ailleurs, la réflexion sur le schéma d organisation de la future Université Paris Saclay a abouti à distinguer les schools dans une logique d organisation des filières de formation, de porte d entrée pour les étudiants et de point de repère pour leurs futurs employeurs et les départements scientifiques dans une logique d organisation des activités de recherche. Un principe de découplage fort entre les périmètres des schools et ceux des communautés scientifiques a été acté. A ce stade, le schéma retenu provisoirement pour les Sciences du Vivant distingue : trois schools (intitulés provisoires) Biologie, Médecine, Pharmacie, Biologie ; Biodiversité, Alimentation, Sociétés, Environnement ; Sciences du sport et du mouvement humain ; un département scientifique Sciences du Vivant (Dépt-SdV). 1 Cet intitulé est adopté en cohérence avec le texte déposé lors de l appel à projet IDEX.

8 Le département Sciences du vivant rassemble l ensemble des communautés scientifiques en sciences du vivant de la future UP-Sa. C est un point de rencontre entre toutes les unités de recherche contribuant aux progrès des connaissances en sciences du vivant et leurs hiérarchies scientifiques, que ces dernières relèvent d organismes, d universités ou de grandes écoles. C est un lieu central d animation des communautés et notamment d échanges sur la construction d une stratégie scientifique partagée au sein de la future UP-Sa. Pour mener à bien sa mission, le département Sciences du vivant s appuie sur un comité de pilotage (CoPil-SdV), moteur de l animation et en charge du pilotage opérationnel des projets phares du département. Par ailleurs, pour accompagner sa réflexion et apporter un regard extérieur sur ses travaux, le Co-Pil : assurera une interaction régulière avec le sénat académique, notamment via les représentants des différents collèges relevant des sciences du vivant et ceux des domaines disciplinaires aux interfaces ; pourra mettre en place un Conseil scientifique et stratégique consultatif rassemblant des personnalités scientifiques extérieures à la communauté scientifique en Sciences du Vivant de la future UP-Sa et reflétant sa très grande diversité ; ce conseil pourra rassembler des personnalités académiques et des représentants du monde socio-économique. Comité de pilotage pour les Sciences du Vivant Rôle/missions Le CoPil SdV est, chargé d animer la Communauté scientifique en Sciences du Vivant de l UP-Sa. Il rend compte au Comité exécutif de l IDEX puis de l Université Paris Saclay. Il est responsable de l animation : il organise le dialogue entre les unités de recherche de manière à faire émerger des projets, à identifier les priorités, à faciliter l émergence de propositions innovantes ; il rend compte annuellement de ses activités auprès de l ensemble des directeurs d unité et partage avec eux les perspectives de l année à venir ; il organise le dialogue avec les communautés pertinentes dans les autres départements, communautés susceptibles d être mobilisées au profit de l avancée des connaissances en sciences du vivant ; il organise le dialogue avec les schools ayant une offre de formation dans le champ des sciences du vivant ; il propose la mise en place des groupes de travail nécessaires au bon fonctionnement des communautés ; il organise les interactions avec les représentants pertinents au sein du sénat académique (notamment représentants élus et nommés dans les collèges relevant des sciences du vivant) ; il organise ou contribue à l organisation de séminaires/journées scientifiques thématiques, ouvertes largement aux communautés scientifiques du département. 2

9 Il choisit et valide les initiatives à mener : il examine leur bien fondé au regard de la stratégie de l IDEX ; il s assure de la qualité de ces initiatives, en visant le niveau d ambition le plus élevé possible ; à cette fin, il s entoure si besoin d autres avis compétents ; il étudie leur faisabilité et leur traduction en actions (cahier des charges, chef de projet, gouvernance, moyens, ) ; il propose leur mise œuvre au Comité exécutif, assorti d une recommandation de financement. Dans l immédiat, le CoPil - SdV sera mobilisé pour assurer le suivi des projets retenus par la gouvernance de l IDEX parmi ceux déjà décrits au paragraphe Biology Chemistry de la partie Scientific strategy of the Université Paris-Saclay: 4-year actions and objectives, pp du document de candidature à l appel à projets IDEX (phase de sélection). Il procède au suivi de chaque action : il s assure du bon fonctionnement et de l atteinte des objectifs ; avec les animateurs de l initiative, il identifie les freins et les difficultés, fait toute proposition pour les surmonter et procède à la révision des objectifs et des calendriers. Il coordonne l animation sur la mutualisation et les projets d évolution des plateformes et plateaux techniques en Sciences du Vivant à l échelle du campus, et ce en étroite concertation avec le GIS IBiSA, l ANR et le CGI, pour tout ce qui relève des plateformes et infrastructures qu ils soutiennent. Il entretient le dialogue avec les Schools, co-construisant avec ces dernières des éléments assurant un transfert rapide et original des connaissances vers la formation par et pour la recherche (M/D) : modules, TP innovants mobilisant les plateaux et plates-formes technologiques de l UP-Sa, formations de haut niveau pour des doctorants, etc. Il est force de proposition : il rassemble les informations concernant les initiatives issues d autres domaines (Mathématiques, Ingénierie, STIC, Physique, Chimie, Sciences humaines et sociales) ayant trait aux Sciences du Vivant ; il soumet à l exécutif de l IPS des initiatives permettant de renforcer la cohérence de sa politique dans le domaine ; il est force de proposition pour développer et amplifier la stratégie scientifique partagée de la future UP-Sa, en sciences du vivant ; il contribue, par valorisation de son activité de suivi et d accompagnement des communautés et par ses propres réflexions, à la consolidation de la stratégie de l IPS. Pour mener à bien ces différentes missions, le CoPil-SdV se réunit une fois par mois. 3

10 Composition et gouvernance Le comité est composé : De représentants des organismes et établissements d enseignement supérieur qui sont impliqués dans les recherches et formation en sciences du vivant : CEA, CNRS, INRA, INRIA et INSERM pour les organismes ; AgroParisTech, ENS Cachan, Ecole Polytechnique, Université Paris-Sud, UVSQ ainsi que l UEVE, pour les établissements d enseignement supérieur ; De représentants des directeurs d Unités et responsables de Labex et Lidex, intervenant dans le champ des sciences du vivant. Le Directeur délégué à la recherche de l IDEX est invité permanent aux réunions du Comité. Il a pour correspondants privilégiés : les directeurs des unités actives dans le domaine des Sciences du Vivant ; les chefs de projet, animateurs de l ensemble des actions dont il assure le suivi ; les animateurs des LabEx et des LIdex dans le champ des Sciences du Vivant ; les animateurs des LabEx hors champ Sciences du Vivant dont le projet comporte des éléments d interface important avec ce domaine ; les représentants pertinents au sein du sénat académique ; les animateurs/responsables des schools émargeant en sciences du vivant ou proposant des formations dans ce domaine. Le Co-Pil pour les Sciences du vivant est présidé par un membre élu en son sein. Le Président s entoure de quelques personnes (vice-présidents ou chargés de mission) - nommés par le président après avis du CoPil ainsi que d une personne en charge du secrétariat, pour l accompagner dans sa tâche d animation et de coordination des activités du département. 4

11 Appel à projets recherche mai 2013

12 Critères Le financement Idex doit être considéré comme un fond d amorçage sur une durée de 2-3 ans. Le financement sur le long terme par les établissement partenaires ainsi que leur engagement constituent un critère majeur Impact (capacité à obtenir rapidement des résultats) sur la qualité et contenu de la recherche structuration et rayonnement du périmètre scientifique Paris Saclay Positionnement et enjeux stratégiques de la thématique par rapport à la situation régionale, nationale et internationale Articulation et complémentarité par rapport aux autres acteurs locaux Utilisation du budget et articulation avec d autres sources : établissements partenaires, sources externes (ANR, organismes, Europe), industriels, Détermination de quelques objectifs clairs et organisation des équipes afin de les atteindre S ajoutent à ces critères des questions spécifiques adressées à chaque projet 2 AAP Idex Recherche 2013, 14/05/2013

13 Modalités De manière exceptionnelle, projets identifiés lors de l élaboration de la stratégie scientifique Sélection en deux phases Pré-sélection Fiche de 2 à 3 pages Date butoir : 19 novembre 2012 Décision du Comité Idex : 21 novembre 2012 Validation pré-sélection + avis sur la provision budgétaire pour l action recherche 2013 par l Assemblée : 28 novembre 2012 Sélection Lancement : 29 novembre 2012 Date butoir : 16 janvier 2013, minuit Evaluation par au moins un expert extérieur par projet Retour experts : 31 mars 2013 Auditions des porteurs + premier classement : 9 avril 2013 Sélection Comité Idex + budget par projet : 17 avril 2013 Validation sélection + budgets par le CA FCS : 24 avril AAP Idex Recherche 2013, 14/05/2015

14 Les projets concernés 1. ALIAS, Stéphane Aymerich 2. Institut de Modélisation des Systèmes Vivants, Vincent Fromion 3. Biotechnologies et chimie bio-sourcée et bio-inspirée, Jean-Luc Pernodet 4. Réseau énergie-climat de l Université Paris-Saclay, Jean-Marc Agator 5. Institut de Physique Avancée, Denis Ullmo 6. Matériaux Innovants, Christian Serre 7. Integrative genome biology, Frédéric Boccard 8. Plateforme de Nano-Design, Jean-Noel Patillon 9. NeuroSaclay, Philippe Vernier 10. Physique et Ingénierie pour la Médecine (PIM), Irène Buvat 11. Développement de techniques innovantes de Simulations hybrides 3D appliqué au Risque sismique (DESYR), Marie Pierre Bohar, Alain Le Maoult 12. Interactions Science Innovation et Sociétés (ISIS), J. Pélisse, Ch. Bessy, Ch. Licoppe 13. Institut de la Société Numérique, Nozha Boujemaa 14. Nanosatellites Paris-Saclay, Daniel Vidal-Madjar 4 AAP Idex Recherche 2013, 14/05/2013

15 Projet Porteur Type Partenaires UPSa Taille (C/EC/Ing ass) Budget ALIAS S. Aymerich Labex ~ M BIG F. Boccard Labex M Biotech J.-L. Pernodet Labex M DESYR A.Le Maoult Plat-Institut M Energie Climat J.-M. Agator Réseau-Valo 8 4+comités 0.78 M IMSV V. Fromion Réseau-Inst. ~16 plus. cent M ISIS Ch. Serre Labex ~ M ISN M. Schoenauer Labex M Matériaux Ch. Serre Réseau M NanoDesign J.-N. Patillon Platef-Valo M (7ans) NanoSat D. Vidal-Madjar Cluster M NeuroSaclay Ph. Vernier Labex M PIM I.Buvat Labex M Budget total demandé : 20.5 M 5 AAP Idex Recherche 2013, 14/05/2013

16 PROJETS RETENUS Projet Porteur Adresse mail Budget (phase probatoire) ALIAS S. Aymerich 1.38 M BIG F. Boccard frederic.boccard@cgm.cnrs-gif.fr 1.43 M IMSV V. Fromion vincent.fromion@jouy.inra.fr 1.00 M ISIS ISN Ch. Bessy Ch. Licoppe J. Pelisse M. Schoenauer N. Boujemaa christian.bessy@idhe.ens-cachan.fr christian.licoppe@telecom-paristech.fr jerome.pelisse@uvsq.fr 0.97 M marc.schoenauer@inria.fr nozha.boujemaa@inria.fr 1.75 M NanoDesign J.-N. Patillon jean-noel.patillon@cea.fr 1.94 M NeuroSaclay Ph. Vernier philippe.vernier@inaf.cnrs-gif.fr 2.00 M 6 AAP Idex Recherche 2013, 14/05/2013

17 NON RETENUS MAIS AVEC UN BUDGET D ACCOMPAGNEMENT Projet Porteur Adresse mail Budget (2013) Biotech J.-L. Pernodet jean-luc.pernodet@igmors.u-psud.fr 20 k Energie Climat J.-M. Agator jean-marc.agator@cea.fr 20 k Matériaux Ch. Serre serre@chimie.uvsq.fr 20 k 7 AAP Idex Recherche 2013, 14/05/2013

18 Les Départements de Recherche de l Université Paris Saclay Projets actuels (estimation des tailles : commission électorale du 5 janvier 2012) Sciences de la Vie : 1800 (+1000?) Physique Ondes et Matière : 770 P2IO : 750 Chimie : 480 Géosciences : 210 Math : 370 SHS : 760 E&OE : 450 Mech Eng : 500 STIC : > AAP Idex Recherche 2013, 14/05/2013

19 IDEX Paris-Saclay APPEL A PROJET RECHERCHE IDEX 2013 Digital Society Institute Project, January 16 th 2013 Project Name : Project Type : Digital Society Institute (DSI) Multi-Disciplinary Project DSI Chair : Marc Schoenauer Office phone number :+33(0) DSI Deputy Chair : Patrick Duvaut Mobile phone number :+33(0) Director at INRIA/ Saclay Ile de France marc.schoenauer@inria.fr Research Director of Telecom-Paristech patrick.duvaut@telecom-paristech.fr Executive Summary The Digital Society Institute (DSI) will be the UPSa IDEX catalyst for multidisciplinary research on societal challenges inherent to elife/life digitization. DSI research uniquely combines human oriented requirements for better acceptance of elife equipments/services with innovative technological advances in order to improve user digital life experience. Digital Society Institute research topics implicate both Information and Communication Technologies and Sciences (ICTS) and Social, Human and Economical Sciences (SHES) disciplines while current UPSa IDEX initiatives such as DigiCosme, Digiteo, CapDigital, SystemX, 3S,... explore topics from a single of the ICTS or SHES perspectives. Digital Society Institute partners, inspired by the Europe 2020 agenda, propose a strategy tailored to the multidisciplinary questions revolving around elife, focused on behavioral triggers of elife adoption (termed Societal Enablers of elife or SEeL that encompass both ICTS and SHES triggers) in all our daily activities : professional, medical, educational, entertainment, social, legal, economical, etc. The Digital Society Institute strategy is to discover, define, evaluate, capitalize, and certify these Societal Enablers of elife. SEeL from DSI research will address social, legal, ergonomic, psychological and economical requirements in all aspects of the Digital Society, across the full ecosystem of digital growth. DSI plans to be one of the European leading institutes fostering multidisciplinary research across ICTS & SHES, dedicated to the societal challenges inherent to digital life. DSI will become the leading European expert in certification, rating and standardization of elife equipments and services (ehealth, eeducation, eidentity, eprivacy, elaw, etc), leveraging its strategy of focusing on Societal Enablers of elife, SEeL and Quality of elife (QeL) measuring. Besides bridging horizontally across SHES and ICTS, UPSa IDEX expertise and research collaboration, DSI activities will be an efficient agent in the vertical digital innovation ecosystem, locally and nationally. All DSI results, know-how and methodological platforms will be made available to local and national SMEs for innovation development and productization. The DSI light governance will rely on a single, wide participation, decision committee, the DSI Scientific Committee, that will convene once a month. Day-to-day operations and DSI outside representation will be managed by a three-member DSI Bureau that will be in touch once a week. As of January 16, 2013 DSI already hosts two ready to kick-off major research projects : (1) Human and Machine Coevolution (evolutionics) and (2) Privacy/digital identities. Other projects described here will be mounted in the first six months of DSI operation. 1

20 Table of Contents 1 What is the Digital Society Institute (DSI)? 3 2 Why DSI will be the Flagship in Multidisciplinary research of UPSa IDEX dedicated to societal challenges of elife? Positioning Strategy and 2016, 2019 milestones : Focus on Societal Enablers of elife, (SEeL) National & International Ambitions, benchmarking DSI expected Impacts on research, education, innovation Which Organizations are involved in the DSI? Research Organizations Industry Partners Key Partnership with MINATEC IDEAs Labs Who are the targeted users of DSI achievements? 6 5 What are the key differentiators of the DSI w.r.t. other UPSa IDEX projects? DSI differentiators from the SHES-oriented UPSa ISIS project DSI differentiators from UPSa ICTS projects How the different multi-disciplinary teams will work together? 7 7 What is the DSI ramp up budget plan? Initial launching Perennial Financing What is the DSI Governance? 8 9 Which research projects are affiliated with the DSI? Immediate Kick-Off Projects Joint Human & Machine Evolution : Societal Enablers of elife based (SEeL) on Collaborative, Ubiquitous and Multimodal Interactions : INTERCO INTERCO1. QUALIA : Quality of elife (QeL) : autonomic management of resources across a neighborhood of smart houses INTERCO2. MATIN : Multi-activity, ATtention and INteraction in mobility situations Privacy and Digital Identity Information leakage, virtual footprints Personal identity, anonymity Big Data Short/Medium term kick-off Projects ehealth. Project icaretify : Assessed and Certified Contact-less ecare Systems and Services (Societal Enablers of elife and Quality of elife that pertain to ehealth) eeducation Business models, Digitality and Ecosystems Dynamics INTERCO3. Conflicts with Embodied Conversational Agents in Virtual Worlds ejustice INTERCO4. emoi : e-mbodied M-iniature m-o-bile Interactions A Teams Involved in DSI, January 16th B Five Selected Papers per Lab involved in DSI 22 Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 2

21 1 What is the Digital Society Institute (DSI)? The Digital Society Institute (DSI) will be the UPSa IDEX catalyst for multidisciplinary research on societal challenges inherent to elife/life digitization. Our Digital Society Institute research, by nature, will cut across Social, Human and Economical Sciences (SHES) and Information and Communication Technologies and Sciences (ICTS). The technology-centric ICTS disciplines make elife a reality : our current virtual offices ; spreading ecommerce and ebanking altering the way we spend, save and invest ; recent advances in eeducation & ehealth. A population of smart grids, robots, interfaces and machines has emerged that helps us in our everyday tasks, transports and challenges ; the Internet of Things exists ; new economy giants trading personal data world wide have arisen in spite of privacy and trademarks rights issues ; ubiquitous, multimodal and interactive multimedia invades entertainment, etc. The SHES disciplines tame the ICTS onslaught by putting human beings at the center of the Digital Society (r)evolution. SHES establish a human-centric debate about ergonomics, comfort, acceptance, ethics, psychological and legal aspects as well as the economical dimensions in the unstoppable digital transformation of life. This digital transformation poses also important organizational issues in the business arena. Digital Society Institute research will join ICTS & SHES expertise to tackle these necessarily multidisciplinary issues that concern the emerging and future digital life of human beings. 2 Why DSI will be the Flagship in Multidisciplinary research of UPSa IDEX dedicated to societal challenges of elife? 2.1 Positioning In spite of personal computer penetration, widespread high speed Internet access, rapid mobile phone diffusion, skyrocketing tablets sales, and the advent of anytime/anywhere communication, recent surveys show that users do not see these ICTS applications and eservices as alleviating the challenges of their daily lives, limiting declared benefits of digital life to communication and entertainment. Why so limited? This difficult question, albeit crucial to Digital Society growth, is at the heart of our DSI studies. People are not yet ready to accept many digital solutions because of persistent concerns : lack of trust, lack of security, lack of ergonomics, lack of psychological adaptation, lack of new business models, lack of suited and relevant legal framework (especially regarding personal data, digital identities, privacy), ownership of intellectual property, trademark rights, and more. Digging deeper these issues require close collaboration between SHES and ICTS experts who are already part of UPSa IDEX, especially in the School of Economics and Social Science, School of Business, School of Law and in the School of Engineering Information Science and Technology. DSI research uniquely combines human oriented requirements for better acceptance of elife equipments/services with innovative technological advances in order to improve user digital life experience. These research topics implicate both ICTS and SHES disciplines. Current UPSa IDEX initiatives such as (but not limited to) : DigiCosme, Digiteo, CapDigital, SystemX, 3S, etc. merely dig deeper into topics from a single of the ICTS or SHES fields. Besides horizontally bridging across SHES & ICT, UPSa IDEX expertise and research collaboration, DSI activities will be an efficient agent in the continuous vertical digital innovation ecosystem, locally and nationally. Expected DSI achievements encompass conceptual problems Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 3

22 solving, the use/design of methodological platforms (living labs, focus groups, serious games and virtual world experimentations), prototyping, certification, and standardization of elife protocols, and interactions with machine, robots, and cars, etc. All DSI results, know-how and methodological platforms will be made available to local and national SMEs for innovation development and productization. Methodological platforms and elife prototyping will leverage the UPsa IDEX Equipex, such as DigiScope (EVE Virtual Reality Cube, WILD, etc.) and the SmartHouse Mobilemii. UPSa IDEX value-chain services, industry connections and regional instances relationship will be core assets of DSI activities integration along the innovation axis. 2.2 Strategy and 2016, 2019 milestones : Focus on Societal Enablers of elife, (SEeL) Digital Society Institute partners propose a different, innovative strategy, tailored to the multidisciplinary questions revolving around elife, focusing on both behavioral and technological triggers of elife adoption, that we call Societal Enablers of elife (SEeL that encompass combined SHES and ICTS triggers), in all our daily activities : professional, medical, educational, entertainment, social, legal, economical, etc. DSI strategy is to unveil, define, evaluate, capitalize, and certify these Societal Enablers of elife. SEeL are expected to be the DSI research drivers that meet social, legal, ergonomic, psychological and economical requirements in all aspects the of Digital Society and across the full ecosystem of digital growth. DSI objectives until 2016 are to unveil, define and evaluate SEeL and QeL in key fields of Digital Society, health, education, law, wellness, energy. Beyond 2016 and up to 2019 DSI activities will focus on prototyping, capitalizing and certifying SEeL. Fine objectives are detailed per projects in section 9. Practically, DSI strategy will combine specific levers at different levels. In addition to industry partners, public organizations involved in health, law, personal rights (CNIL, Arcep, Hadopi, CERNA, OECD) will be active members of DSI Think-Tanks and the scientific committee (agreements have already been signed between DSI agents and the CNIL for instance). Dedicated behavioral-oriented experimentation platforms will contribute not only to validating conceptual approaches but also to helping local and national SMEs, boosting the impact of SME developments and products via SEeL awareness. Different measures of Quality of elife (QeL) according to different societal fields (health, education, law, etc.) will be introduced to support needed certification and normalization activities. Focusing on SEeL is necessarily at the heart of the triptych : human being, Digital Technology and Nature/Environment. Identifying, defining and capitalizing SEeL will contribute to 21st century challenges such as the renewable energy, the lengthening of life, new needs for wellness, the scarcity of natural resources, climate change, ecitizen rights, mass education and information based jobs. 2.3 National & International Ambitions, benchmarking DSI plans to become one of the European leading institutes fostering multidisciplinary research across ICTS & SHES, dedicated to the societal challenges inherent to digital life. DSI also expects to be the leading European expert in certification (see for instance icaretify project), rating and standardization of elife equipments and services (ehealth, eeducation, eidentity, eprivacy, elaw, etc), leveraging its strategy of focus on Societal Enablers of elife, SEeL and Quality of elife (QeL) measuring. Nationally, DSI is the first project on elife multidisciplinary research in the French Digital Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 4

23 Ecosystem. As a prime mover, DSI will request, with the help of UPSa IDEX and its partners, recognition from the Ministère de l Economie Numérique (MEN), as the French DSI. As such it could benefit from dedicated MEN fundings and subsequently gain critical mass and subsequent impact on national education, research, innovation. We know of at least one other European multidisciplinary institute located in Sweden, the Lund Institute for Internet LUii, that also deals with societal aspects due to life digitization. LUii, established in early 2012, hosts an Advanced Study Group (ASG) on the Digital Society and states The aim of the ASG is to create a multi- and cross-disciplinary research program centered on prospects and challenges of digitization in society, as well as to identify key issues within this broad field in order to catalyze the formation of research regarding these key issues. We, at the DSI, plan to connect with LUii to identify common research topics, methodological platforms and complete a broader international benchmarking of such multidisciplinary institutes, possibly joining forces for European funding. 2.4 DSI expected Impacts on research, education, innovation The DSI will contribute to UPSa IDEX core missions by naturally leveraging its multidisciplinary approaches towards : more specialized research involving UPSa IDEX Départements, education degrees that will provide students with a multi-disciplinary understanding of the impact of the digital society on individuals, organizations and society as a whole, the main issues and challenges of the digital society, preparing students to be active citizens in a digital society and part of the digital economy. DSI will also contribute to local and national economic growth, aligning digital market demands and the ICTS products/services features, through Societal Enablers of elife (SEeL) awareness. DSI impact on research, education and innovation is expected to go beyond the UPSa IDEX perimeter, with objectives that are consistent with the Europe 2020 strategy and flagship initiatives that advocate multidisciplinary actions to boost economic growth. 3 Which Organizations are involved in the DSI? 3.1 Research Organizations The following research institutions are committed, sometimes through several different laboratories (already demonstrating the interdisciplinarity of the targeted research themes) : CNRS, ENS Cachan (ISSP, STEF, LSV) Université Paris-Sud (ADIS/PESOR/Chair on intellectual capital, CERDI, LRI) Télécom-ParisTech (LTCI : SES, INFRES, TSI, et COMELEC) UVSQ (CHCSC, CESDIP, DANTE, ESR, PRINTEMPS) CEA LIST LIMSI (ILES, AA, TLP, ACA, VENISE, CPU) INRIA Saclay Île-de-France (AVIZ, GRACE, COMETE, IN-SITU, OAK, REGULARITY, TAO) Ecole Centrale (MAS) Ecole Polytechnique (Chaire IRSN/PREG, LIX) Supelec (IHS/E3S, SSE/E3S, Télécom et réseaux/l2s, CIDRE, Economie) HEC (Laboratoire EOLE) Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 5

24 3.2 Industry Partners Numerous partnerships discussions and negotiations are going on, especially with Renault, EDF, Ubisoft, Thalès, Orange, many SMEs. Nevertheless, to make any further commitment, Companies are waiting for the official selection of the DSI project by the FCS. 3.3 Key Partnership with MINATEC IDEAs Labs DSI and MINATEC IDEAs Lab are currently building a key partnership that will help to foster multidisciplinary research activities across ICTS and SHES, revolving around elife. MINATEC IDEAs Lab has a unique experience in multi-field studies joining technologists and SHES experts to address the issues of human beings evolution in the emerging Digital Society. This will definitely be a valuable asset to kick-off DSI activities. 4 Who are the targeted users of DSI achievements? Several potential partners have already expressed interest in the Institute and in its results : Private companies : Thales, Orange, Renault, Ubisoft, EDF,... ; Public regulation and lawmaking organisms : CNIL (with whom Inria, Université Paris Sud, Institut Mines-Telecom are already officially collaborating), Arcep, Hadopi, Assemblée Nationale (OPECST) ; CERNA, the Allistène think-tank dedicated to ethical issues in digital sciences and technologies research ; the GIS Culture-Média et numérique, and the CNN (Conseil National du Numérique) ; International institutions, like the Institute for Prospective Technological Studies), and OCDE ; European projects : Futur ICT, the FET Flagship, whose goal is to build a global model of the society, including social, political, economical, and cultural aspects). 5 What are the key differentiators of the DSI w.r.t. other UPSa IDEX projects? 5.1 DSI differentiators from the SHES-oriented UPSa ISIS project The UPSa IDEX project called Interactions between Science, Innovation and Society (ISIS) will inherit the contents of two previous IDEX proposals : (i) LISI, targeting Innovation and Entrepreneurship and (ii) 6S, aimed at boosting research collaboration amongst SHES communities of UPSa. ISIS will also foster new emerging topics, such as Science, Law and Technology. Though ICTS topics might be objects of research, the ISIS project is only focused on SHES research activities with no ICTS research undertaken in ICTS fields. The Digital Society Institute studies tackle joint ICTS and SHES issues inherent to societal challenges of the Digital Life. Life digitization is the main driver of DSI multidisciplinary studies, which is not the case of ISIS. 5.2 DSI differentiators from UPSa ICTS projects UPSa is a key actor in field of Information and Communication Sciences and Technologies (ICTS) with a research community of more than 2600 scientific staff in 23 laboratories. This community is well structured, starting with Digiteo research cluster, scientific projects of excellence created in 2004 by the main actors of academic research in the Saclay area : CEA, CNRS, INRIA, Ecole Polytechnique, Supélec and University Paris-Sud, augmented by Associate partners : Ecole Centrale Paris, ENS Cachan, University of Versailles-Saint-Quentin, Institut Mines-Telecom, Mines-Paristech, and ENSTA-ParisTech. These scientific partners decided to join efforts to develop their research in ICTS coherently, increasing the economic impact of this Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 6

25 research. The scientific spectrum of Digiteo has been defined as the theory, design, development and validation of software-intensive systems, from system-on-chip to high performance computing and large software, including embedded systems and robots. Spanning fundamental to technological developments, the ambition of Digiteo is to help make Saclay one of the best places for research into ICTS at the international level. This ambition translates into three main objectives : to optimize the scientific potential of Digiteo, to increase the cluster s attractiveness, and to amplify its economic impact. The strategy is built on a common view of the scientific program, technology transfer policy and governance. In the framework of the Investments for the Future Program (PIA), the UPSa ICTS community is involved in DigiCosme, a Laboratory of Excellence (Labex), and in Digiscope, an Equipment of Excellence. DigiCosme, an integral part of Digiteo, unites researchers from 11 higher education and research institutions (CEA, CNRS, EcolePolytechnique, Supélec, Inria, Université Paris-Sud, Ecole Centrale Paris, ENS Cachan, ENSTAParisTech, Institut Mines-Télécom and Université Versailles St Quentin). The mission of this LabEx is to deliver an effective technical response to the needs created by the digital revolution and the growing importance of Information and Communication Sciences and Technologies (ICTS) in the scientific and economic landscape, focused on the challenges posed by the efficient processing of massive data and secure data access. Digiscope is a network for experimentation on remote collaborative interactions with complex data. The EquipEx Digiscope provides a set of diversified and collaborative capabilities on devices for interactive visualization and virtual reality. It combines world-renowned teams with already existing means of massive computing (Maison de la Simulation, meso-center of the ECP, Teratec). This equipment addresses technical issues concerning the industrial design processes, experimental sciences and decision as a digital pedagogy support. The Equipex Digiscope is a set of equipment dedicated to experimentation in ICTS and members of Digiscope will provide access to them to projects developed in the framework of DSI. The objectives of both Digiteo and DigiCosme are to accelerate research in the ICTS field to impact the socio-economic world. As they are focused on the technical challenges, they are clearly positioned upstream of the DSI project providing to society new breakthrough technologies. These Digiteo, DigiCosme and Digiscope initiatives have brought to light the currently unsatisfied need to assess the compliance of their technological solutions with the key social challenges addressed by DSI, in particular, security, reliability, liability, responsibility, etc... Thus the DSI project is key facilitator for both Digiteo and DigiCosme, allowing them to validate and promote their results within the larger socio-economic world. 6 How the different multi-disciplinary teams will work together? Expected Format of collaboration. DSI participants do not underestimate the major difficulty in the multidisciplinary execution of transversal research projects, stretched across ICTS and SHES. Though Intra-field multidisciplinary research studies, within ICTS or within SHES, may be accomplished by a singularly gifted PhD student supervised by a mix of ICTS or SHES experts, Inter-field multi-disciplinary research work, across SHES and ICTS, with their different skill sets and goals, seems beyond the achievement of a single PhD student. This is why we recommend that DSI projects, that necessarily require research in both ICTS and SHES fields, be accomplished under a unique multi-expertise team of supervisors by two tightly collaborative researchers, one of them more specialized in ICTS studies, the other one more SHES oriented. The tightly collaborative researchers could be a combination of PhDs, Postdocs, visiting researchers, etc. Dedicated program management will organize the different executive milestones of both collaborative researchers to assure that the underlying cross feeding can efficiently occur. Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 7

26 DSI research execution will be ICTS & SHES tandem-centric. It is worth also mentioning that several DSI protagonists have a long history of successful large scale multidisciplinary research projects, as challenging as DSI. This will be a valuable asset of DSI execution reliability. 7 What is the DSI ramp up budget plan? 7.1 Initial launching The total budget needed for the first 3 years of the Institute is 1.75 Me. Details : PhD grants : 5 interdisciplinary PhD grants will be allocated for the 3 years. They cost 50keper scholarship per year, i.e., in total 750 ke over the 3 years. Summer Schools : will be run during years 2 and 3. The cost is 50 ke per School, hence 100ke in total for the first 3 years. Think-Tanks : we want to run 3 Think-Tanks per year, one with physical lock-in meetings (estimated cost 40ke), and 2 where most participants use audio-conferencing (estimated cost 20ke each). In total, this amounts to 80ke per year, 240ke for the 3 years. Workshops : 3-4 thematic workshops will be organized every year, for an estimated cost of approximately 100ke per year, i.e. 300ke for the 3 years. Chaires/Post-docs : One chair of excellence, or 2 Post-doc grants will be allocated every year, costing 120ke per year. Total 360ke for the 3 years. 7.2 Perennial Financing After the first 3 years, with an established record of DSI activities, we can build a strong case for national and EU funding on our own, with the target of financial autonomy a few years later. Several participating institutions have already indicated that they would target some of their own resources (PhD grants, post-docs positions,...) to topics relevant to the Institute activities. We will ask for yearly financial contributions from the participating academic institutions and industrial partners (see Section 3). We will also apply to regional call for DIM (Domaine d Intérêt Majeur, 8 What is the DSI Governance? Light Governance. During the first 6 months, DSI participants favor a light governance to manage immediate activities kick-off without initially relying on any particular legal structure that could turn out to be inadequate, costly and/or redundant to transversal services of the UPSa IDEX or of its numerous partners. This first 6 month period would nevertheless be used to evaluate different legal frameworks possibilities in close collaboration with the FCS. According to the conclusions of this 6 month evaluation, a special structure would be created, if necessary. Rationale. Because the future DSI is part of the UPSa IDEX and will be supported by contributing research and education institutions (already having their internal services for contracting, financing & hiring doctorate students and postdocs, etc.), all DSI management and startup tasks can be accomplished right away without launching any legal structure. Bureau and Scientific Committee. The DSI light governance will rely on a single, wide coverage (one member per contributing organization), decision committee, called the DSI Scientific Committee (SC) that will convene once a month. The day-to-day operations supervision and DSI outside representation will be managed by a three-member DSI Bureau that will be in touch once a week. The DSI Bureau will prepare issues to be decided upon by the SC, such as budget allotment, expenses, new projects kick-offs, former projects closures, workshops, PhD & postdoc financing, etc. The SC will also collect the inputs from DSI Think-Tanks about Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 8

27 potential projects to launch. The SC will evaluate once a year on going projects. The first SC gathering will confirm its own and the Bureau members. 9 Which research projects are affiliated with the DSI? As of January 16, 2013 DSI hosts two categories of projects : (1) projects that have matured enough the last 6 months for immediate kick-off and (2) emerging projects that still require coordination to sharpen the milestones, road map, the budgetisation and to confirm partnership with key public institutions. These latter DSI projects can kick-off in the short to medium term, within a 6 month consolidation period, that will mainly be leveraged to hold workshops to fill-in the blanks. Both ready-to-be-launched and short-term kick-off projects are listed hereafter. With DSI s dynamic mode of operation (see Governance), these two lists are permanently open to revision, according to DSI Think-Tanks recommendations and Scientific Committee decisions/evaluations. Since most DSI members institution have expressed interest to join all the listed projects, to avoid repetitive lists of potential research partners, we only mention the originators of each project. Numerous big companies (named in section 3.2) and SMEs are keen to officially join DSI initiative, provided it is selected by the FCS. 9.1 Immediate Kick-Off Projects Joint Human & Machine Evolution : Societal Enablers of elife based (SEeL) on Collaborative, Ubiquitous and Multimodal Interactions : INTERCO Motivation : Evolutionics. The rapid emergence of sophisticated man-machine interfaces, robots and numerous gizmos that keep us almost permanently connected have already started to impact and modify our behavior, our reasoning capabilities, the way we socialize. In return, we have come to expect digital mutations of these same machines who have truly become digital species. We can now see machines and human beings as being inextricably engaged into a sometimes seamless, joint and continuous coevolutionary process. This joint humanmachine coevolution, termed evolutionics, is a new emerging field of research that straddles the boundaries of SHES and ICTS disciplines. Evolutionics can be neither machine-centric nor human-centric but can only be understood and anticipated by relying on joint expertise on how a hybrid population of man and machine will jointly evolve. INTERCO : Societal Enablers of elife based on Collaborative, Ubiquitous & Multimodal Man-Machine Interactions. One central evolutionics issue is the collaborative role of increasingly ubiquitous, increasingly multimodal interfaces, machines and robots. These machines can become digital buddies of human beings, helping them by providing interactions tailored to individual and/or collective situations. This smart (in a non-marketing sense) behavior relies on the knowledge of particular personal habits or on group collective behavior. The INTERCO project has prepared two ready-to-kickoff sub-projects around digital coaching, adapting collaborative machines to real-life scenarios : (1) Quality of elife (QeL) : Collaborative management of resources in smart neighborhood, (2) Multi-activities and attention in driving situations. A preparatory INTERCO coordination and information workshop already took place on January 10th 2013, at Télécom-Paristech INTERCO1. QUALIA : Quality of elife (QeL) : autonomic management of resources across a neighborhood of smart houses Context. Intelligent homes are at the heart of contemporary technical and societal issues, concerning energy efficiency, comfort, home care assistance, well-being, safety of possessions and persons and sharing of contents. In order to ensure user acceptance, intelligent home design and implementation must be based on the study of human practices at home and in a neighborhood. In order to ease their integration and maintenance, intelligent homes components must be capable of self-management/self-adaptation Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 9

28 by observing themselves and their environment, by analyzing the situation, planning and executing actions. Intelligent management must lead effectively to the correct and efficient utilization of resources to be shared between several houses in a given neighborhood (water, electricity, collective heating, etc.). Energy management must be mastered in such a way as to encourage and promote the effective use of intelligent services by human beings. In the neighborhood of intelligent homes context, autonomic computing and psychological ergonomics find a perfect testbed for the study of collaboration between artificial systems and human beings (between systems, between humans, mediated by systems, and between humans and systems), on different levels of granularity (house, neighborhood, region, country), based on models of human-machine dialogue, interpersonal interaction and task-oriented collaboration between humans. Whether autonomous, autonomic or not, machines work for and with human beings ; they must transform the objectives expressed by users into technical objectives that are understandable by the system, detect and manage possible conflicts, uncover information where it can be found, present it differently according to the device used, and adapt dynamically their interfaces for communication with human beings. In this project, we are particularly interested in indicators that measure the quality of collaboration in order to evaluate on one hand the gap between individual objectives and global goals, and on the other hand, the degree of satisfaction expressed with respect to the human-machine interaction. Objectives. This research project is multidisciplinary, bridging domains of human and social sciences (psychological ergonomics) and of information and communication technologies (autonomic systems, distributed computing and human-machine interfaces). The global objective of the project is to design and evaluate a system where artificial agents and social actors (home inhabitants, local authority officials, representatives of energy companies, etc) reach a collective decision in order to manage shared resources at the level of a neighborhood. The decision must take into account external fluctuating factors (price of electricity, water, usage rate, technologies available, etc). Such situations therefore involve multiple actors, multiple expertise, variable shared knowledge, management of multiple constraints, collective decision-making in a dynamic system based on discussion, negotiation and argumentation. We propose two cross feeding PhD theses, each of which will contribute to the other, one primarily focused on psychological ergonomics and the other on autonomic computing. The strong link between the two theses will be established by working jointly on the design, implementation and evaluation of a serious game for management of energy resources. Experimentation of such management will be conducted through the use of a simulation prototype of interconnected intelligent homes, already developed at Telecom ParisTech as well as in the environment of the real intelligent home platform MobileMii being constructed at Nano-Innov Saclay. The prototype will evolve to take into account the results obtained in both academic disciplines throughout the duration of the interlinked PhD projects. Regarding the psychological ergonomics discipline, the experimental study of the collective decision-making situation will establish the empirical basis in terms of human practices of collective decision-making concerning energy management, to which the PhD in autonomic computing will refer. The research will emphasize development of methods for analyzing communicative task-oriented interactions between human actors and between them and machines, drawing on previous results of research on modeling quality of collaboration. Previous work has shown a bilateral relationship between quality of collaboration and effective advancement in collaborative tasks, where a sufficiently high degree of quality of each is a requirement for the other. Such models are multi-criteria, and concern factors such as grounding (inter-comprehension), fluidity of (non-) communicative action coordination and crucial in this situation strategies for cooperative resolution of verbal conflicts in and by argumentation dialogue. The interactive circulation of affect, and the resolution of interpersonal tensions, will also be studied. Regarding the autonomic computing discipline, the evaluation of models will be based primarily on analysis of the quality of collaboration between humans, humans and machines and between machines, in relation to the optimality of the result obtained in terms of electric power resources management. The first step will be to define a collaborative autonomic management system (implementing the self-management loop) capable of communicating with other such Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 10

29 systems or humans. The system will be inspired by existing models of human collaboration and will define and evaluate new ones. Several strategies will be developed as a function of dynamic interactions between human and machines, as well as between humans. The second step will be to explore human intentions, potentially in conflict, transform them into objectives that can be dealt with by an autonomic manager (constructive resolution or compromise building). The third step will be to propose feedback that is understandable by humans, regarding the justification of choices made by the artificial agents, as well as explanations of strategies used to achieve technical objectives. A temporal balance will have to be found between artificial and human elements of the complex system. Self-management loops must indeed manage the frequencies with which they function and take into account human temporality (slow reactivity, possible errors). Regarding the evaluation of our approach, the population of subjects/players will be students in different courses (economics, engineering, biology,...), which will allow investigating multicompetence decision-making. The relevant variables will be the nature of the rules of the game, the extent to which participants share knowledge concerning the situation and its constraints. Other relevant variables will be identified during pilot studies involving face-to-face collaboration, in the real world (MobileMii platform) and pencil-and-paper versions of the game, as a means of design and implementation. Road map, Milestones (M) & Deliverables (D) : T : M starting 2 theses : Towards autonomic management centered on the quality of collaboration with humans : application to an intelligent neighborhood and Quality of collaboration for decision-making in a dynamic situation, T+12 : D state of the art, common principles (psycho-ergo and autonomic) for the modeling of collaboration and the evaluation of the qualities, specification of the serious game, T+18 : D first version of the models, first prototype of the serious game, T+24 : D final version of the models, T+30 : M starting an engineer working on the MobileMii platform, T+36 : D final version of the prototype of the serious game, evaluation of the models, T+36 : M end of the two theses, D for thesis 1 and D for thesis 2, T+48 : M end of the engineer work, D real-world focus group evaluation on the MobileMii platform. Originators of the project. Psychology ergonomics : M. Baker and F. Détienne (Research Directors), Telecom Paris- Tech Autonomic computing : I. Demeure (Pr.) ; A. Diaconescu & R. Sharrock, (Ass. Pr.), Telecom ParisTech NanoInnov and MobileMii platform : B. Dorizzi (Pr.), Telecom SudParis INTERCO2. MATIN : Multi-activity, ATtention and INteraction in mobility situations Objectives. Attention distribution between the driving activity and other parallel activities is a normal and common way of behaving, but it generates a risk for the security on the road. It is then essential to study this phenomenon of distributed attention very carefully. Due to the automation of some functionalities of the vehicles (e.g. cruise control systems), and due to the development of mobile communication technologies, drivers are more and more tempted to develop activities in parallel to the driving task ; it is important to help them to deal with this multi-activity safely. However, these attentional moves and micro-regulation of the multi-activity are very complex phenomena to study. Some studies have been performed in an experimental context of simulation The studied situations then remain artificial and their ecological validity may be questioned. Furthermore they do not take into account (1) attentional moves independent of the gaze (I look in front of me but I am mainly attentive to a sound), (2) the effect of some events on attention quality, such as important, urgent, worrying events which captures the attention, (3) the attentional strategies that drivers may develop to perform these multiple activities, finding for instance contextual moments or gestures which are safer. The study of the way people naturally deal with multi-activity (we will focus mainly on Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 11

30 driving and communicating via new technologies : sms, social network, ...) is essential to design adequate technologies and to adapt the HCI modes, in order to maximize safe driving while allowing people to maintain multi-activity. This study will then propose ergonomic specifications to adapt the instruments for communicating while driving. Road map and deliverables For analyzing these processes of multi-activity and distributed attention in natural settings of driving, we will combine two types of methodologies which are complementary : Detailed analysis of videotaped behaviors during the drive and of videotaped context of the driving scene (ethnomethodological approach) ; the contextual moments when the drivers switch their attention, their gaze movements and the gestures will be analyzed. Analysis of the lived experience of the user (psycho-ergonomic approach) during these moments of multi-activity (focus of attention, thoughts, feelings, risk perception,...), gathered with post-activity interviews (Explicitation Interview and Self-Confrontation interviews). This fine-grain study will implicate drivers followed during several days. Their level of driving expertise, age, and communication tools used will vary (with visual, audio and tactile modes). The ergonomic objective of this study is to improve the reliability of the activity system in the vehicle by orienting design choices (embedded systems, interaction modalities and other HCI points). The results will then be interpreted to inform the design of new HCI tools. T0+6 D : state of the art on distributed attention, multi-activity and ICT use in mobility, T0+12 D : set up of the methodology : population and situations studied ; techniques of investigation ; different conditions of use, T0+24 D : analysis of the ecological processes of attention, change of focus, and feelings associated during multi-activity, depending of the context (road situation, tools used, type of message), T0+36 D : prescriptions for the design of adapted HCI modalities and tools Originators of the project. (SHES) Béatrice Cahour, Christian Licoppe, Julien Figeac from SES Télécom Paristech. (ICTS) Eric le Colinet, James Egaan, Yves Guiard from INFRES, Télécom-Paristech Privacy and Digital Identity Context. Privacy and digital identity have become major issues in the digital society. Individuals and their personal data are increasingly exposed on the Internet : First, technology is able to capture, store and process increasing amounts of data. Second, social norms governing privacy are changing profoundly as a result of the behavior of individuals. Third, the digital economy is often powered by the commercial exploitation of personal data as a source of advertising revenue or to create innovative personalized services. These technological, social and economic changes raise difficult problems of regulation. On one hand, the use of sensitive personal data can cause great harm to individuals (discrimination, intrusion into personal affairs, identity theft, ad pollution...). On the other hand, personal data are needed to develop new services, not only commercial services but also administrative, health and other services. Regulation has to keep a balance between the protection of privacy and the dynamics of innovation. These multidimensional issues require cooperation from different disciplines, specifically between researchers in Information and Communication Sciences and researchers in Social Sciences (economists, lawyers, sociologists). The Saclay Campus provides great opportunities to develop such a cooperation within the proposed Digital Society Institute by mobilizing researchers belonging to research organizations members of Saclay Campus and already interested in the problems of privacy and digital identity. Objectives. This program could begin with the launch of the Institute, since some DSI research teams are already engaged in collaborative operations (research programs) or proposals. Program will be focused on 3 directions. Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 12

31 Information leakage, virtual footprints Users of Internet services, mobile phones, actively publish information on social networks, in an active manner. Passively, they also leave traces : geolocation, customers habits, relationships, without deliberately doing so, for instance using urban services. Both information flows can then be used to track, analyze and profile users. From a computer science perspective, several disciplines can be invoked to analyze the flows, and to enhance privacy. Information Theory, for instance, provides measurements, metrics, and tools for quantifying information leakage. It can also be used to enhance privacy, with new tools like differential privacy. Social Science social requirements must also be respected, for example, to provide the acceptable level of privacy. The right to be forgotten, the right of individuals to have their data deleted when they are no longer needed for legitimate purposes, is often claimed as an essential element of privacy. But the application of this right is difficult to enforce. Many business models of web firms, especially on the mobile Internet, are based on the exploitation of digital traces. How to allow Internet users to keep some control over the use of their personal data (and not just over the data collection) without restricting the emergence of new services? Different strategies can be imagined, such as user control over data protection measures (anonymization, cryptography, randomization...), or legal definition of fair use of such data by web firms. The DSI objectives are : (a) to evaluate the feasibility of these strategies on the economic, legal and technical level, and (b) to develop specific techniques, based on (possibly a combination of) the previous strategies, suitable for some case-study applications. Short term objectives. Assess precisely the relevance and suitability of the various privacy-bydesign and information leakage frameworks with respect to social needs, usability, and acceptance. Estimate the consequences on economical models Personal identity, anonymity Impassioned debates surround the notion of identity and anonymity, as illustrated by the media coverage of Google or Facebook asking users to universally identify themselves by using their Google or Facebook identifier. Normally, each user has multiple identifiers to access online services, generating two problems : (i) transaction costs for users (data manipulation costs, cognitive limits of individuals), and (ii) service providers must bear users authentication costs. The need for a universal identifier is growing. But authentication needs are different, depending on characteristics of transaction (health, ecommerce, taxes...). Service providers swing between light systems that create low entry barriers for users and stronger ones for the needs of marketing, billing or certification of the transaction. Some users are eager to protect themselves, while others remain unconcerned. Among those who want to protect themselves, some are not ready to accept the requirements of anonymisation tools. Very strong upstream and downstream tools can be used to enforce anonymity. For instance, anonymous r ers, strong crypto are applied upstream to prevent revealing true identities, while, on one hand downstream law enforcement may punish bodies violating anonymity. Advanced cryptographic protocols can provide ultra-strong privacy. However, they are counter intuitive, and we hardly imagine wide public adoption of these tools. On the other hand, a proposition is the vision of trusted cells : personal data servers running on secure smart phones, set-top boxes, secure portable tokens or smart cards to form a global, decentralized data platform that provides security yet enables innovative applications. We argue that protecting users at the edges of the Internet, as opposite to the cloud, could trigger a sea change and give the control back to the user on her data. Very strong anonymity, high networking can also allow criminal activities, see for instance SilkRoad which lays the ground for forbidden traffic. Our DSI objective here is to compare the characteristics of anonymization tools with user requirements, whether on the Internet users side or on the web firms side, and with legal issues. Our DSI objective is to develop anonymization techniques satisfying the needs of both the Internet users and the web firms, and abiding by the law. Short term objectives. Assess the suitability of the various kind of anonymization techniques with respect to social needs, human rights, nation sovereign rights, both from the users and from the industrial points of view, while taking into account also legal and economical issues. Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 13

32 Big Data Current ICTs can provide huge data sets (big data) on consumers and citizens, stored by firms or available on social networks. Big data are a key challenge for technical reasons, related to the size and the complexity of unstructured data, and for socio-economic and legal reasons, especially in the field of privacy. Moreover, big data often consists of many heterogeneous pieces of information gathered from many sites, on which so-called big data analytics is run and may lead to discovering new (derived) information, raising its own challenges to privacy, which require a careful analysis from a legal and technical perspective. Data provenance is one possible technical tool to trace the origin of derived data and accordingly the who has the right to have it and use it. Technical solutions to protect both privacy and innovation based on the use of Big Data have led to a debate about Privacy-by-Design, in which data protection is embedded from the early design stage of software, services or business models. But the concept is still fuzzy, at the border between technology and law, incentives for firms to adopt it are weak and perverse effects can be produced on users. Interdisciplinary work such as the DSI can provide is needed to clarify this notion which will play an important role in the coming European privacy regulation. Software firms and web firms are also directly involved in this task. Short term objectives. Highlight areas of compatibility or non-compatibility between privacy tools in the case of big data, incentives to adopt them for firms or end users, current evolution of legal rules. In the first year, the DSI will organize 3 Workshops involving research laboratories, companies and institutions (such as the CNIL) around these three themes to enable the researchers to get to know each other and to define joint research programs (e.g., ANR). Budget. The requested budget is focused on the first year. Three workshops (W1, W2, W3) W1 in March 2013 : Technical and economic challenges of the Proposed Regulation (published by the European Commission in January 2012). Law, Economics and Information Science. W2 in June 2013 on Big Data. Managed by Telecom Paris Tech and Université Paris Sud (ADIS, CERDI) W3 in September on Information leakage, privacy, and anonymity. To start quickly, 2 PostDoc are required, on the topic of protection of sensitive information, integrating computer science, legal, and socio-economical perspectives. INRIA Comete has a candidate, and Université Paris-Sud, ADIS, has agreed to find one. Originators of the project. Daniel Augot, Catuscia Palamidessi, Philippe Pucheral, (INRIA). Alain Rallet, Serge Pajak, Mathieu Manan, Antoine Latreille, Ioana Manolescu (Université Paris Sud). 9.2 Short/Medium term kick-off Projects ehealth. Project icaretify : Assessed and Certified Contact-less ecare Systems and Services (Societal Enablers of elife and Quality of elife that pertain to ehealth) Objectives. In-home ecare is an attempt to limit the time spent in hospitals or nursing facilities for seniors with diminished autonomy, reducing health care while fostering self-sufficiency and community insertion of elderly persons appreciating home and family care. The project s objectives are to identify the chain of risks and responsibilities of ecare systems and to improve the critical elements, laying the ground for future systems of certification. The operation of a system providing contact-less exchanges to and from a person relies on a set of essential building-blocks : patient-machine collaborative interfaces, home (private) network, access network requiring a service provider (2G, 3G, even POTS), supervisor (artificial/human), away from the patient home. Some elements, e.g. the wireless segment, are prone to temporary or permanent failures. Guaranteeing a very high reliability level of devices and of the life connection will require dedicated scientific developments. Redundant/resilient systems must take into account acceptability and the wider issues of human agency, negotiating the boundaries between private and public social Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 14

33 contexts, especially under impairments (e.g. neurological). Another issue is privacy and security by design, so that the system only collects adequate, relevant and not excessive personal data, under appropriate security measures, also accounting for information ownership. Responsibility is furthermore a fundamental question in quantifying the chain of liabilities due to wired/wireless connectivity failure, sensors/activators malfunction, and erroneous medical assistance. Finally ethical and individual responsibilities are also key issues. The project is deeply multi-disciplinary, requiring expertise and cooperation between researchers and key actors in electronics, communications, health, law and social sciences. Road Map, Resources & Deliverables 1st phase ( ) : investigation of the key issues M0 to M6 : State of the art, Inviting potential partners and building the steering committee, M6 to M18 : 1. identification of ecare systems weaknesses and initial studies (2 Post-doctoral researchers + student internships) ; 1 report provided at M18 2. preparation of proposals intended for complementary funding (ANR, FUI, CIFRE...), M12 to M36 : launching of sub-projects ; DSI support maintained for upstream work. 1 report provided at M36. 2nd phase ( ) : provision of certification procedures and tools. This phase will require a major participation of the interested stakeholders. The project output will be a set of standardized procedures and tools in order to certify the security, reliability, acceptability and privacy of a candidate contact-less ecare technology. Originators of the Project. (SHES) Antonio Casilli & Claire Levallois-Barth (SES, Télécom- Paristech) ; (ICTS) Alain Sibille, Jean Claure Belfiore, Philippe Ciblat, Jean-Luc Danger, Lirida Alves de Barros Naviner, Christophe Roblin (Comélec, Télécom-Paristech). Dedicated potential partners to ehealth project. Operators/access providers : Orange. About 15 SMEs active in ehealth have already been identified Insurers (Axa, mutuelles ), hospitals (CHU) : TBD. Communities of patients : Institutions & Agencies : CNIL, ASIP Santé eeducation Education is a key theme in the digital society institute of Paris-Saclay university. Education is now considered as an integrated and ongoing process of life long duration, taking place in formal, semiformal and informal settings, growingly relying on information and network technologies, which have a huge impact on the contents to be learned, pedagogical approaches, and organizational aspects. Several SHES and ICTS levels (macro, meso, micro) are intertwined. For example, the MOOC (massive online open courses) phenomenon can be studied at a macro level (its role in the global educational market), at a meso level (persons involved, course organization), at a micro level (student activities, interactions, feedback and so on). Social processes and discussions (among students, tutors) can be supported and analyzed on these different levels, with different linguistic and cultural features. Personalization takes into account characteristics of the learner and requires expertise not only in IT but also in educational sciences. Several dimensions have to be joint SHES and ICTS concerns : economical and law issues, contents and curricula, certifications and diploma, educational resources (from simple ones to complex simulations or serious games) including their description (metadata and norms), actors (human and non human)... not to forget linguistic, cultural and ethical issues. Educational issues are also an important component of other DSI themes, in the research process itself and in research dissemination. Paris-Saclay is designing advanced S&T courses and platforms to be shared with all institutions part of this university. Designing, implementing and testing such platforms is a great challenge which we address. The first objective of this project is to concentrate on the key problems required by the development of MOOCs. Concerning resources and learning trails : which Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 15

34 personalization? How to take into account past experiences? How to adapt them to different learner profiles? How to identify relevant learner profiles? Concerning team work : How to provide the cartography of students involved? How to help in team constitution? Which links between teams can be identified? How to integrate social networks? Design tools for tutors and learners to help managing collaborative work (a very active field internationally) How can we transform courses and their related educational resources in different MOOC formats? Which learner activities are supported by MOOCs? Possible launch of the project : October Two workshops will be organized in March 2013 and June 2013 in order to finalize a road-map for this project. Originators of the project. Eric Bruillard (STEF, ENS Cachan), Yolaine Bourda (E3S, Supélec), Frédéric Chazal, Nozha Boujemaa, (INRIA), Pierre-Jean Benghozi (Polytechnique), Joelle Toledano (Supélec) Business models, Digitality and Ecosystems Dynamics Issues. The competitive landscape of firms and economies is undergoing a deep transformation, due to the digital acceleration, leading to a democratization of innovation and the emergence of new forms of business models. The ubiquity of digitality poses important questions, related to the time-span of competitive advantages, to the modes of coordination between the vertical organization the large enterprise- and emerging forms of exercising activities - small businesses, communities, work in solo, clusters and intermediate forms of exercise activities. Technologically, the emergence of big/open data phenomenon will deeply transform the ecosystem of firms and their organizing models. These models need to be understood conceptually as well as in terms of the impact on established businesses and the sources of their value creation. Understanding the dynamics of these new business models requires a multidisciplinary approach ranging from technology, to business and law (for instance with regards to data ownership). It also needs a deep understanding of the dynamics of interaction between technological artifacts and systems (the Internet of Things-IOT, not only about things but organizations, societies and people), the emergence of new platforms for socioeconomising (for crowd-sourcing, open innovation, horizontal links...). Research, policy and business Gaps. There is a need to understand business models from a multidisciplinary approach. This is can be done by looking at how the potential of technologies can and are being leveraged by firms and other forms of organizations. We need to better understand how ICTS are transforming lines of businesses, at what speed, and what are their economic, legal and business ingredients from an SHES viewpoint. Tasks. We will develop a series of workshops (2 in 2013) aimed at the articulation between ICTS issues and SHES (business, legal, economics) perspectives, to develop an common and articulated work-plan. This is in the perspective- in the next phase, (starting Mid- 2013) to better : Assess the generic nature of digital technologies and their mode of diffusion Document key technologies developments and their potential use for new business models focussing on big/open data issue Document the modalities of diffusion of these technologies and their impact of specific sectors of activities Provide a typology of business models, identifying the most likely to be successful Originators of the project. Ahmed Bounfour, Antoine Latreille, Alain Rallet (Université- ParisSud) ; Pierre-Jean Benghozi (Polytechnique) ; Valérie Fernandez (Télécom-Paristech) INTERCO3. Conflicts with Embodied Conversational Agents in Virtual Worlds Context. Numerous studies have shown that humans apply emotional behavior toward systems and spontaneously attribute intentions, beliefs, desires, or even strategies to their interaction (Dennett, 1992). They naturally talk and respond using verbal and non-verbal modes. They Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 16

35 are sensitive to messages sent by the interaction systems. This bidirectional interaction is very prominent when the interaction takes the form of a humanoid agent. Expressive conversational agents, virtual and robotic autonomous entities, are able to communicate verbally and nonverbally with users. To account for the bidirectional interaction, they must have capabilities allowing them to detect and interpret socio-emotional signals of humans, to plan and communicate appropriate behavior. Objectives & Deliverables. What are the different expressions of conflicts in interactions? What is the part of violent and aggressive behaviors? What is the share of verbal and nonverbal behavior? How do explosiveness, bad mood, irritation, annoyance, deception, or disgust express themselves? How do the answers of user covariate when behavioral traits related to conflicts are activated by a virtual humanoid? How do users obey various articulations of those expressive traits? One particular topic from experimental sociology of interactions that the DSI will study is the influence of the gender parameter : how does the fact that the humanoid is a woman (versus a man) influence the user reactions? Another aspect of our DSI studies is to proceed to an ethnographic exploration of natural situations of conflicts with artificial agents on the web (Non-Player Characters in video games, or Bots in massive collaborative projects). What are the dynamics of conflictual HRI (Human Robot Interactions) in those different, ludic or serious but natural, contexts? What is the influence of the transposition of the observation settings in a video game culture (by transforming it into a social game) on the user behaviors? Survey system. The Greta and Semaine platforms will be used in this DSI project for the conversational agents. Agents will be adapted to show confrontation. Interactions with naive users and different agents will be used as basis for the study. Methodology : A dual system of investigation will be considered : 1. The experimental study and observation of the interaction of an observer with an agent in a laboratory. This will be done from the design of a humanoid avatar with confrontational behavior in a situation of mini-interaction, such as coaching or learning requires the reprimand of a user. The software allows us to vary certain pragmatic and semiotic parameters. The choice of the parameters will be defined due to the postdoc work. 2. The study and observation of interactions of players and artificial agents (Non-Personal Characters, or Bots) in natural existing online contexts. In both cases, user reactions will be video recorded (facial expressions and exclamations, due to a recording with voice quality). Some post-experience complementary interviews will be done to confront users to the recordings or to better understand the emergence of conscientious dynamics of conflict. Originators of the project. (SHES) Nicolas Auray (SES-Télécom-Paristech) ; (ICTS) Catherine Pélachaud (TSI-Télécom-Paristech) ejustice In criminal as well as in civil domains, information and communication technologies (ICT) are now parts of usual procedures and practices. To some extent, paths are now open to the digitalization of justice systems, or to a process of digitalization of justice. Questions raised by ejustice deal with certification processes, neutrality of technological tools, identification techniques and the circulation of personal data. More generally, ejustice puts the stress on the place of technologies in human interactions that are by definition strongly framed by human proceedings in a word, the new technological tools can be adapted to law or to formal legitimacy. DSI research teams have so far, as kind of examples, worked on CCTV uses, on videoconferencing in remote hearings, or on the digitalization of civil procedures. Our aim is now to have the DSI investigate the way justice system s stakeholders figure out the role of different technical tools, how they frame their demands addressed to the suppliers, if there is a way to a sort of ejustice in France and what this ejustice should look like in their eyes. These stakeholders can be found at the local level (judges, lawyers, bar associations, police services...) and at the national level Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 17

36 (ministries of Justice and Interior, the National Council of Bars Conseil national des barreaux which implements the French e-bar project for instance, etc.) The DSI team currently includes SHES research fellows. In a first step, our aim is to strengthen the research network with the ICTS Canadian cyberjustice laboratory that focuses on digital software technologies in civil law, criminal procedure and negotiation-mediation processes. In the same time, we would conduct in-depth discussions within DSI ICTS partners and with the stakeholders in the French Justice and Interior ministries in order to list their agenda and discuss what their main projects are in the domain of ICT. This program will seek to launch a series of seminars set up together with the Ecole nationale de la magistrature and the Ecole nationale supérieure de police (respectively schools for the magistrates and for high-ranked police officers in France), with a focus program on technologies and criminal evidence. CESDIP is used to working closely with both of these institutions. Originators of the projects. Fabien Jobard (CESDIP-UMR8183) ; Christian Licoppe (LTCI- UMR5141) ; Benoit Bastard, Laurence Dumoulin (ISP-UMR7220) ; Tanguy Le Goff (Institut d aménagement et d urbanisme, Région Ile de France), Pierre Piazza (U-Cergy), Frédéric Vesentini (UVSQ-CNRS) INTERCO4. emoi : e-mbodied M-iniature m-o-bile Interactions emoi area of research concerns miniature mobile computing from both SHES & ICTS perspectives. For instance, digital jewelry aims at reducing computing objects to small enough sizes that they look attractive while allowing intuitive and efficient interaction. This requires the development of a whole variety of new forms of multimodal interaction. Surfaces, materials, clothes (wearable computing), even the open space surrounding the user, can be exploited through 2D or 3D gestural interaction so as to increase the interaction bandwidth between the user and the system. Even the user s body can serve as an input or output surface, not to mention the immediate environment (furniture, walls, floor). This research direction makes it important to understand the functions and forms of gesture and the possible articulations between gestures for communication/collaboration and gestures for interacting with a (task) artifact. This question is especially interesting in mobile collaborative situations, where the task is not predefined and the encounter is more opportunistic (either local and/or distant). It is then necessary to take into account emerging and evolving aspects of the collaborative situation, so as to understand the shared context and its evolution. Another specific aspect of our project is that we plan to take advantage of the rigorously defined concepts of information theory. Recourse to the mathematical theory of communication will help strengthen the theoretical aspects of our research in HCI. Given the dematerialization of the computer (or what is visible of it), and its embodiment (meaning that the user s body becomes the essential interaction substrate) one may envision tighter connections between body signals and computing systems. Here we must mention reflective technologies, thanks to which people receive immediate feedback on their activity as well as their physiological or emotional states, and which record traces for later individual or cooperative analysis. Road Map & Deliverables : Multidisciplinary workshops and two related PhD theses (interaction techniques for digital jewelry and mobile collaborative interaction) : Prototyping of embodied miniature body-centric interactions & Seamless co-located and distant mobile collaborative interaction. Originators of the project. (SHES) Michael Baker, Françoise Détienne, Béatrice Cahour (SES Télécom-Paristech) ; (ICTS) Eric Lecolinet, Olivier Rioul, Yves Guiard (INFRES & Comélec Telecom-ParisTech). Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 18

37 A Teams Involved in DSI, January 16th 2013 Nom, prénom du responsable Benoit Bastard Alain Rallet Christian Licoppe Gérard Memmi Yves Grenier Bruno Thedrez Frédéric Chazal Christian Delporte Fabien Jobard Statut DR CNRS PR, co-directeur de l ADIS PR CR Laboratoire, Etablissements de tutelle Institut des sciences sociales du politique, ENS de Cachan Laboratoire d économie gestion ADIS/PESOR Université de Paris Sud 8 représente le nombre de personnes impliquées au sein du laboratoire économie gestion de Paris Sud. Thèmes : privacy, modèles d affaires du numérique, systèmes d information Professeur, coresponsable du Département Sciences Economiques et Sociales, (SES), Télécom- Paristech Directeur du Département Informatique & Réseaux, (INFRES), Télécom- Paristech Directeur du Département Traitement du Signal et des Images (TSI), Télécom- Paristech Directeur du Département (Communication Numériques) COMELEC, Télécom- Paristech Directeur de Recherche LTCI-UMR 5141-CNRS & Télécom- ParisTech LTCI-UMR 5141-CNRS & Télécom- ParisTech LTCI-UMR 5141-CNRS & Télécom- ParisTech LTCI-UMR 5141-CNRS & Télécom- ParisTech Taille équipe Commentaires éventuels, Nombre Enseignants / Chercheurs impliqués dans l ISN 9 2 : 1DR + 1CR Geometrica 15 2 CHCSC (Centre d histoire culturelle des sociétés contemporaines), UVSQ CESDIP (Centre de recherches sociologiques sur le droit et les institutions pénales), UVSQ membres de SES UMR 5141 sont susceptibles d être impliqués dans l ISN (d expertises en ergonomie cognitive, sociologie, éthique, Interaction, mobilité et infrastructures) 5 membres d INFRES UMR 5141 sont susceptibles d être impliqués dans l ISN (d expertise en informatique autonomique, interactions, cognition et complexité) 4 membres de TSI UMR 5141 sont susceptibles d être impliqués dans l ISN (d expertise en identité audiovisuelle, postures, avatars et mondes virtuels) 4 membres de COMELEC UMR 5141 sont susceptibles d être impliqués dans l ISN (d expertise dans le partage du secret en théorie de l information et dans la sécurité en ICTS) 6 (+ 1 au 01/09/13) : 1 PR, 3 MCF, 1 PAST, 1 IGE (+ 1 MCF) 6 : 2 DR, 2 MCF, 1 ch. IAU-IDF, 1 IE CNRS Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 19

38 Nom, prénom du responsable Muriel Chagny Laura Kendrick Jerôme Pelisse Pierre Zweigenbaum d Ales- Christophe sandro Jean-Luc Gauvain Jean-Paul Sansonnet Patrick Bourdot Jean-Claude Martin Eric Bruillard Statut PR PR MCF DR CNRS DR DR DR DR Professeur Sud PR Laboratoire, Etablissements de tutelle DANTE (Droit des affaires et nouvelles technologies), UVSQ ESR (Laboratoire Etats, religions, sociétés, Antiquité-Temps modernes), UVSQ PRINTEMPS (Laboratoire Professions, institutions, temporalités), UVSQ LIMSI, UPR 3251 CNRS CNRS LIMSI, UPR 3251 CNRS CNRS LIMSI, UPR 3251 CNRS CNRS LIMSI, UPR 3251 CNRS CNRS LIMSI, UPR 3251 CNRS LIMSI, UPR 3251 CNRS STEF, Cachan UP- ENS- Jean-Daniel Fekete DR Aviz / INRIA 15 Daniel Augot Catuscia Palamidesci Wendy McKay / Michel Beaudoin- Lafont Ioana Manolescu DR DR DR/PR DR Grace / LIX INRIA et Polytechnique Comete / LIX INRIA et Polytechnique In-Situ / LRI - INRIA et UPS Oak / LRI - IN- RIA et UPS Taille équipe Commentaires éventuels, Nombre Enseignants / Chercheurs impliqués dans l ISN 24 4 : 3 PR, 1 MCF 19 3 : 1 PR, 1 MCF, 1 IGE 20 2 : 1 CR, 1 IGE chercheurs concernés (traitement données écrites, en particulier médicales et économiques et de la langue des signes) 3 chercheurs concernés (Art, création et ICTS) 5 chercheurs concernés (traitement documents multimédia, données et interaction homme-robot) 3 chercheurs concernés (réseaux sociaux, agents conversationnels, bâtiments intelligents, Art, création et ICTS) 1 chercheur concerné (travail collaboratif immersif) 2 chercheurs concernés (Perception et interaction homme-machine) 4 chercheurs concernés, axe Technologies et cultures informatiques : questions didactiques 3, Analyse et visualisation de données complexes de grande taille 9 2, cryptologie et théorie des codes 15 3, langages pour la sécurité des systèmes distribués, Modèles et techniques pour la protection de la vie privée et des données confidentielles 20 4, Interaction Homme-Machine 15 3, Big Data distribuées, modèles et langages pour données complexes Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 20

39 Nom, prénom du responsable Jacques Lévy-Véhel Marc Schoenauer Serge Abiteboul Pierre-Jean Benghozi Vazirgian- Michalis nis Antoine Latreille Ahmed Bounfour Yolaine Bourda Stéphane Font Pierre Duhamel Joelle Toledano Me Ludovic Alain Busson Statut DR DR DR Directeur PR, directeur du Cerdi Pr, PESOR et Chaire européenne de management de l immatériel Chef Département ISH Chef Département SSE DR. Pr. Pr. Professeur affilié du du Laboratoire, Etablissements de tutelle Regularity / MAS ECP et INRIA TAO / LRI - IN- RIA et UPS Webdam / LSV ENS Cachan et INRIA Chaire IRSN / PREG, Ecole polytechnique- CNRS LIX, Polytechnique et CNRS Laboratoire de droit Cerdi (EA 3537) / Université Paris-Sud PESOR (EA 3546), Université Paris-Sud, Equipe ISH Informations et systèmes hétérogènes, composante de E3S Supélec Sciences des Systèmes Equipe SSE : Signal et Systèmes Electroniques- E3S- Supélec Equipe Télécom et Réseaux- L2S- Supelec Equipe Economie -Supélec Equipe Cidre- Supélec HEC Laboratoire EOLE Karine Josse Directeur CEA LIST 10 David Mercier Responsable IDEA Lab CEA LIST / IDEA lab Frédéric Abergel Professeur MAS EA Marilyne Laurent Philippe Pucheral Professeur Professor Samovar-UMR 5157 SMIS/INRIA and UVSQ Taille équipe Commentaires éventuels, Nombre Enseignants / Chercheurs impliqués dans l ISN 2, processus stochastiques, analyse fractale, finance, sciences juridiques 4, apprentissage et optimisation, serious games et énergie 2, modèle formel pour les données sur le Web Partie de l équipe PREG-CRG potentiellement directement concernée par le programme 9 enseignants-chercheurs impliqués dans les domaines de la propriété intellectuelle, de la vie privée ou de la cybercriminalité 3, business models, systèmes d informaton, actifs immatériels, innovation 3 Systèmes hétérogènes avec applications à l ambiant. Personnalisation avec applications à l éducation Tatouage et sténographie de documents multimédia Protection de données personnelles et privées Prospective management de la création et de l innovation 3 Départements : DIASI, DILS, DCSI 6 EC impliqués dans l ISN (équipes LOGIMAS & Regularity ) 58 4 EC impliqués dans l ISN 5 2, Personal databases and privacy Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 21

40 B Five Selected Papers per Lab involved in DSI ADIS & CERDI (Université Paris Sud). Cecere G. et Rochelandet F., 2012, Modèle d affaires numériques, données personnelles et site Web. Une évaluation empirique, Revue Française de Gestion, vol. 38/224, p Chauvet D., 2011, Regard sur la vie privée au travail : l usage d Internet par les salariés, Revue Lamy Droit de I Immatériel, février, n 68, p Cecere G., Le Guel F. et Soulié N., Perceived privacy concerns on social network websites in Europe, Management and Economics of ICT, Munich, 29 février 2 mars Le Guel F., Measuring the Invisible Economy of Smartphone Applications, Amsterdam Privacy Conf., Amsterdam, 7-10 octobre Manant M., Pajak S. et Soulié N., Do recruiters like it? Privacy and Social Network Profiles in Hiring : A Randomized Experiment, Asia Pacific Innovation Conf., Seoul, octobre Rallet A. et Rochelandet F., 2011, La régulation des données personnelles face au web relationnel : une voie sans issue?, Réseaux, vol. 29, n 167/2011, p STEF Bruillard Éric (2012). Le déploiement des ENT dans l enseignement secondaire : entre acteurs multiples, déni et illusions, Revue française de pédagogie 177, oct.-déc. 2011, p Cisel Matthieu et Bruillard Éric (2012). Chronique des MOOC. STICEF, Volume 19, 2012, ISSN : , mis en ligne le 15/01/2013, http ://sticef.org Reffay Christophe, Dyke Gregory and Betbeder Marie-Laure (2012). Data sharing in CSCR : towards in-depth long term collaboration. In Collaborative and Distributed E-Research : Innovations in Technologies, Strategies and Applications, Angel Juan, Thanasis Daradoumis, Meritxell Roca, Scott Grasman, Javier Faulin Editors,, IGI Global http :// ISBN Reffay Christophe, Teplovs Christopher, Blondel François-Marie (2011). Productive re-use of CSCL data and analytic tools to provide a new perspective on group cohesion. In Connecting Computer-Supported Collaborative Learning to Policy and Practice : CSCL2011 Conf. Proceedings. Volume II short papers, Hans Spada, Gerry Stahl, Naomi Miyake, Nancy Law (Eds.), ISLS, pp , 4-8 july, 2011, Hong Kong, China. Preprint in archive. Tort Françoise (2012). The TEN project : use of tablets in French junior high schools. Invited Conf. Workshop Showcasing operator led meducation innovation and Education Sector/Mobile Industry collaboration MLearn th World Conf. on Mobile and Contextual Learning, Helsinki, October LTCI UMR5141 (Télécom-Paristech) F. Détienne, M. Baker & J.-M. Burkhardt (Eds.). (2012). Special issue, on Quality of collaboration in design. CoDesign : Int. Journal of CoCreation in Design and the Arts, Vol. 8, Issue 4. F Alvares de Oliveira Jr., R. Sharrock, T. Ledoux, Synchronization of Multiple Autonomic Control Loops : Application to Cloud Computing, Int. Conf. on Coordination Models and Languages (COORDINATION 2012), Stockholm, Sweden : Springer, Lecture Notes in Computer Science G. Georg, C. Pelachaud, M. Cavazza, Emotional Reading of Medical Texts Using Conversational Agents, Seventh Int. Joint Conf. on Autonomous Agents and Multi-Agent Systems, AAMAS 08, Estoril Portugal, May Cahour, B. et Licoppe, C (2010). Confrontation aux traces de son activité : Compréhension, développement et régulation de l agir dans un monde de plus en plus réflexif. Revue d Anthropologie des connaissances 4, Perrault S, Lecolinet E., Eagan J., Guiard Y. (2013). WatchIt : Simple Gestures and Eyes-free Interaction for Wristwatches and Bracelets. In Proc. ACM SIGCHI Conf. on Human Factors in Computing Systems (CHI 13). ACM. To appear. INRIA M. S. Alvim, M. E. Andrés, C. Palamidessi : Quantitative information flow in interactive systems. Journal of Computer Security 20(1) : 3-50 (2012). K. Chatzikokolakis, C. Palamidessi, P. Panangaden : On the Bayes risk in information-hiding protocols. Journal of Computer Security 16(5) : (2008). N. Anciaux, P. Bonnet, L. Bouganim, B. Nguyen, I. Sandu Popa, P. Pucheral. Trusted Cells : A Sea Change for Personal Data Services. Proc. of the 6th Biennal Int. Conf. on Innovative Data Systems Research (CIDR), Asilomar, USA, January Benjamin Nguyen, Antoine Vion, François-Xavier Dudouet, Dario Colazzo, Ioana Manolescu, Pierre Senellart. XML content warehousing : Improving sociological studies of mailing lists and web data. Bulletin de Méthodologie Sociologique 112, 1 (2011) D. Augot, A. Canteaut, G. Kyureghyan, F. Solov eva, Ø. Ytrehus, eds. Special Issue on Coding and Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 22

41 Cryptography. Designs, Codes and Cryptography (66), Issue 1-3, January E3S Bellik, Y., Rebaı, I., Machrouh, E., Barzaj, Y., Jacquet, C., Pruvost, G., and Sansonnet, J.-P. Multimodal Interaction within Ambient Environments : An Exploratory Study. In Proceedings of INTERACT 2009, Part II (Uppsala, Suède, 2009), no. LNCS 5727, Springer, pp. pp Dubus, G., Popineau, F., and Bourda, Y. A formal approach to personalization. In Proceedings of 23 rd IEEE Int. Conf. on Tools with Artificial Intelligence (Boca Raton (Floride), Etats-Unis, 2011), pp Jacquet, C., Mateos, M., Bretault, P., Jean-Bart, B., Schnepp, I., Mohamed, A., and Bellik, Y. An Ambient As- sisted Living Framework Supporting Personalization Based on Ontolo- gies. In Proceedings of AMBIENT 2012, The Second Int. Conf. on Ambient Computing, Applications, Services and Technologies (Barcelone, Espagne, 2012), IARIA, pp ISBN Mohamed, A., Jacquet, C., and Bellik, Y. A fault Detection and Diagnosis Framework for Ambient Intelligent Systems. In Proceedings of the 9th IEEE Int. Conf. on Ubiquitous Intelligence and Computing (Fukuoka, Japon, 2012), pp ISBN /12. Zemirline, N., Bourda, Y., and Reynaud, C. Expressing Adaptation Strategies using Adaptation Patterns. IEEE Transactions on Learning Technologies 5, 1 (Jan. 2012), Pesor (Université Paris Sud) Bounfour A.Grefe.G. (forthcoming) : Designing sequences for knowledge exchange, The Hau-Ba model. Knowledge and Space, Vol 6. Springer (Peter Meusbeurger Ed.) Bounfour A. (2011), Acceluction in Action. The First report of the ISD (Information Systems Dynamics) Int. research programme, Cigref Foundation, Paris / Bounfour A. (2010), : Les systèmes d information, des objets-frontières de la transformation des entreprises, Entreprises et Histoire, n 60, p. Numéro spécial, de l Information aux systèmes d information, dans les grandes entreprises. Nabeth T, Maisonneuve, N. (2011) ; Managing Attention in the Social Web : The AtGentNet Approach ; Book Chapter in Claudia Roda Ed. (2011), Human Attention in Digital Environments, Cambridge University Press Nabeth T., Razmerita, L. and A. A. Angehrn, Claudia Roda (2005) ; InCA : a Cognitive Multi-Agents Architecture for Designing Intelligent & Adaptive Learning Systems ; A special issue of ComSIS journal, Vol. 3, No. 2., December. Cerdi Code Lamy droit de l immatériel, éd. Lamy, 2008, 2100 pages, direction éditoriale et contributions pour la création de l ouvrage (Jean-Baptiste Auroux, David Mélison) Code de la Propriété intellectuelle, collection Codes annotés Dalloz, codirection 2012, réédition tous les ans Copyright throughout the world, dir. Silke von Lewinski (Institut Max Planck, Munich), 2010, ouvrage de droit d auteur comparé, partie française confiée au Cerdi sous la dir. de Pierre Sirinelli Les mesures techniques de protection et d information avec la collaboration de T. Maillard, Fascicule Jurisclasseur n 1660, décembre 2004, 30 p., refonte mai 2007 et mai 2011 La réception normative des dispositifs de protection et d information avec la collaboration d Alexandra Bensamoun, in Droit sciences et techniques : quelles responsabilités? Litec, 2011, Débats & Colloques n 35, p. 217 à 240. LIMSI M. Courgeon, C. Clavel, N. Tan, J-C. Martin, Front view vs. side view of facial and postural expressions of emotions in a virtual character, Journal Transactions on Edutainment (TOE), 2011, vol. VI, J-P. Sansonnet, F. Bouchet, Integrating psychological behaviors in the rational process of conversational Assistant Agents, 24th Int. FLAIRS Conf. (FLAIRS 2011), Palm Beach, Florida, May 18-20, 2011, P. Bourdot, T. Convard, F. Picon, M. Ammi, D. Touraine, J-M. Vézien, VR-CAD integration : multimodal immersive interaction and advanced haptic paradigms for implicit edition of CAD models, Journal of Computer-Aided Design, 2010, vol. 42, n 5, A-L. Minard, A-L. Ligozat, A. Ben Abacha, D. Bernhard, B. Cartoni, L. Deléger, B. Grau, S. Rosset, P. Zweigenbaum, C. Grouin, Hybrid methods for improving information access in clinical documents : concept, assertion, and relation identification, Journal of the American Medical Information Association (JAMIA), 2011, vol. 18, n 5, A. Mohamed, C. Jacquet, Y. Bellik, A fault detection and diagnosis framework for ambient intelligent systems, 9th IEEE Int. Conf. on Ubiquitous Intelligence and Computing (UIC 2012), Fukuoka, Japan, 04/09 au 07/09, 2012, Digital Society Institute, (DSI) Presentation - 16/01/2013 Page 23

42 IDEX Paris-Saclay CALL FOR IDEX 2013 RESEARCH PROJECT PROPOSALS Project title: Paris-Saclay Space Cluster (PS 2 C) / Nanosatellites Type of project: Research Project coordinator: Vidal-Madjar Daniel Function: Space Cluster Project Coordinator for the Paris-Saclay campus Laboratory: University of Versailles Saint Quentin/OVSQ daniel.vidal-madjar@orange.fr; Tel: In the center: the Nanosatellite cinema developed at the Berkeley Space Sciences Laboratory. The nanosatellite contains an ASIC developed at CEA-Irfu, one of the members of the Paris-Saclay Space cluster. Around the central image are various nanosatellite projects from this proposal (LATMOS, IAS, Irfu-SApAIM, LPP). 0

43 Introduction: The Paris-Saclay University to be created in 2014 will gather more than faculty staff and about students. It will be home to a very significant amount of space-related activities. The various space laboratories of the future Paris-Saclay have decided to coordinate their activities in a Paris-Saclay Space Cluster (PS 2 C). These are IAS, IDES, IRFU- SApAIM, LATMOS, LLR, LMD, LPP, LSCE, LTCI, OVSQ, E3S, L2S under the aegis of various supervisory bodies within the Idex: CEA, CNRS, Ecole Polytechnique, ONERA, Paris Sud University, Supélec, Telecom ParisTech, Versailles - Saint Quentin University. A permanent staff of 387 is involved (see Table hereafter) and of more than 500 when including nonpermanent staff. The laboratories cover a broad spectrum of topics (Earth-environment, solar system, planetary science, astrophysics, cosmology) and skills (management and realization of space instruments, multi-wavelength detection, qualification/testing/calibration, data analysis, etc.); they have access to large-scale space instrument qualification/testing/calibration platforms, take part in training and are closely linked to the space-related industries. Name, first name of manager Table 1: Teams taking part in the Space cluster Status Supervisory laboratory, facilities Team size, including IT Comments Langevin, Yves Dr IAS, Paris Sud University, CNRS 90 Astrophysics, Planetary science, Sun Chassefière, Eric Dr IDES, Paris Sud University, CNRS 10 Earth Observation, planetary science Lagage, Pierre- Olivier Dr IRFU/SAp, CEA +other Irfu technology departments Astrophysics, planetary science, Sun Hauser, Danièle Dr LATMOS, CNRS, UVSQ, UPMC 40 Earth observation, planetary science, sun/planets relationships Giebels, Berrie Dr LLR, Gamma astronomy team, Polytechnique 11 High-energy astrophysics (X-rays, soft, hard ) Vincent Cassé Dr LMD, Ecole polytechnique, ENS, UPMC, CNRS 30 Earth observation and Planetary science Rezeau, Laurence Dr LPP, Space Plasma Team, Polytechnique 28 Space Physics, Planetary Science, Plasmas, Plasma propulsion Moulin, Cyril Dr LSCE, CEA, CNRS, University of 15 Earth observation, Climate (Sun) Versailles Saint Quentin Godin-Beekmann, Dr OVSQ 5 Integration and Testing Platform Sophie Dumur, Didier Pr Supélec, E3S- Automatic Control 10 Satellite estimation and control Department Vannier, Jean- Pr Supélec, E3S- Energy Department 19 Propulsion and Energy Chain Claude Duhamel, Pierre Dr Supélec, L2S- Telecoms and Networks 7 Telecommunications, distributed source coding Nicolas, Jean- Marie Pr Telecom ParisTech, LTCI 15 Earth observation, satellite communications Our analysis convinced us that the IDEX call was a unique opportunity to strengthen our participation in the major programmes of space agencies (CNES, ESA, NASA, JAXA, etc.), via the development of a multi-year nanosatellite program. 1

44 Nanosatellite Context 1) Present situation At the beginning of the space age, only small satellites (a few kilos) could be launched. The size and weight of satellites subsequently increased, and can now reach tons. However, in the 90 s, the concept of nanosatellites (1-10 kilos) have been re-introduced in the US, mainly for student training purposes (see Figure below, from Janson, Siegfried 25 Years of small Satellites, The Aerospace Corporation; 9 Aug 2011). Nanosatellites can be entirely managed by a University: design-construction of the nanosatellite (instrument, platform), satellite control, data reception, processing and analysis; and they can be launched as piggy-back. Global Nanosatellite (1-10 kg) Launch History (Successful Launches) As can been seen in the Figure, there is a clear trend toward a strong increase in the number of nanosatellite launches. Indeed after the pioneering work at Stanford and other Californian Universities, many Universities in the US and around the world have developed a student nanosatellite program. In Europe, an ambitious program has been accepted by the European Commission as a FP7 program in January 2012: the QB50 program, which aims at developing in various Universities all over the world 50 nanosatellites to study the lower Earth thermosphere; a dedicated launch is scheduled in 2015 ( the Von Karman Institute (VKI) in Belgium is leading the program. Several international conferences about nanosatellites are organized each year. So far, a single French nanosatellite has been launched, the ROBUSTA nanosatellite developed by Montpellier University, which has thus pioneered the use of nanosatellites to 2

45 train students in France (2006). It was launched in 2012 with the first Vega European rocket. There are now 10 student nanosatellite projects, including 4 associated with QB50, which benefits from strong technical support and partial funding by CNES (Janus project). Ecole Polytechnique, part of PS 2 C, has set up a Centre Spatial Etudiant (student space centre) and is hosting one of the QB50 nanosatellites. 3

46 2) Trends for future a) More and more nanosatellite launches In the near future the number of nanosatellite launches will continue to increase as can be seen in the Figure below and next page (from Nano/Microsatellite Launch Demand Assessment 2011 by Dominic DePasquale and AC Chariana). About 100 nanosatellites are expected to be launched per year in Projection of the number of nanosatellite launches b) more and more applications for nanosatellites Another trend is the use of nanosatellites for purposes other than student formation. A few examples of nanosatellite use other than for student formation is given in the figure next page (again from Nano/Microsatellite Launch Demand Assessment 2011 by Dominic DePasquale and AC Chariana). One can see that many fields can benefit from nanosatellites: Scientific Research, Technology demonstrations, Earth Observations / Remote sensing, telecommunications, Biological Experiments /Pharmaceuticals, Military Applications. 4

47 In the US, about ½ of the future nanosatellites are developed with a primary purpose different than student formation. The use of nanosatellite for Research is still limited, mainly for Earth or Sun observations, but with the improvement of nanosatellite performances, we can foresee a larger scientific scope. The first conference on Interplanetary Small satellite is for instance scheduled in 2013 at Caltech. c) Companies providing nanosatellites bricks Ten years ago, spin off companies from Universities in the US started to provide standardized nanosatellite payload accommodations and flight opportunities. Such companies exist now in Canada, UK, Netherlands, Denmark ( In France, Novanano ( a young (2009) French Innovative company, can provide such services. 3) The IDEX call: a unique opportunity to catch up on nanosatellites and prepare for the future In France, there is no nanosatellite development other than in the framework of student nanosatellites. However laboratories of PS2C are involved in Research/Development 5

48 nanosatellites through international collaborations. With regard to technology, Irfu is participating in the Cinema program involving 3 nanosats from the Berkeley Space Science Laboratory, by supplying ASICs, which will thus achieve a TRL 9 (Technical Readiness Level). It should be noted that the Cinema program combines training, research and technology aspects. On the research side, the IAS and Irfu/SAp-AIM have been approached for participation in nanosatellites to observe the Sun: the FIDI project from the University of Arizona and NASA-GFSC, and the COSXIP project from FHNW in Switzerland. LATMOS envisages using nanosats to study the Earth s radiation balance and the Earth s upper atmosphere. LPP has a rocket program (jointly with NASA and with Norway) designed to validate the R&T and enhance the technological maturity of its instruments; the participation in a nanosat program represents an excellent alternative of instrumentation testing during longer flights. The IDEX proposal is therefore a unique opportunity to give the boost needed for the Saclay-Paris University to catch up and to become a recognized international partner in nanosatellites, as well as to develop international collaborations in that field. In the field of student training and based on the existing project at the Ecole Polytechnique, a vast inter-facilities educational program, with a particularly significant learning through the project component, could be set up on the campus with the help of all the partners, and in particular through the collaboration currently being discussed with the Orsay IUT, the ENS and the Cachan IUT, Telecom Paristech, Ensta-ParisTech, Supélec and the Institut d Optique. It would enable students from a wide variety of training backgrounds to work together: mechanical, optical, information and communication technologies, complex systems, etc. A large number of Master s courses should also benefit from this project, in particular: Tools and Systems for Astronomy and Space, Astronomy, Astrophysics and space engineering and the Master in Aerospace Engineering (MAS), jointly organised by Centrale Paris and Supélec. The problems of nanosatellite attitude estimation and control lie at the heart of the training proposed by this Master. In the past, Supélec students have already taken part in CNES PERSEUS project, by studying nano-launchers. Collaborative ventures on student training could be set up with foreign universities developing nanosatellites. From the point of view of the students, space remains an attractive field and is a way of leading them to the scientific disciplines. Because their time-frame is compatible with the duration of a university course, nanosat projects are also a means of letting students deal with the management of demanding projects. On the research side, there is a nanosatellites research segment, concerning priority topics for the P2IO and IPSL labex. Even if the limited mass of the nanosatellite is a major constraint, it should however be noted that technological developments in the field of miniaturisation (a prime example being integrated optics) will boost the research potential of nanosats. The studies being conducted at Supélec on avionics suitable for objects of this type (which are highly sensitive to environmental disturbances owing to their small size and low mass), on their propulsion, etc., will also help improving nanosatellite performances. On the technology side, the policy implemented in recent years by ESA has led to a significantly increased demand for more upstream R&D and increased technological maturity (TRL) of the instruments. For example, whereas beforehand it was possible to develop new detectors as part of a project (examples: ISOCAM, INTEGRAL, HERSCHEL), a project cannot today be accepted unless it has demonstrated technological maturity up to level TRL 5 (validation of a component and/or mock-up in an environment representative of space). Nanosatellites have a key role to play in technology demonstrations and thus a strategic role in positioning the Idex laboratories in the future projects of the major space agencies. This program is focused on high TRL levels and thus complements the 6

49 involvement in 3 labex working on upstream R&D developments, that is P2IO (IAS, Irfu), ESEP (LATMOS, LMD) and FOCUS (Irfu-SApAIM). The IDEX funding will be used to secure the QB50 project, bringing the ½ of the money not provided by CNES. to develop the first French Research/Technology nanosatellite. Note that using the services of the Novanano company for the platform and to provide piggy-back launch opportunities would secure the development of this young innovative company. to foster the improvement of nanosatellite performances. to build a nanosatellite operation center to control and receive data from nanosatellites (S-band, 2 Gigabits). A large antenna will be installed, which will not only be used for the Paris-Saclay nanosatellites but also as part of a network to receive data from the various nanosatellites. Visible results will be obtained within the next 3 years: the QB50 nanosatellite will be built and delivered in 2014 and hopefully launched in the Research/Technology nanosatellite will be built, space qualified in the facilities of PS 2 C in 1,5 year and hopefully launched in The fact that nanosatellites are built by space laboratories is a guarantee of success; (about 1/2 of the student nanosatellites have failed). a nanosatellite operation center will be operational and well visible (large antenna on a building); it will also be used to outreach and has good chance of obtaining regional funding. The Paris-Saclay University will then become a privileged partner to CNES in the field of nanosatellites, will be in a position to propose nanosatellite programs to ESA, to the Horizon 2020 EC framework program Note that the nanosatellite program opens opportunities for applications other than Earth or celestial bodies observations and could be used in other fields of the Paris Saclay University. Organisation 7

50 The Nanosat project activities will be coordinated by P.-O. Lagage who will report to the Paris-Saclay Space Cluster on a 3 month basis. He will rely on coordinators for the various workpackages (A. Herzog/A. Hilgers for WP1; at the moment there are 5 sub-wp2 (P. Keckhut, F. Leblanc, F. Auchères, O. Limousin, C. Verdeil) which will be subject to prioritisation see p.10) ; M. Kieffer and S. Tebbani for WP3-1 and 2; A. Claret for WP4). Monthly meetings will be organized between the coordinator and the WP coordinators to follow the advancement of the projects. The Workpackage management also includes scientific animation activity (organisation twice a year of a seminar on Nanosat, invitations of nanosatellite specialists to spent a few months at Saclay; organisation in 2015 at Paris-Saclay of an international conference on Nanosatellites; ) and outreach activity (Web-site, visits to the nanosat operational center, organisation of an exhibition, ). Note also that radio-amateurs around the world play an important role in receiving data from nanosatellites; contacts will be established with the Essonne radio-amateur community. The project will then contribute in a significant way to the national and international visibility of the Paris-Saclay University. The coordinator will be assisted by a project assistant and by a technical project manager. Budget and resources requested The partners will provide manpower give access to their technical platforms o to realized part of the instrument (for example mechanics, robotic, at the Cachan IUT) o to qualify, test and calibration the nanosatellites (IAS, Irfu-SApAIM, OVSQ ) use the data centers to store and make the data available to the scientific community (Virtual Data; for example IAS is owning the Solar Physics data center). The permanent allocated to each workpackage is indicated in the Table below: WP0 WP1 WP2 WP3 WP4 1.5 man.yr 3 men.yr 6 men.yr 3.3 men.yr 1 man.yr The request submitted to the Idex concerns the hardware, missions, PhD students and post-docs. The request is for a total of 1.88 M broken down in: Student Nanosat: 125k ; Paris-Saclay Research/Technology nanosat: 800k ; operation centre: 200k ; improving nanosat performances: 330k ; Travel/seminars/invitations/conference organisation/ web site/ outreach: 150k ; project assistant fixed-term: 180k. The project assistant will also work part time at the level of the Paris-Saclay Space Cluster (organizing meetings, web site ). A budget of 30k a year (90 k in total) at the level of the Space cluster has been included. Idex financing to kick-start this activity will enable us to compete on an equal footing in the nanosat field with possible European partners and set up winning consortiums in which France could be represented by the Paris-Saclay Space Center. Subsequent financing will then be provided by responding to calls for project proposals, in particular from the EU; the future Horizon 2020 programme will have a space sub-programme that we hope will be significant. This program will focus primarily on technology, which could very well make use of nanosats. 4) Commercial perspectives With continued advances in the miniaturization and capability increase of electronic technology and the use of satellite constellations, nanosatellites are increasingly capable of performing commercial missions that previously required heavier satellites. For 8

51 example, a 6U CubeSat standard has been proposed to enable a constellation of 35 8 kg Earth-imaging satellites to replace a constellation of five 156 kg RapidEye Earth-imaging satellites, at the same mission cost, with significantly increased revisit time: every area of the globe can be imaged every 3.5 hours rather than the once per 24 hours with RapidEye constellation. More rapid revisit time is a significant improvement for nations dealing with disaster response, which was one of the purposes of the RapidEye constellation. Additionally, the nanosat option would allow more nations to control their own satellite for off-peak (non-disaster) imaging data collection (Tsitas, S. R.; Kingston, J. (February 2012) "6U CubeSat commercial applications". The Aeronautical Journal 116 (1176): ). The development of such capacities could be of crucial importance for the future of the European Space flagship program GMES (Global Monitoring of Environment and Security). 9

52 WP1 Developing a Student Space Center for the Paris-Saclay University PS 3 C Coordinators Albert Herzog and Alain Hilgers Nanosatellites as a way to attract and train students The objective of this work package is to develop a Paris-Saclay Student Space Center (PS 3 C) based on the extension of the newly created Student Space Center of Ecole Polytechnique (CSX), with the QB50 nanosatellite currently developed as a first space project. While the global number of students enrolled in academic fundamental science programmes tends to diminish in recent years in Europe, space sciences remain attractive for young people interested in new technologies. Nanosatellites obviously provide one appealing way for training students to space activities and more generally to complex technological projects, from fundamental and engineering sciences to project management and communication. Designing a nanosatellite actually demands that students first understand the scientific or technological goals of the mission, then imagine technological solutions (mechanics, sensors, electronics) to perform measurements. It also means developing a power system for the instruments, as well as a way to communicate the observations to the ground. In parallel, software must be developed on small on-board microprocessors, and on the ground for the receiving station. Furthermore, the relatively short time span of student nanosatellites enables the students to conduct the projects essentially by themselves, which implies that they have to learn (likely for the first time in their lives) notions of professional project management (organisation, schedule, reviews, funding plan, etc.) Lastly, such nanosatellite projects provide opportunities to get into contact with space industries, and thus for students to better understand which kind of professional careers can be followed in such companies. They also strengthen relations between students and researchers and engineers in laboratories, as the students have to use facilities located in laboratories (e.g. white rooms, testing devices, simulation software, etc) and learn from experienced persons to achieve their project. Several universities around the word (e.g., the University of Surrey in the UK, Caltech in the US, etc.) have devoted special attention to setting up Space Centres aimed at involving students in developing new technologies that can be implemented in small satellites. Yet, such academic Space centres are still very few in France, despite the strong history and activity of France in Space research. The setting up of the new Paris-Saclay University provides a unique opportunity in that respect, as many French space research laboratories are within the University and as the University already proposes teaching units in both fundamental sciences and applied technologies related to space activities. Our project thus aims at developing and promoting within 3 years (before the end of 2015) a Paris-Saclay Student Space Center. The proposed approach is to build on the newly created Student Space Center of Ecole Polytechnique (CSX). CSX is actually involved in the European QB50 project 1, a constellation of 50 2-unit student cubesats for studying the upper atmosphere, which will be launched by the end of The CSX proposal to build one of the 2-units student cubesats has successfully passed the first selection that was aimed at evaluating its technical readiness. This nanosatellite and the CSX are supported by two laboratories involved in space activities: Laboratoire de Météorologie Dynamique (LMD) and Laboratoire de Physique des Plasmas (LPP). It is furthermore supported by Thalès Alenia Space and the French Space Agency (CNES). As this first nanosatellite project

53 is advancing, knowledge in electronics, space communication, informatics will become more acutely needed, and students from Ecole Polytechnique will seek competences within other Paris-Saclay University members: contacts with IUT Cachan have for instance already been initiated, and students from Orsay Institute of Technology (IUT) could also be associated as part of this activity. Also CSX is thinking of developing an attitude control subsystem for cubesats, which can be done in partnership with Supelec. Therefore this cubesat project is an excellent opportunity to quickly federate competences in space technology within Paris-Saclay. In parallel, new space projects will be matured based partly on WP2 activities and partly on a call for ideas open to the Paris-Saclay laboratory to be organised as part of WP1. It is expected that new frontier sensors or electronic parts could be developed and accommodated on student nanosatellites to test their readiness for future research missions. Prior to satellite accommodation, it could also be foreseen to test these devices either on sounding rockets or on stratospheric balloon flights: several Paris-Saclay laboratories (LMD, LPP, LATMOS) actually have long experience of such near-space missions. These missions have even shorter time frame than student nanosatellite and could be performed within one year by a group of motivated students. CNES strongly supports these kinds of student space project activities, since they train future engineers and raise student awareness of space technologies. Therefore, CNES committed already to provide 50% of the total cost of the 2-units cubesat development at CSX for QB50. The funding required for this work package will allow to cover the second half of the cost while ensuring that it is performed through collaborations within Paris- Saclay. Furthermore outreach activities will be organised based on the QB50 cubesat development and launch (which is planned to take place in 2015) such as to promote the technological know-how, both within the University Paris-Saclay and toward future students and industrial partners. The funding request for this work package is 125 k which is essentially covering nearly half of the development of the QB50 2-units cubesat. Details of the 2-unit cubesat cost The cost of the whole Cubesat project is estimated as follows: Mechanical and thermal model: 6 k Engineering model: 41 k Electronic boards (power, transmission, data acquisition) and antenna: 11 k Attitude control module: 24 k Solar cells: 6 k Qualification model: 47 k Mechanical structure: 6 k Electronic boards (power, transmission, data acquisition) and antenna: 11 k Attitude control module: 24 k Solar cells: 6 k Flight model: 47 k Mechanical structure: 6 k Electronic boards (power, transmission, data acquisition) and antenna: 11 k Attitude control module: 24 k Solar cells: 6 k Spare Boards: 20 k Computer (for board tests and satellite development): 3 k Ground station: 10 k Mechanical interfaces for qualification tests: 6 k Missions (Toulouse, Brussels, and workshops associated with the project): 60 k Contribution to satellite launch: 20 k Satellite integration and testing: performed at Test and Integration Platform, OVSQ: for free 11

54 Total satellite cost: 260 k Funding already granted: 135 k (CNES: 125 k, Thalès Alenia Space: 10 k ) Funding demand associated with this project: 125 k Contribution of partners: Ecole Polytechnique/LMD: - François Danis (IR), 50%: QB50 project manager (together with Gérard Auvray). - A. Hertzog (Maître de conferences), 20%: PSC tutor of the QB50 project (PSC is a teaching module in Ecole Polytechnique devoted to scientific and technological student projects). - Engineers with the technical department of LMD: Students involved in the QB50 project are encouraged to have discussions with experienced engineers in LMD. Some of the mechanical parts can also be manufactured by LMD staff. - clean room, thermal chambers. Ecole Polytechnique/LPP: - Ch. Coillot (IR), 10%: PSC tutor of an attitude control system for nanosat Ecole Polytechnique: - Alain Hilgers, 20% : Polytechnique Student Space center coordinator. - Gérard Auvray (Nanosatellite expert, retired), 30%: QB50 project manager (together with François Danis). WP2 : Developing Nano-satellites for Research and Technology Five projects have been submitted. We will make a 4 months phase 0 study of each of the projects and make a priority list. An important criterion will be the development time. Indeed the aim is to have a nanosatellite launched before the end of The study will also provide opportunities to train student; CNES will contribute in this training. As part of the WP0, a committee will be set up to prioritize the 5 Research/technology nanosatellites which have been proposed. The committee will be chaired by the coordinator of PS 2 C (Daniel Vidal Madjar) and composed of the head of each laboratory/institute member of PS 2 C (or his/her representative); a representative of CNES will be invited to participate to the Committee meetings. The way to reach decision will be consensus. The committee will meet in September It will start with a presentation of the results of each of the nanosatellite phase 0 studies. The following criteria will be used, with in the background the demand of the IDEX to have results by the end of 2015: 1) Research/technological impact. 2) Maturity of the project; technical feasibility; risks; credibility of the planning; margin. 3) Support of the laboratory. 12

55 WP2-1 : SERB : A nano-satellite to study the Sun and the Earth Proposed by P. Keckhut, M. Meftah, A. Sarkissian, A. Hauchecorne; CNRS/LATMOS/IPSL/UVSQ Science goals The "Solar irradiance and Earth Radiation Budget", SERB, is an innovative nano-satellite, with three science goals, which have been defined based on the experience of LATMOS with space instrumentation, Earth radiation budget, and solar irradiation: - Establish a radiation balance of the Earth with an accuracy better than 1% in differential, - Continue Total Solar Irradiance variability measurement (TIM/SORCE, PICARD/PREMOS & SOVAP, ), - Improve the knowledge of the absolute value of the Total Solar Irradiance. Among the natural causes that can affect the climate of the Earth, solar variability is probably one of the most important. Observation of Solar-Climate-Atmosphere of the Earth allows us to analyze the study of the relations involved. Context This proposal is based on the triptych "Research, Innovation, and Training". SERB is ideal for cost-effective missions focusing on technological research, low-cost science, and commercial proof-of-concept missions. The establishment of a multidisciplinary consortium of partners including academic (research), industrial, and foreign (IRMB - Royal Meteorological Institute of Belgium) leads us to propose the development of this original mission. The framework for implementation and costs are well known and controlled, since the nano-satellite will be developed from repeating units of qualified flight hardware subsystems (Technology Readiness Level: TRL 8 9) from GOMspace, ISIS, ClydeSpace, or from PICARD (space radiometers, and ground segment). A scientific payload called SERB, and dedicated to this study has already been proposed in the frame of the CNES R&D and as part of a broader international proposal. UPSa activities will be greatly valorized with SERB in educational and scientific terms. Many UPSa laboratories are involved in space payload developments and in Sun Climate studies, LATMOS, LSCE, IAS, LMD, IDES, Irfu/AIM... and most of us are teaching related lectures in the Masters of the IDEX; the list is too long to be given here. Then, this proposal, extended eventually to other laboratories of the IDEX, will set up collaboration. The Space Segment The key element of the SERB mission is the Space Segment, containing the nano-satellite (300*100*100 mm, 4 kg, and 4 W) that includes the payload (100*100*100 mm, 1 kg, and 1 W) and the avionics that will support the mission. Main elements are: the structure, the electrical power supply system, the solar panels, the mission computer, the antenna system, the attitude determination and control system (reaction wheels and fine sun sensors), the GPS (position of the nano-satellite), and the harness. All these packages will be integrated into the nano-satellite. The nano-satellite's pointing accuracy will be less than 1 along the axis of the Sun. The downlink speed will be less than 9600 kbps, and the uplink speed will be less than 1200 kbps. The maturity level of this platform is very high. The payload with its instruments will implement the observations and programs: SERB-ER (Solar irradiance and Earth Radiation Budget - Earth Radiometer) measures the Earth radiation budget, SERB-SR (Solar irradiance and Earth Radiation Budget - Sun Radiometer) measures the solar irradiance, and its variability. Mission analysis The details of the launch as still to be determined, however the current assumptions on the orbital characteristics are: orbital altitude of 500 km, orbital inclination ~

56 degrees, and orbital period of 5680 s. From this altitude the mission lifetime of 1 year can be supported without active orbit altitude control. It is important to note that, due to the inclination, the orbital plane will drift, causing the orbit Right Ascension of the Ascending Node (RAAN) to vary as the mission progresses. This means that throughout the mission the orbital plane will go from in plane with the incoming solar radiation (like in a Sun Synchronous Orbit) to being nearly perpendicular to the incoming radiation (like in a Dusk Dawn type orbit). The orbital plane basically rotates around the Earth North-South axis every few weeks due to the orbital parameters. The SERB nano-satellite will be launched by a Shtil-2.1 rocket from Murmansk in Northern Russia or by another launcher; (for a launch in the beginning of 2015). The Ground Segment The ground station kit includes an antenna tower (UHF/VHF) for on the roof mounting and a rack with all the radio equipment, which can be installed indoors. The rack also includes a compact computer containing all the software required for antenna tracking and for communicating with SERB platform (from GOMspace). Strategic issues Because SERB is based on an existing package to be assembled together as a simplified experiment, deadlines for its development will respect fully the expected program and will be short, one or two years of developments, launch and then one year in orbit condition and data analysis to be used for SERB final developments. Because SERB will be developed by LATMOS, by the IDEX students in multidisciplinary field (including electronics, thermic, mechanic, software, etc.) with a very serious scientific achievement, the image of Paris- Saclay University will be greatly valorized in educational, and scientific terms. We have in our laboratories all the elements to present and to valorize this action internationally. Budget implementation : 290 k + launch (SERB platform: 150 K ; SERB payload:50 K ; Ground Segment: 75 K ; Data Exploitation:15 K ) Organization Structure and organization of the documentation will be based on CNRS/LATMOS standards. There is a Project Manager (40% ETP), a Ground Segment responsible (40% ETP), an electronic engineer (50 % ETP), two technicians (50% ETP), a student group, an industrial team, and a scientific team. Schedule Development, and test: 2013, and 2014 Launch: April 2015 Commissioning phase: Until May 2015 Exploitation: Until May

57 WP2-2 : Spectrometry of the Earth Thermosphere : density and energy measurements (SETDEM) Proposed by F. Leblanc, LATMOS-IPSL/UVSQ Objectives Scientific objective: to realize a measurement of the total density in the Earth thermosphere and exosphere at various local time, various geomagnetic latitudes and for various solar conditions (the typical density expected is between 10 8 O/cm 3 at 400 km to 10 5 O/cm 3 at 1200 km, Hubert et al. 1999). As suggested by many space missions, the thermosphere/exosphere density varies significantly with solar photons and wind conditions (Lühr et al. 2004). What has not been done so far is a measurement of the neutral density above 600 km in altitude AND of the energy of these particles. Expected to be between the thermal energy and few evs for the oxygen component (atomic), density and energy should vary with solar conditions being produced by the photo-chemical reactions in the lower thermosphere. As an example, the dissociative recombination of the thermospheric molecular ions, which is an exothermic reaction, should generate O and C atoms with energy of the order of the electron-volt. Beside contributing to the atmospheric escape observed so far only through its ionized component (André and Cully 2012), the exospheric energy could therefore be interpreted as a tracer of the photochemical reactions leading to the production of oxygen atoms which then in part control the cooling rate by CO 2 NIR emission in the low thermosphere/upper mesosphere (Schmidt et al. 2006). A better understanding of what control these photo-chemical reactions in the Earth atmosphere would also provide important information for Mars and Venus where such type of photo-chemical reactions are one of the main driver of atmospheric evolution (Chassefière and Leblanc 2004). Figure 1: Left : mechanical drawing of the ionization source aimed to be used for SETDEM. Right : Picture (in black) of the carbon nano-tubes used for the electron emission presently tested in LATMOS (CNES R&T) and of the extraction device developed at LATMOS. Technological objective: to validate a concept of ionization of the neutral particle in low density environment. Indeed, it is now two years that LATMOS is developing, testing and validating a new concept of ionization source based on the emission of electrons from carbon nano-tubes (R&T development supported by CNES, "Source ionisation basse consommation pour spectro de masse" started at the end of 2011). The main originality of this ionization source concept is a very large efficiency, allowing a measurement of very low density (below few tens of neutral particles per cm 3 ), for a low power consumption (below 1 W). We are looking for opportunity to test in space our concept of ionization source in order to gain the needed TRL maturity (demonstration of feasibility in representative space conditions). 15

58 Educational objective: to approach students eager to develop an experience in space exploration. It is our interest and role to form students to our field of research and to share our experience. Moreover, for our instrumental development, we permanently need to attract young and motivated students to complete our technical and engineering teams. To develop a project with engineering schools and university is clearly an efficient way to reach this goal. Mission design A first concept of the instrument that could be put on a nano-satellite has been designed (Figure 1) so that we are able to evaluate the resources needed to do so (mechanically, electronically and in term of telemetry). A mass of less than 400 g is foreseen for the instrument, associated with a total consumption of less than 2 W and a telemetry budget around 100 bits/s. These numbers are therefore within the budget of a double or triple Cubesat (30x10x10 cm, <10kg, 3 W). The preferred orbit could be circular above 500 km in altitude on a polar orbit, preferentially non helio-synchrone. The instrument could be worked in a continue way with a minimum of command/control. A control of the attitude of the nano-satellite is requested in order to avoid direct Sun light within the instrument (implying a attitude restitution around 1 with some Sun sensor to maintain a given guard angle). Financial support The industrial cost of a platform of the type foreseen for SETDEM has been estimated as being around 150 k. The payload development is based on an on-going two CNES R&T (total budget of 65 k ) which will end beginning of 2014 on a fully spatialized concept of ionization source (TRL 4). We estimated that a payload budget of 45 k will be enough for this project. Ground segment development (75 k ), launch cost (~100 k ) and science exploitation (10 k ) will lead to a total cost for SETDEM of 380 k. A potential partner is the LABEX ESEP which goals are in particular to support educational projects in planetology (the present project being done by HEPPI/LATMOS department part of the LABEX ESEP). Organization The LATMOS will have the charge of the development of the instrument described before and of the scientific exploitation of the measurements. LATMOS manpower will correspond to a project Manager (40% ETP), a Ground Segment responsible (40% ETP), an electronic engineer (50 % ETP), two technicians (50% ETP) and of a scientific team (beyond LATMOS ones). We plan to add to the development team a student group and an industrial team. References André M. and C.M. Cully, Low energy ions: a previously hidden solar system particle population, Geophys. Res. Let., 39, L03101, 2012 Chassefière E. and F. Leblanc, Atmospheric escape and evolution ; interaction with the solar wind, Planetary Space Science, 52, 11, , Hubert et al., Effect of hot oxygen on thermospheric OI UV airglow, J. Geophys. Res., 104, 17139,1999 Lühr H. et al., Thermospheric up-welling in the cusp region: evidence from CHAMP observations, Geophys. Res. Let., 31, L06805, 2004 Schmidt et al., The HAMMONIA chemistry Climate model: sensitivity of the mesopause region to the 11-year solar cycle and CO2 doubling, J. Climate, 19, 3903,

59 WP2-3 : Flare Initiation Doppler Imager (FIDI) Proposed by F. Auchère, IAS The YOHKOH Bragg Crystal Spectrometer observed over 200 flares in a single year above a threshold irradiance corresponding roughly to a class C6 flare resolution (Mariska, Doscheck & Bentley, 1993; Gan & Watanabe, 1997), with no spatial resolution. Most of these events showed full-sun averaged Ca XIX Doppler shifts of 50 to 100 km/s, with a few greater than 200 km/s less than predicted by numerical simulations, which is not surprising, as averaging over multiple flows will result in line broadening with centroids that do not reflect the highest velocities seen. Doppler shifts during the brief flare initiation are difficult to observe with a slit spectrometer. This has been achieved only once, through a combination of carefully selected and fortuitous pointing of CDS on SOHO by Brosius & Phillips (2004), and only with a spatial resolution of 20 arcsec and cadence of ~10 s. In He II, red and blue shifts of 30 km/s were detected, but only a small fraction of the flare loop was observed for this single event. The Helium Doppler Imager (HeDI) is a 3U CubeSat payload designed to provide spatially resolved Doppler shifts during the impulsive phase of solar flares. By monitoring the entire solar disk for Doppler shifts in He II 304 Å over a period of months during solar maximum (2013), HeDI will observe multiple C and M class flares, with a significant probability of observing larger flares as well. HeDI will provide a measure of the He II 304 Å Doppler shift with a sensitivity to shifts of 30 km/s and greater, resolved on a spatial scale of 10 arcsec the typical scale of active region features such as loop foot points where coronal heating and electron beams can result in fast upflows of evaporated Figure 1. HeDI preliminary design. chromospheric material. Since HeDI is designed to monitor the solar disk on every orbit during the mission lifetime (90 days target, 30 days minimum) with a cadence of 5 s (25 ms integration), He II Doppler shifts would be observed to provide unique constraints on energy deposition during the flare impulsive phase. The HeDI telescope is shown on Figure 1 and 2. Using high reflectivity multilayer-coated optics, like the Al/Mo/B4C structures that are developed by the Institut d Optique and Institut d Astrophysique Spatiale for the Solar Orbiter mission, a compact Cassegrain telescope will image the solar disk in two passbands, both 10 Å wide (FWHM), and centered at 300 and 308 Å, to image the red and blue wings of He II 304 Å with a spatial resolution of 10 arcsec. The difference of the two images provides a measure of the He II 304 Å Doppler shift with a sensitivity to shifts of 30 km/s and greater. The two images will be formed side-by-side and captured by the same focal plane array, a thinned backilluminated CMOS sensor. The HeDI telescope is shown on Figure 1 and 2. Using high reflectivity multilayer-coated optics, like the Al/Mo/B4C structures that are developed by the Institut d Optique and Institut d Astrophysique Spatiale for the Solar Orbiter mission, a compact Cassegrain telescope will image the solar disk in two passbands, both 10 Å wide (FWHM), and centered at 300 and 308 Å, to image the red and blue wings of He II 304 Å with a spatial resolution of 10 arcsec. The difference of the two images provides a measure of the He II 304 Å Doppler shift with a sensitivity to shifts of 30 km/s and greater. The two images will be formed side-by-side and captured by the same focal plane array, a thinned back-illuminated CMOS sensor. 17

60 Figure 2. The two images are formed side by side on a single detector. A Doppler shift produces an inverse intensity variation in the two channels. Two redundant thin (150 nm) aluminum filters along the optical path prevent visible light from illuminating the focal plane. The filter in the entrance aperture serves to reject visible and UV solar radiation (heat), as well as provides contamination control. It will be replaced prior to launch. The short exposure time of 25 ms will limit image blur due to smear and jitter to less than one pixel, while providing more than sufficient signal. Downlinked data will be selected by comparing with soft X-ray flux from GOES to determine flare initiation times. By monitoring the entire solar disk for Doppler shifts in He II 304 Å over a period of months during solar maximum, multiple C and M class flares will certainly be observed, with a significant probability of observing larger flares as well. Imaging instruments such as AIA on SDO will provide high-resolution context images for the HeDI observations, including higher temperature ions, Imaging instruments such as AIA on SDO will provide high-resolution context images for the HeDI observations, including higher temperature ions, but are not designed specifically to detect Doppler shifts, while full-sun spectrometers obtain sun-averaged spectra, from which flows are difficult to detect and impossible to locate, and a slit spectrometer must be pointed at exactly the right place and right time before the flare onset, which is not something that can currently be predicted. Since this payload will monitor a large region of the solar disk during the mission lifetime, high velocity (> 30 km/s) flows of ionized helium, if present, would be observed, and provide important data to constrain models of solar flare initiation. HeDI is developed by the Goddard Space Flight Center (PI Joe Davila), and the platform is built by the University of Arizona. The main objective is the feasibility demonstration for a full scale payload. The development time is thus short, but reaching the low Earth orbit allows data acquisition over a longer period of time than with sounding rockets. The instrument will use only readily available components. The Institut d Astrophysique Spatiale and the Institut d Optique will provide the EUV multilayer optics, based on the developments ongoing for the Solar Orbiter mission. The activities at IAS and IO will include first modeling work on the design of the coatings. Then, we will fabricate the mirrors and deposit the coatings, following a well-controlled procedure developed for the EIT/SOHO and EUVI/STEREO projects. After calibration of the coatings reflectivities, the mirrors will be delivered to GSFC. The requested funding for these activities is: Funding requested : 56k (Mirrors (1 flight + 1 spare + 6 samples): 19 keuros; Coatings (1 flight + 1 spare + 6 samples): 20 keuros; MGSE: 8 keuros; Travel:Two visits of 5 days for two persons at GSFC and University of Arizona: 9 keuros) Man power provided: 0.5 FTE 18

61 WP2-4: BEEP: Bright Eruptive Event Polarimeter Proposed by O. Limousin, A. Meuris, CEA-Irfu-SApAIM The mission concept proposed in the following is originally proposed by Dr. Casadei, FHNW, Switzerland, for a nanosat mission to image bright solar flares from low earth orbit and to offer a unique polarization measurement of such events. The idea of the proposal is to build two nanosats, one in France, BEEP, one in Switzerland, COSXIP. Both satellites are developed separately and will be equipped with exactly the same payload described hereafter. The Swiss Space Center shall manage launch service of the two sats together or most likely one after the other. The international collaboration (France, Switzerland) will share the science data and science return and possibly some key technological developments. The collaboration will possibly be extended to USA (Berkeley and Boulder), Russia, South Korea, Poland, Germany, UK and Columbia. 1 SCIENTIFIC CONTEXT It is well known that Solar corona is very active region which is the seat of many phenomena related to magnetic energy release in large range of sizes and occurring on time scales going from a few seconds to less than a hour. Physical processes leading to energy release is a hot topic of research as well as particle acceleration processes in solar flares and justifies major in situ missions such as Solar Probe, Solar C, Solar Orbiter and Inter Helio Probe. Our group and consortium is currently involved in two of these missions and we propose to build BEEP payload to reinforce the domain providing a observation of solar flares from the Earth orbit. 1.1 What does BEEP bring to solar physics? The most promising result expected from BEEP and its Swiss brother COSXIP will be the first measurement of polarization fraction in the hard X-ray (HXR) energy range expected to occur in bright solar flares. According to our expectations, BEEP will bring a unique near Earth observation of very bright Solar flare to study with high imaging resolution their geometry and dynamics. Moreover, viewing in coincidence bright flares from Solar Orbiter/STIX and/or COSXIP would offer 3D view of such events. The HXR emission is expected to be significantly different from one direction to another. Combining observations with BEEP/COSXIP and STIX will allow checking the hypothesis of beamed emission. Note that, for this particular goal, BEEP needs to be a good spectrometer but doesn t necessarily provide fine imaging. Contemporary Observations involving BEEP and STIX is also important in case of Solar Limb occultation of the flare footpoints from the earth and not from the Solar Orbiter orbit. As a matter of fact, this would enable a separate observation of the coronal emission without the disturbance of the footpoints. For this prospective, BEEP does not need fine imaging capabilities but needs to be a spectrometer. 1.2 What does BEEP bring to technology? BEEP nanosat is an opportunity to bring new detector technologies in space and to further improve their technological maturity. Performance and reliability 19

62 allow reaching TRL9 to CEA Caliste CdTe pixel detectors [2] and subsystems. CEA is deeply interested in correlating the radiation effects on detectors and electronics as predicted after ground test with in-flight behavior. Eventually, the payload will innovative electronic parts and embedded software s that are not currently used into space due to lack of maturity but showing promising behavior in R&D programs. 2 Mission concept We propose to use the same indirect imaging technique as RHESSI to easily achieve fine angular resolution with good detection efficiency hard X-rays. The idea to associate collimators made of grids with CdTe semiconductor detectors to measure the spatial Fourier distribution of the source [3]. Achieving a good angular resolution (few arsecs) with compact imager requires very thin slit pitchs down to 5 µm, realized on silicon wafers coated by thick gold layers (200 µm). BEEP will provide images for approx. 10 to 20 bright eruptive events (M and X-Class) up to 50 kev in one-year operation time. For energies above 100 kev, Compton scattering starts to be a significant interaction mode in CdTe. For diffusion at 90, the scattered photon can escape the pixel and be absorbed further away in a neighboring pixel, hopefully, as far as possible. If the light is polarized, directions of scattering in the plane are not randomly distributed any longer. The distribution of angles gives information of the fraction of polarization of the source. BEEP will see few (3-5 at solar max) X-Class flares offering enough photons to measure the polarization in HXR. BEEP payload shows a 5,8 W power budget for only 1,75kg including 4 detectors, aspect system, optics, readout electronics and mechanical structure. This payload fits nicely into a Novasat 2G (10x10x40 cm3) from Novanano [4] for instance. BEEP optimal orbit is a crepuscular SSO with a permanent view of the Sun. This king of LEO is polar. However, equatorial orbits are good for background. 3 PROJECT PRELIMINARY EVALUATION BEEP is a three years program. During that period the payload is developed at CEA. The satellite is developed into the industry with participation inputs of IDEX work packages for telecom, ground segment, SCAO and UHF link or more. The overall cost is 1983 k. the nanosat and its payload represent 600 k. Item Unit cost a year Quantity K CEA staff m.y 876 PhD students 30 6 m.y 180 Students 12 6 m.y 72 Payload and equipment test NanoSat and PPod Travel Expense

63 TOTAL 1983 k TOTAL IDEX Students +1/2 PhD 162 TOTAL IDEX HW 690 TOTAL IDEX 852 k 4 REFERENCES [1]. Benz at al., The Spectrometer/Telescope for Imaging X-rays (STIX), SPIE Proc., 8443 (2012) [2]. Meuris et al., Caliste HD: A new fine pitch Cd(Zn)Te imaging spectrometer from 2 kev up to 1 MeV, IEEE NSS/MIC, conference record, [3]. G. Hurford at al., The imaging concept for the spectrometer/telescope for imaging X-rays (STIX) on board Solar Orbiter, SPIE Proc., 8443 (2012) [4] WP2-5 R & T: CubeSat project for ion mass spectrometers Manager : C. Verdeil (LPP) LPP develops instruments, mainly ion mass spectrometers and magnetometers (search coils) for space missions. On one side, the technology of these instruments evolves (improvements, new concepts, new designs, ), and on the other one, modifications are naturally included to fit the scientific requirements of each specific mission. As a result, there is not a standard type of instrument, and each new prototype for each new mission has to be tested in realistic flight conditions. This step allows increasing the technology readiness level (TRL) of the instruments, and this is quite necessary to support instrument proposals for new projects. One way to achieve tests in flight conditions consists to implement the instruments onboard rockets, as recently performed by LPP teams for magnetometers in collaboration with NASA or Norway. CubeSats provide an excellent opportunity to test instrumentation and to return data on longer time periods (months) instead of rather short-duration flights with rockets (minutes). Test search coils and antennas can be easily implemented on CubeSats in terms of mass, size and consumption. Concerning ion mass spectrometers, LPP teams propose the following simplified design, capable to test recent concepts, and specifically adapted for CubeSats. R & T: CubeSat payload proposition for ion mass spectrometers (LPP) LPP develops ion mass spectrometers onboard spacecraft. Several instruments have already flown onboard missions (ex: Interball / CNES Russia, Cassini / NASA) or are going to fly (Bepi Colombo / ESA-JAXA to be launched in 2015). Recent improvements involve new technologies or designs that are tested in ground-based chambers but that need to fly in order to be tested in realistic conditions. In this framework of new project developments, LPP proposes a cubesat payload based on an ion mass analyzer that will be able to measure densities, energies and composition of plasma ions in the immediate vicinity of the satellite. This simplified instrument will provide an opportunity to improve the TRL of technology already develop at LPP, especially during CNES R&T project, and to test new designs for parts of both optics and electronics that could be used for the forthcoming missions. As illustrated in Figure 1, the instrument is based on the measurement of particle ToF (Time of Flight) between a thin carbon foil and a thick Aluminum foil. After an energy selection at the entrance (left-hand side), the ions are accelerated through a carbon foil that will emit electrons on each side. These electrons are collected by MicroChannel Plates (MCP) as a START signal and are used to open a time window. After interaction of the foil, the ions exit as neutrals and hit a thick Al Foil. The impact produces secondary electrons 21

64 that are measured as a STOP signal which closes the time window. Then the ion mass can be determined from the particles time of flight, and thus their speed, inside the chamber. Deflectors/ Attenuators MCPs Carbon foil Sweep4 kv -5 kv -5 KV/0 V Al Foil Emissive Surface Power Supplies High Voltage Low Voltage 100 V 2000 V 2200 V 0 V 3.3V Charge Discriminator Time of Flight and amplifiers counting Figure 1 : Instrument Schematic With this simplified design, we would like to implement and test two innovations. The first one concerns the optics and is based on the transparency of a not too thick Al foil with respect to the electrons. This could be used to obtain an additional START signal that, depending on the conditions, could be used to improve the efficiency of the first signal or as an additional coincidence, allowing discriminating noise counts due to the electronics or the external environment (penetrating particles, high temperature, etc ). The second innovation is the design of an ASIC (Application Specified Implemented Circuit) dedicated for the measurement of the time of flight (ToF) and the counting. This improvement of a currently used design will allow decreasing the size, the consumption of our electronics. All other LPP supplies are based on previous mission heritage or recent R&T (R&T CNES: RS11/SU ). This payload may be contained in a classical cubesat configuration unit (10cmx10cmx1kgx1W). Solar arrays, avionics controller and transmitter will require an external contribution to LPP. Experts in these fields can be found among other institutes involved in this IDEX Planning: The optics can be achieved over 1 year; the electronics over 2. ASIC Transmitter Human resources will be provided by LPP engineers (1.5 m.year for the project) and training students. Nevertheless equivalent of 1 Full Time position for 1 year should be considered over the 3 years (1 m.year: 45 k ). Budget: LPP will provide the white room, the plasma chamber, electronics, ion sources, software licenses, consumables. Materials and manufacturing (25 k ), detectors (10 k ), electronics components, anode manufacturing and GSE (15 k ) and ASIC design and manufacturing (50 k ), giving a total of 100 k, are considered for the complete payload of the project. These costs do not include the building and operation of the nanosat platform. Total estimated budget: 145 k (including CDD). 22

65 WP3: Improving the performances of Nanosatellites WP3.1 Nanosat and control problems (Coordinator Sihem Tebbani, Supélec) Nanosatellites represent an interesting alternative to traditional ones, mainly because they reduce design, development, launch and operating costs. However, the miniaturization of the system and the aim of reducing costs lead to the use of less accurate sensors and less effective actuators. In this context, attitude estimation and control, and optimal trajectory of nanosat raise challenging technological and theoretical control problems. In space research, the Cubesat standard is usually considered. A Cubesat satellite is a 1kg- 10cm cube and uses Commercial-Off-The-Shelf (COTS) equipment in order to reduce costs. Several CubeSat satellites were developed by universities to test proposed algorithms and technological solutions for problems raised by nanosat. These projects were carried out by researchers, PhD students and students, in collaboration with space agencies (e.g. NASA s CubeSat Launch initiative, ESA, CNES). The first French Cubesat satellite is ROBUSTA, developed by Montpelier University students in collaboration with the French Space agency CNES. It was launched on February 2012 by VEGA launcher. Feedback from these past experiences enhances that researches on estimation, attitude and trajectory control have to be carried on in this nanosat project with in-depth studies following the two research axes detailed below: 1. Attitude estimation and control Mainly two techniques are used for satellite stabilization: passive and active controls. The passive control scheme uses either the gravity gradient to stabilize the satellite with the long axis, or orients the satellite along the earth magnetic field thanks to a magnet. However, this kind of approach leads to weak accuracy and needs a fine mathematical simulation of satellite dynamics. On the other hand, active control leads to high accuracy. It is made of the Attitude Determination (ADS) and Attitude Control System (ACS). The ADS uses miniature sensors: magnetometers, gyroscopes, Earth sensor, Sun sensor and star tracker. The Inertial Measurement Unit (IMU) data and measured observation vectors are then used to estimate satellite attitude (using Extented Kalman Filtering for example). However, the star tracker sensor is the most mass, power, cost and space expensive. Thereby, several research projects consider the removing of this sensor by proposing COST sensors. A GPS sensor seems to be the best solution but still raises some challenging estimation problems. Indeed, accuracy cannot be guaranteed and novel estimation technique should be proposed. Once the satellite attitude is well measured, this information is then used as input for ACS that rotates the satellite into a desired attitude (to compensate disturbances torques or to orient the satellite to a desired direction). Magneto-torques, thrusters or reaction wheels are usually used as actuators. The control law must be developed is order to achieve a high accuracy despite model mismatch and measurement errors. In addition, it must also be developed so that the computation burden is reduced since the CPU and memory resources are limited. Developments in this axis can be of interest to WP Trajectory control Satellite trajectory optimization and control is the second main topic related to control problems. 23

66 The main axis concerns the orbit acquisition and station keeping of the nanosat. The orbit acquisition consists in computing optimal thrust maneuvers to transfer the satellite to its final position (by minimizing propellant consumption and/or time transfer and assuring high accuracy acquisition). Once the satellite achieved its final position, it is maintained on its orbit by the station keeping maneuvers. In the case of nanosat, electrical thrusters are used in order to reduce mass propellant (plasma thruster for example). However, this kind of micro-propulsion gives very small level of thrust (with longer transfer duration). In addition, since nanosats have generally Low Earth Orbit trajectories, atmospheric disturbances levels become very important in comparison to thrust ones (mainly atmospheric drag and Earth oblatness). This thrust technology uses solar power in order to reduce battery size. However, thrust cannot be delivered when the satellite is in the Earth shadow, leading to coast arcs trajectories. Thus, optimal thrust maneuvers should be determined considering this continuous-time constrained dynamical behavior (impulsive maneuvers hypothesis cannot be used in this case leading to a more complex optimal problem). Developments in this axis can be of interest to WP2-1. The following table summarizes the main experience of SUPELEC-E3S/Automatic Control Department related to past projects in the field and gives proposal projects. Topic challenge SUPELEC-E3S Control Department experience Attitude Determination Attitude control Orbit control Noise rejection Star tracker removal Robust attitude control station keeping of LEO trajectories 1PhD thesis with ISL (Institut franco-allemand de recherches de Saint- Louis). 1 patent. 2 PhD theses on attitude control, in collaboration with CNES and Astrium. 1 PhD on LEO electric thrust spacecraft. SUPELEC-E3S Control Department work proposal Robust attitude estimation using gradient gravity and/or GPS. Robust control law against parametric uncertainties and noise measurements. Adaptation of existing algorithms and methods to the nanosat paradigm. Supélec students may be concerned by the project, being involved in: Proposed project duration 3 years ( ) 1 year ( ) - Research project (6 months): carried out by students that follow the Master s degree Aerospace Engineering (MAS). - Design projects (2 months) in the first and the second year engineer degree: consisting of a comprehensive theoretical study, following bibliographic research and laboratory work. This can also be integrated in the WP1 actions. Budget : 140k - One PhD grant, to work on research related to attitude determination and control: 90k. - One year post-doc position to work on orbit control: 50k Contribution of partners: 0.5 man/year - Sihem Tebbani (Associate professor): 20%. Coordinator of the project and contributes to the trajectory and attitude control topics. - Dominique Beauvois (Professor): 10%, for the attitude estimation topic - Gilles Duc (Professor) : 10%, for the attitude control topic - Houria Siguerdidjane (Professor): 10%, for the attitude and trajectory control topics 24

67 - Supélec students (for both WP1, WP2-1 and WP3-1 actions). They are supervised by Supélec researchers. Estimation Some References (SUPELEC-E3S, Automatic Control Department) Beauvois D.; Changey S.; Fleck, V., "Method for determining the attitude, position, and velocity of a mobile device", patent, US A S. Changey, V. Fleck, D. Beauvois, "Non linear filtering for attitude estimation with magnetometer sensor", 5th International Conference on Mathematical Problems in Engineering and Aerospace Sciences, INCPAA 2004, Timisoara, Romania, June V. Fleck, E Sommer, S Changey, D. Beauvois, "On-Board measurements with Magnetic sensors: determination of the atttitude and the trajectory position", 22nd International Symposium on Ballistics, Vancouver, Canada, novembre Attitude control Student projects with CNES in PERSEUS project ( ). Y. SOMOV, H. SIGUERDIDJANE, V. RUTHOVSKY. Postgraduate Education and New Challenges on Stability and Adaptive-Robust Control in Aerospace. 9 th IFAC Symposium on Advances in Control Education, Nizhny Novgorod, Russia, June 19-22, H. Siguerdidjane, H. Rodriguez. Regulation of spacecraft angular momentum using Port Controlled Hamiltonian structure. 15th IFAC Symposium on Automatic Control in Aerospace, Bologna/Forli, Italy, September H. Sira-Ramirez, H. Siguerdidjane. A redundant dynamical sliding mode control scheme for asymptotic space vehicle stabilization. International Journal of Control, vol. 65, n 6, pp , 1996.Student projects. Low-thrust Trajectory optimization Student project with CNES (2005). H. Siguerdidjane, S. Cavalier, A. Badatcheff, J-B Moussel, G. Maurino. Improved 3D Design Guidance Law of a mini Unmanned Aerial Vehicle via Frenet Framework : Flight Simulator Implementation Results. IFAC Workshop on Embedded, Guidance, Navigation and Control in Aerospace, Bangalore, India, February S. Tebbani, R. Bertrand, J. Bernussou, M. Racois, M. Romero, «Comparison of direct and indirect methods in optimizing multiple-burn low-thrust orbit transfers», 52nd International Astronautical Congress, Toulouse, S. Tebbani, I. Queinnec, J. Bernussou, «Optimal finite thrust rendezvous using beneficial effects of the earth oblateness», AAS/AIAA Astrodynamics Specialist Conference, Quebec, S. Tebbani, J. Bernussou, «Quasi circular orbit transfer by means of impulsive thrusts», 2nd International Workshop on Satellite Constellation and Formation Flying, Haifa, S. Tebbani, J. Bernussou, E. Lasserre, «Near circular orbital transfer optimization of impulsive thrusts», 50th International Astronautical Congress, Amsterdam, S. Tebbani, E. Lasserre, J. Bernussou, F. Dufour, «Station acquisition of a homogeneous constellation by linear and nonlinear optimization», 14th International Symposium on Space Flight Dynamics (ISSFD'XIV), Foz do Iguaçu, WP3-2: Telecommunications and Nanosatellites (coordinator Michel Kieffer) Cubesat radio communication telecommunications context Cubesats are generally placed on a low earth orbit. This has two main consequences: 1. Their lifetime is very limited, generally around 3 months; 2. The access time (line of sight visibility from earth ground) is limited, generally less than 10 minutes. Because of this low orbit, the line of sight attenuation stays limited and this enables relatively good SNR for radio communications, but the relatively high scrolling speed generates important Doppler shift. However, as the object trajectory is fully deterministic, these parameters can be estimated and predicted with high accuracy. Usually Cubesat use amateur radio bands for their radio communication, adding the 25

68 following constraints: Downlink or Uplink is restricted to narrowband communications (some KHz), in the 144 MHz, 430 MHz or 2300 MHz band. Because of the limited lifetime of the satellite, we could probably get clearance to use wider band modes Ground to ground transmissions on these bands can cause severe interferences, in Downlink or Uplink, Depending on the authority giving frequency clearance (the IARU for amateur bands clear messages should be used (no cryptography). Challenges to be addressed: Two main challenges (which are strongly correlated) can be distinguished, namely, (i) Reducing the power consumption (ii) Improving the communication reliability. In both case, one should take into account that the on-board processing power is limited while ground stations could be much more powerful. Moreover, due to low cost of nanosats, one can think of a set of satellites communicating with the ground, without any communications among them. A- Reducing the power consumption 1. Power efficient communication systems, in telemetry/command links for example; 2. If several nanosats are measuring the same data, the quantities that are measured will be strongly correlated. Therefore, the rate of the communications between these satellites and the ground can be greatly reduced compared to separate communications, each one willing to transmit independent data. If one benefits form this distributed compression setting, the on-board processing remains simple, and the added complexity is inside ground stations [1]. This should have a large impact on the on-board energy consumption. B- Improving the communication reliability 1. Because of short access time, multiple ground stations are required when long messages are transmitted. One should search for the best coding scheme / protocol / modulation to cope with this situation [2] 2. With a sparse but known ground station set, what is the best communication scheme for long messages transmission? One may think of the distributed MIMO solution, but this should be carefully checked. 3. Due to the frequency bands used, many amateur radio receivers with unknown locations may get the packets transmitted by the nanosats and transmit them to some data collection point. One could think of using rateless codes in this context. 4. Because of the deterministic trajectory of the satellite, the communication channel or its evolutions over time might be predictable with some accuracy. This property can obviously be used with classical transmission schemes to improve the link reliability, but this may also open new possibilities.[3-5] 5. To prevent embedded radio transceiver failure, the communication should rely on highly robust schemes. Here also specific solutions should be searched [6,7] The above list contains some items that are clearly long term, and will not be implemented at the end of the project. Only realistic simulations will be provided. The main direction which can be given to this WP is to search for the best ways of benefiting of the good predictability of the channels combined with dissymmetric computing capabilities. Short term result: to demonstrate the improvement brought by channel predictability in actual nanosat systems. 26

69 In terms of support for this WP : - Two years of engineers or post docs, to integrate the source/channel coding techniques and the transmission protocols in a demonstator : 140 keuros if Engineers, 100 keuros if post docs - One PhD grant, to work on long-term research related to one of these communication / coding problems : 90 keuros Contribution of partners : 0.6 man/year - Michel Kieffer(associate professor): 20 % Coordinator of the WP and contributes essentially to the distributed source coding topic - Pierre Duhamel (DR CNRS): 10 % contributes to the improvement of reception based on predicatibility of channels and coalition between nanosatellites - Merouane Debbah (Professor, Supelec, Alcatel Luvent Chair) 10 % contributes to the improvement of reception based on predicatibility of channels and coalition between nanosatellites - Sylvain Azarian (Associate professor, Supelec) 20 % contributes to the improvement of reception based on predictability and connections with the radio-amateur community. Students and post docs will be supervised either by L2S or by Alcatel-Lucent chair [1] P. L. Dragotti, M. Gastpar, Distributed Source Coding: Theory, Algorithms and Applications, Academic Press, [2] Genso [3] L.M. Davis, I.B. Collings, R.J. Evans Estimation of LEO Satellite Channels ICICS97- Singapore [4] E. Lutz, D. Cygan, M. Dipp old, F. Dolainsky, and W. Papke, The land mobile satellite communication channel - recording, statistics and channel model" IEEE Trans. on Vehicular Technology, vol. 40, pp , May [5] B. Vucetic and J. Du, Channel modelling and simulation in satellite mobile communication systems" IEEE Journal on Selected Areas in Communications, vol. 10, pp , Oct [6] Antoine Dedave, Study and demonstration of the use of Software Defined Radio (SDR) for the AX.25 and D-STAR radio communication protocols aboard a nanosatellite, Master in Electrical Engineering at the Applied Science Faculty of the University of Liege, Academic year [7] Jonathan Pisane, "Design and implementation of the terrestrial and space telecommunication elements of the student nanosatellite of the university of Liege" - Master in Electrical Engineering at the Applied Science Faculty of the University of Liege, Academic year

70 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Acronym of the project Project title in English Project manager Requested funding Scientific field(s) of the project NeuroSaclay Toward the creation of NeuroSaclay, a scientific center for Neuroscience and Brain Imaging VERNIER Philippe, Research Director CNRS e- mail : vernier@inaf.cnrs- gif.fr Tél : 33- (0) M for 3 years (VAT included) Life Sciences 1

71 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Partners and Institutional affiliation Research Teams and Personnel Unit names Unit number organization Institut de Neurobiologie Alfred Fessard (FRC2118, CNRS) 12 teams : Researchers : 31 Unité Neurobiologie & Engineers/technicians : non- Développement (Philippe UPR3294 CNRS permanent Vernier) Post- docs : 25 PhD students :19 Unité Neurosciences, Information et Complexité (Yves Frégnac) Centre de Neurosciences Paris- Sud (Serge Laroche) UNITE de neurosciences cognitives (Stanislas Dehaene) UNITE d imagerie et de spectroscopie par IRM à très haut champ magnétique UPR3293 UMR8195 CNRS CNRS, U. Paris- Sud NeuroSpin (I2BM/DSV,CEA) (D. Le Bihan) U992 (C. Poupon) CEA, Inserm CEA 7 teams: Researchers : 10 Engineers/technicians : non- permanent Post- docs : 10 PhD students : teams: Researchers: EC Engineers/technicians: non- permanent Post- docs: 8 PhD students: 23 4 teams: Researchers : non- permanent Engineers/technicians : non- permanent Post- docs : 11 PhD students : 10 3 teams: Researchers: 8 Engineers/technicians: 5 Post- docs : 3 PhD students : 11 UNITE de traitement de l information, des données et des images UNITE de recherche Clinique et Translationnelle Equipe Hervé Daniel Institut de Biophysique et de Biologie Cellulaire et Moleculaire Equipe Ronald Melki Laboratoire d Enzymologie et Biologie Structurale (V. Frouin) (L. Hertz- Pannier) UMR8619 UPR3082 CEA, INRIA CEA, INSERM, AP- HP Other teams CNRS, U. Paris- Sud CNRS 3 teams: Researchers: 8 Engineers/technicians: non- permanent Post- docs : 4 PhD students : 12 3 teams: Researchers: 4 Engineers/technicians: 9 Post- docs : 2 PhD students : 5 Contractants: 5 1 team Researchers: 4 Engineers/technicians: 1+ 1 non- permanent Post- docs: 2 PhD students: 2 1 team Researchers: 5 Engineers/technicians: 1+ 1 non- permanent Post- docs: 3 PhD students: 2 2

72 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Abbreviations used: Amagen: Genetic engineering for Aquatic models CEA: Commissariat à l'energie Atomique et aux Energies Alternatives (Agency for Atom Energy and Alternative Energies) CNPS: Centre de Neurosciences Paris- Sud (Center of Neuroscience Paris- South) CNRS: Centre National de la Recherche Scientifique (National Center for Scientific Research). EPPS: Etablissement Public Paris- Saclay (Public Institution Paris- Saclay. IDEX: Initiative d Excellence (Initiative of Excellency) INAF: Institut de Neurobiologie Alfred Fessard (Institute of Neurobiology Alfred Fessard) INCF: International Neuroinformatics Coordinating Facility INRIA: Institut National de la Recherche en Informatique et Automatique (National Research Institute in Informatics and Automation) Inserm: Institut National de la Santé et de la Recherche Médicale (National Institute for Health and Medical Research). TEFOR: Transgenèse pour les Etudes Fonctionnelles sur les ORganismes modèles (Transgenesis for Functional Studies on Model Organisms). UNIC: Unité de Neurosciences, Information et Complexité (Unit of Neuroscience, Information and Complexity). UPS: Université Paris- Sud (University Paris- South) 3

73 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Table des matières Partners and Institutional affiliation... 2 Executive Summary :... 5 Context of the NeuroSaclay project within Idex Paris- Saclay:... 7 Historical ground:... 7 The Investissements d Avenir and IDEX context:... 7 Challenges and Strategies:... 9 Rationale of the project:... 9 Summary of the Research developed by the NeuroSaclay teams Objectives NeuroSaclay within the regional, national and international context Strategic analysis (SWOT): The IDEX Neuroscience Projects: Annex 3 : List of Publications of the Teams for the 4 Research Units The construction planning of the new Neuroscience Building Education and Training: Master Program International PhD Program Life- long Training ( Formation Permanente ) and Summer Schools Application and Innovation: Governance Budget IDEX Why do we need the IDEX support: Actions supported by the IDEX Paris- Saclay Support from Institutions

74 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Executive Summary : The ultimate goal of this project is to establish a large, synergistic, highly visible and internationally recognized Center of Excellence in Neuroscience named NeuroSaclay. The NeuroSaclay Center will associate neuroscientists covering the whole range of their discipline, with physicists, mathematicians, theoreticians, physicians to successfully tackle an ultimate challenge of modern Neuroscience a multi- scale analysis of brain functions and their dynamics, from embryos to adults. It will create on the Saclay Plateau a unique scientific and technical environment devoted to multidisciplinary and multiscale Neuroscience united within two buildings, the existing Neurospin and the future Neuroscience Building, financed by the Investissements d Avenir on the open part of the campus of the CEA (Commissariat à l'energie Atomique et aux Energies Alternatives). The project of Neuroscience Building is ongoing and will be completed by 2017, the time when all the Neuroscience teams will join together on the CEA campus. At present, the Neuroscience teams of the Paris- Saclay area are spread over three main locations: the campus of University Paris- South in Orsay, the Research Center of CNRS (Centre National de la Recherche Scientifique) in Gif- sur- Yvette and the CEA campus in Saclay. The Neuroscience task force currently represents 46 teams most of them (but not all) within four research units or service, with more than 380 collaborators. The overall project comprises two major steps over time, each with specific goals and means. It derives from the previous Labex project NeuroscaleX, but with significant refocusing and changes. This NeuroSaclay project has taken into account the criticisms made by the international Labex jury, and also integrates the dynamic nature of the ongoing process, which will, in the end, lead to the move of the Neuroscience teams of Gif and Orsay into the new Neuroscience Building in Spring The first step (January December 2015) consists in reorganizing and strengthening the current research units in the context of their institutional renewal, every five years. This first step includes the support asked to IDEX within this Call. Three main objectives are pursued: a. Setting up new collaborative projects between the teams of Neurospin, Orsay and Gif- sur- Yvette in order to foster interdisciplinary, cutting- edge research in basic neuroscience and connected disciplines, and to make new concepts and methodologies emerge. b. Improving and reorganizing the Neurosciences teaching and training program, in order to better fit with the research topics developed by the team of NeuroSaclay, developing internationally recognized seminars and summer schools for young scientists, with a special emphasis on interdisciplinary programs. c. Promoting the application of innovative developments and discoveries to human health and well being by way of specific actions to improve the applications of our discoveries and intensified interactions with companies from the pharmaceutical, healthcare, biotech and IT sectors. Accompanying this reorganization and new project, specific governance has been established through a Scientific and User Committee, created in November 2012, with 16 representatives of all the components of the NeuroSaclay project. 2- The second step (January December 2017) will be the preparation and realization of the move into the new building, of the teams and platforms from Orsay and Gif- sur- Yvette, as well as newly recruited teams. The research projects will thus take a new dimension due to the gathering of all the teams at the same place and the improvement and impulse that the new location will give to scientific collaborations, and the much easier and efficient use of our technical facilities and platforms. The Research Units and Teams contributing to the NeuroSaclay project combine expertise from molecular, cellular and system neuroscience to computational and cognitive neuroscience. They are reinforced by methodological platforms (brain imaging in NeuroSpin, animal transgenesis and behaviors in the other places) as well as by facilities (animal facility, advanced microscopy.etc), whose cutting- edge performance strongly increase the scientific potential of the overall project. 5

75 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Complementariness and synergy of the NeuroSaclay partners create a significantly stronger structure, fundamentally more efficient than the simple sum of its parts. Research topics are organized along five axes, which are the backbone of the current and future researches and actions of NeuroSaclay: 1) From embryo to adult 2) From animal models to human and from norm to pathology 3) From synaptic plasticity to learning and emotional regulation of behaviors 4) From perception to cognition 5) From modeling the animal and human brain to biologically- inspired computing architectures. Collaborative projects: Most teams of NeuroSaclay already collaborate and have long- standing interactions through the existing structures and scientific animation, highlighted by many common publications. But this must be further improved, especially by favoring collaboration between disciplines that are not yet fully used to work together. Thus, the Scientific Committee of NeuroSaclay (see below) chose to develop for the next three years 3 strong and ambitious scientific projects, to promote interactions between the teams of Neurospin, Gif and Orsay, and to foster multidisciplinary collaborations, including with the methodological platforms. Education and Training : NeuroSaclay will be a major partner for Higher Education and Training of the IDEX Paris- Saclay. NeuroSaclay is going to implement a Training and Education Program through four main actions: 1) a refurbished and extended Master program ; 2) an international PhD program in Neuroscience and Cognition ; 3) interdisciplinary training programs and Summer Schools in the field of Neuroscience and Complex Systems; 4) continuing training and education program. Translational research, Innovation: NeuroSaclay will be a new instrument to foster technology transfer to industry, both pharmaceutical and technological. The goal here is to facilitate the development in our structure of a first link in the translational chain of research, both for the diagnosis and treatment of neurological and psychiatric diseases, and for Information Technology. Governance : The project partners have formed a Scientific and Users Committee with representatives from the different research axes, methodological platforms and Education and Training Program and an operational director. Its role is to coordinate the NeuroSaclay Actions, with the help of a Scientific Advisory Board, and to validate the proposals of the Project- Group taking care of the construction of the new Neuroscience Building. NeuroSaclay Actions will require a mean budget of 2 M, with 3 different Action types (Projects, Education & Training, and Valorization). Actions will support cutting- edge collaborative research and methodological advances, improve Training and Education to attract the best students and scientists, and facilitate transfer and translation to medical and industrial applications. NeuroSaclay has the ambition to emerge as one the very best international clusters of Neuroscience. This ambition is grounded in the quality of its research teams and its interfacing and synergies with scientists from other disciplines, physicists, mathematicians, chemists. NeuroSaclay thereby both contributes to and benefits from the world- renowned concentration of scientific excellence in the University Paris- Saclay region. NeuroSaclay in Numbers: 46 teams and about 380 Staff Members: 126 Permanent Researchers, 123 Engineers and Technicians, about 80 Post- Docs (50% from foreign countries) and 70 PhD students (30% from foreign countries). More than 150 publications/year with about 30 in journals with IF> Patents Academic Excellence: 3 CNRS Silver medals, 2 Académie des Sciences members, ERC : 1 senior, 1 junior; 2 IUF members, 10 International Scientific Prizes, 22 French Prizes including 3 Grand Prix of the Institute of France, 3 chairs of Excellence (ANR senior, 2 University juniors). Running Grants: 61 ANR, 22 European Grants (7 coordinators), 4 PHRC, 3 NIH grants, generating more than 12 M in

76 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Context of the NeuroSaclay project within Idex Paris- Saclay: Historical ground: The NeuroSaclay project stems from a long- standing process of interactions between the research units and teams in the field of neuroscience, in the Paris- South area (triangle Gif- Orsay- Saclay). 1- The creation in 1996 and 2005 of two Federative Research Institutes, respectively IFR 49, NeuroFunctional Imaging (dir. D. Le Bihan), and IFR 144, NeuroSud Paris (dir. J. Champagnat) fostered strategic plans and scientific collaborations. 2- In 2007, Neurospin (a CEA Service, Dir D. Le Bihan) opened on the CEA campus of Saclay, and housed outstanding research groups that joined forces to develop both methods and experimental models to study brain function through the development of highly innovative, cutting- edge imaging technologies. This includes the UniCog Unit (Inserm- CEA, dir. S. Dehaene) and four CEA laboratories. 3- In 2010, guided by a long- term scientific logic, three Research units were created based on remodeling of previous Units and located on the grounds of University Paris XI : the Centre of Neuroscience Paris- South, (CNPS, dir. S. Laroche) and on the CNRS Research Center of Gif- sur- Yvette : the Unit Neuroscience, Information and Complexity (UNIC:, dir. Y. Frégnac) and Neurobiology & Development (N&D, dir. Ph. Vernier), these two latter forming a CNRS Research Federation (FR INAF: Institute of Neurobiology Alfred Fessard). The three partners are now at the core of the current project. In addition, this renewed research organization promoted the acquisition of considerable and costly equipment (microscopy imaging, multiscale electrophysiological recording systems, animal facilities etc) through concerted actions via funding from the Region Ile- de- France. The Investissements d Avenir and IDEX context: 1- In 2010, the decision of creating a pole of excellence on the Plateau de Saclay area met the objectives of the Neuroscience Research Units of Gif- sur- Yvette and Orsay, strongly committed to develop the necessary scientific and technological environment for understanding the logics of brain assembly and its multi- scale, dynamic complexity of functions. Accordingly, together with NeuroSpin, they proposed to join forces to create in the long run an integrated Center of Neuroscience (NeuroSaclay) with advanced tools and recognized experts in Neuroscience at all scales. This proposal received strong support from our Institutions (CEA, CNRS, Inserm and University Paris- Sud) and a specific funding ( 50M ) was allocated through the Investissements d Avenir action, in order to build a Neuroscience Building, close to the Neurospin Building, within the framework of the program développement scientifique et technologique du Plateau de Saclay (scientific and technological development of the Saclay Plateau) and Operation Campus. 2- In the mean time, Investissements d Avenir also launched a call for the creation of Laboratories of Excellence (Labex). The application to the Call Investissements d Avenir through the labex NeuroScalex made by the Neuroscience Units in 2010 and 2011, with the collaboration of the Laboratoire Optique et Biosciences (LOB, Ecole Polytechnique, dir. J- L Martin), appeared a natural extension of the coordinated process, which aimed at gathering and synergizing all the forces in Neuroscience within the Saclay Plateau area, to meet the challenges of modern Neuroscience. Unfortunately, this Labex application was not short- listed despite the recognition of the scientific excellence of the teams and of the project. However, the international jury raised doubts on our capacity of working together, as well as to develop a really novel environment for training and education, as well as for application our researches and data. However, the Labex was not a goal in itself, and the neuroscientists of the Paris- Saclay area have pursued their effort toward the organization of synergic actions in neuroscience and neuroimaging, as well as the construction of the Neuroscience Center on the CEA campus of Saclay. Thus, the current application has re- focused its objectives and it fully takes into account the few criticisms and suggestions of the Labex Jury reports. 7

77 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay 3- In addition to the new Neuroscience Building, several platforms directly linked to the Neuroscience Units have been recognized by the Investissements d Avenir action, either as Equipex (Morphoscope, located mostly at Ecole Polytechnique in Palaiseau, but with a very significant contribution about 25%- of the Neuroscience teams), or part of the National Research Infrastructure networks: (i) The Ile de France South node of France Bio- Imaging (coordinating outstanding imaging and microscopy facilities), (ii) Amagen (Genetic engineering for Aquatic models) is part of Cellphedia the national large- scale infrastructure Network for animal facilities (Creation, Breeding, Phenotyping, Distribution and Archiving of vertebrate models), and (iii) TEFOR (a structure to support Transgenesis for Functional Studies on Model Organisms) are all located at INAF in Gif). (iv) The main node of France Life Imaging (coordinating outstanding biomedical imaging facilities) is Neurospin in Saclay. 4- In addition to this large input of the Investissements d Avenir on our environment, other platforms and facilities greatly increase the attractiveness of our Units and Institutes: (i) the French node of the International Neuroinformatics Coordinating Facility (INCF) run conjointly by UNIC and NeuroSpin, (ii) the Amatrace platform for studying fish behaviors, which is part of the European Network EUFishBioMed, and an Antenna of the Complex Systems Institute in Ile de France, to help analyzing and modeling complex neurobiological systems. Map showing the location of the main components of the Paris- Saclay University, including the campuses of the University Paris- Sud in Orsay, of the CNRS in Gif- sur- Yvette (both in the Chevreuse Valley) and of CEA on the Saclay Plateau. 5- The relocation on the Plateau de Saclay, close to Neurospin of all the Neuroscience Units, Facilities and Platforms currently in the Chevreuse Valley will make a very significant task force, starting from currently 46 Research groups and more than 380 people, most of them having a high international recognition. Scientific indicators point to the excellence of these teams. Thus, Neuroscience is a major component in the Chemistry- Biology Field of IDEX Paris- Saclay. The goal of this significant action of re- localization of the Neuroscience teams is also to boost the dynamics and attraction power of our institutes and to increase the critical mass of researchers by about 15-20%. Numerous interactions and a dense network of collaborations also exist between the teams of NeuroSaclay and other labs of the Idex Paris- Saclay, such as collaborations for microscopic imaging with the Laboratory of Optics and BioSciences of the Ecole Polytechnique, with mathematicians and physicians of several laboratories of the University Paris- Sud and INRIA, or with other research units on the INRA campus of Jouy- en- Josas (National Institute for Agricultural Research), in the Kremlin- Bicêtre Hospital, and of course on the Orsay campus of the University. 8

78 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Challenges and Strategies: Rationale of the project: The driving ambition of the NeuroSaclay consortium is to constitute a task force specialized in the multi- scale analysis of brain functions and their dynamics, from embryos to adults. Although the goal can be formulated in simple terms, it is a considerable endeavor, which very few research centers in the world are able to tackle. Taking the question seriously needs to assemble a novel and ambitious scientific, methodological and technological environment, designed to achieve an integrated understanding of the logics of brain organization and its dynamic complexity across multiple scales, ranging from molecules to the organism s behavior and cognition. Understanding the brain as a complex dynamic system is a leading- edge challenge for science of the XXI st century, which requires innovative interdisciplinary approaches at the interface between Physics and Biology. The Neuroscience teams contributing to NeuroSaclay have the ability and willingness to combine forces to meet this challenge. They have a highly recognized scientific and methodological expertise and most of them have a high international profile. The overall project aims at fostering interdisciplinary research spanning the different spatial and temporal scales that are relevant for neuroscience. The multi- scale issue is twofold, regarding both the nervous system itself, and the techniques that need to be improved for its study, e.g., from microscopy to whole brain imaging. This research is therefore highly interdisciplinary and conducted at the interface between different disciplines of neuroscience and physics, mathematics and cognitive sciences. Although the current organization of the research Units and Institutes of Neuroscience in the Paris- Saclay areas have been rationalized over the ten last years, but an effort of organization toward a better synergy is still needed. This was begun with the NeuroScalex project, and pushed here into a really integrated and functional scheme. Five research axes have been defined (see below, next paragraph) to give the main directions to be followed by the scientific policy of NeuroSaclay. In addition, new plans and collaborations project have been chosen and designed to promote new or stronger collaborations between the teams of the Orsay and Gif Institutes and those of Neurospin. We present below projects specifically designed to reinforce links between neuroscience and neuroimaging, and focused on three topics. The first one will reinforce our means to study across non- human and human brains the neural mechanisms underpinning functions from sensory coding and low- level perception to higher (semantic) cognition. The second one will investigate the neural representation of temporal sequences and of nested language structures, both in humans (by direct study with brain imaging and intracranial recordings) and in animal models (monkeys, mice, and birds). A third and complementary line of research will address the dynamics of molecular and cellular interactions (genetic and signaling networks), which govern functions of neural stem cells in cerebral plasticity and how it determines specific adaptive behaviors. Overall Organization of NeuroSaclay in 2017: The current dynamic process of reorganization and rationalization of the Neuroscience research within NeuroSaclay will lead from separate units spread over 3 locations to a single Research Center with two buildings, NeuroSpin and Neuroscience. This latter will be organized in fours scientific poles, platforms and facilities and will include space for graduate and doctoral training 9

79 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay In addition, we have decided to found a new institute in Theoretical Neuroscience, to attract high profile researchers and foster interdisciplinary neuroscience research in the context of European Flagships (Human Brain Project) and international collaborations. Summary of the Research developed by the NeuroSaclay teams. Objectives NeuroSaclay represents a major step forward in gathering forces and increasing their efficiency in interdisciplinary collaboration to cover a continuum of scales from molecular and cellular biology through systems and theoretical neuroscience, and, ultimately, approaches to behavior and human cognition. The main objectives to be fulfilled in the project are: Implementing and supporting innovative, multidisciplinary, multiscale projects Completing the design and construction of the new Neuroscience Building Setting up the new governance of the NeuroSaclay cluster as well as of its different components, mostly inside the new Neuroscience building. Establishing a new standard in high level education in all fields of science covered by the teams of the NeuroSaclay Center Increasing the international recognition and visibility of the NeuroSaclay Center NeuroSaclay within the regional, national and international context. Local- regional: The Units of the INAF in Gif- sur- Yvette, CNPS in Orsay and NeuroSpin in Saclay, are forming together the largest Neuroscience community of the Paris- Ile de France Area. Their re- location at the same place (the CEA campus of Saclay) will make NeuroSaclay a highly visible and attractive Center. In addition, the research topics developed in the NeuroSaclay project have little overlap, if any, with the other Research Centers of the Paris area. NeuroSaclay has clearly strength in brain development and evolution, analysis of the neural mechanisms of behaviors and cognitive functions, sensory and cognitive neuroscience, theoretical and computational neurosciences. In contrast, and to take a few examples only, the groups of the Ecole Normale Supérieure and Collège de France, united inside the MemoLife Labex, develop mostly molecular and cellular neurosciences (biology of the synapses, neuronal plasticity, neuronal networks, early brain development) which are not really represented in the NeuroSaclay teams. Similarly, the groups belonging to the Bio- Psy Labex (Fer- à- Moulin Institute, Jussieu, Pasteur Institute, Mondor Hospital) are entirely devoted to study models and mechanisms of psychiatric diseases and corresponding translational researches, with topics which are not studied in the NeuroSaclay project. Again, the teams of the Institut du Cerveau et de la Moelle (Brain and Spinal Cord Institute) of the Pitié- Salpêtrière Hospital are mostly focusing on neurodegenerative diseases and human neurogenetics, which are not the main focus of NeuroSaclay, but with whom we are several strong collaborations. Similar observations can be made with other centers like the Vision Institute or the St Pères Institute. Thus, a great deal of complementarity exists between the main neuroscience research centers in the Paris- Ile de France Area. 10

80 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay This division of labor has been organized over years and greatly facilitated by the existence of two regional organizations: the DIM Cerveau & Pensée (Brain and Mind Regional Organization) supported by the Region Ile de France, and the Network (RTRA- Réseau Thématique de Recherche Avancée) supported by the French Ministry of Research. The first one has catalyzed the organization of neuroscience teams in centers, as well as collaborations, by financing mostly medium- to- large equipment. The second one has helped attracted excellent foreign students in our laboratories and developing attractive training and PhD program for foreign students. The teams NeuroSaclay have been very active in participating and organizing these networks. They have also been successful in this context, and our new organization will undoubtedly receive a large support from these two (tighty linked) regional organizations. National: As for the local context, the place of NeuroSaclay is very well positioned in France. It will be one of the largest Neuroscience Center in the country, and the specificity and strength of the NeuroSaclay research topics are highly recognized. The other large French centers outside Paris are in Bordeaux, Marseille and Lyon, and to a lesser extent in Montpellier, Strasbourg and Lille, the other centers being still smaller. The teams of NeuroSaclay are at the head or belong to the Boards of several national networks such as GDR (Groups of Research) on Memory, on Developmental and Evolutionary Biology, in Cognitive and Computational Neuroscience (RISC network for example, or Complex System Institute) or the French Society for Neuroscience. This highlights the excellent integration and prominent place that many teams of NeuroSclay have in the national neuroscience community. All the teams of NeuroSaclay have been recognized and appointed by one of our major Institutions either CEA, CNRS or Inserm. All the teams are also linked by contract to the University Paris- Sud. Most of them have been highly ranked by the previous national evaluation (A+ and A for 90% of the teams), and most of them have been successful in getting grants from the National Research Agency (ANR) or the European Union or other international and national grants. International: 11

81 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay The scientific recognition of our teams is excellent, as ascertained by the invitation as keynote speakers to international meetings, attractiveness for foreign students and post- docs, and other indicators. No doubt that the creation of NeuroSaclay will still increase this international visibility on the long range. In addition, the scientific actions of the NeuroSaclay Units are integrated at the international level in high profile consortia or excellence networks (Europe: FET Facets, Brain- Scales and Brain- i- nets for UNIC, or ITN ZF- Health and INsecTIME for N&D, Memoload Consortium for CNPS). Some large- scale European flagship projects have recently reinforced tight scientific collaborations between Units of the NeuroSaclay consortium (The Human Brain project links NeuroSpin and UNIC for instance, and several ANR projects involve active collaborations between teams of the current Units). Two International Associated Laboratories (LIA of the CNRS) have also been established with New York University (USA) and Oxford University (UK) for the CNPS. Strategic analysis (SWOT): Strengths - Organization: Scientific complementarity of research agencies (CNRS, CEA, University Paris- Sud, Inserm). Status of permanent researchers, technicians and engineers, allowing risk- taking and sustainability of technological achievements and the development of the platforms. Long- standing collaboration between the teams inside the Institutes and the pre- existing IFRs (Federative Research Institutes, IFR 42 on Brain Imaging dir. D. Le Bihan; IFR 344 NeuroSud Paris- dir. J. Champagnat ). Excellent methodological platforms (Neurospin, Amagen, TEFOR, Amatrace). - Internationally competitive themes and teams: Development of the nervous system, executive functions and behaviors, sensory neuroscience, cognitive neuroscience, brain imaging. Weaknesses - Organization: Insufficient scientific coordination between the Institutes, isolation of some teams. Spreading of the current institutes on a relatively large area. Lack of some major neuroscience disciplines in the teaching programs, reducing the ability to attract the best students from foreign countries. Insufficient application and valorization of the research data both in Neurological Medicine and IT. Opportunities - More coordination between agencies to support the project (CNRS, CEA, University Paris- South, Inserm). - Construction of a new Neuroscience Building, already financed by the Investissements d Avenir. - Collaboration with Schools and CHU for research training and applied research; developing recruitment policies of interdisciplinary neuroscientists, clinician- scientists and teacher- scientists. - Determining funding priorities within the NeuroSaclay project, increasing funding for recruitment of post- docs and students and to support young researchers (Avenir and ATIP). - Interdisciplinary research (mathematics/computing for modelling and systems biology, physics for imaging, chemistry for drug development, etc). 12

82 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Threats - Isolation and marginalisation of basic sciences threatening the existence of high quality research into the fundamental mechanisms of life (non- thematic, non- directed). - Rigidity of management culture and lack of administrative responsiveness of the various research agencies, compromising the effectiveness of platforms and laboratories. - Weakening of partnerships between academic teams and drug or biotechnology companies. The IDEX Neuroscience Projects: Three main Specific Projects have been selected to be fostered by the IDEX support. They have been chosen to be clearly focused on challenging questions in Neuroscience. They are novel as well as based on the recognized expertise of the teams and they are the best possible means to build the requested scientific synergy, which is the main motivation and ambition of the project. These projects are by essence collaborative between teams of Neurospin and those of Orsay and Gif. The expected result is to strengthen the links between the two main components before they join together in 2017, and synergistic, multidisciplinary projects between neuroscience teams and teams of the IDEX, for example those of the LOB of Ecole Polytechnique, highlight the strong motivation and long standing commitments of the teams for collaboration with physicists, mathematicians, informaticians and physicians. The overall goal of the projects is to overcome some of the bottlenecks in the multiscale exploration and understanding of the function and structure of the nervous system, and advance our current understanding of the neural bases of behaviors and cognitive functions in animals including human. It is designed to promote internationally- recognized, high- level research in fundamental neuroscience and to foster interdisciplinary research to allow the emergence of new concepts and new methodologies. The scientific project is organized along three transversal Research Axis and one structuring action Plan, as summarized below: Axis 1. Merging Senses: From unisensory integration to supramodal perception This research axis will combine multiscale electrophysiological, neuroimaging and computational approaches to identify «emergent» features of unisensory and multisensory integration in non- human and human brains. The long- term aim is to unravel neural processes enabling access to the conscious experience of a supramodal representation unified through the interactions across various sensory modalities. Axis 2. From sequence learning to language acquisition This second research axis will investigate the neural representation of temporal sequences and of nested language structures, both in humans (by direct study with brain imaging and intracranial recordings) and in animal models (monkeys, mice, and birds). Axis 3. Biology and Pathology of Adult Neural Stem Cell Pools The last research axis will combine multi- scale approaches, from single cell genetics to animal behaviour, to generate an integrated understanding of the homeostasis of adult neural stem cell (NSC) pools, its response to environmental/pathological challenges, and its output on brain physiology. We will rely on several animal models for their different NSC supplies and their technical complementariness; 13

83 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay International Action: Foundations for a European Institute for Theoretical Neuroscience The goal of this structuring scientific action is to create an Institute for theoretical neuroscience which will be hosted in the new Neuroscience building. The aim is to foster the interaction between theoreticians and experimentalists collaborating in the Region Ile de France Sud. It will serve to attract high level international scientists and organize their stay, and encourage interdisciplinarity, which is an important aspect of the Idex proposal. We will therefore allocate significant space and access to parallel multi- node computing facilities in the new building, specifically devoted to welcome visitors and postdocs, which will work on both theoretical and experimental aspects of the Idex project (the fact of working on both aspects will be a requisite for eligible candidates). The following documents necessary for the evaluation of the project have been grouped in three annexes : - Annex 1 : Full Presentation of the scientific projects - Annex 2 : Collaboration Table between Units and Teams - Annex 3 : List of Publications of the Teams for the 4 Research Units The construction planning of the new Neuroscience Building. The design, programming and construction of the Neuroscience Building are supervised by the Direction of the Life Sciences of the CEA. The program is organized and followed by a Project Team headed by the Project Director (P. Vernier, CNRS) and the Project Manager (X. Charlot, CEA). The Project Team is made of 16 people representative of the different Institutions supporting the project, with the necessary expertise to fulfill the requirements of designing and programming the new Building. They supervise the working groups that have been organized with all the Units related to the project that will move in the new Building. The orientation and necessary choices of the project are validated by the Director Committee composed of the Presidents of the University Paris- Saclay and Inserm and the directors of the Life Science Institute of CNRS, and the Life Science Divison of the CEA. The financial operations are supervised by the Ministry of Research (MESR) and the National Research Agency (ANR). The link between the design and program of the Building and the scientific project is made by interaction with the Scientific and Users Committee. Finally, the place and interaction of the Neuroscience project with the other components of the Paris- Saclay University is discussed and organized in collaboration with the Public Agency Paris- Saclay (EPPS) (see figure below). General organization of the Neuroscience Building project. Legend: PD, project director; PM Project Manager; EPPS, Etablissement Public Paris- Saclay; ANR, Agence Nationale de la Recherche; MESR, Ministère de l Education Supérieure et de la Recherche. For the other abbreviations see list on page 2. 14

84 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Education and Training: This is a chief priority and challenge for our project, and this is discussed between the professors in charge of the Neuroscience training program at University Paris- Sud and the other training components at University Paris- Sud, Ecole Polytechnique, Supelec, and other specific program (cognitive sciences especially). Involvement of Neuroscience to the Education and Training project of Paris- Saclay University is also very significant and includes components from Ecole Polytechnique, ENS Cachan, and the Kremlin- Bicêtre Faculty of Medicine in addition to the Faculty of Sciences in Orsay. It is the core of the Neuroscience development and future within Paris- Saclay University. Special effort are made to foster new specific educational programs (complex systems, Physics/Biology interfaces, PhD program for medical students, program for industrial partners see below- ) and Summer Schools for students in the field of multi- scale analysis and associated priorities of the Neuroscience project. The Training and Education Program of NeuroSaclay fully takes for itself the agenda of the Training Program of the IDEX Paris- Saclay, which is to offer training excellence in basic and applied research: 1) a high- level basic training well visible and recognized by industry and internationally; 2) being a strong part of the Shared Doctoral Space of the IDEX Paris- Saclay, and 3) offering interdisciplinary courses bridging the gap between the Grandes Ecoles and Universities, 4) thus attracting the best students ( new minds ), and 5) promoting international training. An Education & Training Committee is dedicated to the organization of the training program inside NeuroSaclay. This committee is chaired by Hervé Daniel, Professor of Neuroscience at University Paris Sud and includes 4 other professors and researchers representing the different axes of NeuroSaclay. Training and Education Program of NeuroSaclay will be implemented through four main actions: Master Program High- quality training modules in Neuroscience are already existing at the University Paris- Sud. These courses are often original within the Paris area, in particular those in evolutionary neurobiology, neuropharmacology, integrative neurosciences, cognitive sciences, computational neurosciences and neuroinformatics. In addition, the basis of Neuroscience are presented at the License level (L3) and also contributed by NeuroScalex members. However, these training programs remained poorly coordinated together, and not easily visible or accessible to the students, especially foreign students. Thus, the Master Program will be organized by NeuroScalex Education & Training Committee through a new Entry Point and a corresponding website to orient the students toward the right path and help them with the administrative questions. The Master degree comprises 2 years of Training, Master 1 and Master 2. The Master 1 program is mainly devoted to introduce advanced neuroscience concepts (Neuroscience basics have been acquired at the Licence or equivalent level (Bachelor of Science). The Master 1 training program includes one or two rotations (short stays 2-3 months) in research labs. It includes 2 sections: Molecular, Cellular and Integrative Neuroscience (Person in charge: Pr H. Daniel). Neurogenetics, Development and Evolution of the Nervous system (person in charge A- H Monsoro, F. Bourrat). All these courses of Neuroscience, are part of a multidisciplinary training in biology. They are complemented by courses in Statistics and English, to provide student with sufficient background The Master 2 program is a series of advanced courses in all aspects of Neuroscience, with a strong emphasis on multiscale analysis and interface with Physics or Mathematics. It is international in essence (all courses in English) and includes specialized sections, which either already exist or will 15

85 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay be strongly remodelled to accommodate the quality charter of the IDEX Paris- Saclay. The teaching programs include 150h of courses and one or two internships in laboratories, where the students develop a research project under the supervision of one researcher of NeuroSaclay. They will allow access to teaching modules at the Ecole Polytechnique and Ecole Supérieure d Electricité (Supelec), which will be selected and validated according to the specificity of each of the Masters : - A Master in Molecular, Cellular and Integrative Neuroscience (MCIN), organized by University Paris- Sud with the NeuroSaclay researchers, assistant- professors and professors. - A Master in Developmental/Evolutionary/Behavioural Neuroscience and Genetics (DEBNG) also organized by University Paris- Sud in Partnership with Ecole Normale Supérieure de Paris, with the NeuroSaclay researchers and professors. - A Master in Cognitive Neuroscience (CogMaster), which associate a teaching staff from NeuroScalex and Polytechnique with teachers from other centers of cognitive neuroscience in Paris (Cognitive Science department of the Ecole Normale Supérieure, de Paris. - A Master training at the Interface between Physics and Neuroscience (IPB), co- labelled by University Paris- Sud and University Paris- Diderot, and organized mostly by the researchers and professors of NeuroSaclay. The program includes an introduction to molecular, cellular and evolutionary biology and a course in Multiscale Approaches in Neuroscience and Models and two or three courses in physics of soft matter and optics applied to biology and Brain Imaging. Some of the modules will be common between Masters, in order to avoid a too large load of teaching and overlaps. International PhD Program NeuroSaclay will establish a new PhD program in Neuroscience, which currently does not exist as such in the Paris- Sud area. The teams of NeuroSaclay are affiliated to up to 6 different doctoral schools, not only at the Paris- Sud University, but also at other Parisian Universities : BioSigne, ED419, Paris- Sud ; Genes, Genomes, Cells, ED426 Paris- Sud, Therapeutic Innovations, ED425, Paris- Sud ; Informatique, ED427 Paris- Sud; Brain- Cognition- Behaviour, ED158, Univ. Pierre et Marie Curie, Frontières du Vivant, ED 474, Univ. Paris Descartes/Paris- Diderot/Pierre- et- Marie- Curie, EDX Ecole Doctorale de Polytechnique. NeuroSaclay members are in the board of 3 of these doctoral schools (ED419, ED426, ED158). A major outcome of NeuroSaclay will be to set up the PhD program in Neuroscience within the Doctoral Space of the University Paris- Saclay, probably by being part of a new multidisciplinary doctoral school including Neuroscience. Discussion on this topic has begun, and will find an outcome in the coming months. The main goals of the International PhD program will be: - To attract the best master students from foreign Universities in the PhD program, participate in the educational program and augment the number of PhD fellowship in collaboration with industrial partners. There are currently more than 200 PhD students registered in the different doctoral schools with about 30% coming from other countries. NeuroSaclay will offer 4 PhD fellowships/year to students after a selection process based on academic grades and a presentation of the scientific project by the students in direct link with the Paris School of Neuroscience (ENP), a network of excellence for international Neuroscience training (most NeuroSaclay Team are members of the ENP. Scientific projects proposed to the student will be selected by the NeuroSaclay Training and Education Committee based on the scientific quality and priorities given by the NeuroSaclay scientific Steering Committee. The PhD program will be advertised using current communication tools such as web site, diffusion of information in the scientific network of NeuroSaclay. - Marie Cure Training Program : NeuroSaclay also plans to make a network of European doctoral schools in Neuroscience and Complex System analysis through the Marie Curie Programs of the European Community to help students educated with the Paris- Saclay University to go abroad. - Despite the fact that the Labex Units are already strongly involved in, a major goal of the Educational program of the Labex will be to strengthen and enlarge the bridges between disciplines 16

86 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay multidisciplinary approaches and teaching. This kind of Education and Training obviously concern a limited number of students only, but they are among the best students, and they should become the future leaders in our field.: o Biology- Physics- Maths- Computer_Science Interfaces: The existing Master courses, mostly designed for physicists wishing to work in biology and neurosciences will be expanded to mathematicians and informaticians. Courses topics will be also widen to reach Complex Systems theory applied to biological objects, from embryo to dynamic functioning of neural entities (e.g. neocortical networks during cognition). Conversely, it will also provide neurobiologists with appropriate education in physics and maths. All students will have the opportunity of a dual training in Biology and Physics/Maths. o Biology- Medicine/Pharmacy Interface: The NeuroSaclay members are concerned about the lack of sufficient numbers of physician- scientists trained in basic research and able in their future career to either undertake a full- time research work or to carry out necessary clinical research, with a good interaction with fundamental neuroscientists. In connexion with the Ecole de l Inserm, arrangements will be made with the Schools of Medicine to allow the students to spend three years of full- time research in one of the teams of NeuroSaclay, during their university time, preferably after their Internship). Special fellowships will be given to selected students to make this double formation possible. Life- long Training ( Formation Permanente ) and Summer Schools. Multiscale analysis, data processing and modelling, progress in instrumentation, both in new microscopies and brain imaging require to make a strong effort to train the personnel of our laboratories as well as of other laboratories either academic or industrial, in these very interdisciplinary issues. Thus, specific international theoretical and practical courses will be organized every two years by the NeuroSaclay members, as it has been already done recently for new microscopy methods, neuropharmacology or complex system analysis. In addition, a Summer school in multiscale analysis will organized for one month each year, around the technical platforms of NeuroSaclay, with a strong emphasis on data processing and modelling (collaboration with the Institute of Complex Systems Ile de France). Application and Innovation: A new frame of the valorization project has now been defined, and represents a significant improvement compared to the NeuroScaleX project. It includes: - Education and training program (at the level of the Doctoral School) toward industrial partners and to stimulate access of PhD students to Industry. - Platform activity strongly used by industrial partners, such as Amagen, Amatrace and the imaging facilities of Neurospin. - Specific project with partners of the pharmaceutical and brain imaging industry: providing means, platform access and expertise to develop industrial project: A dozen of projects are currently under way, including some with aerospace industry. More specifically, and in the frame work of this IDEX call, we have selected two projects, which will be specifically supported. Theses project aim at deciphering mechanisms linking inappropriate perinatal environments with major adult brain pathologies. They are presented in the Annex to this document. An original long- term translational application to the field of Science Technology and Communication will be the study of Brain- inspired computational architectures, other than Turing machines, which can implement neural- based computation and emulate the cognitive operations of the human brain. This type of development is presently supported by collaboration with Physics and Electronics departments (Khirchoff Institute at Heidelberg, NeuroSpinnaker, University of Sheffield, UK) and neurormorphic implementation of computers inspired by the brain are the focus of 17

87 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay initiatives interesting technological industrial centers (Thales) and CEA- Polytechnique (memristor) in the Paris- Sud region. - Relationship with our medical and translational laboratories: development of a dozen of specific projects with direct medical applications with groups in Kremlin- Bicêtre Faculty of Medicine but also at other hospitals in Paris, France or foreign countries. Most importantly, a Committee for Application and Innovation has begun to work with the interested group leaders of Neurosaclay to identify those of the data and/or projects, which are mature and of interest to be developed as an application. Three of these projects Governance The governance of the overall NeuroSaclay project has now been put into place. A Scientific and Users Committee of 16 members has been appointed with two missions: (i) supervising and coordinating the Scientific projects and especially collaboration between the teams of NeuroSaclay (answer to this call is an example) or the elaboration of the new research projects to be evaluated by our Institutions by the beginning of 2014 (institutional quinquennium); (ii) validating the proposals of the Project- Group taking care of the construction of the new Neuroscience Building. The Scientific Committee will also supervise the Actions to be supported in the framework of this IDEX project, with the help of a Scientific Advisory Board (SAB). This SAB of about 15 foreign members covering all the fields of neuroscience studied by the NeuroSaclay teams is being contacted now and will meet for the time early in June this year (2013). The SAB will be of utmost importance to accompany and suggest adjustments for the projects and future governance of the Neuroscience Building and of NeuroSaclay. The composition on this Committee is given in the table below and includes the Project Director and the Directors of the existing Units from Neurospin, Orsay and Gif, as well as representatives of the main scientific components and platforms contributing to the project. The deadlines we are facing are summarized in the following figure. We have to: - prepare the scientific projects to be presented for institutional evaluation at the end of discuss and propose the new scientific and administrative organization of the Research Units located in Gif- sur- Yvette (N&D and UNIC at the Institute of Neurobiology Alfred Fessard) and Orsay (CNPS) with the same deadlines. The proposed organization of the Neuroscience building includes 4 scientific poles and other Platforms, services and facilities (see figure page 9 and below). The planned gouvernance status is still under discussion to decide wether these poles will be independent departments of a single Institute or whether they will operate as 4 independent Units united within a 18

88 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Federation (or a mixed scenario as in NeuroSpin or the Curie Institutes). In any case, it will be a mixed structure supported by CNRS, Inserm and University Paris- Sud (may be the CEA also, but this has not been decided yet). A key feature of the project is that NeuroSaclay will reunite all the Neuroscience and NeuroImaging partners (ie NeuroSpin and the Neuroscience building) into a highly visible and synergic federation. Its strength will be its size and scientific power, the breadth of multiscale techniques and the complementariness of the research. - finalize the Governance of the Neuroscience building, which will take the shape of a Directory Board with decisional role comprising the heads of the 4 scientific poles/units, including an executive director chosen among the 4 pole heads, as well as a General Secretary, to be appointed soon (candidates will be interviewed soon). - prepare the move of the teams from Gif- sur- Yvette and Orsay, with all the question regarding the Administration of the Neuroscience Building, the organization of the large animal facility, the organization of all the technical service and platforms, the necessary reorganization of the personnel, and the move of the scientific teams themselves. Budget IDEX Why do we need the IDEX support: As already stated, the teams of NeuroSaclay are already well used to collaborate and work together. Most of them are well supported by contracts from the ANR, Europe or other sources, including our Institutions. Nevertheless, A support from IDEX is mandatory The IDEX support will be seeding money, to support key- actions that will speed- up and foster key- programs of the Neuroscience Project to become more solid and tangible. Since the period covered by the IDEX action will precede the installation in the new building, we will primarily consolidate integration across existing teams at Neurospin and Gif/Orsay before the move rather than recruiting new teams. This second step, of course necessary on the medium term perspective and adding new blood to the present teams, will require a specific funding plan starting in 2015, two years before the building infrastructures become operational. Actions supported by the IDEX Paris- Saclay Currently, three main actions are necessary to achieve the goal of the project. Projects: The defined specific projects will be supported for their highly innovative and risky outcome that falls within the scope of the defined Programs, as well as to foster collaborations between the components of the Neuroscience Project. Such projects are not always easy to fund by institutions such as ANR. The projects will have to be fully multidisciplinary, ambitious, and implicate several of the teams belonging to several units, as a prefiguration of what the programs would be, when everybody will gather into the new building. Typically, three projects will be funded each year with an average of 200 k per project for the first year and a duration of 2- to- 3 years, depending on the topic and its purpose. The specific aspects to be funded will be chosen inside the collaborative projects presented above. Nevertheless, if an urgent need outside these projects is put forward and fully justified it could be also funded. The choice of specific action to be funded will be made by the SAB. The methodological platforms are clearly one strength of NeuroSaclay, and will be used in the projects. Thus, corresponding running and maintenance costs could be covered in part by the project funds. It will help in keeping on duty a reasonable number of men power to help these platforms running smoothly, due to the lack of flexible support for such platforms. The corresponding budget could be used either for hiring post- docs, buying small- to- medium size equipment or covering the running cost of the project. The relay of these funds for the future 19

89 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay will have to be taken by application to national and international project calls (ANR, European grants ). A specific attention will be given to this relay by the Scientific Committee and the SAB A small part of the budget will also allow us to launch the foundations of an International Institute for Theoretical Neuroscience. This will be done in synergy with European actions in Information and Technology, including the Human Brain Project where partners in NeuroSaclay participate actively. This action is necessary so that the Institute becomes operational as soon as we will move to the new location. During the period covered by the Idex, the hosting of external scientists will be shared by NeuroSpin and the CNRS Campus in Gif- sur- Yvette. Requested budget from IDEX: 1 st year 2 nd Year, 3 rd Year Application and Valorization: There is an expressed need among teams of Neurosaclay for a support to allow a few projects with high applicable outcome to go up the proof of concept, which will then allow a patent to be more easily taken, or to gain support from a French valorization Agency (OSEO for example). Currently, at least three teams have been identified within such a situation. Their project involve respectively: the development of drug interfering with major cell signaling mechanisms during development and cancer (the hedgehog signaling pathway), the development of new in vivo models of endophenotypes of psychiatric disease (Attention Deficit with Hyperactivity), and diagnostic tests for food toxins (cyanotoxins). These projects are well advanced, patents have been taken, but a detailed proof of concept and strong evidence for the interest of these findings are still lacking. The goal of the financial support that could be provided by the Idex Paris- Saclay will be thus to help these teams to go further and get the data which allow them to develop a large and efficient translational research. The potential for creating small companies from these data has been evaluated as being very good by specialists from our Institutions or from the private sector. Requested budget from IDEX: 1 st year 2 nd Year, 3 rd Year Education & training: As a hallmark of the Neuroscience project, special effort will be made to foster new specific educational programs (complex systems, Physics/Biology interfaces, PhD program for medical students) and Summer Schools for students in the field of multi- scale analysis and associated priorities of NeuroSaclay. A large part of the money will go to help the teams recruiting PhD students and Post- docs, especially for short period of time that are not easily funded by other sources. Support is needed to organize the courses and publicize them. Requested budget from IDEX: 1 st year 2 nd Year, 3 rd Year Total IDEX Budget: 2M 20

90 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Support from Institutions. The four Institutions linked to the project, that is CEA, CNRS, Inserm and University Paris- Sud, have proven their commitment to the project since a long time. The personnel of the Neuroscience project is made of members of the four cited Institutions and it is the responsibility of these Institutions to maintain and fill- in the necessary needs in personnel on the project, and cover the infrastructure costs associated with the new Neuroscience Institute. A written commitment of these Institutions will be sent to the IDEX direction, and representatives of these Institutions at the IDEX will directly explain their support to the project. (NB the letter of support of the CNRS is in the Annexes of the document). All Platforms associated to the project are also supported by the same Institutions (Neurospin Imaging Facility, INCF, Amagen) and some of them are supported by the Investissements d Avenir (TEFOR, FBI, FLI, Morphoscope). Nevertheless, is very high, and cannot be entirely supported by the teams that use them. In particular here, the funds will be used to fill the gap between the deficit in specific expert workforces on certain multidisciplinary platforms, and by the commitment of our Institutions supporting the project to recruit them. It is thus anticipated that all the support provided by the IDEX, which, again will be essentially seeding money to help new and risky collaborative projects, our effort for Applications and Innovation, and the attractiveness of our Training and Education program for young scientists, especially foreigners, will be fully supplemented by the Institutions. The ambition of the NeuroSaclay project has been high from the very beginning and we are on the right track to construct and organize a highly visible and original Centre of Neuroscience in synergy with the Paris- Saclay University. The IDEX label will greatly help the efforts of the contributors to the Neuroscience project to increase supports from the French and International Agencies and Private Foundations, after the tree- year period of this project. 21

91 IDEX Paris- Saclay Call for Proposals 2013 NeuroSaclay Annexes

92 NeuroSaclay Idex Project Research Axis 1 Merging Senses Axis 1. Merging Senses: From unisensory integration to supramodal perception Summary Statement: This research axis will combine multiscale electrophysiological, neuroimaging and computational approaches to identify «emergent» features of unisensory and multisensory integration in non- human and human brains. The long- term aim is to unravel neural processes enabling access to the conscious experience of a supramodal representation unified through the interactions across various sensory modalities. Scientific Goals: The emergence of generalization and abstraction processes in perception through various sensory modalities is shared at least by birds and mammals (Tolman, 1948, Murphy et al, 2008; Shettleworth, 2010). This includes the simplest form of spatial and temporal Gestalt laws such as grouping by spatial proximity, contour completion, continuity extraction or filling- in features in the spatial domain and common fate detection in the time domain (Kofka, 1935). In mammals, sensory representations interact with each other through long distance connections, within and across cortical areas. In parallel, top- down feedback from other primary and associative areas provides a concomitant access to a knowledge reservoir of internally stored priors. Such priors provide a first amodal constraint to the building up of sensory- specific and multisensory representations. The hard (e.g. Gestalt laws) and soft constraints (priors) that shape the analysis of incoming sensory inputs complement the various modality- specific facets of object recognition in changing environments. However, the computational rules mediating integration across these various dynamic informational streams in primary and higher sensory cortical areas remain largely speculative and the mechanistic principles that yield efficient object recognition in spite of the variability of sensory input and its modality prevalence need still to be understood. The challenge is to define the computational role of feedforward, lateral/horizontal and feedback connections in shaping uni- and multi- sensory cortical representations. This requires explaining the contextual dependency of the neural code guiding the multisensory combination of distinct sensory representations, and address the neural and network interaction mechanisms which make the global percept become largely independent of the sensory channels used to transmit information. To address these issues, 15 teams of the four research units (UNIC, UNICog, NeuroSpin, CNPS) will combine their expertise in the study of sensory analysis across (i) sensory modalities (vision, audition, olfaction, haptic sense, electrical sense), (ii) networks and anatomical scales (e.g. subcortical, thalamic and cortical structures in the mammalian brain and their equivalent in other species) and (ii) species (electric fish, sealion, songbird, mouse, rat, guinea pig, ferret, cat, monkey). The NeuroSaclay consortium will thus provide an unprecedented interdisciplinary and multiscale approach to multimodal perception using invasive (electrophysiology; microscopic bi- photonic and mesoscopic intrinsic (IOI) and extrinsic voltage sensitive dye (VSDI) imaging) and non invasive (EEG, MEG, DTI, fmri, MRI) Brain imaging techniques, as well as state- of- the art computational methods. Multiscale approaches will be developed with the aim to establish functional, and if possible causal, links between the synaptic and cellular mechanisms operating at a microscopic level, and the mesoscopic perceptual processes in higher mammals and humans in the context of (i) low level tasks in the anaesthetized animal (e.g. pop- out phenomena, arguably not requiring attention) and (ii) attention- dependent integration tasks in behaving animals and humans. Research Objectives Our research plan, organized in 5 work packages will pursue the following four main objectives ranging from pre- attentive (low level) perceptual processes to attention- controlled access to awareness: - 1 -

93 NeuroSaclay Idex Project Research Axis 1 Merging Senses - Identify generic biological and computational principles of neuronal integration, subserving sensory subcortical and cortical- like representations of our sensory environment through different senses (audition, vision, olfaction, haptic sense, electrosensory sense). - Identify generic principles of functional adaptation of sensory cortical primary and associative representations to contextual input statistics - Understand and simulate the emergence of a unified amodal perception - Understand and simulate consciousness / awareness in information processing on the basis of synaptic and cellular dynamics and network interactions. Detailed Project WP1 - PI. Bridging the gap between micro- and mesoscopic scales in sensory processing Andrew Davison, Brice Bathellier, Alain Destexhe, Jean- Marc Edeline, Valérie Ego- Stengel, Yves Frégnac, Cyril Monier, Daniel Shulz Background and Current data: This WP is focused on neural- based processing in the early sensory (thalamo- cortical) systems and the various contextual factors that condition the temporal precision of the neural code and the possible sparseness of the cortical representations. For low- level perception, brain dynamics specific to the main sensory modalities (vision, audition, touch, olfaction, electrical sense) are currently quantified using invasive recording and imaging methods in the anesthetized and awake behaving animal. Accordingly, sensory evoked brain activity will be recorded in species selected for their behavioral relevance (electric fish, mouse, rat, guinea- pig, ferret, cat, monkey and man) along with the appropriate neural structures (electrosensory lobe (ELL), olfactory bulb (OB), sensory thalamus (LGN, MGN, VB), visual (V1), auditory (A1) and somatosensory (S1) cortex). Structure/Function correlates will be described for these different sensory systems in order to extract common generic principles of integration, both at biological and computational levels. In particular, we will study how neural coding and representation sparsening in higher centers (V1, A1, S1, OB, ELL) adapts to the specificity of the processed sensory modality. Objectives/challenges: We will address at various levels of integration (conductance, single cell spiking and network 2- photon, LFP and MEA recordings, IOI and VSDI imaging) the following issues: 1. Does the sensory code depend on input statistics and context? 2. Does natural sensory statistics optimize sparseness of the code for primary cortical areas? 3. Spatio- temporal dynamics of cortical responses and long- distance synchronization 4. Perceptual read- out strategies applicable for neuroprosthetics and Brain machine interface Means and strategies/ Experiments: The electrophysiological and imaging techniques (see WP5) will be optimized to detect correlations between evoked neural activity, perception/behaviour, during a single trial if possible. The studied behaviors (target acquisition, eye- movement scanpath, vibrissal exploration, electrocom- munication, vocalization, olfactory discrimination..) will be selected to match the natural environment specificities in regards to each species. In the behaving animal, comparable approaches will be used to link neural ensemble activity and sensory- guided (vision, touch, olfaction, hearing) and social (electrocommunication and vocalization) behaviours, both in open loop and closed loop contexts. Learning paradigms will make use of morphing techniques to test the separability of neural representations for key features mediating specific behaviours. Expected results: The multiscale data sets will be used by modelers to test a working hypothesis: Neural sensory maps are optimized (in terms of sparseness, spike coding efficiency, inforate..) to provide mesoscopic compressed representations of the stimulus features proven relevant to drive a behavioral repertoire adapted to a natural environment. They will also allow to test whether the - 2 -

94 NeuroSaclay Idex Project Research Axis 1 Merging Senses revealed map metrics are the most efficient to predict the subject perceptual decision. This will eventually lead to the identification of read- out algorithms applicable in neuroprosthetics. WP2- Bridging the gap between network dynamics and low- level perception : Self- organization of network belief propagation and priors PI. Andrew Davison, Thierry Bal, Brice Bathellier, Alain Destexhe, Valérie Doyère, Jean- Marc Edeline, Isabelle Ferezou, Yves Frégnac, Kirsty Grant, Cyril Monier, Marc Pananceau, Daniel Shulz, Bertrand Thirion, Virginie van Wassenhove Background and Current data: In spite of differences in the code timescales and the tonic/phasic nature of the various sensory responses, some biases (e.g. perceptual biases for certain combinations of attributes, Gestalt principles..) in the elaboration of more invariant representations of our environment are shared across the different cortical sensory systems. The implementation of these computational principles likely involves multiple cortical levels using primary sensory cortices as a dynamically reconfigured high resolution buffer (Lee & Mumford, 2001; Bullier et al, 2001; Friston, 2003). Such processing depends on the existence of sparse and distributed neural representations interacting via long- range connections and shaped by top- down expectation, internal propagation of prior knowledge (Frégnac et al, 2010) and memory. These different signals reflect multiple spatial/anatomical and temporal constraints resulting from functional hetero- geneities in axonal propagation delays (Bullier and Nowak, 1995; Bringuier et al, 1999). The collective integration of these different streams by sensory cortices (V1, A1 and S1), or related structures (OB and ELL) poses a formidable challenge for neural- based computation. Whether attribute binding and temporal inference operate cortically or subcortically is not yet known. Objectives /Challenges: In this WP dedicated to the emergence and self- organization of internal knowledge, we will tackle, using multiscale approaches, the following issues: - Determine the dependency of the sensory transfer function of a cortical neuron on (i) the current ongoing state and (ii) top- down feedback and priors. This will be achieved both in vivo and in vitro using dynamic clamp techniques to replay the contextual feedback of higher cortical areas. - Study the impact of horizontal/lateral connectivity (Bringuier et al, 1999; Moore and Nelson, 1999) in neural analogs of association fields (Hess and Field, 1993; Frégnac, 2012) in V1 and S1 - Demonstrate that laterally propagating waves in V1 and S1 can i) self- organize to generalize priors to the rest of the network, and ii) be trained to represent an externally imposed prior. - Study processing for stimulus expectancy (temporal conditioning) in sensory subcortical nuclei and within or between primary and/or associative cortical structures(v1, S1, A1, and if possible ELL).. - Develop realistic conductance- based models of the early sensory pathways (up to the primary cortex) to implement Gestalt rules (such as perceptual completion) at neuronal/population levels. Means and strategies/experiments: Research will be focused on the visual, auditory and tactile systems: all three show strong similarity for dynamical feature extraction, prediction and ambivalent perception. Sensory expectancy will be also studied using paradigms where complex sequences of stimuli are degraded or truncated, or temporally manipulated. Data observed in higher mammals will be compared with psychophysical and neuroimaging studies of predictive coding in humans, performed at L- UNIcog by van Wassenhove (audiovisual, speech) and Thirion (vision). In order to uniformize parametric control of the environment across several sensory modalities, we will develop advanced methods that go beyond the state of the art in natural stimulus synthesis ( clouds ) in collaboration with Mathematicians (ERC Gabriel Peyré). This will allow us to explicitly control the structural complexity of the stimuli, with different scales of smoothness in the spatio- temporal dynamics as displayed by natural scenes. This statistical optimization approach will be extended to the auditory (RDK: van Wassenhove) and haptic (simulating natural texture: Shulz) modalities

95 NeuroSaclay Idex Project Research Axis 1 Merging Senses Expected results: We will investigate low- level mechanisms underlying Gestalt rules (form binding, motion smoothness, apparent motion, filling- in) at single neuron (intra- cellular recordings) and population levels (tetrode multiple arrays, FlexMEA, 2- photon imaging, VSDI). Our data should provide mechanistic scenarios through which the functional connectivity between lateral columns diffuses information along inferred integration paths in visual, auditory or tactile space. The network belief broadcasting will be simulated using large- scale but realistic conductance- based models. WP3- PI. Bridging the gap between mesoscopic cortical representations and multisensory perception : Visuo- auditory processing of conspecific vocalizations Catherine Del Negro, Jean- Marc Edeline, Isabelle Ferezou, Cyril Monier, Virginie van Wassenhove. Background and Current data: Acoustic communication is probably the most ubiquitous modality. The human voice carries speech information but also non- speech identity information. Consequently, we can often recognize a person simply by hearing a few words on the telephone, leading the concept of voice as auditory face. Recent findings show that visual cues also strongly impact on the perception of communication sounds (Belin 2006, in humans; Fitch 2000; Lemasson et al 2005; Ghazanfar, 2009 in monkeys): the vocal production is co- occurring with specific facial /postural displays and vocal communication is naturally multimodal. Our project aims at neuronal mechanisms underlying integration of visual information in the processing of communication sounds and at dissecting the neural bases of visuo- auditory interactions in voice processing. Objectives /Challenges: - Auditory multiscale studies of conspecific vocalisation encoding in different areas. - Multisensory (hearing, vision) multiscale studies (from single unit and LFP to optical imaging). - Similar protocols in humans to probe visuo- auditory interactions during acoustic communication. Means and strategies/experiments: In the present WP, the use of multi- site neuronal and population recordings across different cortical areas will uncover in real- time the functional streams of interactions within and between cortical areas. Large- scale multi- site neuronal recordings (up to 64 channels) will be realized in the core and belt areas of the auditory cortex. By combining UNIC and CNPS expertise using optical imaging (IOI- VDSI), we will quantify both the spatial spread of activation triggered by different vocalizations and the temporal organization of this activation across core and parabelt cortical areas. The guinea pig is a well- suited model for this project because (i) its audiogram is similar to humans (see Research Axis 2); (ii) it is a highly vocal animal with a repertoire of vocalizations associated with particular behaviors (Berryman 1976; Harper 1976; Grimsley et al 2011) and (iii) it has been already used for cortical IOI and VSDI imaging (Nishimura et al 2007). Optical imaging will be performed before electrophysiological recordings. We will quantify mutual information in the spike trains and information transfer between simultaneously recorded neurons (Gourévitch and Eggermont 2007), and characterize the relationship between spike emission and the LFP phase during audio- visual perception. Lastly, by recording large sets of LFPs in different cortical areas (decheveigné et al 2013), we will analyze the directed coherence between areas, indicating the interaction strength between areas during multimodal processing of communication sounds. Expected results : By scrutinizing relationships between evoked activity and specific vocalization patterns in awake behaving animals, we will obtain crucial results to build a coherent view of the neural bases of acoustic communication. By documenting simultaneously electrophysiological responses with imaging, we will obtain in guinea pigs a comprehensive view of the spatio- temporal patterns of neuronal activation of visuo- auditory interactions across the whole cortical hemisphere. WP4- PI. Bridging the gap between mesoscopic cortical representations and multisensory perception: towards a unified supramodal representation of peripersonal space Brice Bathellier, Andrew Davison, Valérie Doyère, Jean- Marc Edeline, Valérie Ego- Stengel, Yves - 4 -

96 NeuroSaclay Idex Project Research Axis 1 Merging Senses Frégnac, Daniel Shulz, Virginie an Wassenhove Background and Current data: Humans and many mammals can extract meaningful objects from complex multisensory scenes more reliably than any computer program. The working hypothesis is that cortex constructs neural representations of the external environment according to a set of self- generated expectations or internal models of the environment. According to this predictive coding schema (Rao and Ballard, 1999), the representation of an object in the brain corresponds to a set of crossmodal expectations. For example, we expect that an object which looks like a bell can also make a sound or that a cloth whose visual texture looks like silk will also have a soft touch. The proposal that internal models might be deeply rooted in the brain wiring is strongly suggested by the wealth of sensory illusions evidenced in human psychophysics experiments, such as the ventriloquism (Thomas, 1941) or the McGurk- MacDonald effects (Mc Gurk and Mc Donald, 1976), and by synesthesia (Rich and Mattingley, 2002; Hubbard et al, 2005). Thus, object perception would be based on comparisons between goal- directed internal inferences with the sensory inputs, mediated by extensive cross- talk between cortical areas. Despite these psychological evidences, most computational models of object recognition are mostly feedforward and multilayered (Riesenhuber and Poggio, 1999; 2002). We will, on the contrary, start from the assumption that that sensory cortices may process both sensory inputs and higher order information, representing inferences about the incoming stimulus (Rao and Ballard, 1999). A certain number of observations show indeed that extensive bidirectional connectivity exist between sensory, associative and motor areas, as well as across sensory channels (Felleman and Van Essen, 1991; Hupé et al, 1998; Clavagnier et al, 2004). Likewise, some reports show that heteromodal and reciprocal anatomical interactions occur as early as in primary sensory areas, which might considerably affect the way stimuli are processed (e.g. Rockland et al, 1979; Falchier et al, 2010; Cappe and Barone, 2005; Kayser et al, 2009; Cohen et al, 2011; Fetsch et al, 2012). Similar evidence comes from functional recordings (fmri and electrophysiology) in primary sensory cortices which show boost or attenuation of activity in primary uni- sensory cortices during multimodal stimulation (Downar et al, 2000; Watkins et al, 2007). Objectives/ Challenges: While these recent studies obtained both in primate and rodent models show the existence of functional interactions between modalities at early cortical processing stages, it remains unknown whether this connectivity is necessary in the emergence of amodal perception. We will explore the following issues: - Characterize the main mechanisms by which crossmodal interactions shape unisensory representations at the cortical level - Demonstrate whether multimodal integration obeys optimality (Banks et al, 2002; Alais and Burr, 2001; Ma et al, 2011), or not. - Demonstrate whether (or not) primary representations of any object sensed through an ambiguous sensory channel can recover the complete object map during multisensory integration and thus elicit the appropriate behavioral strategy. - Determine how changes in temporal constraints between sensory stimuli and a rewarding/aversive predicted stimulus are detected in associative subcortical and cortical networks. Means and Strategies/Experiments: To track the emergence of amodal perception, targeted pharmacological inactivation and optogenetics in the behaving mouse during population recordings will be applied to directly explore the space of neuronal representations, and to compare it with the perceptual space through combined behavioural experiments. Access to cortical representations in primary and associative sensory areas will be gained thanks to two- photon calcium imaging and high density electrode recordings performed in head- fixed behaving mice during an auditory- visual or an olfactory- tactile discrimination task, and in freely- behaving rats during auditory- somatosensory associative tasks. Such artificial associations, which do not have the ethological relevance of visuo

97 NeuroSaclay Idex Project Research Axis 1 Merging Senses auditory associations during speech (see Research axis 2) or vocalization (see WP3), or do not correspond to pre- established synesthesia links, present however the advantage of being fully parametrized using only a limited number of key features. The use of more complex but more behaviorally relevant associations will be used if needed at a later stage. Mice/rats will be trained to attach a behavioral label (rewarded/non- rewarded) to two categories of multisensory stimuli including unisensory ambiguities. The connections/areas underlying multi- sensory interactions will be tested using patterned optogenetic perturbations and re- coding experiments based on light- sculpting techniques. Population recordings and optogenetic interference experiments will be used to constrain simplified models of multimodal processing. Expected results: Although the multisensory repertoire of higher mammals and humans is far superior, the rodent model was chosen here because of the variety of genetic tools that can be used, at least in the mouse, to precisely interfere with precise components of neurons and circuits. The project will explore auditory- visual, olfactory- tactile and possibly auditory- tactile interactions in order to assess whether early cross- sensory interactions in the cortex correspond to a generic optimization computational process required for supramodal perception, or are rather specific processes reflecting innate constraints in the processing of certain sensory pairs. It will allow testing whether concomitant information from one sensory channel can bias an ambiguous representation in another channel towards the full object expected by the animal, as early as in primary cortices. WP5 - Methodological advances: Bridging scales of integration and linking electrophysiological and neuroimaging observables PI. Thierry Bal, Claude Bedard, Luisa Ciobanu, Philippe Ciuciu, Andrew Davison, Alain Destexhe, Yves Frégnac, Denis LeBihan, Cyril Monier, Jean- Baptiste Poline, Michelle Rudolph, Bertrand Thirion Background and Current achievements: Brain dynamics are investigated here from the neuronal (microscopic) and local populations (mesoscopic) scales, up to (macroscopic) scales integrating the activity signal over more distributed areas. Each scale is associated with its specific set of physical signals ( observables ) and experimental techniques to measure them, for example conductance and intracellular measurements at microscopic scales, multi- electrode, VSD imaging or local- field potentials at mesoscales, and EEG, MEG, fmri, DTI and MRI measurements at macroscales. Theoretical techniques are thus needed not only to understand the underlying signals measured, but also to relate these signals to neuronal activity. Within the NeuroSaclay consortium, the various WPs will contribute to build or consolidate large databases collected at these different scales. The resulting ensemble of measurements will be particularly adapted to conceive novel analysis techniques (eg by correlating signals across scales and across observables) and test the respective limitations and failures of pure spike- based or neuroimaging models. Objectives /challenges: We will proceed in three steps: (1) Apply biophysical concepts from electromagnetism theory (Maxwell equations) to model the electric and magnetic signals related to neuronal activity, either at the level of single neurons, or from large populations of neurons. The modeling will also be extended to Manganese- enhanced MRI (MEMRI) signals, which provides direct recordings of neuronal activity simular to calcium signals. (2) Design computational model- based analysis techniques adapted to each level of resolution. For example, receptive field identifications resulting from the extraction of optimal linear- nonlinear (LN) models, or obtained by spike- triggered covariance (STC) analysis, are very powerful, both at the conductance (Monier et al, 2008; Fournier et al, 2011) and spiking (Estebanez et al., 2012) levels to reveal the coding principles of a given neuronal population in V1 and S1 cortex. Another example at a more mesoscopic level is the development of specific methods (inspired from mean- field and dynamic system theory) applied to neuronal population ensembles and VSD imaging, etc. (Destexhe et al, 2003) to provide global measures of cortical correlation states and evoked attractor dynamics - 6 -

98 NeuroSaclay Idex Project Research Axis 1 Merging Senses (Marre et al, 2009), which can be unified whatever sensory modality used (Rabinovich et al, 2008; Luczak et al, 2009; Estebanez et al, 2012). (3) Provide methods to bridge the gap between scales. The mean- field techniques used by physicists is a typical example of a method to investigate the large- scale effect of microscopic properties such as electric- field interactions, bursting neurons, correlated firing, etc. Another example would be to use multifractal analysis of intracellular signals on one hand (Frégnac and Destexhe) and MEG and fmri signals on the other hand (Ciuciu and Thirion) to capture scale- free dynamics of ongoing and evoked brain activity, and its link with unisensory (El Boustani et al, 2009) and multisensory learning (Ciuciu et al, 2012; Zilber et al, 2012). These different measurements could be used as a mesoscopic marker of the impact of external sensory statistics on the network dynamics and its functional plasticity. Means and strategies/experiments: These modeling and theoretical methods will will be adjusted to the different data available, from single- neuron electrophysiological recordings (in vivo and in vitro) or magnetrode recordings (in vitro), up to the mesoscopic dynamics of neuronal populations as recorded using LFP, VSD of multi- electrode recordings (in vivo). Machine learning and statistical analysis tools developed at Neurospin will be adapted to better fit and decode functional maps such as those obtained with VDSI. The same principles will be applied to larger scales such as EEG and MEG recordings. Here, the insight obtained by the modeling will serve to better characterize the electric and magnetic «generators» in cerebral cortex, and lead to the development of new techniques to estimate neuronal activity from EEG and MEG measurements. Expected results: By this multiscale approach, we hope to provide methods to investigate aspects not accessible to date, such as the role of network states in sensory processing (see WP2 below), as well as many possible applications in EEG- MEG source imaging. Complementariness of competencies, Synergy and International Impact Of note, two research units of the Idex (UNIC and UNICog), both also members of the French Federative Institute of NeuroFunctional Imaging (IFR 49, Dir. Denis Le Bihan), are participating partners in the proposal of a large scale European Flagship Project (100 MEuros per year for a 10 year period), the Human Brain Project led by Henry Markram (EPFL) and Karlheinz Meier (Heidelberg). Within this European consortium, Stanislas Dehaene and Alain Destexhe lead respectively the Cognition and Theory Pillar, and Yves Frégnac, Andrew Davison and Kirsty Grant participate respectively to the Neuroscience/Cognition, Neuroinformatics and Education/Diffusion pillars. UNIC and NeuroSpin are also running together (Yves Frégnac, Andrew Davison and Jean- Baptiste Poline) the French node of the International Neuroinformatics Coordinating Facility, an international infrastructure based in Stockholm (Dir. Sten Grillner). UNIC has been also at the interface between sensory perception and neuromorphic computation (FP6 and 7 EC grants: SenseMaker, Facets, Brain- i- nets and now BrainScaleS), and several of the team leaders currently participate to EC thinktanks in the planning of Life- like perception initiatives. Team Members Publications related to the Idex Research Axis 1: 1. Unisensory Processing Vision in mammals - UNIC El Boustani S, Marre O, Béhuret S, Baudot P, Yger P, Bal T, Destexhe A, Frégnac Y, (2009). Stimulus- dependency in the power laws of the subthreshold activity of V1 cells. PLoS Computational Biology, 5(9): e , pp (Cover of the Journal). Fournier, Julien, Cyril Monier, Marc Pananceau and Yves Frégnac, (2011). Adaptation of the simple or complex nature of V1 receptive fields to visual statistics, Nature Neuroscience 14: , (2011)

99 NeuroSaclay Idex Project Research Axis 1 Merging Senses Vision in Humans NeuroSpin (Parietal) Thirion B, Duchesnay E, Hubbard E, Dubois J, Poline JB, Lebihan D, Dehaene S. (2006). Inverse retinotopy: inferring the visual content of images from brain activation patterns. Neuroimage. 33(4): Haptic sense in rodents - UNIC Estebanez L, El Boustani S, Destexhe A, Shulz D, (2012). Correlated input reveals coexisting coding schemes in a sensory cortex, Nature Neuroscience 15 No12: Jacob V, Le Cam J, Ego- Stengel V, Shulz D, (2008). Emergent Properties of Tactile Scenes Selectively Activate Barrel Cortex Neurons, Neuron 60: Audition in rodents UNIC (ATIP) Bathellier B, Ushakova L, and Rumpel S, (2012). Spontaneous association of sounds by discrete neuronal activity patterns in the neocortex. Neuron, 2012 (in press). Audition in guinea- pigs - CNPS Huetz C, Philibert B, Edeline J- M (2009). A spike timing code for discriminating conspecific vocalizations in the thalamocortical system of anesthetized and awake guinea- pigs. Journal of Neuroscience, 29, Laudanski J, Edeline J- M & Huetz C (2012). Differences between spectrotemporal receptive fields derived from artificial and natural stimuli in the auditory cortex. PLoS One, 7(11) e Audition in humans NeuroSpin (UniCog) van Wassenhove V, Nagarajan SS (2007) Auditory- cortical plasticity in learning to discriminate modulation rate. Journal of Neuroscience 27 (10): Electroreception in the electric fish UNIC Metzen MG, Engelmann J, Bacelo J, Grant K, von der Emde G. (2008) Receptive field properties of neurons in the electrosensory lateral line lobe of the weakly electric fish, Gnathonemus petersii. J Comp Physiol A 194(12): Olfaction in Drosophila N&D Murmu MS, Stinnakre J, Martin JR (2010). Presynaptic Ca 2+ - stores contribute to odor- induced response in Drosophila olfactory receptor neurons. J. Exp. Biol., 213, Olfaction in mice UNIC (ATIP) Bathellier B, Margrie TW, and Larkum ME. (2009). Properties of piriform cortex pyramidal cell dendrites: implications for olfactory circuit design. The Journal of Neuroscience, 29(40): Bathellier B, Buhl DL, Accolla R and Carleton A. (2008). Dynamic ensemble odor coding in the mammalian olfactory bulb: rate versus temporal information. Neuron, 57(4): Multimodal integration Rodent - CNPS Diaz- Mataix L, Bush DE, Doyère V & LeDoux JE (2010) The amygdala encodes specific sensory features of an aversive reinforcer. Nature Neurosci, 13(5), Díaz- Mataix L, LeDoux JE & Doyère V (2011) Sensory specific associations stored in the lateral amygdala allow for selective alteration of fear memories. J Neurosci, 31(26), Electrocommunication in the electric fish - UNIC Engelmann, J, Bacelo J, Metzen M, Pusch R, Bouton B, Migliaro A, Caputi A, Budelli R, Grant K and Von Der Emde G, (2008). Electric imaging through active electrolocation: implication for the analysis of complex scenes, Biological Cybernetics 98: , Vocalisation in songbirds - CNPS Briefer E, Osiejuk TS, Rybak F, Aubin T. (2010) Are bird song complexity and song sharing shaped by habitat structure? An information theory and statistical approach. J Theor Biol. 262(1):

100 NeuroSaclay Idex Project Research Axis 1 Merging Senses Lehongre, K., Del Negro, C., Representation of the bird s own song in the canary HVC: contribution of broadly- tuned neurons. Neuroscience 173, Vocalisation in sea lions and otaries - CNPS Charrier I, Mathevon N, Jouventin P. (2001) Mother's voice recognition by seal pups. Nature, 412(6850): 873. Pitcher BJ, Ahonen H, Harcourt RG, Charrier I. (2009) Delayed onset of vocal recognition in Australian sea lion pups (Neophoca cinerea). Naturwissenschaften. 96(8): Time perception and multisensory expectancy in Humans NeuroSpin (UniCog) van Wassenhove V, Buonomano D, Shimojo S, Shams L (2008) Distortions of subjective time perception within and across senses. PLoS ONE 3(1): e1437. Skipper J, van Wassenhove V, Nusbaum HC, Small S (2007) Hearing lips and seeing voices: how cortical areas supporting speech production mediate audiovisual speech perception. Cerebral Cortex 17(10): Methods and Computational models Multiscale electrical signals Destexhe, A. and Contreras, D. (2006) Neuronal computations with stochastic network states. Science 314: Peyrache, A., Dehghani, N., Eskandar, E.N., Madsen, J.R., Anderson, W.S., Donoghue, J.S., Hochberg, L.R., Halgren, E., Cash, S.S., and Destexhe, A. (2012) Spatiotemporal dynamics of neocortical excitation and inhibition during human sleep. Proc. Natl. Acad. Sci. USA 109: , Bedard, C. and Destexhe, A. (2011). A generalized theory for current- source density analysis in brain tissue. Physical Review E 84: Conductance- based Models and Large scale simulations Davison A, Frégnac Y, (2006). Learning cross- modal spatial transformations through spike timing- dependent plasticity, J Neurosci 26: Davison A, Brüderle D, Eppler J, Kremkow J, Muller E, Pecevski D, Perrinet L, YgerP, (2009). PyNN: a common interface for neuronal network simulators, Frontiers in NeuroInformatics 2: doi: / neuro Marre O, Yger P, Davison A, Frégnac Y, (2009). Reliable recall of spontaneous activity patterns in chaotic cortical networks. The Journal of Neuroscience 29(46): Marre, O., El Boustani, S., Frégnac, Y. and Destexhe, A. (2009). Prediction of spatio- temporal patterns of neural activity from pairwise correlations. Physical Review Letters 102: , Neuroimaging signals Ciobanu L, Reynaud O, Uhrig L, Jarraya B, Le Bihan D. (2012). Effects of anesthetic agents on brain blood oxygenation level revealed with ultra- high field MRI. PLoS One. 7(3):e PubMed PMID: , PMCID: PMC Ciuciu P., Varoquaux G., Abry P., Sadaghiani S. and Kleinschmidt A. (2012). Scale- Free and Multifractal Time Dynamics of fmri Signals during Rest and Task. Front Physiol. 3: 186. Michel V., Gramfort A., Varoquaux G., Eger E., and Thirion B. (2011). Total variation regularization for fmri- based prediction of behaviour. IEEE Transactions on Medical Imaging, 30(7): Varoquaux G., Gramfort A., Poline J.- B. and Thirion B. (2010). Brain covariance selection: better individual functional connectivity models using population prior. In Richard Zemel and John Shawe- Taylor, Advances in Neural Information Processing Systems, Vancouver, Canada. Zilber N., Ciuciu P, Abry P. and van Wassenhove V. (2012). Modulation of scale- free properties of brain activity in MEG. Proc. of the 9th IEEE International Symposium on Biomedical Imaging, May 2012, Barcelona, Spain, pp

101 NeuroSaclay Idex Project Research Axis 2 Language acquisition Axis 2. From sequence learning to language acquisition Summary Statement: This research axis will investigate the neural representation of temporal sequences and of nested language structures, both in humans (by direct study with brain imaging and intracranial recordings) and in animal models (monkeys, mice, and birds). Scientific goals. Language is often considered a key cognitive trait that distinguishes humans from other animals. Indeed, the breadth of human vocabulary and the recursive aspects of human syntax point to mechanisms that are uniquely developed in the human species(hauser, Chomsky, & Fitch, 2002). However, others, such as the capacity to store a sequence of tones, are present in non- human species. Indeed, the closest animal analogue of human language is bird song, which presents remarkable parallels to speech in its production, perception and development, brain circuitry and even genetic mechanisms (e.g. the role of FoxP2 gene). How neuronal networks encode complex communication sequences, and how this code differs for linear versus recursive structures in humans remain unsolved problems. We propose to address these issues by developing a joint effort across multiple teams, focused on the development of simplified models of language and sequence learning, while respecting the complexity of the repertoire of each species. We will study language network in vivo in humans using brain imaging technique, but also capitalize on the fact that artificial sequences of tones or syllables of well- understood complexity can be learned and recognized by both human (Bekinschtein, et al., 2009) and non- human species (Fitch & Friederici, 2012; Petkov & Wilson, 2012). We will also endeavor for convergence through the development of joint methodologies, including electrophysiology (human intracranial EEG and single- neuron recordings) and fmri (human- monkey comparisons, but also comparison with songbirds, taking advantage of high- field manganese MRI techniques, with reference to established anatomical data). Research Objectives Map the regions of the human brain involved in the representation of nested language structures, and separate them from those involved in mere linear sequence learning. Develop simplified sequence- learning paradigms, varying in complexity, that can be used in both human and non- human species. Study the development of speech and non speech sequence learning in human infants both at a structural and a functional level. Analyze intracranial neurophysiological recordings in humans during sentence processing, and evaluate the neural correlates of key aspects of language, such as constituent structure. Develop a monkey fmri model of sequence learning, and probe the complexity of the sequences that can be represented, and the parallels with human language networks. Study birdsong models of sequence learning, evaluate the parallels with language acquisition, and investigate their neural mechanisms, using neurophysiology and MRI. Analyze the genetic and anatomical conditions of emergence of language by comparing the corresponding basal organization and connections in the pallium of birds and mammals. Develop a mouse model of vocal communication, and use it to investigate the neurophysiological correlates of sequence learning in mice. Detailed Project The workplan will be organized in six workpackages (see below) WP1 - Human fmri experiments on the perception of structure in sequences PI. Christophe Pallier, Bertrand Thirion, Philippe Pinel Our previous work aimed at identifying the brain regions involved in building up linguistic structures during sentence comprehension (Devauchelle, Oppenheim, Rizzi, Dehaene, & Pallier, 2009; Pallier, 1

102 NeuroSaclay Idex Project Research Axis 2 Language acquisition Devauchelle, & Dehaene, 2011). This has led to identify a set of regions whose activation is modulated by the size of constituents (coherent "chunks" of words). We plan here to investigate whether these results obtained with natural language stimuli hold with much simpler stimuli generated by artificial grammars which can be learned within a few hours. This will allow us to contrast "chunking" due to the grammar's rules and to the statistical regularities of the training language, and determine which brain networks are sensitive to each of these properties. We will compare the networks activated by these paradigms with those activated by standard language sentences of variable complexity. We will also examine whether the brain activity patterns elicited by different abstract structures, e.g. (AB)C vs. A(BC), can be reliably decoded using multivariate methods. If successful in human adults, this will be tested in infants and monkeys. WP2 - Anatomical and functional mechanisms of language in infants PI. Ghislaine Dehaene- Lambertz, Jessica Dubois Several brain imaging studies show a strong structural and functional cortical organization in the regions subserving language from the preterm period onwards(dehaene- Lambertz, Dehaene, & Hertz- Pannier, 2002; Leroy, et al., 2011). A second remarkable result from our team is the early involvement of high- level frontal and parietal associative cortices, challenging the classical bottom- up view of learning(dehaene- Lambertz, et al., 2002). Our project is thus to better describe the early human cerebral organization and its particularities relatively to other animals, with a focus on the neonatal period and on top- down processes. The main functional networks will be examined in infants at the structural level using MRI indices (T2 values, cortical thickness, diffusion tensor indices) and at the functional level through the study of resting state networks observed in fmri/nirs and MEG/EEG. This multi- modal imaging strategy (see also Idex research axis 1) is absolutely essential to detect different aspects of maturation and uncover connected areas. In parallel, we will launch a hierarchy of auditory experiments to target increasingly abstract representations of the rules governing speech sequences using EEG. By manipulating both the temporal structure and the pattern of stimulation, we will explore the type of expectations built by infants at a given age and, ultimately, whether these computations involve human- specific syntactic recursion. We will correlate the level of successful coding in the hierarchy with cortical maturation and compare speech and non- speech stimuli to determine the linguistic specificity of these computations. Finally, we will compare the computational complexity reached by infants at a given age and by other animals, to question whether local or long- distance connections are key components of language capacities. WP3- Search for a neuronal coding of linear and nested sequences PI. Stanislas Dehaene This WP will probe the neuronal encoding of linear sequences and embedded constituent structures in humans. Using non- invasive MEG, or using intracranial recordings in or over the temporal lobe of epilepsy patients, local- field potentials and even single neurons can be recorded while human subjects read or hear sentences of controlled complexity (data are sent to us from Salpêtrière, Boston and Stanford hospitals). Capitalizing on our prior tools for quantifying LFPs, their causal relations and their nested frequency patterns (Gaillard, et al., 2009), we will search for neural responses to specific words, concepts, or syntactic categories, then examine how their modulation as function of the grammatical role and position of these items inside a larger constituent structure. The research is guided by X- bar theory, a theoretical construct of linguistics which assumes that, at an abstract level, similar internal structures are used in noun, adjective, verb and prepositional constructions, and even for more abstract structures such as tense. We will automatically generate syntactically labeled sentences combining multiple X- bar structures and spanning a broad array of syntactic and semantic categories, in three languages (French, English, Dutch). Automated information- based analysis searches for mutual information between the MEG signal, LFP or spike train at time t after the presentation of a word, and each word or linguistic label of interest 2

103 NeuroSaclay Idex Project Research Axis 2 Language acquisition describing the sentence structure (e.g. accusative, plural, subject; number of nodes up to this point, etc). Activity evoked by the same items presented in lists of unrelated words will be used as control. WP4- Monkey- human comparison using fmri and electrophysiology PI. Bechir Jarraya, Stanislas Dehaene, Cyril Monier, Primate electrophysiologist to be recruited In this WP, we will capitalize on our capacity to scan macaque monkeys with fmri using the NeuroSpin 3T fmri scanner, with well- established methods (e.g. Arsenault, Nelissen, Jarraya, & Vanduffel, 2013), and thus to compare both human and non- human primates. Here we will compare the brain networks for coding linear and embedded structures. In awake monkeys, trained to fixate a dot, we will present short auditory sequences of tones or syllables. In short blocks, the animal is habituated to hearing a specific sequence or a type of sequential structure (e.g. four identical tones followed by a distinct one: AAAAB). We then probe whether brain networks react to a deviant sequence (e.g. AAAAA). The figure indicates that, in both humans and monkeys, similar regions in auditory cortex and dorso- lateral prefrontal cortex respond to different types of sequential violations (Uhrig, Jarraya, Dehaene et al, in preparation). This basic paradigm for sequence learning will be extended by examining how fmri responses are affected when varying (1) the complexity of the sequence being learned; (2) the place and type of violation. Variations from repetition (AAAAA) to alternation (ABABA ), nesting (A n B n ), replication (ABCABC), symmetries (ABCCBA) and other nested patterns, allow testing of the type of grammar learned by monkeys and humans (Fitch & Friederici, 2012). The same protocols could be used with visual stimuli, and assayed not only with fmri but also with eye- movements, pupil dilation and EEG novelty responses. We will thus be in a position to determine whether monkey- human parallels are present in the cortical networks for sequence learning and novelty detection, and whether sequences that require nested or recursive coding involve uniquely human networks. Once the active regions are identified in the monkey, invasive electrodes will be directed there to record from LFPs and single- neurons, thus examining how neural firing varies at different stages of such sequences, and whether abstract groups or constituents are labeled by specific firing patterns. WP5- Learned sequence generation in songbirds. PI. Catherine Del Negro, Jean- Marc Edeline, Thierry Aubin, Philippe Vernier. Human- monkey comparisons using functional MRI at NeuroSpin. In response to global deviants, both humans and monkeys display activations of a large fronto- parieto- temporal network, in homologous brain areas. The paradigm can easily be extended to the learning of sequences of arbitrary complexity using various sensory modalities. Bird songs are elaborate learned vocalizations composed of syllables, organized according to sequential rules. However, little is known about vocal sequence generation. Our projects exploit the diversity of songbirds species to elucidate how song element sequences are encoded, generated and learned. Different methodological approaches will be used at multiple scales of brain organization. One brain area associated with song production and learning is the nucleus HVC which encodes for a precise auditory vocal correspondence. HVC neurons show selective auditory responses to playback of the bird s own song and singing- related activity. In the canary (Serinus canaria), sequences of 3

104 NeuroSaclay Idex Project Research Axis 2 Language acquisition syllables within a song provide information as to the singer s identity. Our project aims at understanding how the song is encoded in HVC, and how singing- related activity gives rise to these acoustic features and their sequential combinations (C. Del Negro; J.M. Edeline). We will examine whether HVC neurons are sensitive to song element sequencing and whether the firing patterns of HVC neurons recapitulate during singing the patterns while hearing the same sequences. We will record extracellularly single- units in freely moving canaries using a lightweigth telemetric system. Comparative studies yielded contradictory reports between HVC volume and repertoire size across species (e.g. Gahr, Metzdorf, Schmidl, & Wickler, 2008; Gahr, Sonnenschein, & Wickler, 1998). We will try to solve this discrepancy by comparing within/across species the degree of motor pathway convergence reflected by the size of upstream brain areas (HVC) relative to their downstream targets (RA) (T. Aubin and M. Gahr, Seewiesen, Germany). Brain tissues in Skylarks (Alauda arvensis) with known song repertoires will be collected to examine the density of neuron populations identified by molecular markers (androgen/oestrogen receptors). Song learning shares striking similarities with speech acquisition and requires a basal ganglia- thalamo- pallial circuit. However, it remains uncertain whether the bird DVR (a kind of ventral pallium), regrouping HVC and other song related structures, is homologous to the mammalian neocortex (Jarvis, et al., 2005). Building upon our earlier work (Yamamoto, Ruuskanen, Wullimann, & Vernier, 2011; Yamamoto & Vernier, 2011), the best possible evidence for homology will be obtained by analyzing the thalamo- pallial and basal ganglia connections with reference to molecular markers of cortical layer 4 (Eag2, ROR- β) found also in the bird DVR. This description coupled to genetic manipulations of this connectivity (gene gain- and loss- of- function) will provide a basis for evaluating the similarity of the genetic mechanisms underlying song and speech acquisition and their plasticity in the pallium of both birds and mammals (P. Vernier & K. Yamamoto). This circuit could play a transient role in driving vocal variability required for song learning. As learning proceeds, its relative contribution would be reduced, allowing the motor pathway to drive an increasingly stereotyped song. However, this view comes from a particular species which produces a single stereotyped song only during a fixed period early in life. We plan to extend our studies to the adult canary, which can modify its song throughout their life (C. Del Negro and A. Leblois). Exploiting our expertise with canary neuroarchitecture (e.g. Lehongre & Del Negro, 2011), we will lesion or transiently inactivate the output nucleus of the basal ganglia- thalamo- pallial circuit in order to observe how syntactic sequencing is affected in both juveniles and adult canaries. Genetic similarities might also exist between songbirds and humans. The FoxP2 gene, involved in language evolution(fisher & Scharff, 2009), and whose polymorphisms modulate the frontal language networks of the human brain (Pinel, et al., 2012), is similarly expressed in the basal ganglia and executive areas of the pallium, both in humans and songbirds, more especially in the dopaminoceptive areas (striatum, prefrontal cortex in mammals, nidopallium caudale in birds). Since dopamine plays a role for song learning and maintenance (Kubikova & Kostal, 2010), we will test the role of FoxP1/2 genes in song (and language) learning by modulating the expression and effect of dopamine systems on the learning and motivational processes (P. Vernier & K. Yamamoto). Finally, behavioral studies will investigate propagation of bird vocal culture in natural environments (Briefer, Rybak, & Aubin, 2010). By field experiments on an open- ended learner, the blackcap (Sylvia atricapilla), with automatic broadcasting and recording equipments, we will determine if new syllables are more/less easily learnt than new syllable orders (T. Aubin & H. Courvoisier). WP6- Neural and genetic mechanisms of vocal communication in the mouse PI : Sylvie Granon et Lia Prado De Carvalho 4

105 NeuroSaclay Idex Project Research Axis 2 Language acquisition It has been shown in humans as well as in rodents that social behaviors rely on prefrontal cortex networks. Our team showed in mice that social behaviors can be tightly quantified (de Chaumont, et al., 2012) and that the prefrontal cortex integrity and the neuronal nicotinic receptors - nachrs- are necessary for adapted social behaviors (Avale, et al., 2008; Granon, Faure, & Changeux, 2003). Social behaviors encompass various communication skills that are altered in various psychiatric disorders like autism spectrum disorders. However, despite recent studies on ultrasonic vocalizations in mice and rats, their neurobiological, neurochemical and genetic bases are unknown. In rats, a role of a balance between cholinergic and dopaminergic systems in the production of "positive" and "negative" emotional and motivational vocalizations has been suggested. Mice lacking nachrs, which show a major unbalance of monoaminergic and cholinergic systems (Coura et al., submitted), exhibit drastic impairment of acoustic communication during social interaction (preliminary data). These data lead us to study acoustic communication in normal and mice lacking nachrs, to understand (1) whether mice use specific types of vocalizations for distinct social approaches; (2) which brain areas and pathways are specifically activated during vocal production and integration, particularly in social contexts. We will measure c- fos expression after hearing of vocalizations, which will allow a first delineation of circuits involved in acoustic communication. Manganese MRI imaging experiments will be conducted in both normal and mice lacking nachrs during hearing of vocalizations previously identified as associated with "positive" or "negative" emotional states. Pharmacological experiments will consist of peripheral and intra- prefrontal injection of dopaminergic and cholinergic agonists/antogonists in mice during social tasks. Expertise complementariness, synergies and impact The new Saclay Neuroscience Institute and NeuroSpin combine a remarkable potential for collaboration on these topics, as their existing teams already specialize in human imaging of language networks and their development (Dehaene, Dehaene- Lambertz, Pallier), fmri comparisons of monkey and human brains (Jarraya), birdsong models (Aubin, Edeline, Del Negro), comparative development and anatomy of birds and mammals (Vernier) and mouse models of sequence learning (Granon). With this ambitious project, we will, for the first time, attempt to combine these expertises in a complementary manner, while respecting the diversity of behaviors present in humans, non- human primates, birds and mice. We are confident that, in the course of the project, more synergies will become obvious and we will converge towards a narrower set of theoretically driven paradigms for describing different types of sequence learning and their neural and genetic bases. Indeed, the present project should play a key role in prefigurating and delineating some of the new paradigms that will bloom more fully in the new Neuroscience building in Saclay. The topic of sequence learning and how it might critically differ in humans, with the advent of nested language structures, is one of the hottest research areas at the frontier between linguistics and neuroscience (Fitch & Friederici, 2012; Hauser, et al., 2002). The current teams have all been making important contributions to this area in the past, as attested by publications in Science, PNAS or Neuron (see a partial list further below). By being able to compare monkeys and humans with the exact same stimuli and methods, as well as by providing invasive neurobiological data in mice, birds and even humans, Saclay is in a unique position to contribute importantly to this issue. In particular, the data provided by the current project should play a key role in developing neural network models of how sequential and recursive tree structures are encoded in the human brain, an endeavor to which theory teams should strongly contribute (see Axis 4 Theoretical Neuroscience Institute). 5

106 NeuroSaclay Idex Project Research Axis 2 Language acquisition Team Members Publications related to the Idex Research Axis 2 : Arsenault, J. T., Nelissen, K., Jarraya, B., & Vanduffel, W. (2013). Dopaminergic reward signals selectively decrease fmri activity in primate visual cortex. Neuron, in press. Avale, M. E., Faure, P., Pons, S., Robledo, P., Deltheil, T., David, D. J., et al. (2008). Interplay of beta2* nicotinic receptors and dopamine pathways in the control of spontaneous locomotion. Proc Natl Acad Sci USA, 105(41), Bekinschtein, T. A., Dehaene, S., Rohaut, B., Tadel, F., Cohen, L., & Naccache, L. (2009). Neural signature of the conscious processing of auditory regularities. Proc Natl Acad Sci USA, 106(5), Briefer, E., Rybak, F., & Aubin, T. (2010). Are unfamiliar neighbours considered to be dear- enemies? PLoS One, 5(8), e de Chaumont, F., Coura, R. D., Serreau, P., Cressant, A., Chabout, J., Granon, S., et al. (2012). Computerized video analysis of social interactions in mice. Nature Methods, 9(4), Dehaene- Lambertz, G., Dehaene, S., & Hertz- Pannier, L. (2002). Functional neuroimaging of speech perception in infants. Science, 298(5600), Devauchelle, A. D., Oppenheim, C., Rizzi, L., Dehaene, S., & Pallier, C. (2009). Sentence syntax and content in the human temporal lobe: an fmri adaptation study in auditory and visual modalities. J Cogn Neurosci, 21(5), Gaillard, R., Dehaene, S., Adam, C., Clemenceau, S., Hasboun, D., Baulac, M., et al. (2009). Converging intracranial markers of conscious access. PLoS Biology, 7(3), e61. Granon, S., Faure, P., & Changeux, J. P. (2003). Executive and social behaviors under nicotinic receptor regulation. Proc Natl Acad Sci USA, 100(16), Lehongre, K., & Del Negro, C. (2011). Representation of the bird's own song in the canary HVC: contribution of broadly tuned neurons. Neuroscience, 173, Leroy, F., Glasel, H., Dubois, J., Hertz- Pannier, L., Thirion, B., Mangin, J. F., et al. (2011). Early maturation of the linguistic dorsal pathway in human infants. J Neurosci, 31(4), Pallier, C., Devauchelle, A. D., & Dehaene, S. (2011). Cortical representation of the constituent structure of sentences. Proc Natl Acad Sci USA, 108(6), Pinel, P., Fauchereau, F., Moreno, A., Barbot, A., Lathrop, M., Zelenika, D., et al. (2012). Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language- related regions. J Neurosci, 32(3), Yamamoto, K., Ruuskanen, J. O., Wullimann, M. F., & Vernier, P. (2011). Differential expression of dopaminergic cell markers in the adult zebrafish forebrain. J Comp Neurol, 519(3), Yamamoto, K., & Vernier, P. (2011). The evolution of dopamine systems in chordates. Front Neuroanat, 5, 21. (see annex : Collaboration Matrix within the NeuroSaclay consortium) 6

107 NeuroSaclay Idex Project Research Axis 3 Stem Cells Axis 3. Biology and Pathology of Adult Neural Stem Cell Pools Summary Statement: The research axis will combine multi- scale approaches, from single cell genetics to animal behaviour, to generate an integrated understanding of the homeostasis of adult neural stem cell (NSC) pools, its response to environmental/pathological challenges, and its output on brain physiology. We will rely on several animal models for their different NSC supplies and their technical complementariness. Scientific Goals. The concept of neural stem cells (NSCs) has opened three major questions in modern neuroscience: their function during normal physiology of the central nervous system (CNS), their involvement in ageing, cognitive disorders and brain cancers, and their potential for cell- based repair strategies. Teams of the Saclay Neuroscience Consortium develop since many years integrated and multi- scale approaches in different animal models to explore how NSCs build the brain, can underlie brain plasticity, and are involved in learning and memory. These groups also analyse the recently discovered role of NSCs in developmental, neurological and cancer diseases. The genetic manipulation of different vertebrate animal models by transgenesis and viral infections, associated with emerging technologies for live imaging in whole brain, cell- specific optogenetic control of neuronal activity, and NSC lineage tracing, will allow us to synergize to attack key issues such as NSCs homeostasis, the adult plasticity of the neurogenic process, and its role in behavioural and cognitive functions. We will also seek to understand how NSC functions are altered in pathological contexts such as developmental and cognitive diseases or cancer stem cells, and start to elaborate genetic, cell- based or chemical strategies to rescue physiological functions. These new perspectives will provide the first simultaneous assessment in vivo of the molecular, cellular and functional features of adult NSCs, filling a major gap in our understanding of brain physiology and providing hypotheses/ models to manipulate NSCs with therapeutic purposes. Research Objectives This structuring and unifying project groups teams with complementary expertise towards a common goal: Analyse the biology of NSCs Decipher how pathological conditions, environment and experience modulate NSC properties to support repair/regeneration or learning and memory, Understand how NSC dysfunctions are responsible for developmental anomalies, cognitive disorders and brain cancer. Detailed Project The workplan will be organized in three workpackages (see below) WP1 - Homeostasis of neural stem cell pools PI. Laure Bally- Cuif, Jean- Stéphane Joly, Muriel Perron, Martial Ruat Current data and future achievements: NSC pools vary largely in extent, mobilization and neurogenic potential between species, brain territories and pathophysiological conditions, but it remains unclear how single- cell, local and long- range parameters come together to control the dynamics of adult NSC populations. We aim to generate a qualitative and quantitative modelling of the molecular, cellular and systems mechanisms that sustain adult NSC pools homeostasis and mobilization potential along life in the adult vertebrate. The groups involved possess expertise on key NSC pools of the postembryonic CNS, such as the sub- ependymal zone and the hippocampal subgranular zone in mouse, the corresponding pallial domains enriched in NSCs in zebrafish, and the retina and optic tectum, which display similarly organized NSC zones, in fish and Xenopus. This combination provides an unprecedented comparative platform to probe NSC behaviour in vivo. Objectives/Challenges: 1

108 NeuroSaclay Idex Project Research Axis 3 Stem Cells 1. To define the regulatory logics and the function of a set of NSC specific factors, 2. To characterize the integration of niche signals (Wnt, Notch, Hedgehog and the Hippo signalling pathways) encoding NSCs properties, in comparative analyses between different vertebrates, 3. To reveal the cell population dynamics governing concerted NSC behaviour in germinal zones. Means and strategies / Experiments: Our previous expression- based gene discovery screens, and genome- wide identification of intellectual disability genes in humans (see Aim 3), identified important new sets of NSC factors. We built transgenic lines expressing fluorescent reporters in mouse and zebrafish to highlight NSCs, their activation status, and the stimulation of regulatory pathways; these lines will be used for large- scale sequencing of the transcriptome and translatome of sorted NSC (sub)populations. The recovered NSC genes will be tested in genomic and in vivo functional approaches to dissect the regulatory logics of NSC expression and the molecular correlates of NSC activation, stemness and multipotency. This will be facilitated by in house expertise in the design of chemical inhibitors. In parallel, clonal analyses, whenever possible complemented by live imaging, will reveal in time and space, at the single cell and population scales, the cellular hierarchies involved in the formation, maintenance and recruitment of NSC pools. The response of these lineages to the manipulations of the most relevant NSC genes above will be monitored. Expected results: The expression, lineage and functional data sets generated will be merged to model the molecular and cellular events underlying the dynamics of NSC pools, their robustness and variations between CNS territories and species. This will serve as a useful qualitative and quantitative framework to evaluate further pathological or environmental challenges leading to NSC dysregulation or mobilization (WP2 and WP3). WP2. Neural stem cell plasticity PI: Laure Bally- Cuif, Jean- Viannay Barnier, Sophie Creuzet, Jean- Stéphane Joly, Serge Laroche, Muriel Perron, Martial Ruat Current data and future achievements: Pathological conditions can trigger a switch from quiescent to active NSCs in neurogenic regions. This constitutes a key step in neural tissue repair, whose efficiency varies tremendously among vertebrates. Adult neurogenesis may also be enhanced, or compromised, upon diverse macro- environment cues. We aim to an integrated view of the molecular and cellular correlates of NSC plasticity and its regulatory limits. We will confront NSC potentials in various experimental contexts and animal models, and will also probe the genetic and micro- environmental perturbations that can transform NSCs into cancer- initiating cells. Objectives/Challenges: We will tackle the question of NSC plasticity by making use of different biological contexts: 1. NSC mobilization in pathological conditions to restore lost cells and replace cellular functions 2. NSC plasticity under cognitive challenges 3. Neural progenitor recruitment and reprogramming to restore stemness following NSC depletion 4. NSC transformation in tumorigenic contexts Means and strategies / Experiments: To unravel the mechanisms underlying NSCs mobilization in pathological conditions, we will investigate their behaviour in the brain, spinal cord or retina under diverse neurodegenerative paradigms: natural aging, induced lesions, mutant and in house- generated transgenic animal models. In these contexts, we will interfere with the most relevant genes or pathways uncovered in WP1 to dissect the genetic network sustaining NSC- based regeneration process. Such data gathered in vertebrate models exhibiting great differences in their regenerative potential should reveal common and distinct features and provide the basis for innate quiescent NSCs activation in mammals. Lines with NSC drivers are also currently being generated, in collaboration with the national infrastructure TEFOR, to conditionally trigger NSC ablations 2

109 NeuroSaclay Idex Project Research Axis 3 Stem Cells and assess the regeneration of NSC pools. To address the influence of learning or cognitive deficits on NSC plasticity, behavioural tests and mutant mice will be employed (see also below WP3). Finally, we will tackle the controversial field of cancer cell of origin by investigating the molecular context leading to NSC malignant transformation in human, murine and zebrafish models of brain cancer. Expected results: This work should shed light on the multi- layered environmental regulation of NSC behaviour. The identified molecular and cellular mechanisms will help i) the design of therapeutic strategies to harness NSC for repair and regeneration in neurological diseases and ii) the discovery of new drug targets in cancer stem cells. WP3. Adult neural stem cells and cognitive functions PI. Jean- Vianney Barnier, Philippe Fossier, Serge Laroche, Martial Ruat Current data and future achievements: Mammalian hippocampus plays a central role in encoding and storing new episodic memories. Recent evidence shows that young new neurons are selected and recruited by some forms of learning and are essential for memory formation and recall. It shows that defective adult neurogenesis may be a key factor underlying cognitive disorders associated with ageing and certain neurological and psychiatric diseases. Deciphering the exact role of adult neurogenesis in cognitive functions and identifying what goes awry in brain diseases such as intellectual disability would open novel and highly promising therapeutic prospects. Objectives/Challenges: 1. Determine how neuronal activity controls NSCs homeostasis and the maturation, selection and integration of newborn neurons; analyse how new neurons impact on network properties and function, 2. Analyse whether adult- born hippocampal neurons in rodents and primates serve episodic memory, 3. Test how and to what extent dysfunctional adult neurogenesis contributes to cognitive deficits in intellectual disability syndromes due to gene mutations, 4. Determine whether behavioural enrichment and/or genetic manipulations promoting neurogenesis facilitate memory processing and rescue the deficits associated with intellectual disability syndromes Means and strategies / Experiments: We will capitalize on the expertise of several NeuroSaclay research teams to undertake a multi- scale and comprehensive analysis of the functional role of adult hippocampal neurogenesis in memory and explore potential rescue strategies in dysfunction. We will combine (i) in vivo analysis of the different stages of hippocampal neurogenesis using imaging of biochemical markers, (ii) retroviral and optogenetic manipulations of newborn neurons coupled with electrophysiology of their properties and plasticity and (iii) behavioural assays of cognitive functions in normal rodents and relevant animal models of human intellectual disability disorders. In collaboration with P. Hantraye (MIRCEN), we will characterise adult neurogenesis in the primate and identify its role in episodic memory using established memory paradigms in primates. We will (i) investigate the temporal dynamics of hippocampal neurogenesis and the ability of newborn neurons to be recruited by learning/recall, (ii) characterise the properties of hippocampal stem/ progenitor cells and maturing newborn neurons in syndromic and non syndromic forms of intellectual disability, and (iii) manipulate environmental and genetic parameters to rescue learning/memory deficits. Expected results: We will gain novel insight into the function of adult hippocampal neurogenesis, and into its characteristics and function in primates. In link with Aims 1 and 2, we will establish the role of relevant intellectual disability genes in adult neurogenesis in link with cognitive functions. Finally, we will explore the potential of environmental and genetic manipulations of adult neurogenesis as a rescue strategy. Expertise complementariness, synergies and impact 3

110 NeuroSaclay Idex Project Research Axis 3 Stem Cells Synergy: This proposal constitutes a unique opportunity to gather cognitive neuroscience, embryology, system biology and pharmacology into an integrative stem cell biology program. Together, this work will uncover the molecular bases of the NSC state and fate, their robustness and plasticity in pathological contexts, and the relevance of adult neurogenesis through a range of functions. It will foster novel strong interactions and collaborations between members of the new Saclay Neuroscience consortium. International impact: Members of this project are internationally recognized in their respective fields and are regularly invited at international meetings. Within the frame of this project, they are involved in large European scientific networks (FP7 IP ZF- Health, co- coordination) and structuring Actions (COST Action EUFishBioMed, vice- chair), are founding members of international scientific societies (European Society for Fish Models in Biology and Medicine), or, in coordination with these networks, are leading large National Infrastructures in Biology and Health (TEFOR, scientific and technical coordination) and platforms (AMAGEN, AMATrace). Team Members Publications related to the Idex Research Axis 2 : Angot E, Loulier K, Nguyen- Ba- Charvet KT, Gadeau AP, Ruat M, and Traiffort E. (2008) Chemoattractive activity of sonic hedgehog in the adult subventricular zone modulates the number of neural precursors reaching the olfactory bulb. Stem Cells 26: 9, Borday C, Cabochette P, Parain K, Mazurier N, Janssens S, Tran HT, Sekkali B, Bronchain O, Vleminckx K, Locker M & Perron M. (2012) Antagonistic cross- regulation between Wnt and Hedgehog signaling pathways controls post- embryonic retinal proliferation. Development 139: Bruel- Jungerman E., Veyrac A., Dufour F., Horwood J., Laroche S., Davis S. (2009) Inhibition of PI3K- Akt signaling blocks exercise- mediated enhancement of adult neurogenesis and synaptic plasticity in the dentate gyrus. PLoS One, 4(11): e7901. Chapouton P, Hesl B, Moore J, Madelaine R, Kremmer E, Faus- Kessler T, Blader P, Lawson N and Bally- Cuif L (2010) Notch activity levels control the balance between quiescence and recruitment of adult neural stem cells. J. Neurosc. 30: Combeau G, Kreis P, Domenichini F, Amar M, Fossier P, Rousseau R, and Barnier JV. (2012) The p21- activated kinase PAK3 forms heterodimers with PAK1 in brain implementing trans- regulation of PAK3 activity. J. Biol. Chem. 287: Coolen M, Thieffry D, Drivenes Ø, Becker TS and Bally- Cuif L (2012) mir- 9 controls the timing of neurogenesis through the direct inhibition of antagonistic factors. Dev. Cell 22 : Creuzet S.E. (2009) Regulation of pre- otic brain development by the cephalic neural crest. Proc Natl Acad Sci USA 106: El Yakoubi W, Borday C, Hamdache J, Parain K, Tran HT, Vleminckx K, Perron M* and Locker M* (2012) Hes4 controls proliferative properties of neural stem cells during retinal ontogenesis. Stem Cells 30: * co- senior Ferent J, Zimmer C, Durbec P, Ruat M, and Traiffort E. (2013) Sonic Hedgehog signaling is a positive oligodendrocyte regulator during demyelination. J Neurosci. In Press. Haeussler M, Jaszczyszyn Y, Christiaen L, Joly JS. (2010) A cis- regulatory signature for chordate anterior neuroectodermal genes. PLoS Genet. 15;6(4) Kaya F, Mannioui A, Chesneau A, Sekizar S, Maillard E, Ballagny C, Houel- Renault L, Dupasquier D, Bronchain O, Holtzmann I, Desmazieres A, Thomas JL, Demeneix BA, Brophy PJ, Zalc B, Mazabraud A. (2012). Live Imaging of Targeted Cell Ablation in Xenopus: A New Model to Study Demyelination and Repair. J Neurosci. 32: Leucht C, Stigloher C, Wizenmann A, Klafke R, Folchert A and Bally- Cuif L (2008). MicroRNA- 9 directs late organizer activity of the midbrain- hindbrain boundary. Nature Neurosci. 11:

111 NeuroSaclay Idex Project Research Axis 3 Stem Cells Perronnet C, Chagneau C, Le Blanc P, Samson- Desvignes N, Mornet D, Laroche S, De La Porte S, Vaillend C. (2012) Upregulation of brain utrophin does not rescue behavioral alterations in dystrophin- deficient mice. Human Molecular Genetics, 21: Renaudineau S., Poucet B., Laroche S., Davis S., Save E. (2009) Impaired long term stability of CA1 place cell representation in mice lacking the transcription factor zif268/egr1. Proc. Natl. Acad. Sci. USA, 106: Rothenaigner I, Krecsmarik M, Hayes JA, Bahn B, Lepier A, Fortin G, Götz M, Jagasia R and Bally- Cuif L (2011) Clonal analysis by distinct viral vectors identifies bona fide neural stem cells in the adult zebrafish telencephalon and characterizes their division properties and fate. Development 138: Roudaut H, Traiffort E, Gorojankina T, Vincent L, Faure H, Schoenfelder A, Mann A, Manetti F, Solinas A, Taddei M, and Ruat M. (2011) Identification and Mechanism of Action of the Acylguanidine MRT- 83, a Novel Potent Smoothened Antagonist. Mol Pharmacol 79: 3, Solinas A, Faure H, Roudaut H, Traiffort E, Schoenfelder A, Mann A, Manetti F, Taddei M, and Ruat M. (2012) Acylthiourea, Acylurea and Acylguanidine Derivatives with potent Hedgehog inhibiting Activity. J Med Chem 55: 4, Thévenot E, Moreau AW, Rousseau V, Combeau G, Domenichini F, Jacquet C, Goupille O, Amar M, Kreis P, Fossier P, and Barnier JV. (2011) The p21- activated kinase 3 Regulates AMPA Receptor- dependent Synaptic Transmission through its Interaction with the Nck2/Grb4 Adaptor. J. Biol. Chem. 286, (see annex : Collaboration Matrix within the NeuroSaclay consortium) 5

112 NeuroSaclay Idex Project Structuring Action Theoretical Neuroscience Institute Axis 4. Foundations for a European Institute for Theoretical Neuroscience PI. Alain Destexhe (Director), Andrew Davison, Yves Frégnac, Stanislas Dehaene, Bertrand Thirion Objectives The goal of creating an institute for theoretical neuroscience hosted in the new Neuroscience building is to foster the interaction between theoreticians and experimentalists collaborating in the Region Ile de France Sud. This Institute will attract high level international scientists and facilitate their visit. It will also foster interdisciplinarity, which is an important aspect of the Idex proposal. We will therefore allocate significant space and access to parallel multi- node computing facilities in the new building, specifically devoted to welcome visitors and postdocs, who will work on both theoretical and experimental aspects of the Idex project (the fact of working on both aspects will be a requisite for eligible candidates). Strategy The institute will be located initially close to the institutions concerned here, probably in the Gif campus, or at NeuroSpin, during the period necessary for the new building construction. It will migrate to the new Neuroscience Institute in close proximity to NeuroSpin (200 m 2 of office space have been planned to host the Theoretical Neuroscience Institute as one of the international antennas of the Neuroscience pole in Saclay campus). The institute will run a visitor program (with stipends provided to visitors), as well as a postdoc program to have in permanence 2 postdocs or invited scientists related to the present project. The postocs will take part to both experiments and modeling, and will therefore be explicitly participating to the exchange between laboratories. In addition, the Theoretical Neuroscience Institute will organize a series of workshops with invited speakers from outside of the consortium. Financing has also been asked to the European Community within the framework of the Human Brain Project HBP flagship project, to which the present PIs participate. 1

113 Collaboration Table - Research Axis 1

114 Collaboration Table - Research Axis 2 and 3

115 Medically oriented projects: Plasticity and pathology of neuronal networks: the impact of the perinatal environment Summary Statement: The project aims at deciphering mechanisms linking inappropriate perinatal environments with major adult brain pathologies. The project is structured along three axes: (1) Role of environmental factors in the development of neural networks, (2) Emergence of adult diseases and (3) From molecular to network function: genes, epigenetic factors, metabolic disorders. This project will take an integrative approach using different technologies and models in an interchangeable manner between groups that will constitute the cornerstone for the development of novel strategies to combat major diseases such as autism, schizophrenia, mental retardation, obesity, diabetes, Alzheimer s Disease (AD). Scientific Goals: To determine potential environmental and life style factors during early life, including perinatal period, that play a critical role in shaping of adult emotion, cognition and energy homeostasis; and in the development of neurological disorders. Research Objectives The aims are to explore the role of environmental factors in the predisposition to risky, maladaptive behaviors or neurological diseases using rodent models. The consortium will ask whether negative environmental factors play a role in the development of behavioral or metabolic disorders such as autism, impulsive or compulsive behaviors, obesity, type 2 diabetes (T2D), and AD. Our research plan will be organized in 2 work packages involving 6 teams. WP1 - Social Interactions, autism and environmental factors Current data and future achievements: It is known that stressful events are negative environmental factors that can precipitate behavioral or psychiatric disorders like depression or schizophrenia. Recent data converge towards prefrontal and nucleus accumbens plasticity defects in response to stressful events, associated with impaired decision- making and the emergence of depressive, aggressive or impulsive behaviors. In addition, it has been recently evidenced that childhood stress might lead to anxiety and serious mood disorders seen at the adult age, supporting the view that childhood adversities might have a considerable impact on well- being later in life. Objectives/challenges: The objective of this work package is to identify behavioral and neuronal effects of early and of late in life stress and to target several structure and neurotransmitter pathways. The aim 1: The cholinergic nicotinic system in the emergence of maladaptive behaviors. (S Granon, P Fossier, JM Cancela): The role of the cholinergic nicotinic system in these effects will be study. In particular, we are interested in the putative involvement of neuronal nicotinic receptors - nachrs- known to modulate the release of all kinds of neurotransmitters, including stress hormones. Manipulation of environmental stress, correlated with individual hormonal and neurochemical measures, will help to decipher the importance of nachrs for the cholinergic neurotransmission, either during development or in the adulthood. Using mutant mice (beta2ko mice) lacking nachrs we will study their potential protective role on the emergence of risk- prone behaviors in response to non- stressful or stressful environment occurring throughout development and during adulthood. The putative shaping of the cholinergic nicotinic system by environmental stressors occurring early or late in development, its relationships with brain plasticity and alterations of physiological markers of maladaptive or depressive- like behaviors, will be scrutinized. The aim 2: Calcium signalling pathway in Autism (JM Cancela, P Fossier, S Granon). Autism spans a wide spectrum of disorders and seems highly linked to heredity but genetic determinants and the environment risk factor are largely unknown. Mechanisms of synaptic plasticity (LTP, LTD) are often altered and may affect the functioning of NMDA- and/or metabotropic glutamate receptors underlying learning processing. One signaling component, which may control the establishment of LTD is CD38, the enzyme - 1 -

116 responsible for synthesis of the messengers cyclic ADPribose and NAADP. Some mutations (CD38) or deletion of loci coding for its receptor (TPC) are implicated in familial autism. We aim to explore the consequences of a deficiency of CD38 and a new player, the endo- lysosomal channel "two- pore channel" (TPC) of the NAADP receptor in the neural network functions such as LTP, LTD in the prefrontal cortex. The aim 3: Impact of early life amygdala plasticity on adult emotional and cognitive functions (V Doyère, N. El Massioui) This aim will be develop and focus on the role of anxiety in the infant, and its primary controlling neuronal structure, the amygdala, in the developmental programming of neural connectivity that may contribute to the genesis of behavioural abnormalities later in life. The amygdala is a limbic structure whose critical role in anxiety and emotional processes has long been recognized. Although the amygdala is functional at birth, its development (connectivity) may not be fully achieved, as its volume increases until 18 years old in humans, thus rendering it sensitive to modifications under natural or pathological conditions. We will test the impact of modifying plasticity in the amygdala early in life on the development of large network connectivity and its functional dynamics during emotional and cognitive processes in adulthood. This project will provide insights both on autism- like emotional phenotypes as well as development of neuropsychiatric disorders of neurodegenerative diseases (e.g. Huntington disease). Means and strategies/ Experiments: Behavioral tasks that model in mice the uncertainty of everyday life situations in which subjects make multiple decisions by evaluating their costs and benefits will be used. This would test social interaction, impulsivity and the ability to avoid risk, using a gambling task. All these behaviors require normal functioning of the prefrontal cortex. We will focus on the role of neuronal nicotinic receptors - nachrs. We will also combine electrophysiology (excitation- inhibition balance, studies LTP- LTD) and calcium imaging by confocal microscopy of cortical slices to study the hypothesis that CD38 and TPC deficiency plays important roles in diseases of the nervous system such as autism. Furthermore, an analysis of social behavior of mice deficient in CD38 and TPC following stress exposure will be conducted. We also aim at analysing the long- term effects of modifying early life amygdala synaptic functioning on the development of anxiety trait, emotion and cognitive functions. We will use a lentiviral transduction method which uniquely allows targeting a specific brain area with the highest temporal and spatial resolutio to the amygdala in rat early in life to assess (in normal and transgenic rats) its efficacy on modifying synaptic plasticity, morphometry and emotional and cognitive behaviour later in life. Expected results: We anticipate these results will be two- fold: firstly we will identify risk factors that may trigger the behavioral spectrum associated with autism and secondly the molecular mechanisms associated with interaction between environmental and genetic factors that underscore these behavioral deficits. WP2- Alzheimer disease, metabolic disorders and risk factor Current data and achievements: Recent epidemiological and experimental studies have brought new insights into the ontogeny of obesity and T2D. The relationships between the environment of the perinatal period and susceptibility of adults to metabolic disorders led to the concept of developmental programming. Nutritional and hormonal status during fetal development and early life appear to determine long- term control of energy metabolism, particularly by programming the future food behavior and energy expenditure. Novel approaches and animal models designed to explore the mechanisms underlying AD and to evaluate potential therapies to combat AD have to date failed. Although transgenic mice models contributed significantly to our understanding of the pathogenesis of AD, an alternative and potentially more fruitful approach would be to consider the role of dysfunctional mechanisms associated with risk factors for AD. Objectives /Challenges : Aim: 1 Hypothalamic programming of obesity (M. Taouis) In this project, we will focus on the comprehension of the mechanisms underlying the metabolic programming of rats progeny consequently to endocrine (using leptin antagonists) and metabolic (using inappropriate diets) environments in early life. This will be achieved by combining complementary approaches. We will investigate, mainly at the brain level and more specifically in individual hypothalamic nuclei, the impact of these metabolic and endocrine changes on the: 1) cyto- architectonic organization, 2) - 2 -

117 responsiveness and signaling pathways of leptin, insulin and resistin (an adipokine) 3) expression profile of micrornas and target mrnas. In conclusion, the ground- breaking nature of our project is to determine how inappropriate endocrine and metabolic environments during early life durably impair hypothalamic neuronal organization and leptin/insulin signaling, and whether these dysfunctions are attributed to changes of hypothalamic nucleus microrna expression patterns. Aim 2: Alzheimer s disease and diabetes type 2 as a risk factor (S Davis) Failure of clinical trials in AD has begun to cast doubt on the causal role of amyloid plaques in the dementia associated with AD. An alternative and potentially more fruitful approach would be to consider the role of dysfunctional mechanisms associated with risk factors for AD and how these may promote a dysfunction neuronal milieu to favour the development of the classic amyloid pathology and ensuing dementia. T2D, which develops in middle age is considered a t major risk factor. A principle dysfunctional mechanism linking both diseases is disruption of insulin signaling that results in destabilisation of glucose metabolism and homeostastis. Although overwhelming evidence suggests a role for T2D contributing to the development of AD, we lack understanding of the mechanisms by which this would be mediated. Here, we will use an epigenetic (interuterine growth restriction) and a pharmaco- environmentally induced (high fat diet and low dose STZ) model of T2D to determine whether we can exacerbate cognitive deficits and induce brain amyloid pathology we observe with icv injected soluble amyloid peptides. Aim 3: Alzheimer disease and hypothyroidism (V. Enderlin). Accumulation of data suggests a link between AD and thyroid dysfunctions. AD and hypothyroidism are conditions that become more prevalent with advancing age. AD is characterized by progressive loss of cognitive functions and hypothyroidism may also have profound behavioural consequences such as anxiety and impaired memory. Localized hypothyroidism of the CNS has been suggested in some patients with AD. Prospective studies are needed to further elucidate how low thyroid hormone level may favour the development of AD. Our hypothesis suggests that hypothyroidism could have an impact on processes modulating Tau and/or APP processing, the two pathological hallmarks of AD, together with an impact on other alterations such as inflammation or synaptic plasticity impairments leading to cognitive impairment. Means and strategies/ Experiments: The main strategy for the aim 1 : We will examine by which mechanism(s) alteration of leptin action during early life affect energy homeostasis and predispose to obesity and insulin resistance in adulthood. Our objective will be achieved by combining different complementary approaches. We will use inappropriate diets or leptin antagonists to investigate, mainly at the brain level and more specifically in individual hypothalamic nuclei, the impact of hormonal and metabolic environment during early life on: 1) the cyto- architectonic organization, 2) the signaling pathways of leptin, insulin and resistin (an adipokine), 3) the expression profile of micrornas (mirnas) and of mrnas coding proteins of the leptin, insulin and resistin signaling pathways. The main strategy for the aim 2 : We will undertake a multi- level analysis combining identification of neuroanatomical hallmarks of AD, detailed molecular analyses of the ERK and PI3K- Akt cell- signaling pathways, suggested to be key biochemical pathways linking T2D to AD, electrophysiological analyses of synaptic plasticity in the hippocampus, a central structure affected in early stages of AD and which plays a crucial role in memory processes, and longitudinal characterisation of behavioural performance of the animals. This project will provide for the first time a mechanistic understanding of a major risk factor for AD, which is likely to open promising therapeutic prospects. The main strategy fort the aim 3 : Experiments will be performed on rats submitted to disruption of thyroid status using an antithyroid molecule that decreases thyroid hormone levels. With this physiological model, we have reported that hypothyroidism increases the vulnerability to the formation of amyloid deposits. We will investigate the link between T3 hypo- signalling and AD- related pathological hallmarks (i.e. Tau phosphorylation, APP processing, formation of amyloid deposits, neuroinflammation) and associated functional aspects (memory, plasticity- related markers.) using molecular, biochemical and behavioural approaches. Similar experiments will be realized in hypothyroid rats administrated with thyroid hormones. Expected results: We anticipate the results from this workpackage will bring new insight in the impact of hormonal and metabolic environment driving the onset of brain resistance to respond to normal energy homeostasis - 3 -

118 regulators (such as insulin, leptin and thyroid hormones) that promotes metabolic disorders and neurodegenerative diseases such as AD. List of participating teams and complementariness of competencies List of Teams/Units o CNPS (Orsay): - El Massioui Huntington disease, executive functions; Doyère Amygdala plasticity, emotion; Sabrina Davis Signalling pathway regulation during memory processing and plasticity in normal and pathological memory processing; Mohammed Taouis Hypothalamic programming of obesity and insulin resistance; Philippe Fossier neuronal network modulation; José- Manuel Cancela calcium signalling in the nervous system; Valérie Enderlin thyroid hormone signaling, Alzheimer s disease, synaptic plasticity. Synergy The project is innovative, as it will provide a multi- scale approach ranging from the cellular level to the behavioral level to investigate plasticity and pathology in neuronal networks. This will be done within the same institute (as the named member have expansive expertise and world wide recognition in aspects of this research project, that will enable us to cement a new scientific approach for tackling the development of the much needed strategies to combat neurological disorders. In this project, the teams of Philippe Fossier and José- Manuel Cancela (CNPS) will together bring dual competence in electrophysiology and in live cell imaging by confocal microscopy of the central nervous system and Mohammed Taouis, Valérie Enderlin and Sabrina Davis groups will bring the pharmacological, biochemical and molecular approaches. Finally, the group of Sylvie Granon, Valérie Doyere, Nicole El Massioui bring a complementary high expertise in animal behavioral analysis. International Impact F V Doyère et N El Massioui: International Associated laboratory (LIA LearnEmoTime) and Partner University Fund grant (with J. LeDoux and R. Sullivan, New York University) for Franco- American exchange of students and post- docs. Sabrina Davis, EU FP7 MEMOLOAD (Memory Loss in Alzheimer s Disease) Consortium members : Pr Heikki Tanila, University Eastern Finland; Pr Botond Penke, University Szeged; Pr Tibor Harkany, Karolinksa Institute Stockholm; Pr Denise Managhan- Vaughan, Ruhr University Bochum; Pr Richard Morris, University of Edinburgh, Pr Michael Rowan, Trinity College, Dublin. Cancela JM, Fossier P and S Granon European Associated Laboratory - - LEA (Centre de Neurosciences Paris- Sud (CNPS) CNRS and Professor Antony Galione, department of Pharmacology, university of Oxford, UK). M Taouis: Procope support for student exchange (France- Germany) involving Pr. Haring (University of Tubingen); Platon project with University of Athens (ongoing PhD thesis); long- term collaboration with Pr. A. Gertler (University of Jerusalem). Publications relevant to the projects: Selected Publications of the teams linked to the project ( ): Avale ME, Chabout J, Pons S, Serreau P, De Chaumont F, Olivo- Marin JC, Bourgeois JP, Maskos U, Changeux JP, Granon S. (2011) Prefrontal nicotinic receptors control novel social interaction between mice. FASEB J. 25(7): Beauvieux MC., Ghenimi Rahab N., Raffard G., Enderlin V., Pallet V., Higueret P., Gallis JL. The Early Decrease in N- Acetyl Aspartate / Glutathione, a Brain Health Marker, Induced by Vitamin A Deprivation in Rat is Reversed by Retinoic Acid. The Open Magnetic Resonance Journal, 2, 71-79,

119 Benomar Y, Berthou F, Vacher CM, Bailleux V, Gertler A, Djiane J, Taouis M. Leptin but not CNTF induces PTP- 1B expression in human neuronal cells (SH- SY5Y): putative explanation of CNTF efficacy in leptin- resistant state. Endocrinology. 2009, 150: Bezin S, Charpentier G, Lee HC, G Baux, Fossier P, Cancela JM. (2008). Regulation of nuclear Ca2+ signalling by translocation of the Ca2+ messenger synthesizing enzyme ADP- ribosyl cyclase during neuronal depolarization. J Biol Chem Oct 10;283(41): Bourgeois JP., Meas- Yeadid V., Lesourd AM., Faure P., Pons S., Maskos U., Changeux JP., Olivo- Marin JC., Granon S. (2011) Modulation of the mouse prefrontal cortex activation by neuronal nicotinic receptors during novelty exploration but not by exploration of a familiar environment. Cerebral Cortex, in press. Bruel- Jungerman E, Veyrac A, Dufour F, Horwood J, Laroche S, Davis S. (2009) Inhibition of PI3K- Akt signaling blocks exercise- mediated enhancement of adult neurogenesis and synaptic plasticity in the dentate gyrus. PLoS One, 4(11): e7901. Cosker F, Cheviron N, Yamasaki M, Menteyne A, Lund FE, Moutin, MJ Galione A and Cancela JM. (2010). The ecto- enzyme CD38 is a mammalian NAADP synthase which couples receptor activation to Ca2+ mobilization from lysosomes. J Biol Chem. Dec 3; 285(49): Couvreur O, Ferezou J, Gripois D, Serougne C, Crépin D, Aubourg A, Gertler A, Vacher CM, Taouis M. Unexpected long- term protection of adult offspring born to high- fat fed dams against obesity induced by a sucrose- rich diet. PLoS One Mar 25;6(3):e de Chaumont F, Coura RD, Serreau P, Cressant A, Chabout J, Granon S, Olivo- Marin JC. Computerized video analysis of social interactions in mice. Nat Methods Mar 4;9(4): Diaz- Mataix L, Bush DE, Doyère V & LeDoux JE (2010) The amygdala encodes specific sensory features of an aversive reinforcer. Nature Neurosci, 13(5), Díaz- Mataix L, Debiec J, LeDoux JE & Doyère V (2011) Sensory specific associations stored in the lateral amygdala allow for selective alteration of fear memories. J Neurosci, 31(26), Ghenimi Rahab N., Alfos S, Redonnet A., Higueret P., Pallet V., Enderlin V. Adult- onset hypothyroidism induces the amyloidogenic pathway of APP processing in the rat hippocampus. Journal of Neuroendocrinology 22, , Höhn S*, Dallérac G*, Faure A*, Urbach Y, Nguyen HP, Riess O, von Hörsten S, Le Blanc P, Desvignes N, El Massioui N, Brown BL & Doyère V (2011) Behavioral and in vivo electrophysiological evidence for presymptomatic alteration of prefronto- striatal processing in the transgenic rat model for Huntington disease. J Neurosci, 31(24), Kemppainen S, Rantamäki T, Jerónimo- Santos A, Lavasseur G, Autio H, Karpova N, Kärkkäinen E, Stavén S, Miranda HV, Outeiro TF, Diógenes MJ, Laroche S, Davis S, Sebastião AM, Castrén E, Tanila H. (2012) Impaired TrkB receptor signaling contributes to memory impairment in APP/PS1 mice. Neurobiol Aging, 33(6):1122.e e39. Lucas- Meunier, E., Monier, C., Amar, M., Baux G., Frégnac, Y., Fossier, P. (2009). Involvement of nicotinic and muscarinic receptors in the endogenous cholinergic modulation of the balance between excitation and inhibition in the young rat visual cortex. Cerebral Cortex, 19, Millan MJ, Agid Y, Brüne M, Bullmore ET, Carter CS, Clayton NS, Connor R, Davis S, Deakin B, DeRubeis RJ, Dubois B, Geyer MA, Goodwin GM, Gorwood P, Jay TM, Joëls M, Mansuy IM, Meyer- Lindenberg A, Murphy D, Rolls E, Saletu B, Spedding M, Sweeney J, Whittington M, Young LJ. (2012) Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov., 11(2): Moreau, A., Amar, M., Le Roux, N., Morel, N. Fossier, P. (2010) Serotoninergic fine- tuning of the excitation- inhibition balance in rat visual cortical networks. Cerebral Cortex, 20,

120 Vallortigara J., Alfos S., Micheau J., Higueret P., Enderlin V. T3 administration in adult hypothyroid mice modulates expression of proteins involved in striatal synaptic plasticity and improves motor behavior. Neurobiology of Disease 31, , Vallortigara J., Chassande O., Higueret P., Enderlin V. TRα plays an essential role in the normalization of adult-onset hypothyroidism-related hypoexpression of synaptic plasticity target genes in striatum. Journal of Neuroendocrinology 21, 49-56, Yacir Benomar, Arieh Gertler, Pamela De Lacy, Delphine Crépin1, Hassina Ould Hamouda, Laure Riffault, Mohammed Taouis. Central Resistin overexposure induces insulin- resistance through Toll like receptor 4. Diabetes 2013 Jan;62(1): doi: /db Epub 2012 Sep

121 Table of the Units and teams of the Neurosaclay Project and Center Nom/ Surname Prénom/ First name Poste/ Position Discipline/ Domain Nom de l équipe / Name of the team N&D - Unité Neurobiologie & Développement / Unit Neurobiology & Development (UPR3294) CNRS Bally- Cuif Laure Directeur de Recherche, (DR1) CNRS Creuzet Sophie Chargée de Recherche, (CR1) CNRS Fortin Gilles Directeur de Recherche, (DR2) CNRS Joly Jean- Directeur de Stéphane Recherche, (DR2) INRA Martin Jean- Directeur de René Recherche, (DR2) CNRS Molgo Jordi Directeur de Recherche (DR1) CNRS Perron Muriel Directeur de Recherche, (DR2) CNRS Rétaux Sylvie Directeur de Recherche, (DR2) CNRS Rouyer François Directeur de Recherche, (DR1) Inserm Ruat Martial Directeur de Recherche, (DR2) Inserm Vernier Philippe Directeur de Recherche, (DR1) CNRS Developmental Neuroscience Neurogenetics Developmental Neuroscience Developmental Neuroscience Neurophysiology Developmental Neuroscience Neurogenetics Neurophysiology Neurogenetics Neurophysiology Developmental Neuroscience Evolutionary and Developmental Neuroscience Neurogenetics Neuropharmacolo gy Evolutionary and Developmental Neuroscience Zebrafish Neurogenetics Neurogénétique du poisson zébré Development and Evolution of the Neural Crest Développement et évolution de la crête neurale Integrative Neurobiology of the Brainstem in Embryos Neurobiologie intégrative du tronc cérébral chez l embryon Morphogenesis of the Chordate Nervous System Morphogenèse du système nerveux des chordés Functional Brain Imaging and Behavior (Drosophila) Imagerie Cérébrale Fonctionnelle et Comportement (drosophile) Ionic Transfer and Pharmacology of the Neuromuscular System Transferts ioniques-pharmacologie du système neuromusculaire Stem Cells and Neurogenesis in the Retina Cellules souches et neurogénèse dans la rétine Development and Evolution of the Forebrain Développement et évolution du cerveau antérieur Molecular Genetics of Circadien Rythms Génétique moléculaire des rythmes circadiens Signal Transduction and Developmental Neuropharmacology Transduction du signal et neuropharmacologie développementale Development and Evolution of Neurotransmission Développement et Evolution de la Neurotransmission 1

122 Fregnac Yves Directeur de Recherche CNRS (DRCE) & Professor at Ecole Polytechnique Shulz Dan Directeur de Recherche CNRS (DR2) Bal Thierry Directeur de Recherche CNRS (DR2) Grant Kirsty Directeur de Recherche CNRS (DR2) Destexhe Alain Directeur de Recherche CNRS (DR1) Davison Andrew Chargé de Recherche CNRS (CR1) Bathelier Brice Chargé de Recherche CNRS (CR2) UNIC - Unité Neurosciences, Information, Complexité (UPR3293) CNRS Neuroscience and computational neuroscience Neuroscience Neurocybernetics Neuroscience Computational Neuroscience Neuroinformatics Neuroscience Cognisciences: Integration and synaptic plasticity in the visual cortex Cognisciences: Intégration et plasticité synaptique dans le cortex visuel Sensory processing neuromodulation and neuronal plasticity Traitement sensoriel, neuromodulation et plasticité neuronale Cybernetics of thalamic and cortical microcircuits Cybernétique des microcircuits thalamiques et corticaux Influence of actio-linked predictions on the dynamics of sensory processing Influence des prédictions liées à l'action dans la dynamique des processus sensoriels. Oscillating and stochasic dynamics of thalamo-cortical networks Dynamique oscillante et stochastique des réseaux thalamocorticaux Neuroinformatics and databases NeuroInformatique et Bases de Données Sensory multimodality and amodal perception Multimodalité sensorielle et perception amodale Aubin Thierry Directeur de Recherche (DR1) CNRS Doyère Valérie Directeur de El Massoui Nicole Recherche (DR2) CNRS Barnier Jean- Directeur de Vianney Recherche (DR2) CNRS Fossier Philippe Directeur de Recherche (DR2) CNRS CNPS Centre de Neurosciences Paris- Sud (UMR 8195) CNRS- Paris Sud Integrative Neuroscience, Ethology Integrative Neuroscience Molecular Neuroscience Neurophysiology Integrative Neuroscience Acoustic Communications Communications Acoustiques Neurobiology of Executive Functions Neurobiologie des Fonctions Exécutives Signaling and Neuronal Plasticity Signalisation et Plasticité Neuronales Neuromodulation of Neuronal Networks Neuromodulation des Réseaux Neuronaux Cancela José Chargé de Molecular Calcium Signaling in the Central Nervous System 2

123 Recherche, (CR1) CNRS Edeline Jean- Marc Directeur de Recherche (DR2) CNRS Granon Sylvie Professor (PR2) UPS Laroche Serge Directeur de Recherche (DR1) CNRS Gisquet- Verrier Pascale Directeur de Recherche (DR2) Inserm Mathevon Nicolas Professor (PR1) UPS Taouis Mohammed Professor (PR1) UPS Ciappa Brigitte Chargée de Recherche CR1 CNRS Neuroscience Integrative Neuroscience Behavioural Neuroscience Integrative Neuroscience Integrative Neuroscience Behavioural Neuroscience, Ethology Molecular Neuroendocrinolo gy of food intake control Molecular and cellular biology Signalisation Calcique dans le Système Nerveux Central Sensory Plasticity, Neural Code and Auditory Perception Plasticité Sensorielle, Code Neuronal et Perception Auditive. Neurobiology of Decision-making Neurobiologie de la Prise de Décision Molecular and Cellulet Mechanisms of Plasticity and Memory Mécanismes Cellulaires et Moléculaires de la Plasticité et de la Mémoire Memory Processes : From Norm to Pathology Processus Mnésiques : du Normal au Pathologique Sensory NeuroEthology Neuro-Ethologie Sensorielle Molecular NeuroEndocrinology of Food Intake Neuroendocrinologie Moléculaire de la Prise Alimentaire. Cell Cycle Control by presenilin Contrôle du cycle cellulaire par la préséniline NeuroSpin/UNICOG Unité de Neuroimagerie Cognitive (U992) INSERM/CEA (the research themes are indicated) Dehaene Stanislas Professeur (CdF) Pallier Dehaene- Lambertz Christoph Directeur de e Recherche (DR2) CNRS Ghislaine Directeur de Recherche (DR2) CNRS Kleinschmidt Andreas Directeur de Recherche (DR1) INSERM Cognitive Neuroscience Neurolinguistics DevelopmentalCo gnitive Neuroscience Cognitive Neuroscience Neural bases of human consciousness, for which he has developed the global neural workspace model, and of higher cognitive faculties as numerical cognition and reading. Research uses a wide range of different methods applicable in humans. Neuroimaging to study brain processes related to language, such as speech comprehension and production or analysis of syntactic structure. Further interests are the neural basis of bilingualism and individual differences in learning languages. Neuroimaging and electrophysiology to study the structural and functional bases of cognitive development and language in infants and children, with a special emphasis on experience- dependent acquisition of these faculties and their disturbance in disorders. MRI and EEG/MEG to study generic mechanisms underpinning perceptual representations and the processes that govern sensory awareness. A focus is the study on ongoing activity and its perturbation. 3

124 Poupon Cyril Chercheur CEA Mangin Hertz- Pannier Jean- François Lucie Neurospin (w/o UNICOG), I2BM CEA (the research themes are indicated) Chercheur CEA Chercheur CEA Bottlaender Michel Chercheur CEA MRI Physics Computational Neuroanatomy Clinical Neuroscience Clinical Neuroscience MRI techniques aiming at an improved structural mapping mainly of the human brain. Particular emphasis is on measures of water diffusion that give access to microscopic tissue properties. This line of research also encompasses development of dedicated analysis tools, Signal processing and image analysis tools for computational neuroanatomy. Emphasis is on individual brain variability, development and disorders. Includes INRIA team headed by Bertrand Thirion that focuses on functional neuroanatomy. Neuroimaging research in clinical populations with a particular emphasis on neuropediatrics. Her contribution is across all studies that for methods development (brain imaging) or model testing (cognitive functions) involve access to clinical populations. Animal models of brain disease developing novel imaging biomarkers. Role in the project via this lab s AVENIR group headed by Bechir Jarraya that is developing functional neuroimaging in awake primates for studies of consciousness. IBBMC Institut de Biophysique, Biologie Moléculaire et Cellulaire (UMR8619) CNRS- Paris Sud Daniel Hervé Professor (PR1) Neuroscience Neurophysiology Pharmacology and biochemistry of the synapse Pharmacologie et biochimie de la synapse LEBS Institut de Biophysique, Biologie Moléculaire et Cellulaire (UMR8619) CNRS- Paris Sud Melki Ronald Directeur de Recherche (DR1) CNRS Molecular neuroscience Propagation of protein aggregates in neurodegenerative diseases Propagation des agrégats de proteins dans les maladies neurodégénératives 4

125 IDEX Paris-Saclay APPEL A PROJET RECHERCHE IDEX 2013 Project Title : Aliments, Alimentation et Santé : Accroitre les bénéfices santé et le bien-être, réduire les risques par le biais de l aliment et de l alimentation (Alias) / The Food-Health Connection: Providing health benefits and lowering risks of disease through food and diet, the ALIAS project Type of project : «Labex» Coordinator: Stéphane AYMERICH Directeur d Unité Institut Micalis, INRA (UMR1319) et AgroParisTech Stephane.Aymerich@grignon.inra.fr Tél : Partners of the project: Director Title Laboratory (Affiliation) Staff (tenured scientists and teachers: DR, CR, IR, Pr, MCF ) Aymerich Stéphane DR Micalis (Inra et AgroParisTech) 114 Michon Camille PR Genial (Inra, AgroParisTech, Cnam) 55 Souchon Isabelle DR GMPA (Inra et AgroParisTech) 28 Tomé Daniel PR PNCA (AgroParsiTech et Inra) 16 Soler Louis-Georges DR Aliss (Inra) 30 Blanchemanche Sandrine IR Mét@Risk (Inra) 8 Crenn Pascal PU-PH «Nutrition» team of GRCTH (UVSQ) 2 Associated laboratories 1 : Hercberg Serge PU-PH UREN (Inserm, UP13, Inra, Cnam) 18 Grunberg Alain PU-PH CRNH-IdF (GIS) Les C/E-C restent attachés aux structures associées en GIS Clément Karine PU-PH IHU ICAN et UMR872, Inserm et UPMC 12 Trugnan Germain PU-PH ERL 1057, UMR7203, Inserm et UPMC 10 1 See annex 5 1

126 Summary : Project genesis and responses to comments from the ANR and IDEX p. 3 Abstract p. 4 Program description, ambition, and scientific strategy p. 5 Structure of the research program p. 9 Kick-off research projects p. 14 Kick-off teaching and training actions p. 18 Kick-off innovation and translation actions p. 20 Governance p. 22 Participating laboratories p. 23 Financial demand and institutional supports p. 28 References p. 29 Annexes 1- Current collaborations with other UPSa laboratories 2- Significant industrial partners of ALIAS laboratories 3- Current major research contracts of ALIAS laboratories 4- Organization chart and selected publications of ALIAS laboratories 5- Presentation of ALIAS associated (not full partners) laboratories 6- Comments received by ANR and Idex in previous calls / pre-selection phase 2

127 Project genesis and responses to comments from the ANR and IDEX ALIAS was originally a Labex project presented within the scientific strategy of the IDEX (document B). Although it was not selected for ANR funding, the project received very favorable reviews in two rounds of submission. Since its beginnings in 2007, ALIAS was designed with strong interdisciplinary dynamics that integrate the related societal issues of food, nutrition, and health. As the project matured, we succeeded in defining interactive partnerships with teams both within the ALIAS consortium and outside it, notably with UPSa teams 2 and socio-economic partners (industries, public agencies, and governmental decision-makers) that have extended our vision of the project. This project takes into account points previously raised by ANR and Idex reviewers 3 : - The organization of ALIAS governance will follow the lines of existing Paris-Saclay Labex projects. Thus it will include an Institution Board that will ensure close involvement of partners institutions and FCS in the development of ALIAS policy and strategy. One driving principle of ALIAS is that all the member teams must benefit from their active participation. Especially, this will allow them to increase the socio-economic pertinence of their projects, to attract talented students and to consolidate partnerships for innovation and development. However, IDEX support will be channeled to reinforce the unique, integrative and interdisciplinary character of the ALIAS project. This support is especially valuable, as few if any national or European research calls offer support for ambitious projects of this nature. A particularity of ALIAS governance is in the creation of a Stakeholders Advisory Platform. The food sector includes numerous companies of all sizes, from very small to large international ones. The ALIAS teams have numerous collaborations with many of these actors and it would be counter-productive to associate only one specific industrial partner as a founder pertner. On the contrary, the Stakeholders Advisory Platform will allow to represent these different industrial partners (for instance via representative of pôles de compétitivité ) and associate them to the definition of ALIAS strategy. To date, 15 industrial partners have declared their support for this project. Among them, Danone has a long-standing history of research collaborations with ALIAS teams and has sponsored a chair with AgroParisTech. ALIAS is also directly implicated in the preindustrial demonstration project Métagénopolis (itself partnered to IHU ICAN), and an associated start-up «Entérome». - The ALIAS partner labs have been deeply involved in constructing this project and have obtained strong support from INRA and AgroParisTech scientific leadership, as well as from their other institutions (UVSQ and CNAM). Letters of commitment from these institutions were provided during the pre-selection. They iterate the strategic importance of ALIAS for them, and clearly affirm that their financial support to ALIAS partner units will be at least maintained in the coming years. - ALIAS will unite a broad range of expertise in the food and health fields, which will make it a unique scientific training ground. Its renown will be reinforced by several ALIAS teams that are international leaders in their fields (e.g., health and human intestinal metagenomics). ALIAS teams already participate in international-level training programs, and the actions planned in the present project will strengthen, enrich and enhance the visibility of these programs. - We emphasize the importance of having attained the critical scientific mass in the disciplines required to carry out the project. In particular, expertise in gastrointestinal physiology concerns over 12% of ALIAS researchers and academics (and not 1% as in reviewer s comments). - ALIAS will actively participate in structuring the UPSa on the basis of collaborations already in place and those to come by realization of this project. We are determined to build more broadly integrative projects with UPSa scientific groups having complementary interests, and through active participation in two other UPSa Schools in addition to the one primarily associated with ALIAS. 4 2 See annex 1 3 See annex 6 4 See annex 2 3

128 Abstract: Societal issues. Our main objectives are to ensure equitable access to safe and healthy foods and to promote eating habits that are associated with good health. - The increasing prevalence of chronic or degenerative diseases (obesity, diabetes, cancers, etc.) raises complex questions concerning their etiology on both biological and nutritional levels, and treatment strategies. - Emergence of new health risks, due to globalized and changing food technologies and changing eating habits, calls for constant renewal of strategies to prevent and/or control food-related disease. - Pressures on agricultural commodity markets may have a significant impact on food prices and quality. In this context, the food industry is obliged to innovate and diversify its products. Demonstration of health benefits is a main feature sought by food producers. However, new products and processes raise new issues of acceptability, hygiene, and affordability. Meeting these challenges will involve innovation throughout the food chain, new tools for prevention and control, and a better understanding of eating behavior. To put changes into practice will require our implication in political decision-making for drawing up recommendations concerning food and health, and then for evaluating them. The different parameters involved in understanding the relationships between food, nutrition and health require multidisciplinary and integrative approaches, which are at the heart of the ALIAS program. Scientific issues and partner activities. ALIAS is a thematic (as opposed to disciplinary) project that is based on academic excellence of its member and associate research teams, and interdisciplinarity. The project is resolutely aimed towards technical, economic and social innovation. The interdisciplinary nature of the project generates added-value by creating novel interfaces and potentially new types of approaches. The project has a clear objective: to improve human health and well-being, and reduce health risks through diet. ALIAS is structured into four major research areas: - Impact of foods and diet on pathophysiology, in particular, on chronic and degenerative diseases; - Impact of dietary components on the emergence, adaptation and dissemination of opportunist pathogens in the food chain; - Reverse engineering of foods, starting from the desired functional properties and working towards the ad-hoc design of food technologies needed for food production. The goal will be to reduce risks and increase food health benefits; - Determinants of consumer behavior and evolution of the food market in relation to public health policies. ALIAS mobilizes a community of 253 tenured scientists and academics working in seven internationally recognized laboratories, which are in, or will soon join, the Paris-Saclay campus. They all have expertise in the areas needed to achieve project objectives: food science, process engineering, nutrition, physiology, gastroenterology, immunology, microbiology, sociology, economics, mathematics and bioinformatics. The project also involves outside "associated" teams whose already established long-term collaborations with ALIAS members will be valuable for the realization of numerous aspects of the planned projects. The ALIAS teams are deeply involved in training at the Engineer, Masters, and PhD levels, especially in courses offered by AgroParisTech. Their teaching programs extend to the European level, where they are particularly active and visible in the field of "Food Science and Technology." Challenges of innovation and technology transfer. ALIAS partners are inventors of numerous patents, many of which have been licensed. Several researchers are involved in industrial contracts and collaborations with food and pharmaceutical companies. They also intervene as experts in defining public health policy. ALIAS participates in a pre-industrial demonstrator project, "Métagenopolis", one of whose objectives is tackle the technological bottleneck existing between recent findings about human microbiota and applications for diagnosis, functional foods, and preventive and therapeutic nutrition. 4

129 Based on these strengths, Alias has defined specific objectives for innovation: i) innovate food nutrition and production processes to bring accessible health benefits to the public, ii) develop preventive strategies to control safety risks, iii) develop tools for diagnosis and prognosis of chronic pathologies and preventive or therapeutic nutrition strategies, iv) provide expertise for public food and health agencies, and decision-making help for private food- and health- related companies. Priority innovative actions. In preparation for this project call, ALIAS partners and associated laboratories have identified a series of priority actions in research, training, and innovation that can be implemented immediately. These actions are designed to generate significant results on a 3-year time scale, and will expectedly have scientific repercussions in and around ALIAS: - Three highly interdisciplinary research projects that involve strong interfaces between highly diverse fields of research structuring the program; - One or two scientific conferences/workshops, widely open to i) scientific communities with which Paris-Saclay ALIAS has partnerships (e.g. Pharma / Medicine UPSud, LEBS, ISMO, IGM, LCOM, IBBMC, IR4M, I2BC, PIM, LASIPS, Ecole Polytechnique, Telecom, E. Centrale, ibitec-s, Neurospin, LSDRM) or wants to develop new partnerships (including Communication and Information Sciences and Technologies and Mathematics) and ii) R&D scientists within the socio-economic sector who can pinpoint needs that can be addressed by research and can recognize scientific findings with potential for innovation in addition to the yearly ALIAS meeting with selective invitations of some of these academic and private partners/colleagues; - Novel training programs on the regional and European levels with a focus on innovation and industrial development; - Establishment of a stakeholders advisory platform with, in particular, a strong representation of French Pôles de Compétitivité ( Center of Excellence ) to open the way for SMEs into the knowledge and innovation ecosystem built from ALIAS; - Leadership commitment for constructing a Knowledge and Innovation Community in area of food and health (KIC FoodBest project). The ALIAS project will constitute the heart of the French colocation site which associates more twelve industrial companies and Pôles de Compétitivité. Alias will be alert and open for opportunities to expand the consortium and strengthen its structure. This will be considered as a means to better address key project points, confront new scientific challenges in relation to its research objectives, and to establish its leadership. Program description, ambition, and scientific strategy ALIAS, an ambitious interdisciplinary program Meeting the needs of a growing population for foods, assuring equity of access to safe and healthy foods, and reducing the environmental impacts of the food system are major challenges of this century. Research has made significant progress but new safety issues are continuously emerging. Progress in detection of pathogenic or toxic elements, recognition of new sources of risk and the health impacts of globalization, all lead to continued improvement of French and European models for mastering health risks linked to food. The increasing prevalence of chronic metabolic and degenerative diseases (obesity, diabetes, cardio-vascular diseases ), for which foods and diets are important determinants, introduces important nutrition issues for the food chain. Indeed, as in many developed countries in which infectious diseases and infant mortality have been greatly reduced, chronic diseases are associated with aging, nutrient imbalance and food overconsumption. Assuring equitable access to balanced nutrition and well-being calls for solutions that will have to take into account several important issues: - A large proportion of foods are produced today by industrial chains that are confronted by numerous challenges. First of all, the food industry is facing a certain erosion of the productivity 5

130 gains and a significant reduction in its competitiveness. Second, the development of the food industry has been accompanied by increased demands for functionalities which have gradually led to the integration of additional requirements (food safety control, organoleptic attributes, nutritional dimensions, environmental constraints) that have gradually reduced the degrees of freedom. - Basically, the industrialization of food has, on the one hand, occurred alongside changes to lifestyle and responded to growing demands for prepared foods and an externalization of the meal preparation function. Yet on the other hand it has generated feelings of distrust by consumers, linked to this loss of control over food production. - Health impacts of food consumption and the relatively small impacts of current private and public interventions on consumers lifestyles lead to looking for new instruments aiming at changing consumption practices. Moreover health inequities related to lifestyles and food consumption behaviors clearly increase. Safe and healthy foods must be proposed at affordable prices for the entire population, including low-income households. For these different reasons, the food system is today at the crossroads and a new food model is required to restore the consumers trust, to contribute to the development of healthy behaviors, and favor employment and competiveness of the food chains. A project built on scientific breakthroughs towards innovations The food industry is the EU's leading manufacturing sector in terms of turnover, employment and number of companies, but it shows weak investments in research. This is mainly due to the fact that the majority of European food companies are SMEs. In this context, the innovation challenge will be to tailor products and services to changing environment, changing consumer demands, and the rise of a new culture of cooking and eating. Industrial development needs to take into account the diversity of consumer expectations and the limited budget allocated to food purchases by many households. It must be focused on foodstuffs with added value for customers, in particular on foods for which positive impact on health and wellbeing is clearly demonstrated. New technologies such as biotechnology and nanotechnology, development of active and intelligent packaging are some of the innovation paths the food industry needs to look at. In conjunction with the issues of health and well-being, these innovations could lead to further changes in food functionalities, in consumers decisions and information about food choices and supply (using the new technologies for information and education permitting both personalized and interactive communication) and in the domestic usage of foodstuffs (e.g. smart household appliances). But most of these innovation paths are problematic and consumer acceptance of new technologies is not guaranteed. Cultural relationships with food need to re-conciliate technology and innovation with a greater control of the food production process by the consumers. Meeting this challenge requires an integrated approach taking into account biological, medical, technological, economic and social issues. In addition, this journey will only be made possible with the cooperation of stakeholders (consumer organizations, industries, regional and national governing bodies). ALIAS will thus provide a unique opportunity to develop such an integrated approach of the food system by gathering, on the Saclay Campus, the large range of disciplines required to deal with these issues as well as socio-economic partners committed to the co-construction of such a project. Biologists, epidemiologists, food scientists, economists and social scientists will initiate the dynamic of ALIAS through the participation of AgroParisTech, INRA, and UVSQ teams. Existing collaborations with other laboratories 5 (e.g. Pharma / Medicine UPSud, LEBS, ISMO, IGM, LCOM, IBBMC, IR4M, I2BC, PIM, LASIPS, Ecole Polytechnique, Telecom, E. Centrale, ibitec-s, Neurospin, LSDRM) will permit to include immediately UPSa partners. The involvement of other disciplines, such as system 5 See also annex 1 6

131 modeling and information and communication sciences and technologies, is currently sought and collaborations with other Paris-Saclay laboratories will be implemented by the 3-year stop-and-go. The innovation ecosystem, implying research, education and transfer, is already set up and will be leveraged by ALIAS funding by Paris-Saclay IDEX. Indeed, ALIAS teams are already participating to the Institute Carnot Qualiment (certified pole of excellence in public-private innovation, turned towards the agro-food industry), and are leading the pre-industrial demonstrator Metagenopolis (publicprivate investment) for gut microbiome-based diagnoses. ALIAS teams are involved in many research contracts with food companies 6 and in two industrial Chairs: in the field of nutrition and consumer behavior a long time cooperation with Danone ( Chair ANCA ) is on the way; a new cooperation is starting in the field of Sustainable demand and supply Chain with private companies in the field of production of raw material, logistics and distribution of food, transformation ( Chair SDSC ). ALIAS teams are also involved in strong relationships with public decision-makers (Ministries in charge of Agriculture and Food, Health, Environment; National Health-Nutrition Program; Obesity Program). Moreover, it is foreseen that UPSa/ALIAS (provided it is recognized by the UPSa) becomes the main French co-location centre of the European Knowledge Innovation Community Food4Future (KIC Food) that is currently prepared by the European Consortium FoodBest. Finally, it is noticeable that all the teams of ALIAS are well-positioned and recognized teams in the European Research and Education Area. They are leaders in many European collaborative projects, research and training networks (e.g. among many others, MetaHit, ERANET Susfood, ITNs and European Masters ) and perfectly positioned on the three main actions promoted by the Joint Programming Initiative A Healthy Diet for a Healthy Life ( The general objective of ALIAS The general objective of ALIAS is to provide health benefits and to lower risks of disease through food and diet. To achieve this, ALIAS will implement an integrated work program structured along the following main actions: - Improve our understanding of the food-health interactions, dealing with nutrition issues on the one hand and with safety issues on the other hand. Acute effects of foods as well as longer term adaptation to diets must be considered. - Develop new knowledge and methods for food formulation and process engineering that will take into account the multiple dimensions of the food health relationships. - Get a better understanding of consumer behavior and analyze the potential changes in diets and food consumption which could be induced by various instruments used at individual (decision-making aids, health diagnosis, diet coaching, interactive labeling ) and collective levels (web information and database access, consumers networks ). Beside the production of academic results, ALIAS will facilitate and support translation of these results into innovations. Knowledge obtained through the first action will be directly translatable into new preventive strategies and control tools for microbiological and chemical food-borne risks, and into new diagnosis and prognosis tools for chronic diseases and preventive or therapeutic nutritional strategies. Knowledge obtained through both actions will be integrated by reverseengineering into improved foods and processes indeed, rather than producing food, and trying a posteriori to understand its positive or negative impact on human health, a rational construction based on a priori knowledge of the parameters modulating health, and integrating the socio- and economical dimensions will be an important goal. This knowledge will also be used to provide the public bodies in charge of the nutritional and health policies with suitable integrated expertise, and will help decision-making by food producers. ALIAS will unite all scientific disciplines required to implement this program: physiology, nutrition, gastro-enterology, immunology, microbiology, physico-chemistry, engineering, epidemiology, sociology, economics, bioinformatics and mathematical modeling, within highly recognized labs and 6 See annex 2 7

132 excellent research teams. It also includes strong clinical facilities (within the consortium but also through the associated labs) and state-of-the-art technological platforms. ALIAS will not only put these disciplines together but also provide each one with questions from the interfaces between disciplines; ALIAS is organized to implement and drive interdisciplinarity to serve health and wellbeing by acting on the food system. To reach its ambitious goals, ALIAS will: - Carry out in parallel, but cooperatively, individual disciplinary projects dealing with different aspects of food and diet impacts on health, to tackle specific key issues or bottlenecks. - Support interdisciplinary and integrative projects built on the wide panel of resources of the consortium to assess the impact of a relevant series of parameters through successive subsystems of the global picture. This program will be organized into four pillars that have been designed to group close disciplines, to facilitate sharing of materials and methods and to address four main issues that together cover the whole system mentioned above: Pillar 1: Impact of Food and Diet on phenotypes in relation with chronic, metabolic and degenerative diseases Physiologists, microbiologists, immunologists, epidemiologists, clinicians and food scientists will study acute effects of foods and long term adaptation to diets through the different levels of the digestive process, including the recently re-evaluated role of the microbiota. Pillar 2: Assessment of factors in the food chain that impact on pathogen emergence, adaptation and dissemination; development of strategies to limit risks. Food scientists, toxicologists, and mathematical modelers will generate the relevant context and applications for microbiological studies of determinants leading to contamination, pathogen emergence, and infection within the food chain. Pillar 3: Rational and reverse design: from functions to foodstuff. Food scientists and process engineers will closely interact with economists, sociologists, nutritionists and microbiologists to propose rational foodstuff construction, starting from the desired properties to the food construction process Pillar 4: Determinants of food consumption and public health policies assessment Economists, sociologists and epidemiologists will be involved in this pillar for analysing socioeconomic determinants and health impacts of consumption and food market evolution. These works will contribute to fine-tune industrial strategies and public policy design and assessment. ALIAS will simultaneously move on, change its own- and partner- teams, and make Paris- Saclay «the place to go» for study, research and resources in the Food-Health field Sharing a systemic vision of the food, diet and health relationships will incite the ALIAS teams to evolve their research questions and their vision of how to address them. Such a systemic appropriation will, with no doubts, generate projects in which teams of the Paris-Saclay or other campuses will make valuable contributions. In parallel, this systemic vision and its implementation in research actions will irrigate the training activities supported by ALIAS and make them more reactive in integrating research breakthroughs and the changing socio-economic context. ALIAS scientific animation and in-depth, continuous exchanges with the stakeholders advisory platform to be established will i) help each team ask the most relevant questions in the context of ALIAS objectives, ii) increase the number of research contracts with private companies, and iii) facilitate stakeholders access to information that is relevant for reactive decision-making. ALIAS merging of disciplinary skills, expertise and unique experimental facilities in France, original and without strict parallel in the world, its academic excellence conjugated with intense and numerous interactions with enterprises as with public bodies and citizens, has the ambition to: - become one of the most attractive pole worldwide for students and researchers wishing to train and contribute to the Food, Nutrition and Health field; 8

133 - amplify and further expand the industrial partnerships by offering single, integrated and forwardlooking scientific dialogue, particularly through the platform of stakeholders; - multiply the different forms of research and product development; - become the French reference center for public expertise in the food-health field. ALIAS, an essential program for structuring and boosting the dynamics of the future Paris- Saclay University. Food-Health interaction is a strategic field for academic as well as for socioeconomic reasons. With the addition of UPSud and UVSQ Faculties of Medicine in the pipeline, the Paris-Saclay IDEX is capable of becoming a major international player in this field. A shared strategy backed up by multidisciplinary approaches in tandem with other fields will encourage conceptual and methodological advances joined to technological developments. To this purpose, ALIAS will contribute and benefit from the network of numerous, relevant and original technology platforms available at the UPSa. Taking advantage of excellent and large Engineering Sciences, actually one of the most significant in Europe, and Biotechnology communities within the UPSa project, which involves a large part of ALIAS, the ALIAS framework has high potential to generate original research questions for several fields, e.g. mathematics, physics, chemistry and ICST. The initiation of few mature projects as described below, the building up of collaborative projects with Paris-Saclay partners will be one of the milestones within the 3-year support of the IDEX. Among other tools and in addition to a yearly meeting with selected invitations of groups leaders from UPSa, ALIAS will organize an international conference open to the UPSa research community to support the implementation and the development of these collaborations. This conference will also be open to the private and public stakeholders involved in the food and health sectors in order to facilitate the diffusion of the research outputs and the interactive innovation process needed to address the challenges mentioned above. Concerning the long term involvement of ALIAS in UPSa, the implementation of the ALIAS projects will permit to propose research collaborations to different communities. Among the most important future challenges, the implementation of collaborations with the information and communication research community (ICST) is essential as the use of new information technologies appears to be a promising support of changes in health and consumption behaviours. Other links will be important to set up with the health community, including research taking into account the whole chain between engineering of food and gut influence, and vectorization of molecules from food targeting health benefits through personalized food and nutrition or for some specific consumers categories (young or old peoples...). Finally, modelling and combination of deterministic and stochastic models will be another important challenge which needs to set up close collaborations with the mathematic UPSa community. Structure of the research program Pillar 1: Impact of food and diet on phenotypes in relation with chronic metabolic and degenerative diseases State of the art and stakes Foods and dietary factors impact on individual phenotypes and on the incidence and development of prevalent chronic and degenerative diseases, e.g., gut dysfunctions, cancers, cardiovascular diseases, diabetes, obesity, osteoporosis, sarcopenia, neuro-degenerative diseases and associated comorbidities (Ji, 2011; Lund, 2011; Péneau, 2011; Galland, 2010). Most of these common diseases could be reduced by dietary changes (Stepien, 2011; Czernichow, 2009; Touvier, 2011). Human populations are however characterized by genetic polymorphism with different sensitivity to diseases and to the impact of foods and physiological states. Numerous social and environmental factors also modulate the impact of food on diseases. 9

134 Important questions Identification of biomarkers for phenotype flexibility and transition to dysfunctions and diseases: Metabolic diseases are mainly related to dysfunction in metabolic fluxes of nutrients (glucose, lipid, protein) and cooperation between organs (e.g. diabetes, obesity, cardio-metabolic syndrome). There is a need of individual biomarkers for the genetic profile of sensitivity and for the early transition to dysfunction and disease states. Understanding the role of the gut microbiota in relation with physiology and health: The gut microbiota is intimately involved in numerous aspects of normal host physiology and can modulate different components of the host phenotype including metabolic profiles and the inflammatory state. Recent results show that features of the human genome, coupled with those of its unique digestive microbiota, hold the key to understanding disease susceptibilities and the impact of food on these diseases (Qin, 2010, 2012; Arumugam, 2011; Wu, 2011; Qi,2012; Vassy, 2012; German, 2012; Lepage, 2013). Understanding the role of homeostatic and hedonic determinants of feeding behaviour: Disorders in food preferences and intake and overeating are important determinants of many chronic diseases. Information from ingested foods and on the nutritional state to the brain are relayed by a complex signalling network including sensory input, the gut-brain axis and other pathways that continuously record peripheral energy and nutrient sufficiency (Kaiyala, 2011). Intake motivation induced by hedonic factors has neuro-physiological bases different from those involved in homeostatic control, but the two systems seem to interact (Berthoud, 2011, 2012 a,b ). Strategy and objectives ALIAS partners will develop different approaches to evaluate the influence of food intake on development of chronic and degenerative pathologies in order to propose diagnosis and prognosis tools and to design preventive nutritional approaches and even therapeutic strategies. They will integrate genomic, metagenomic, transcriptomic proteomic and metabolomic characterization and functional measurements in order to identify events and markers predictive of dysfunctions and target at risk profiles. They will analyse the neurobiological mechanisms involved in the signalling processes to the brain and in food perception, and their roles in controlling of nutrient homeostasis and associated behavioural responses. Modulation of these signalling pathways by different factors including physiological state, diet composition, food characteristics (composition, structure, texture) and metabolic activities of the microbiota (Calvez, 2011; Ochoa, 2011) will be examined. Such approaches may lead to a database of markers predictive of metabolic dysfunctions, eating disorders and consequent diseases and will allow proposing justified nutritional interventions (Wain, 2011; The Int. Cons., 2011; Hooton, 2011; Speliotes, 2011; Woods, 2009; de Kloet, 2010). Pillar 2: Assess factors in the food chain that impact on pathogen emergence, adaptation and dissemination; develop strategies that limit risk of contamination and infection. State of the Art and Stakes The foods we eat nourish the human host, and also his residing microbes. However, processed foods may contain non-nutritive additives that eliminate microbes (e.g., antibiotics) or confer specific activities (e.g., antioxidants, stabilizers, solidifying agents) (Frankel, 2010; Aruoma, 1990; Lück, 2000). Several common food constituents impact the microbial balance, either directly, upon digestion, or by inducing host responses: i) hydrophobic molecules such as lipids are bioactive and affect cell growth and viability; ii) sugars have major regulatory impact and induce oxidative stress; iii) hemeiron (present in meats) and other metals are taken up by microbes and can stimulate or inhibit them; iv) antimicrobials stress or kill bacteria (Pedersen, 2012; IJssennagger, 2012; Winstedt, 2000; Gruss, 2012; Rothe, 2012; Yamamoto, 2005; Brinster, 2009). Indeed, cell expression is profoundly altered in response to changes in nutritional status and environmental conditions. Controlling food composition is a promising venue for manipulating microbial populations and expression. 10

135 Opportunist pathogens are microbes that may outgrow a population and infect the susceptible host. Infections due to microbial outgrowth in the food chain constitute major health, hygiene, and socioeconomic risks, and engender astronomical costs for health care and food industries. The G20 meeting held September 2011 stressed the necessity of food security, which necessarily involves the control of the emergence of opportunist pathogens in foods. Scientific findings are infrequently applied to food production. ALIAS comprises teams that performed upstream research that led to changes in industrial practices in food industries. For example, a natural food constituent (heme) was shown to have spectacular effects on bacterial growth and/or survival (Duwat, 1998; Pedersen, 2012). This puts ALIAS in a pivotal position for influencing food practices if properly justified by experimental evidence. Main Questions 1. Common food constituents that affect microbiote balance and pathogen emergence: Of interest are i) lipids; ii) sugars; iii) metals or heme (see kick-off project), iv) peptides, and v) food preservatives or food-enhancing agents. Opportunist pathogens under study: Bacillus cereus, Enterococcus faecalis, Listeria monocytogenes, Salmonella typhimurium, Staphylococcus aureus, Streptococcus agalactiae. 2. Mechanisms by which food metabolites impact opportunist intestinal bacteria: Bacterial responses to chosen factors (point 1) will be examined. We will characterize how such factors favor or reduce competitivity between microbiota and opportunist pathogens, e.g., by influencing adhesion, virulence gene expression, genetic transfer, and metabolism. 3. Impact of metabolites on pathogen development and expression in the food matrix and in the host: Foods may provoke changes in microbial populations either directly, or via host-mediated degradation during digestion. Fats, sugars, and biological metals (in meats) are powerful growth promoters or inhibitors that may act directly or may induce new host activities. Nutritionist, toxicologist and microbiology teams will collaborate to develop modular foods and identify substances that impact microbial risk, as will be challenged in animal models. Pillars 1 and 3 will determine whether the primary additive or a metabolized product causes in vivo effects, and iipursue the impact of the additives in inflammatory diseases. Pillar 4 studies will determine the presence of identified bioactive substances in consumer food choices. Bioactive constituents will be developed to retard pathogens and/or favor outgrowth of positive bacteria. Objectives and expected results ALIAS will investigate how specific food constituents, both natural and chemical additives, impact infection by bacterial pathogens in foods and in the host. Genetic, genomic, proteomic, and physiological studies will address the above points. The nutritionists, toxicologists, microbiologists, and modelers in the program will provide the needed vision of the impact of the identified constituents on health. Results can lead to specific dietary recommendations to limit emergence of pathogens, and should help define guidelines for industrial food production. ALIAS teams have made major findings concerning common opportunist pathogens that emerge during food preparation, and/or that reside quiescently and then infect the host (for examples: Houry, 2012; Daou, 2009; Dubois, 2012; Torelli, 2012; Jamet, 2012; Remy, 2013; Brinster, 2009). Teams in the Saclay-associated campuses share interests with ALIAS, particularly in opportunist pathogen behavior, and biochemical and biophysical analyses. The formalization of the Pillar 2 project will incite us to pursue such collaborations. Pillar 3: Rational and reverse design: from functions to foodstuff. State of the art and stakes Consumer preferences for quality, convenience, diversity and health aspects of food, and their legitimate expectations for safe, ethical and sustainable food provide a framework for potential innovations.there is also a real need for research on food for ensuring that the agro-food industrial sector will remain innovative and competitive. New tools and processing approaches must be 11

136 elaborated integrating the effects of processing and product formulation on structure, texture, reaction-induced modifications and nutritional quality, which can lead to the production of attractive products with health-promoting properties (Van Buggenhout, 2012). Beyond the molecular composition in nutrients, the structural dimensions of foods affect the rate and extent to which they are disassembled, modified and absorbed by humans (German, 2011). Important questions Understanding the impact of composition and processing on structuration of foods: Rational design of structured foods as smart vectors of target molecules responsible for sensorial and nutritional properties, with defined physiological and bio-availability features, is a major goal (concept of reverse engineering). Several integrative concepts have been proposed to establish links between process, microstructure and physical properties of foods (Schuber, 2004), but a major issue for research is now the reconciliation between the scales at which the states are observed and those at which reactions are performed during processes (Hill, 2004; Norton, 2006; Costa, 2006; Williams, 2006). The objective would be to manage process/food interactions in order to build tailored food with low energy input, and to deliver composition and structure as fully controllable variable sets to nutrition research. Understanding the impact of the food structure and composition on digestibility: The food matrix structural organization can act as a nutrient-release regulator, controlling the release of nutrients from the mouth to the intestinal lumen (bioaccessibility), their transport across intestinal epithelium (bioavailability) and induce some metabolic responses. Recent reviews have illustrated the importance of structure and composition on digestion kinetics (Lentle, 2010; McClements, 2010; Palzer, 2009). Another important issue is the role of the microflora used in foods with the adaption determinants of the microbial community (Monnet, 2011), and the properties of specific food flora once in the digestive tract (Firmesse, 2008, Cousin, 2012). It has also been shown that the composition of the intestinal microbiota depends on a variety of factors including diet (Claesson, 2012), and may determine the development of diseases (obesity, diabetes type2) (Clarke, 2013; Murphy, 2012; Qin, 2012; Le Roy, 2012). Understanding how the food structure supports an optimal delivery of target functional components, and extending the study to food rations would be an important step. Strategy and objectives ALIAS partners offer an original set of skills that will be aimed at developing an integrated approach to food design, including modelling, from the formulation and structuring of products by processes to their ingestion through the mouth and digestion in artificial digesters and in vivo. The impact of different molecules (proteins, fibres, antioxidants) and their behaviour (states and properties versus treatments, along with the kinetics of degradation or catabolism by microbiota) will be analysed. Consequences on health risk and consumer satisfaction will be analysed in tight connection with the other pillars. Similar questions are addressed at the Riddet Inst. and Massey Univ. (New Zealand), but the ALIAS consortium may offer broader competencies, especially in modelling which is fundamental for reverse approach and function-tailored food process engineering, and to provide decision-making aids. Mechanistic and stochastic models, formalised expert knowledge and other techniques will be developed to i) integrate knowledge at different scales and formats; ii) reconstruct the dynamics of models, management of uncertainty and work towards their reduction/simplification; iii) carry out optimal and viability control. Studies will be coordinated with the Paris Ile de France Complex Systems Network (ISC - PIF), and the LASIPS Labex. Pillar 4: changing food consumption and diet choices by private and public information policies State of the art and stakes 12

137 Consumer behavior is dictated by numerous factors which include economical, sociological, cultural, psychological, cognitive, sensorial, biological and genetic determinants. These determinants have been explored in many research programs at the national and international levels (Etiévant, 2010). Less explored, the means to favour changes in the consumption behaviours are clearly major challenges for the future. Indeed, radical changes in food consumption, and more generally in current lifestyles, seem more and more required for health (chronic diseases, obesity) and environmental issues (waste, carbon footprint...). Changes in consumption behaviours might be induced by various instruments, especially information tools: information and education campaigns, product labelling... It is clear that the effects of these instruments depend on the socioeconomic position of the households, on social and cultural norms (Régnier, 2010) and social interactions (Etilé, 2007), on habits and routines. The reactions to campaigns that promote changes in the lifestyles (food and diet choices, physical activity...) depend also on the levels of confidence in the information source (Kjaernes, 2007), and the very content of the message (Blanchemanche, 2010; Habron, 2008; Verbeke, 2008). Although it is clear that health information targeting consumers is increasingly being used, its diffusion within the population remains poorly understood (Dhanjal, 2012), and, if it is generally accepted that the short term effects on consumer behaviour are limited, little is known about long term effects. Moreover the cost-efficiency of such policies is not clearly proved (Dallongeville, 2010; Blanchemanche, 2010; Marette, 2008, 2011; de Mouzon, 2012) Important questions Generally speaking, the analysis of consumers decisions proposed in ALIAS teams aims at elucidating (i) the effects of social, economic, sensorial and health dimensions on the food and diet choices, and (ii) the observed or potential impacts of private interventions and public policies on consumers behaviours, especially those that are information-based. More precisely, we will deal with the following questions: New use of information and labelling instruments. Generic information and product labelling are important tools used by policy-makers, as well as food companies, for influencing the consumers behaviour. Under which conditions might these tools contribute efficiently to changes towards more sustainable behaviours? Might the use of new instruments (interactive labelling, web decisionmaking aids, diet coaching...) lead the consumers to better take into account health (and environmental) issues? How can these instruments be implemented by the policy makers and the private sector as well? Role of social networks in the dissemination of health information. The aim is twofold: i) analyzing to what extent social networks may amplify the dissemination of consumption and health advisory among targeting population; machine learning and computer modeling methods in simulating information diffusion may help to understand how it spreads and its influence amongst people; ii) assessing the potential impacts of web instruments aiming at supporting behaviour changes. Effects of consumers information on food characteristics. For public health, it is clear that the role of information delivered to the consumers (generic campaigns, nutritional labelling...) is not only to influence the consumers behaviours but also to favour an improvement of the quality of foods by food manufacturers. Under which conditions such a feedback effect may be observed? How to favour and reinforce it such that it leads to positive effects from health, environmental and economic points of view? Domestic use of food and cooking technology (see kick-off project n 3). Strategy and objectives Consumer behavior is dictated by numerous factors which include economical, sociological, cultural, psychological, cognitive, sensorial, biological and genetic determinants. A better understanding of their impacts and the relative role of each of them could help in the design and implementation of public policies, industrial strategies, and the development of new products. The specific goal of this program will be to get a better understanding of (i) the variability and dynamics of consumer 13

138 preferences, especially under the effect of private or public information policies; (ii) the feedback effects on food engineering and product characteristics (quality and prices). Kick-off research projects All the ALIAS teams contribute, at least for the major part of their research activities, to one or several pillars. On this basis, the main goal of the animation is to facilitate and support the expression of the added-value of this multidisciplinary consortium. On the one hand, the animation must help each team to better position its research in terms of pertinence and potential usefulness in the context of other research goals and to society, to share know-how, expertise, technical advances and equipments. On the other hand, the animation must facilitate, support and follow the construction and then the implementation of very interdisciplinary and integrative projects involving teams with complementary expertise, at the interfaces between pillars. Thus the creation of the ALIAS joint program will both fuel excellent disciplinary research and allow reaching thematic, applied objectives that required interdisciplinary approaches. Anticipating the present IDEX call, ALIAS team leaders met during summer and autumn 2012 to propose ambitious, collaborative research projects, on the basis the reflections launched during a plenary ALIAS seminar hold in Sept Three projects were selected, based on scientific ambition, novelty, and potential for short-term achievements (Feb 2016), as well as on their interdisciplinary nature, and social and socio-economic pertinence. Funding for this ambitious starting program will partly rely on independent resources obtained by individual teams. However, IDEX funding will be indispensable for developing the integrative and innovative aspects of the project. Project 1 : Nutrition, intestinal microbiota, feeding behaviour and health Context Although the links between nutrition and health have been clearly demonstrated by numerous epidemiological studies, their complex and multifactorial nature make these links difficult to fully understand. Food structure and composition (cf pillar 3), feeding components, the intestine and its microbiota, the food interface, the host metabolism and physiological responses (cf pillar 1) all have to be taken into account. Recent studies have also implicated the intestinal microbiota as a factor that can alter the impact of foods. Health is characterized by a balanced relationship between a host and its microbiota, and disturbances in this relationship have been shown to be associated with certain pathologies. However, due to the complexity of human microbiota and the large variability of individuals responses, it is in general difficult to fully grasp and interpret the specific relationships between certain structures of microbiota and their impact on host physiology, metabolism and health. Goals The objective of nutritional interventions targeting the microbiota is to restore a balance with the host. Therefore to define biomarkers of the state of microbiota is as important as it is to determine host health and nutritional status. Conforming to pillars 1 and 2, the program aims to evaluate the impact of nutritional interventions on microbiota biomarkers (and hence on microbiota itself) and on the associated variability in host phenotypes and risk factors. The studies will evaluate the role of the microbiota modulation (modification of its profile, diversity and metabolite production) with respect to energy homeostasis (basal metabolism, thermogenesis, thermic effect of feeding). Conforming to pillar 3, reverse engineering approaches will be carried out to develop and formulate foods with compositions optimized for their impact on intestinal microbiota, host physiology and feeding behavior. These approaches will be coupled to studies of consumer behavior and market evolution in order to define and provide recommendations for diets aiming to control food intake and weight gain. Milestones and deliverables 14

139 The program aims to analyze the effect of model food products on metabolism and eating behavior in relation to signaling and metabolism in the proximal and distal intestine. Year 1: development of model foods and characterization methods The project will develop preparation and characterization methods adapted to model foods (marker development) for analyzing their phenotypic impact in relation to microbial biodiversity analysis. This initial use of model systems aims to better understand the role of food characteristics. Nutritional interventions will include foodstuff structure, the presence of probiotics, the presence of components considered to be desirable (such as fibre and oligosaccharides) or undesirable (heme) and the composition and/or activity of the microbiota. Development of model foods, characterisation methods and analysis of digestion: these will focus on structured food products based on milk protein (GENIAL and GMPA). The effect of various eating conditions will be simulated by virtual reality (GENIAL). Protocols describing how to measure the effect of the tasting conditions will be defined (PNCA, GENIAL). These will be complemented by pilot studies of food breakdown, digestion kinetics (including the mouth, stomach and intestine) and tissue culture tests of nutrient availability (GMPA). Influence of foods on microbiota and phenotype in the mouse (screening). The influence of model foods on food intake, microbiota composition and metabolism will be evaluated. Diet compositions with a high potency to modify the intestinal microbiota and generate a major impact on host phenotype (MICALIS/PNCA) will be selected. Year 2: Intervention study in healthy human volunteers Given the likely interindividual variability, studies must be carried out in subjects formerly well characterised for phenotype and feeding behavior. Clinical protocols will be carried out in collaboration with CRNH-IdF in the clinical experimentation centre at Avicenne Hospital. Healthy and overweight volunteers previously characterized for phenotype and feeding behavior will receive a standard diet for 1 week and will then be split into 2 groups entering a cross-over design for 3 consecutive weeks. The diet will be either rich or low in model foods selected from the previous phase. Blood samples and analyses. Metabolism and hormone profiles will be characterized from blood, alongside urine and neuropeptide analysis. Digestive metabolism and associated biological markers will be tracked (PNCA). Feces will be collected and analyzed in order to observe the effect of diets on the composition and functional dynamics of the intestinal microbiota (MICALIS). Year 3: Study of the effect of nutritional intervention on feeding behavior in humans Assuming that certain foods can modify food intake, many questions will still remain about particular behavioral parameters (satiation, satiety, reward processes) and signaling pathways (vagus nerve, hormones, metabolic processes) involved, and the possible influence of intestinal microbiota modification on behavior. This part of the project will analyze the effect of model food products on food intake, behaviour and intestinal microbiota composition in humans. Modification of eating conditions and sensory imagery will be studied (using virtual reality) (PNCA, GENIAL). The effects on brain activity in relation to satiety will also be explored using FMRI (PNCA, + CIERM Saclay and Neurospin). Project 2: Impact of heme on intestinal microbiota and outgrowth of pathogens. Context Our main goal is to identify metabolites that provoke population changes in the intestinal microbiota and outgrowth of pathogenic microbes. Remarkably, a key factor that influences bacterial populations has been overlooked: That factor is heme, the active molecule in blood hemoglobin and a common component of Western diets via red meats {IJssennagger b, 2012;Sesink, 1999}. Heme is both toxic and essential for most cells of all lineages of life. Disease, infection, inflammation, or diet can lead to increased hemoglobin and heme in the intestines. Detection of 15

140 hemoglobin/heme in feces is an indicator of anomalies, and tests are routinely performed worldwide in older adults. Heme can cause changes in epithelial tissue {IJssennagger a, 2012;Wagener, 2001}, and may also alter the balance of the gut microbiota {IJssennagger b, 2012}. Remarkably, while none of the major bacteria of the intestinal microbiota synthesize heme, Bacteroides, a major gut species, has a strict heme growth requirement {Gruss, 2012}. Moreover, opportunist intestinal pathogens such as Streptococcus agalactiae, Enterococcus faecalis and Bacillus cereus require heme (or heme-iron) for virulence {Daou, 2009;Winstedt, 2000;Yamamoto, 2005}; growth of some gut Lactobacilli is stimulated by heme {Gruss, 2012;Brooijmans, 2009}. We hypothesize that heme in the gut may be a key determining factor in the competition between dominating microbiote populations. Goals 1) Assess heme availability in foods and the host: Develop an in vivo heme detection system making use of a patented heme reporter {Lechardeur, 2012; Gruss, 2012}. The convenient reporter system detects as little as 0.6 µg heme /ml sample in laboratory medium. It will be adapted for use in foods and in fecal samples. Note that hemoglobin/heme fecal detection tests are routinely performed on older adults and represent a major medical and economic market as an indicator of intestinal bleeding and inflammation {Schwartz, 1983;Sesink, 1999;Sinatra, 1998}. Our heme reporter, when optimized for use in biological samples, will expectedly provide more sensitivity (up to 5 to 150 times more sensitive compared to tests presently on the market; {Sinatra, 1998}). Expected results: 1. A high-sensitivity heme detector to correlate heme availability and pathogen outgrowth. 2. Application to various types of intestinal dysbiosis (infection, inflammation, cancer), more sensitive than currently used hemoccult-type tests. 2) Determine the impact of heme on outgrowth of opportunist pathogens in foods and in the host. Heme availability varies according to the health and diet of the host {IJssennagger a, 2012;Schwartz, 1983;Sesink, 1999;Sinatra, 1998;Wagener, 2001}. We will examine the impact of dietary heme on outgrowth of heme-requiring pathogens S. agalactiae, E. faecalis, and B. cereus, each of which may cause infection via the gastrointestinal route. Mutants defective in heme metabolism will be constructed and examined for their ability to survive and compete with either natural or defined intestinal microbiota (in conventional or colonized germ-free mice) in animals supplemented or not with dietary heme. As heme provokes oxygen damage {Wagener, 2001}, oxygen radicals will be measured from feces in the animal studies. 3) Devise an in vivo heme depletion system based on bacterial heme capture. Free heme is toxic, but complexed heme is not. Bacteria that efficiently incorporate heme might reduce risks due to free heme released in the intestine. Competitions between heme-using bacteria will be performed to identify bacteria that efficiently eliminate free heme. In particular, some bacteria produce hemecatalases that reduce oxidative stress {Abriouel, 2004; An, 2010}. Results may lead to diet supplementation with bacteria such as Lactobacillus plantarum to sponge away toxic heme, which may prove useful in persons who have undergone antibiotic or chemical treatments, when the gut population is most susceptible to outgrowth of pathogens. 4) Correlate consumer habits to heme availability in the diet. The extent to which meats are cooked impacts on heme availability {Martinez-Torres, 1986}. Consumer cooking practices may thus affect the microbial balance in the intestine via heme. Meat cooking practices is one of the parameters to be analyzed in kick-off Project 3. Task 2 should tell us whether a correlation exists between establishment of opportunist pathogens and the heme status. If so, the combined results might lead to dietary recommendations (or bacterial therapy as above) for individuals prone to infection (e.g., after antibiotic or chemotherapy treatments). Collaborations: Work in this area involves collaborations with Ecole Polytechnique {Lechardeur, 2012}, CEA Saclay {Lechardeur, 2010}, and Pasteur Institute {Lechardeur, 2010;Yamamoto, 2006;Yamamoto, 2005}. It also involved collaboration with the Chr Hansen 16

141 company {Garrigues, 2006; Gruss, 2012;Pedersen, 2008;Pedersen, 2012} with whom the hemereporter patent was developed. Micalis has piloted work on heme in Gram-positive bacteria since 1998 (16 publications and 3 patents). Milestones/deliverables Task 1: Heme detection system in complex environments (food, intestinal contents): Micalis, PNCA. 18 months possible new patent Task 2: Impact of heme on outgrowth of opportunist pathogens in foods and host: Micalis, GMPA to evaluate oxygen radicals in animals according to dietary heme and bacterial status. 36 months Task 3: In vivo heme depletion system based on bacterial heme capture. Development by Micalis. Assessment of ROS in feces by GMPA to follow success of concept. 18 months possible new patent Task 4: Correlate consumer habits to heme availability in the diet. ALISS. 36 months Project 3: The use of foods and food processing technologies by consumers in at-home context (Aliss, UREN, GMPA, GENIAL, Met@risk). Context Up to now, few studies have been focused on meal preparation and processing of foods by consumers in at-home context, and their consequences on nutritional intake and nutritional status. Yet these dimensions are important to consider both for improving the health risk-benefit balance related to food consumption and reducing the environmental impacts of domestic practices (energy use, waste ). Such an issue is clearly at the interface of several disciplines involved in Alias. For social scientists, different types of social norms are promoted to govern the eating practices of households, whether these social norms address nutritional or environmental issues. These norms are not only related to foods to consume more (ex: fruits and vegetable) or less (ex: red meat) but also increasingly on domestic practices (meal preparation, losses, food waste ). A better understanding of the effects of these norms on households and their practices is an important, but little-explored, scientific issue to identify to what extent consumers behaviors could realistically change to reach public health and environmental goals. For epidemiologists, available studies showed that the frequency and the degree of complexity of the meals, as well as the investment in the preparation of meals or the level of cooking skills, are positively correlated to the nutritional quality of the diet. But, although the literature suggests that loss and devaluation of culinary practices could contribute to unbalanced diet and an obesogenic environment, evidence concerning the effect of the culinary practices on obesity and chronic diseases remains low. For researchers in food engineering, a better understanding of the domestic use of foods and culinary technologies could return original questions. For instance, it could give new insights on the need to fully process the foods at the industrial level versus leaving the consumer to process partially them at-home. It could also highlight the impact of the packaging on the supply, storage and cooking consumers practices and their potential effects on the safety or nutritional dimensions. Moreover, the design and the realization of new foods are today carried out assuming a consistent and homogeneous use by the consumers. This assumption is likely wrong and new research on the consumers use of foods and culinary technologies would be necessary to redefine robust food engineering tools and better integrate the multi dimensionality of the food consumption (sensory, nutritional, technological, practical, health...). Objectives Following first recent attempts 7 to analyze at-home consumers behaviors related to food supply, meal preparation and food waste, a new project will be launched at the cross-roads of social 7 Studies implemented by UREN and Aliss units in 2011 and

142 sciences, epidemiology and food sciences. It will be focused on two main issues: (i) the packaging of foods and its effects on supply, storage, and cooking consumers decisions in relation to safety (transfers between the packaging and the food), waste and losses issues; (ii) the diversity of at-home processing practices and meal preparation in relation to health (nutritional quality of foods and diets according to the domestic processing practices) and environmental (use of meal remains, energy use) issues. The research goal will be first to identify the current consumers practices and perceptions, and the trade-offs they make between the hedonic, usability, health and sustainability dimensions. Then, it will be to identify the critical points, according to the types of consumers (depending on their age, social categories, education levels ), from the health and environmental points of view. Finally it will be to assess their willingness-to-accept and their willingness-to-pay new technologies which could be designed and proposed by food engineers, as well as the potential effects of new recommendations which could be proposed by epidemiologists (e.g. public health and prevention campaigns related to food preparation and cooking) and environmentalists (e.g. campaigns on food waste or water and energy use). The main challenge will be to set up close collaboration between the disciplines involved in the project in order to design common questionnaires to use in web surveys and direct interviews of consumers. It will be also to combine consumers surveys and lab and at-home experiments to analyze non-currently adopted practices and technologies. Milestones and expected results The project will be based on existing tools like the Health-Nutrinet-Cohort (UREN research unit), which allows implementing specific web surveys on a sample of more than individuals in France. This tool has been used in a first study dealing with domestic culinary practices in Similarly, a large survey based on direct interviews has been implemented in 2011 (Aliss research unit) on a sample of 600 households. The same sample will be used in this new project. At-home experiments will be made in a sample of 20 households. Task 1: design of the web survey and the face-to-face survey protocols (questionnaires). Task 2: realization of the web and face-to-face surveys; design of complementary experiments in lab and at-home context. Task 3: implementation of experiments in lab and at-home context; data analysis; results on the relationships between consumers practices and health and environmental issues; identification of potential innovations in food packaging, and domestic processing technologies. Among others operational results, we expect outputs in the design of web services for consumers information and smart technologies; in the types and the supports of recommendations dealing with foods and their use in domestic contexts; in food engineering and packaging design allowing the optimization of health and environmental issues by better taking into account the domestic uses by consumers. Kick-off teaching and training actions Coordination of a unique network of expertise related to Food ALIAS associates a unique network of complementary expertise in food science and engineering, microbiology, nutrition, feeding behaviour, food and public health, economics and sociology of Food, and consumer science. A part of these expertises is already involved in national and European education programs organized or co-organized by AgroParisTech. The additional contribution of INRA as well as the involvement of other institutions from the IDEX will contribute to strengthen the international visibility of UPSa. Coordination of this network will make ALIAS one of the main international players for education in the area of Food. Such coordination will be performed through a dedicated working group constituted by a limited number of members including teachers and researchers from actual and future ALIAS teams, members from other contributing institutions of UPSa, and other members from external institutions and companies. The role of this working group, 18

143 working in close collaboration with ALIAS executive committee, will be to define strategies and means to conduct the selected education activities as described below and to evaluate the progression of these actions. Valorization of the multidisciplinary coverage in high level master and PhD education programs in relation to innovation ALIAS will add value to the broad multidisciplinary coverage through high level training focused on innovation. The challenge is to make students aware of the complexity of the issues within the scope of Food and allow them to "contextualize" within ALIAS specific disciplinary approaches to those led at discipline interfaces. The content of training should involve ALIAS skills and those mobilized in the UPSa and relevant to the issues brought by ALIAS. In this context and for this theme, the content of training will be defined in mobilizing available skills in several schools first and foremost the school "Agriculture, food, environment" but also the schools Economic and social sciences" and "Engineering science and communication: SEIST". Training programs will also associate professionals from the private and public sectors able to provide a more operational vision of the problems of the Food sector. This will be done by the use of interactive teaching methods based on the experience of schools in engineering and the experiences highlighted in other projects (Trophelia, IDEFI, Ecotrophelia, Iseki food combination). These interactive methods include experimental training, case studies with interactive exchanges with professionals from the private and public sector (political economy and public health regulations...), innovation competition with jury constituted by scientists and professionals members. Completing these training programs by international training projects (M, D or post-master) ALIAS will work to develop international training programs (Master, PhD and post-master's) likely to attract students and listeners of all nationalities. These training will contribute to the visibility and reputation of the UPSa in the areas that relate to the challenges of the 21st century on food issues considered in a broad sense - designing foods to their "health" impacts and their marketing. Several European training programs leaded by or involving AgroParisTech already exist in ALIAS fields (Master in European Food studies, funded by companies; Erasmus Mundus Master Course "FIPDes", coordinated by AgroParisTech). The project will support the development of new training courses or modules to complete the offer and build summer universities and international research schools on interdisciplinary or thematic subjects. Training could be organised as summer schools - worn by the UPSa in collaboration with some other European universities with strong reputation in the covered area. They will contribute to the high performance programs open to all PhD students of the UPSa concerned by this subject. Complementary initiatives are also considered such as the project of a KIC on "Food" for which AgroParisTech coordinates the development of the "Education" component (training in innovation, network of Graduate schools, etc.). All of these initiatives will strengthen the visibility and attractiveness of the Master and doctoral spaces shared by the UPSa. Develop and implement lifelong education projects to stimulate the capacity for innovation The project will also seek to develop and implement a lifelong education project, adapted to the needs of the holders of the sector issues in order to stimulate the capacity for innovation in this sector. The development of innovation requires promoting the rapid transfer of the science and technology recent results to holders of issues. They must have the conceptual tools for translation and assembly of new knowledge into innovative projects taking into account all of the scientific, economic and regulatory components. To foster this approach, lifelong education programs will be implemented. They include in particular a summer school for managers and researchers involving several departments of the IDEX to facilitate discussions and exchanges in relation to innovation; the school should also mobilize stakeholders with experience in terms of innovation and expertise in the area of regulatory aspects. They will include also courses and modules constructed from the needs 19

144 expressed in the Stakeholder advisory board (accessible to students and listeners of different levels and for varying periods of time) to facilitate the transfer of new scientific, technical, economic and regulatory knowledge. These trainings will be implemented using non-conventional educational engineering tools including interactivity between participants and put in situation on targeted issues. Milestones and indicators of success for the first three years - 12 months: (i) completing the mapping of European and international training in the ALIAS field; (ii) have defined the operational components of the training of high level project and specified targets student; (iii) INRA and AgroParisTech (two active actors of ALIAS) are also involved in the coordination of the mounting of the record to be filed as a French centre of co-location of a KIC- Food months: (i) have built a summer school program; (ii) defining the operational components of the project of international training and have made it clear the audience and training capacities for the following two experimental years, as well as the annual calendar of implementation; (iii) have identified lifelong training modules/programmes and specified the elements of content for at least two of them; (iv) have been selected as coordinator of the french co-location center of the Food KIC and having initiated the implementation of the "Education" component. - Three years: (i) have implemented the training project innovation (M, D) on two experimental years earning 35% to 50% of concerned students and have made the balance sheet (trainers, students, professionals) in order to propose a consolidated project over the next years. (ii) have led two sessions of summer school with a number of listeners in growth; (iii) to have directed two continuing education modules and deployed them in an explicit plan of training, so as to gradually build in reference centre; (iv) have filed or been selected for one of the international training projects. Funding support asked to the IDEX - Support for the creation of training modules on the theme of "innovation in the field of food" to be inserted in master and doctoral programs (20 k ) - Support for the installation of a project for international training related to food and innovation including e-technology distance learning methods (Information and Communication Technologies in Education - ICTE) on a theme yet little covered at European level (35k ). - Support for summer schools (40k ) including: a) an interdisciplinary project with international ambition on food and innovation; b) an annual summer school for managers and researchers on the transfer of recent results to applications. Kick-off innovation and translation actions ALIAS assembles units having strong structural links to the economic world The food industry, especially the SMEs. The units comprising ALIAS already have close links with the economic industrial world 8. These links are based on numerous structuring and long term contracts and CIFRE 9 PhD theses (30% of doctoral students). Patents (more than 30), licensing (one of which brings the second highest royalty assets within INRA) and intellectual transfer indicate a high level of activity that is primordial, for our research orientations. Start-ups in several fields are linked to ALIAS labs (Enterome, Spectralys, CITRAGE SAS). Public decision-makers in charge of Food, Health and Environment. A specificity of the ALIAS units is their strong links with public authorities. ALIAS labs are involved in numerous programmes, generally 8 See annex 2 9 CIFRE is a French system for helping Ph.D. funded by private companies 20

145 long term projects: Nutrinet, Oqali/monitoring food quality ( PNNS (health policy related to nutrition and obesity), regulation and normalisation agencies, etc. Consumer associations and NGOs are also important to consider in the food and health public debate. Indeed, consumer expectations and acceptance concerning health, environment, and ethical issues are crucial factors for innovation in the food sector. ALIAS labs are involved in the development of new relationships with these stakeholders and of ways to support public debate on a scientific and rigorous basis. Providing new methods for risk management and public controls, new tools for risk exposure analysis, and supports for the design and the evaluation of public policies will reinforce these relationships. Strategy and general goals Even if long time experience is available for cooperation with companies in the frame of ALIAS project, innovation and transfer are still difficult considering the SME principal structure of companies in the Alimentation field. New tools and approaches are necessary, including new skills and activities, increased capacities of integration, and a closer link with research. Specifically, the ability to translate and to transfer rapidly research results is determinant for competitiveness. It is also important that research labs also work with consulting agencies and engineering companies and thus contribute to development of decision-making aids through the diffusion of modeling and simulation tools and databases. Actions and expected results The creation of ALIAS will rely upon existing tools or those in the process of being created. Several actions will complement the implementation of specific and shared tools that the FCS is setting up in Saclay: SATT 10, oriented towards maturation of projects; the Institut Carnot Qualiment 11 run by INRA; the Nutripôle initiative implemented by the French CRNH. Moreover running cooperations through RMTs (FlorePro, Distillate and fermented food, nutrition network, Competitiveness poles like the Vitagora one) will be reinforced and the KIC FoodBest under development will bring numerous significant European partners and companies. ACTION 1. Set up a Stakeholders Advisory Platform composed of industrial partners, representatives of public agencies (ANSES) and ministries, and consumers associations and NGOs. The role of this platform will be to interact with the researchers, upstream and downstream the research projects. They will discuss the general goals of the research programs, the priorities according to the challenges private companies and public sector have to face. They will also discuss the results of the research programs (at least the pre-competitive ones) and suggest potential applications, diffusion or implementation in real-life. Consumers and NGOs are expected to debate the relevance and the acceptability of the innovation-paths and contribute to better take into account the consumers expectations as soon as possible in the upstream steps of the research programs. ACTION 2. Create a unique gateway towards enterprises. The Innovation and Partnership working group of ALIAS will be in charge of handling pertinent requests of enterprises and identifying the appropriate paths to address them to ALIAS. This group will also be in charge of organising workshops with enterprises to identify questions and roadblocks and of convert them into relevant research orientations. ACTION 3. Favour transferability of research results and increase the potential for industrial application. The Innovation and Partnership working group will also be in charge to identify ALIAS findings with potential applicability. This group will analyze their transferable character in consultation with the Stakeholders Advisory Platform. This group will be responsible for internal pre- 10 The SATT activities are downstream of our research, and deal with economical studies, pre industrialisation, and marketing. The SATT will be a contractor for the labex

146 instruction concerning industrial protection, transfer of intellectual property, and software registration. It will help to construct demonstration projects that could be partly supported by ALIAS funds. The annual plenary meeting organized by ALIAS will be largely open to industrials and public decision makers and will propose workshops reviewing new results on important issues for these participants. ACTION 4. Develop Business Chairs (such as the ANCA chair set up by Danone and AgroParisTech) and propose new lifelong training courses. Two industrial chairs are available (ANCA for Nutrition and Consumer behaviour and Sustainable Demand and Supply Chain in the food domain. The objective is to develop new chairs in ALIAS field of expertise. To reach this goal, we will set up targeted initiatives towards new enterprises (especially SMEs) aiming at the creation of 2 new chairs in the next 5 years. ACTION 5. Organize regular meetings for consumers-citizens. There is a crucial need to reinforce the relationships between the citizens/consumers and the researchers. ALIAS goal is to provide direct communication and debates between science and society in the field of food and health. The Innovation and Partnership working group will identify the best means (regular conferences, bar des sciences ) to favour this science/society discussion and will implement it at the Idex level. Governance The overall missions of the ALIAS governing bodies are to ensure, contribute and/or promote the quality and the relevance of the scientific activities, the emergence of innovative projects, the corresponding expansion of the consortium, the valorization and the transfer of the results, the national and international visibility and attractiveness. In particular, the executive committee will manage a novel scientific animation dedicated to our multi-disciplinary consortium and will oversee the construction of very integrative projects that underlie ALIAS ambitious socio-economic objectives. Another important task will be to promote structuring of the future UPSa by i) consolidating existing research collaborations and extending them to other UPSa labs, ii) contributing to teaching programs of different schools, and iii) co-constructing, together with other UPSa communities (e.g. ICST and Maths), projects that go beyond current problematics and increase the potential for innovation. Finally, the executive committee will be in charge of organizing efficient interactions with the entreprises, governmental institutions/agencies and the citizens organizations active in ALIAS field. 22

147 Figure 2: ALIAS Governing bodies Given the socio-economic goals of ALIAS, a stakeholders advisory platform will be set up to advise the executive committee on strategic orientations, monitoring of projects and their respective steering committees, and venues of valorization and possible development of results. Three specific working groups will actively dialog both with the teams and the executive committee, and implement ALIAS day-to-day collective policies for teaching and training, research, and innovation/partnership. In particular, they will establish steering committees for every project supported by ALIAS. An annual ALIAS meeting will be organized to present and discuss on-going work and projects, to which academic (notably from UPSa), private other partners will be invited. Members of the scientific advisory board, the institution board, and stakeholders advisory platform will also be invited to attend. On this occasion, they will all meet the executive committee to discuss its annual report, and give advice on ALIAS strategy and policy. A broadly open international conference covering the different facets of the food-health connection will be organized two years after ALIAS kick-off to contribute to ALIAS and UPSa visibility and to mobilize complementary scientific communities from UPSa to participate in the ALIAS projects and its general objectives. Participating laboratories 12 Partner 1: Micalis (Director: Dr. Stéphane Aymerich) Micalis Institute is a joint research unit (UMR1319) associating INRA and AgroParisTech. Its general goal is to produce original and innovative knowledge in the field of Food and Gut Microbiology for Health. Micalis mobilizes a wide range of competence, using state-of-the-art technological platforms and combining fundamental cognitive research, applied research and transfer activities. Micalis groups over 350 people, of which 93 are permanent scientist and over 130 are doctoral students, post-doctoral researchers, visiting scientists or other fixed-term employees. It is composed of 22 research teams organized in 3 thematic departments: Food and intestinal microbial ecosystems and food-microbiota-host functional interactions - among recent results: Gloux et al. PNAS 2010, Qin et al. Nature 2010 and Nature 2012, Arumugam et al., Nature 2011, and Motta et al. Sci Transl Med Emergence and control of opportunist microorganisms of food origin - among recent results: Brinster et al. Nature 2009, Fernandez et al. Plos Pathog 2010, Houry et al. PNAS 2012, Dubois et al Systemic and synthetic microbiology - among recent results: Dominguez-Escobar et al. Science 2011, Buescher et al. Science 2012, and Nicolas et al. Science Micalis houses 5 open platforms with cutting-edge large equipments that will be highly valuable for the ALIAS project: SouthWest Paris Proteomics Analysis Platform (PAPPSO); Micalis Germ-free Animal Facility (Anaxem); Confined Technological plant (level P2) for cheese/food production (Atalis); and a pre-industrial demonstrator (MetaGenopolis) for Nutrition and Health applications of intestinal microbiota quantitative and functional metagenomics, with one associated start-up (Entérome) emerging from Micalis. Micalis scientists currently participate to 89 research contracts among which 6 European projects plus one ERC Starting Grant and 3 ITNs; 18 are strictly industrial contracts, 31 involved an industrial partner. These teams have published 383 scientific articles since 2010: 101, 36, and 7 in reviews with an IF > 5, IF > 8, and IF > 20, respectively). 21 Micalis scientists have an H index of 20 or above (up to 60). 12 See annex 4 for detailed organization chart and selected publications, annex 3 for major research contracts 23

148 Partner 2: GENIAL (Director: Pr. Camille Michon) The Food and Process Engineering unit (UMR1145 GENIAL) is a Joint Research Unit with AgroParisTech, INRA, CNAM. Its general goal is to understand the mechanisms involved in food processing, from ingredients and raw materials to ingestion. All steps of product design, from elaboration, processing, storage, including packaging to final use, especially domestic, are taken into account. It develops multidisciplinary skills: chemistry, physics, process engineering, sensory and consumer sciences, and modelling, and a focus on Food Science and Food Process Engineering. GENIAL groups over 150 people, of which 89 are permanent people (55 permanent scientists, incl. 23 HDR), and over 50 doctoral students and post-doctoral researchers. It is organized in 5 teams: Products Structuring by the Process (SP2), Construction of Food Quality by Chemistry and Process (CAliPro), Interaction between Materials and Media in Contact (I2MC), Analytical Engineering of Food Quality (IAQA), From Human to Processes (HAP). A transversal project is carried out on modelling and its applications. GENIAL 2011 budget (without salaries of permanent staff) was close to 1.8 M, of which 70% external resources. GENIAL houses 2 technical platforms, both for research, teaching and transfer activities, open to private industrial companies; one is dedicated to food unit operations up to scale 1, the second to cereal transformation and bakery product characterisation. It has also a cluster of computers (236 nods). GENIAL participate to numerous teaching activities, mainly for Food and Process Engineering curricula (in Engineering degrees at AgroParisTech and in Biochemistry at Cnam), and for Master degrees (STVE-Engineering food and processes & Food safety, European master in Food Studies, Erasmus mundus FIPDES master degree). From 2006, GENIAL scientists currently participate to or coordinate 61 research contracts among which 15 ANR projects, 13 European projects, 3 competitive projects and 3 Joint technological networks. 30 are strictly industrial contracts, 31 involved an industrial partner Researchers have published 397 papers in peer-reviewed journals, of which 70% of excellent rank. 7 researchers have an H-index > 14. The average IF is close to 2, what is good in the FST domain. 41 PhD theses have been defended since 2006 and 35 more are underway. Partner 3: GMPA (Director: Dr. Isabelle Souchon The global objective of the Unit «Microbiology and Food process engineering» (UMR 782 GMPA INRA AgroParisTech) is to acquire knowledge on biological and physical processes that govern the transformations of foods and biological materials during processes and up to food consumption. Scientific objectives are structured around 4 priority areas: Dynamics and functionalities of cheese microbial ecosystems food product engineering with the design and control of eco-friendly processes Breakdown of food by humans and modeling of the associated kinetics: from sensory to nutritional properties Knowledge integration, modeling and analysis of complex food and biological systems GMPA groups 71 people from which 24 Researchers, Professors and Assistant-Professors. GMPA houses i) an Experimental Platform dedicated to experimentation up to scale 1 (design original equipments and prototypes...), ii) a Sofware Platform dedicated to data management from food processes and iii) a start-up emerging from GMPA (Bioval Process). GMPA scientists currently participate to 19 research contracts among which 2 European projects, 3 ANR projects; 10 were strictly industrial contracts. GMPA's research Teams have published 160 scientific articles since 2009 (75% in "excellent" revues, CREBI classification), and 11 softwares and patents. 6 GMPA scientists have an H index of 15 or above. Partner 4: PNCA (Director: Pr. Daniel Tomé) 24

149 The AgroParisTech/INRA Research Unit Nutrition Physiology and Ingestive Behavior (PNCA) is recognized at the national and international level for its expertise in the field of protein and energy metabolism and homeostasis, their relationships with the central control of food intake and their involvement in risks of non-transmittable metabolic and degenerative diseases. The scientific production provides added value in the field of Nutrition and Metabolism. Over the period , more than 150 papers have been published in international peer reviewed journals such as: Am J Clin Nutr, Am J Physiol, J Nutr, Br J Nutr, Amino Acids, PLosOne, etc. The average impact factor is 4.00 and 14.4% of the publications are in reviews with IF>5. Moreover, 41% of the publications are in the Nutrition and Dietetics discipline with a distribution of 19% exceptional, 67% excellent, 13% correct, 1% acceptable, 0% mediocre. It is notable that over the period, the unit received over 44 conference invitations. Moreover the H index of D. Tome is 35. PNCA scientists currently participate to 21 research contracts among which 3 ANRs. Several contracts involve an industrial partner. Expertise: Certain members of the unit participate on editorial committees for international scientific reviews (PLosOne, Eur J Clin Nutr, J Nutr, BJ Nutr, Current Nutrition Reviews, Amino Acids, Reproduction-Nutrition-Development, etc). Researchers from the laboratory participate actively in the life of numerous scientific societies in the fields of nutrition, nourishment, behaviour and biology (SFN, AFERO, SSIB ASN, A. Soc. Physiol., etc.). The researchers take an active role in the works of organisations formulating nutritional recommendations (WHO, FAO, EFSA, ANSES, etc.). The laboratory is equipped with a human clinical plant unit, an animal plant unit, an analytical unit (biochemistry, stable isotope methodology, GC-MS, GC-IRMS), a neurophysiology unit (immunohistochemistry, electrophysiology) and a cell and molecular biology unit (cell culture, FACS, PCR). An MRI (7.5 Tesla) system for small laboratory animals is also available. Partner 5: ALISS (Director: Dr. Louis-Georges Soler) The ALISS Research Unit was founded in 2008 as a result of the merger of two units dedicated to, respectively, research programs on consumption behavior patterns (CORELA) and food supply and industrial organization (LORIA). It is composed of economists and sociologists. The activity of the ALISS Research Unit focuses on the following issues: Analyzing the consumption behaviors, their determinants and their effects in terms of food demand, and health (nutrition and safety) risks. Analyzing industrial and retail dynamics among the food chains (corporate strategy, innovation) and the resulting impact on (i) products characteristics (price, variety, quality, safety) and (ii) the creation of economic value and its sharing within the different industries. Analyzing the interaction between the dynamics of food supply and demand under the effect of public interventions aimed at market regulation, public health goals, and the reduction of social inequalities. The research unit is composed of 30 permanent researchers and 20 PhD students, post-doc and temporary members. 200 articles, books and book chapters have been published recently. More than half of the publications are published in A+ and A journals. ALISS is involved in many ANR and European projects. It is also involved in strong relationships with public bodies and ministries in charge of Agriculture, Health and Environment. ALISS unit has been in charge (with ANSES) of the implementation of the French Observatory of Food Quality. Partner 6: Met@Risk (Director: Sandrine Blanchemanche) Met@risk Unit (Methods for Food Risk Analysis) is an INRA unit. The central theme of the unit is risk analysis. All of the works are dedicated to this theme within a very integrated multidisciplinary approach (statistics, informatics, risk assessment and sociology) to aid public 25

150 decision-making. They respond to issues of the three components of risk analysis: risk assessment, risk management and communication about risk. The issues are grouped into three themes: Risk-benefit assessments: evaluating toxicological or microbiological risks and nutritional advantages of foods in the same approach, Socio-economic assessments: evaluating economic and social costs and advantages engendered by a public decision (for example, risk management), Assessment of uncertainties: analysing the different types of scientific uncertainties inherent in precedent assessments and measuring the consequences on management decisions. The Unit has 10 engineers and scientists, 6 doctoral and post-doctoral students and 5 associate researchers. The unit relies on a large multidisciplinary and international network. It has agreements with several universities making it possible to regularly welcome associate researchers (University of California at San Diego UCSD, University of Ghent, University of Munich). Met@risk is a Collaborating Centre of the World Health Organisation (WHO) and has a Memorandum of Understanding with the Food Standards Australia New Zealand (FSANZ). The unit regularly partners with or provides expertises to the European Food Safety Authority (EFSA), the DG SANCO (European Commission), the US Food and Drug Administration (FDA). Since 2007, members of the Unit have published 175 articles in peer review journals. Partner 7: Nutrition team of GRCTH (Director: Dr. Pascal Crenn) Versailles Saint Quentin en Yvelines University: nutrition team of GRCTH-EA 4497-CIC IT Inserm 805 Structure: Coordinator: Pascal Crenn (MD, PhD), H index 17. Researcher: Jean Claude Melchior (MD, PhD), H index 25. Technician 1. PhD student (doctoral school UVSQ-UEVE 423 Des génomes aux organismes ) : 1 Member of DHU HandiMedEx, Hôpital Raymond Poincaré Garches Field: This team is involved in clinic research in nutrition and metabolism for disabled patients. For this research topic, we study patients covering the range from severe undernutrition (with anorexia nervosa as model) to overweight, in order to elucidate the pathophysiological mechanisms involved in nutritional, digestive and metabolic disturbances from the earliest to the latest stage. We will seek to develop an innovative metabolic approach based on the most recent investigation on the relationship between eating disorders, the microbiota, and intestinal motility (neuropeptides, electrophysiology). Main started projects: a) Public contracts: national PHRC Ciproage and national PHRC Ecophen b) Industrial study: Homan (with Nestle France) Publications: 3 to 5 international peer-reviewed publications/year. Recent major publications: Hanachi M, Melchior JC, Crenn P. Hypertransaminasemia in severely malnourished adult anorexia nervosa patients: Risk factors and evolution under enteral nutrition. Clin Nutr 2013 (in press) Crenn P, Hanachi M, Neveux N, Cynober L. Circulating citrulline levels: a biomarker for intestinal functionality assessment. Ann Biol Clin 2011; 69: Leibowitch J, Mathez D, de Truchis P, Perronne C, Melchior JC. Short cycles of antiretroviral drugs provide intermittent yet effective therapy: a pilot study in 48 patients with chronic HIV infection. FASEB J 2010; 24:

151 Funding requested to IDEX and supports by Institutions Research projects : Project 1 : Permanent staff from GENIAL, GMPA, Micalis, and PNCA: Scientists 130 man.months Technicians 118 man.months Non-permanent staff: Two post-docs (funded by IDEX funded) 2 x 30 months = 280 k Three PhD students* 3 x 36 months Total 380 man.months * Teams will apply to: INRA Cepia and Mica divisions joint PhD call, Ile-de-France Regional Council DIM Astrea call, public/private (Cifre) fellowships with Mondelez and/or Danone (who the differing teams partner with regularly), ABIES doctoral School call, and IDEX interdisciplinary PhD call. Operating costs: From IDEX 260 k From other resources 230 k (60% already secured) Project 2 : Permanent staff from Micalis, PNCA, GMPA, and ALISS: Scientists 60 man.months Technicians 40 man.months Non-permanent staff: Two post-docs (funded by IDEX funded) months = 240 k Three PhD students* 3 x 36 months Total 226 man.months * Teams will apply to: INRA Cepia and Mica divisions joint PhD call, Ile-de-France Regional Council DIM MalInf call, ABIES doctoral School call, and IDEX interdisciplinary PhD call. Danone has also expressed interest in aspects of this heme project. Operating costs: From IDEX 220 k From other resources 210 k (70% already secured) Project 3 : Permanent staff from ALISS, UREN, GMPA, GENIAL, Met@Risk: Scientists 38 man.months Technicians 16 man.months Non-permanent staff: 1 Engineer (funded by IDEX funded) 20 months = 70 k Total 72 man.months Operating costs: From IDEX 120 k From other resources 260 k (30 % already secured) 27

152 Teaching/Training actions 13 : (from IDEX) 95 k Animation/Management*: (from IDEX) 60 k * 20 k per year for: annual ALIAS meetings, travel-accommodation of scientific advisory board and stakeholders advisory platform members, International Conference between months 20 and 30 (20 k already secured from Ile-de-France Regional Council), communication, etc.) Administration: (1/3 time secretary CDD, from IDEX) 36 k Total requested to IDEX 1381 k As clearly mentioned in their letters of commitment provided during the pre-selection, the Institutions of ALIAS labs strongly support the ALIAS program and will at least maintain their financial support at the same level in the coming three years. The total financial support brought by the institutions in 2012 was ~23 M /year (staff salaries, operating costs and indirect costs). 13 See p 18 28

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Impact of aeration and heme-activated respiration on Lactococcus lactis gene expression: identification of a heme-responsive operon. J Bacteriol : Pedersen, M. B., P. Gaudu, D. Lechardeur, M. A. Petit, and A. Gruss. Aerobic respiration metabolism in lactic acid bacteria and uses in biotechnology. Annu Rev Food Sci Technol : Péneau S, Galan P, Jeandel C, Ferry M, Andreeva V, Hercberg S, Kesse-Guyot E; the SU.VI.MAX 2 Research Group. Fruit and vegetable intake and cognitive function in the SU.VI.MAX 2 prospective study. Am J Clin Nutr Qi Q, Chu AY, Kang JH, Jensen MK, Curhan GC, Pasquale LR, Ridker PM, Hunter DJ, Willett WC, Rimm EB, Chasman DI, Hu FB, Qi L. Sugar-sweetened beverages and genetic risk of obesity. 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157 Annexes 1- Current collaborations with other UPSa laboratories UPSa lab(s) Alias lab(s) Type/Title of the project Key-words Joint publications Inserm U785, Hop P Brousse, UPSud CNRS et CEA, LABGeM, (Evry) ibitec-s, CEA and CNRS URA2096 Micalis ANR submitted Microbiota and host defensins dialog Micalis ANR Cocogen bacterial genomes evolution, comparative genomics Micalis ANR Dynamophage bacteriophage genomes evolution, bio-informatics LEBS, CNRS Micalis ANR Blanc Tyr-Phos.Net Protein phosphorylation, bacterial tyrosine kinases LEBS, CNRS Micalis NA Protein phosphorylation, bacterial tyrosine kinases LEBS, CNRS LEBS ANR Blanc/Cell.com Quorum sensing, gene expression, Bacillus, 3D structure, signaling peptide, sporulation, virulence ISMO, CNRS- UPSud ISMO, CNRS- UPSud ISMO, CNRS- UPSud ISMO, CNRS- UPSud ISMO, CNRS- UPSud ISMO, CNRS- UPSud ISMO, CNRS- UPSud ISMO, CNRS- UPSud ISMO, CNRS- UPSud IGM, UPSud and CNRS ibitec-s, CEA MICALIS Antimicrobial - Fluorescence - Phototherapy in preparation Touzain F, Denamur E, Médigue C, Barbe V, El Karoui M, Petit M A (2010). Small variable segments constitute a major type of diversity of bacterial genomes at the species level. Genome Biol. 11, R45 Lopes A, Amarir-Bouhram J, Faure G., Petit MA, Guerois R (2010). Detection of novel recombinases in bacteriophage genomes unveils Rad52, Rad51 and Gp2.5 remote homologs. Nucleic Acid Res. 38, Grangeasse C, Nessler S, Mijakovic I. (2012) Bacterial tyrosine kinases: evolution, biological function and structural insights. Philos Trans R Soc Lond B Biol Sci. 367(1602): Petranovic D, Grangeasse C, Macek B, Abdillatef M, Gueguen-Chaignon V, Nessler S, Deutscher J, Mijakovic I. (2009) Activation of Bacillus subtilis Ugd by the BY-kinase PtkA proceeds via phosphorylation of its residue tyrosine 70. J Mol Microbiol Biotechnol. 17(2):83-9. Perchat, S., Dubois, T., Zouhir, S., Gominet, M., Poncet, S., Lemy, C., Aumont-Nicaise, M., Deutscher, J., Gohar, M., Nessler, S., Lereclus, D., A cell-cell communication system regulates protease production during sporulation in bacteria of the Bacillus cereus group. Mol. Microbiol. 82: Grenha, R., Slamti, L., Nicaisse, M., Refes, Y., Lereclus, D., Nessler, S., Structural basis for the activation mechanism of the PlcR virulence regulator by the quorum-sensing signal peptide PapR. Proc. Natl. Acad. Sci. USA (in press). K. Steenkeste, F. Tfibel, M. Perrée-Fauvet, R. Briandet, M.-P. Fontaine-Aupart Tracking the Photosensitizing Antimicrobial Activity of mono(acridyl)bis(arginyl)porphyrin (MABAP) by Time Resolved Spectroscopy, The Journal of Physical Chemistry A 114(9): MICALIS Biofilms -Fluorescence - Diffusion F. Waharte, K. Steenkeste, R. Briandet and M.-P. Fontaine-Aupart Local diffusion measurements inside biofilms by FRAP analysis with a commercial confocal laser scanning microscope, Applied and Environmental Microbiology, 76: MICALIS PhD opf O. Habimana Biofilms -Fluorescence - Diffusion O. Habimana, K. Steenkeste, M-P Fontaine-Aupart, M-N Bellon-Fontaine, S. Kulakauskas and R Briandet Diffusion of nanoparticles in biofilms is altered by bacterial cell wall hydrophobicity, Applied and Environmental Microbiology 77(1): MICALIS PhD of E. Bulard Bacterial adhesion - surface- SFG MICALIS PhD of DADDI-OUBEKKA S. Biofilms - antimicrobials - Fluorescence MICALIS PhD of E. Bulard Bacterial adhesion - surface- SFG E. Bulard, Guo, Z., Zheng, W., Dubost, H., Fontaine-Aupart, M.-P; BELLON-FONTAINE, M-N; HERRY, J-M; Briandet, R. and Bourguignon, B Probing in situ adhesion of bacteria on functionalized SAMs using SFG vibrational spectroscopy. Langmuir. 19;27(8): S. Daddi Oubekka, R. Briandet, M.-P. Fontaine-Aupart and K. Steenkeste, Correlative time-resolved fluorescence microscopy to analyze antibiotic diffusion-reaction in biofilms. Antimicrobial Agent and Chemotherapy 56(6): C7 Bulard E, Fontaine-Aupart MP, Dubost H, Zheng W, Bellon-Fontaine MN, Herry JM, Bourguignon B.Competition of Bovine Serum Albumin Adsorption and Bacterial Adhesion onto Surface-Grafted ODT: In Situ Study by Vibrational SFG and Fluorescence Confocal Microscopy. Langmuir Dec 11;28(49): MICALIS ANR SanBact Bacterial adhesion - surface Lepoittevin, B; Wang, XL; Baltaze, JP; Liu, HF; Herry, JM Bellon-Fontaine, MN; Roger, P Radical polymerization and preliminary microbiological investigation of new polymer derived from myrtenol. EUROPEAN POLYMER JOURNAL Volume: 47 Issue: 9 Pages: MICALIS ANR Sanbact Liu, HF; Lepoittevin, B; Roddier, C; Guerineau, V; Bech, L; Herry, JM; Bellon-Fontaine,; Roger, P. Facile synthesis and promising antibacterial properties of a new guaiacol-based polymer. POLYMER Volume: 52 Issue: 9 Pages: MICALIS MICALIS PhD of K. Hamze Bacillus subtilis - swarming - biofilms Micalis and GMPA ANR EcoMet Sulfur metabolism in cheese ripening microbiota Bech, L; Elzein, T; Meylheuc, T; Ponche, A; Brogly, M; Lepoittevin, B; Roger, P. Atom transfer radical polymerization of styrene from different poly(ethylene terephthalate) surfaces: Films, fibers and fabrics. EUROPEAN POLYMER JOURNAL Volume: 45 Issue: 1 Pages: K. Hamze, S. Autret, K. Hinc, D. Julkowska, R. Briandet, M. Renault, C. Absalon, I. B. Holland && S.J. Séror Single cell analysis in situ in a B. subtilis swarming community identifies distinct spatially separated subpopulations differentially expressing hag (flagellin), including specialized swarmers. Microbiology 157: Hébert A, Forquin-Gomez MP, Roux A, Aubert J, Junot C, Loux V, Heilier JF, Bonnarme P, Beckerich JM, Landaud S. Exploration of sulfur metabolism in the yeast Kluyveromyces lactis. Appl Microbiol Biotechnol Sep;91(5): Hébert A, Forquin-Gomez MP, Roux A, Aubert J, Junot C, Heilier JF, Landaud S, Bonnarme P, Beckerich JM. Study of Yarrowia lipolytica reveals new insights into sulfur metabolism in yeasts. Appl Environ Microbiol Dec 7 LEBS, CNRS Micalis C Martineau PhD Protein synthesis quality control Martineau CN, Le Dall MT, Melki R, Beckerich JM, Kabani M. Molecular and functional characterization of the only known hemiascomycete ortholog of the carboxyl terminus of Hsc70-interacting protein CHIP in the yeast Yarrowia lipolytica. Cell Stress Chaperones Mar;17(2): ibitec-s, CEA and CNRS IGM, UPSud, CNRS; ibitec-s, CEA, CNRS ibitec-s, CEA and CNRS IPSIT, Inserm U996, Fac Med, UPSud, Hop Béclère, AP-HP ibitec-s, CEA and CNRS Inserm U669 and GRCTH UPSud Martin Vos and Micalis Ursula Liebl Ecole Polytechnique IGM, UPSud and CNRS ibitec-s, CEA and CNRS Micalis Genolevures Genomics, yeasts Comparative genomics of protoploid Saccharomycetaceae (2009) Génolevures Consortium, Souciet JL, et al. Genome Res. 19(10): Micalis Genolevures Genomics, yeasts Pichia sorbitophila, an Interspecies Yeast Hybrid, Reveals Early Steps of Genome Resolution After Polyploidization (2012) Louis VL et al. G3 (Bethesda) 2(2): Micalis Allergy, Food Adel-Patient K, Pothelune L, Ah-Leung S, Wal JM, Créminon C, Chatel JM. Block copolymers have differing adjuvant effects on the primary immune response elicited by genetic immunization and on further induced allergy. Clin Vaccine Immunol Jan;17(1): Micalis Hepatobiote Microbiota, non-alcoholic liver fatty disease Micalis Micalis Epidemiology of Eating disorders Heme-regulated functions in lactic acid bacteria Impact on fatty acids on S aureus antibiotic resistance Heme-regulated functions in lactic acid bacteria, Structurefunction of heme regulators Current collaborations between Alias labs and other UPSa labs Le Roy T, Llopis M, Lepage P, Bruneau A, Rabot S, Bevilacqua C, Martin P, Philippe C, Walker F, Bado A, Perlemuter G, Cassard-Doulcier AM, Gérard P.: Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut Nov 29. [Epub ahead of print] Morin S, Fischer R, Przybylski-Nicaise L, Bernard H, Corthier G, Rabot S, Wal JM, Hazebrouck S. Delayed bacterial colonization of the gut alters the host immune response to oral sensitization against cow's milk proteins. Mol Nutr Food Res Dec;56(12): Morin S, Bernard H, Przybylski-Nicaise L, Corthier G, Rabot S, Wal JM, Hazebrouck S. Allergenic and immunogenic potential of cow's milk β-lactoglobulin and caseins evidenced without adjuvant in germ-free mice. Mol Nutr Food Res Nov;55(11): Hazebrouck S, Przybylski-Nicaise L, Ah-Leung S, Adel-Patient K, Corthier G, Wal JM, Rabot S. Allergic sensitization to bovine beta-lactoglobulin: comparison between germ-free and conventional BALB/c mice. Int Arch Allergy Immunol. 2009;148(1): anorexia nervosa, nutrition Mattar et al, Eur J Clin Nutr 2012; Mattar et al, Nutr res Rev 2011 Hemoprotein structure function Fatty acids, triclosan, opportunist pathogens Hemoprotein structure function Lechardeur, D., B. Cesselin, U. Liebl, M. H. Vos, A. Fernandez, C. Brun, A. Gruss, and P. Gaudu. Discovery of intracellular heme-binding protein HrtR, which controls heme efflux by the conserved HrtB-HrtA transporter in Lactococcus lactis. J Biol Chem : in preparation Lechardeur D, Fernandez A, Robert B, Gaudu P, Trieu-Cuot P, Lamberet G, Gruss A. The 2-Cys peroxiredoxin alkyl hydroperoxide reductase c binds heme and participates in its intracellular availability in Streptococcus agalactiae. J Biol Chem May 21;285(21):

158 LSDRM, UMR3299 CEA- CNRS Fac Pharma, UPSud Fac Pharma, UPSud Micalis Micalis Micalis Metal transport in Staphylococcus aureus Menaquinone exchange between dairy bacteria Cobalt nickel Opp transport functions Remy L, Carrière M, Derré-Bobillot A, Martini C, Sanguinetti M, Borezée-Durant E. The Staphylococcus aureus Opp1 ABC transporter imports nickel and cobalt in zinc-depleted conditions and contributes to virulence. Mol Microbiol Dec 23. Menaquinones Lactococcus lactis Bifidobacterium Food and cardiovascular disease Rousseau-Ralliard D, Goirand F, Tardivel S, Lucas A, Algaron F, Mollé D, Robert V, Auchère D, Boudier JF, Gaillard JL, Monnet V, Tauzin J, Grynberg A. Inhibitory effect of αs1- and αs2-casein hydrolysates on angiotensin I-converting enzyme in human endothelial cells in vitro, rat aortic tissue ex vivo, and renovascular hypertensive rats in vivo. J Dairy Sci Jul;93(7): Micalis PolyModE Gut microbiota enzymes Malleron A, Benjdia A, Berteau O, Le Narvor C. Chondroitin-4-O-sulfatase from Bacteroides thetaiotaomicron: exploration of LCOM-eG2M, CNR the substrate specificity. Carbohydr Res May 15;353:96-9. TelecomParisTech Met@risk ANR Non negative matrix factorization Zetlaoui M, Feinberg M, Verger P, Clémençon S., Extraction of food consumption systems by nonnegative matrix factorization (NMF), food risk, consumption (NMF) for the assessment of food choices, Biometrics Dec;67(4): TelecomParisTech Met@risk ANR Social Networks, health information INRIA Met@risk ANR HolyRisk, Uncertainty, Food Risk Regulation (CIERM), Hopital PNCA liquid calories - satiety - fmri - in preparation Orsay brain pathways Ecole Polytechnique Ecole Polytechnique Ecole Polytechnique Ecole Polytechnique Ecole Polytechnique Ecole Polytechnique Ecole Polytechnique Ecole Polytechnique Ecole Polytechnique Ecole Polytechnique CEA, Ecole Polytechnique fmri study of brain activity differences after eating solid, pureed or juiced fruit. Dhanjal C., Blanchemanche S., Clémençon S., Rona-Tas A., Rossi F., Dissemination of Heath Information within Social Networks, In : Vedres B. (ed.), The Unexpected Link: Using Network Science to Tackle Social Problems, Oxford University Press. Software : Uncertainty Navigator ; Publication in progress ALISS Chaire ISR Samer HOBEIKA, Jean-Pierre PONSSARD, Sylvaine PORET, LE RÔLE STRATÉGIQUE D UN LABEL DANS LA FORMATION D UN MARCHÉ LE CAS DE L ISR EN France, Cahiers de Recherche ECOLE POLYTECHNIQUE, DEPARTEMENT D'ECONOMIE, cahier de recherche ALISS Chaire Business Economics Eric Giraud-Heraud, Cristina Grazia, Abdelhakim Hammoudi,, Explaining the Emergence of Private Standards in Food Supply Chains, Cahiers de Recherche ECOLE POLYTECHNIQUE, DEPARTEMENT D'ECONOMIE, cahier de recherche ALISS Chaire ISR Fabrice Etilé, Sabrina Teyssier,, Corporate Social Responsibility and the Economics of Consumer Social Responsibility, Cahiers de Recherche ECOLE POLYTECHNIQUE, DEPARTEMENT D'ECONOMIE, cahier de recherche ALISS Chaire Développemtn durable Guy Meunier, Jean-Pierre Ponssard, Philippe Quirion,, Carbon Leakage and Capacity-Based Allocations.Is the EU right?, Cahiers de Recherche ECOLE POLYTECHNIQUE, DEPARTEMENT D'ECONOMIE, cahier de recherche ALISS Chaire Business Economics Patricia Crifo, Vanina D. Forget, Sabrina Teyssier,, The price of unsustainability: An experiment with professional private equity investors, Cahiers de Recherche ECOLE POLYTECHNIQUE, DEPARTEMENT D'ECONOMIE, cahier de recherche ALISS Chaire Développemtn durable Guy Meunier, Risk aversion and technology portfolios, Cahiers de Recherche ECOLE POLYTECHNIQUE, DEPARTEMENT D'ECONOMIE, cahier de recherche ALISS Chaire Développemtn durable Guy MEUNIER Jean-Pierre PONSSARD,, Capacity decisions with demand fluctuations and carbon leakage, Cahiers de Recherche ECOLE POLYTECHNIQUE, DEPARTEMENT D'ECONOMIE, cahier de recherche ALISS Chaire Business Economics Marie-Laure ALLAIN Claire CHAMBOLLE Patrick REY, Vertical Integration, Innovation and Foreclosure, Cahiers de Recherche ECOLE POLYTECHNIQUE, DEPARTEMENT D'ECONOMIE, cahier de recherche ALISS Chaire Business Economics Marie-Laure ALLAIN Claire CHAMBOLLE, Anti-competitive effects of resale-below-cost laws,, Cahiers de Recherche ECOLE POLYTECHNIQUE, DEPARTEMENT D'ECONOMIE, cahier de recherche ALISS Chaire Business Economics Claire CHAMBOLLE Sylvaine PORET, 2009 Fair trade contracts for some, and insurance for others, Cahiers de Recherche ECOLE POLYTECHNIQUE, DEPARTEMENT D'ECONOMIE, cahier de recherche GENIAL COPOLA Durée de vie des polymères industriels, modélisation moléculaire Ecole Centrale GENIAL NA microscopie environnementale in preparation Upsud, CEA GENIAL NA CEA GENIAL thèse Polytechnique ISC- PIF Equipe projet AVIZ) SOLEIL, UPSud, ENS CACHAN XPS, chimie moélculiare, matériaux analyse données LIMS embarqué, chimiométrie Durand M, Meye H, Benzerar O, Baschnage J, Vitrac O(2010). Molecular dynamics simulations of the chain dynamics in monodisperse oligomer melts and of the oligomer tracer diffusion in an entangled polymer matrix. JOURNAL OF CHEMICAL PHYSICS 132(19) in preparation in preparation GMPA ANR INCALIN algorithmes de complexité 1) Sicard, M.; Perrot, N.; Reuillon, R.; Mesmoudi, S.; Alvarez, I.; Martin, S. (2012), A viability approach to control food processes: Application to a Camembert cheese ripening process. Food Control 23, (2), ) Perrot, N.; Trelea, I. C.; Baudrit, C.; Trystram, G.; Bourgine, P. (2011), Modelling and analysis of complex food systems: State of the art and new trends. Trends in Food Science & Technology 22, (6), GMPA EU DREAM Algorithmes évolutifs, visualisation, interaction GMPA J. Gautier PhD Physique, imagerie infrarouge, Biophysique, imagerie flurescence, couplage AFM- Infrarouge 1) Barriere, O.; Lutton, E.; Wuillemin, P.-H.; Baudrit, C.; Sicard, M.; Perrot, N., (2013) Cooperative Coevolution for Agrifood Process Modeling. In Evolve - a Bridge between Probability, Set Oriented Numerics and Evolutionary Computation, Vol. 447, pp ) Barriere, O.; Lutton, E.; Wuillemin, P.-H.; Baudrit, C.; Sicard, M.; Perrot, N., Cooperative Coevolution for Agrifood Process Modeling. In Evolve - a Bridge between Probability, Set Oriented Numerics and Evolutionary Computation, Vol. 447, pp J. Gautier, F. Jamme, S. Passot, S. Cenard, F. Fonseca. (2013) Assessment of the chemical changes induced in lactic acid bacteria by freezing using Synchrotron infrared spectrosmicroscopy, The Analyst (soumis) + Publications en cours 2- Significant industrial partners of ALIAS laboratories Food: GIVAUDAN, PURATOS, KRAFT, PERNOD RICARD, SYNABIO, BEL, BONGRAIN, BONDUELLE SA, Chr Hansen SA, DANONE, NESTLE, DSM, Téréos, Cargill, ROUSSELOT, CONSERVES France, Mondelez, SOUFFLET, Roquette, Lesieur, Fleury Michon, LDC, McCain, Nutrixo, ITERG, CTCPA, CNIEL, ITFF, Aérial Equipment, and engineering: Cryolog, GEA, Applexion, Bruker, Maguin SA, TechniProcess, LNE, Prosim Health: SERVIER, Mérieux, MERCK Médication Familiale, Pilèje, Biocodex, Boehringer, Nutricia, Sanofi-Aventis

159 3- Current major research contracts of ALIAS laboratories type de projet Acronyme Titre et/ou keywords coord/part partenaires Alias ANR Micalis partenaires UPSa LimoPhosProt Protein phosphorylation and Listeria virulence coord Cell.com Communication cellulaire et switch moléculaire chez Bacillus cereus coord IBBMC EXECO Etude méta-transcriptomique et biochimique de l écosystème part GMPA fromager : pour un contrôle accru de l EXpression d un ECOsystème alimentaire complexe TyrPhos.net Rôle des réseaux de phosphorylation sur la tyrosine dans la coord physiologie et virulence bactérienne ReadRNA Primary and Processed Bacterial transcriptomes for deciphering regulatory networks part SFB impro Analyse fonctionnelle et moléculaire des interactions de l hôte avec part la bactérie commensale Segmented Filamentous Bacterium GB-3G Comparative Genomics, functional Genomics and population part Genomics Glyco-Path Protein glycosylation in pathogenic Gram-positive part bacteria EcoBioPro Exploration of microbial ecosystems of fish and meat products. coord Effects of bioprotective cultures GEMISA GEnétique, Microbiote, Inflammation, et Spondylarthrite part Ankylosante MeniViruCarb Role of the Neisseria meningitidis PTS component HPr in the coord correlation between carbon metabolism and virulence FattyBact Impact of fatty acids on infection by low GC% Gram positive coord pathogens. FunMetaGen A Functional Metagenomic Strategy to decipher Host-Microbiota coord cross-talk in the Human Intestinal Tract FoodMicrobiome Cheese microbiota metagenomics and secondary metabolism coord GMPA Surfing Starter SURFace against INFlammation of the Gut coord GreenSwimmers Sensitizing industrial biofilms to biocide by tunneling the matrix coord with hyper-swimming bacteria IMPRO-Fprau Analyse des effets immuno-modulateurs des peptides issus d'une coord protéine spécifique de Faecalibacterium prausnitzii, une bactérie commensale impliquée dans la maladie de Crohn AD'HOC A Functional Metagenomic Strategy to decipher Host-Microbiota part cross-talk in the Human Intestinal Tract Food-Redox Control of pathogenic and spoilage microorganisms in food products part GMPA by a rational use of the oxydoreduction potential IGM Inserm U687 P Brousse Hosp MIAj EU CryMuc Interactions des toxines Cry insecticides avec mucus du tube digestif coord UIAA Dynamophage Bacteriophage genomes dynamic coord ibitec-s Elaprob-IBD Mechanisms of action of Elafin-expressing probiotics: A possible use part to treat Inflammatory Bowel Disease? SelArom Selective use of aromatic amino acids by radical SAM proteins part VirBactFactory Assembly and dynamics of a bacterial virus part VMS factory PathoBactEvol Evolution of a sporeforming food-borne opportunistic pathogen coord VMS, EDB, MIG PolyModE POLYsaccharide MODifying Enzymes from Intestinal microbiota part BaSynthec Bacillus synthetic biology coord MetaHit Metagenomics of the human intestinal tract coord IHMS Standards in Human Metagenome Research coord MetaCardis Gut microbiota and CardioMetabolic Diseases part ICAN EvoTar Evolution and transfer of resistance genes from human microbiome part ERC St Grant BACEMO Bacterial Morphogenesis (Rut CARBALLIDO-LOPEZ) coord Autres* F-PARIS Nouvelle génération de compléments alimentaires à effet positif coord prouvé sur le SII (Syndrome de l'intestin Irritable) chez l'homme Diacides lipid metabolism engineering for diacides production part HepatoBiote Microbiota and nonalcoholic fatty liver disease coord A Béclère Hosp Probiotique *les projets compétitifs avec un partenaire industriel ne sont pas mentionnés pour raison de confidentialité

160 GENIAL type de projet Acronyme Titre et/ou keywords coord/part partenaires partenaires Alias UPSa ANR OCAD (ALID) Offrir et Consommer une Alimentation Durable Part DESIRABLE (ALID) Conception d une bio-raffinerie d insectes pour systèmes alimentaires Coord SATIN (ALID) Cuisson en moule des pains et biscottes; Maîtrise des risques chimiques et Part enjeux énergétiques DIACODD (ALID) Distribution Alimentaire, Consommateurs et Développement Durable Part SOMEAT (ALID) Safe Organic MEAT Part ALISS CEA RIBENUT (ALIA) Nouvelles approches pour une évaluation du compromis risque microbiologique Part - bénéfice nutritionnel pour les légumes traités thermiquement DOMINOVE (ALIA) Réchauffage domestique au four ou par contacts d'aliments frits Coord SAFEFOODPACK DESIGN (ALIA) REACTIVE POWDER (ALIA) Conception raisonnée d emballages alimentaires plastiques sûrs Contribution des facteurs procédés et des propriétés de surface des particules dans les mécanismes impliqués dans la granulation de poudres alimentaires PACO (EESI) Développement d'une pompe à chaleur à eau fonctionant entre 90 et 130 C part utilisant un compresseur centrifuge à paliers magnétiques COOPERE (SEED) COmbiner Optimisation des ProcédEs, Récupération énergétique et analyse Part Exergétique pour une meilleure efficacité énergétique des sites industriels PIRANEX (P2N) Biomodal instrumentation for detection and identification of biomolecules Part using plasmonic imaging and Raman spectroscopy enhanced by nanostructuration EU DREAM Design and development of REAListic food Models with well-characterised micro-and macro-structure and composition Part CONNECT 4 ACTION Strategies for improving communication between social and consumer Part scientists, food technology developers and consumers POWTECH Integrating research training in particle & powder technology to deliver efficient Part products with high functionality Autres* FUI VALECO FUI SATIAROME Compréhension du rôle de la composition et de l'aromatisation pour le développement de yaourts à effet rassasiant, satiétogène et bien-être Région Pays de Loire compréhension et modélisation des mécanismes de formations des ouvertures U2M ChOp-2 dans les fromages à pâte pressée AGRIFOOD GPS Une Nouvelle Approche Integree pour Anticiper les Risques et Prevenir les Part Crises Alimentaires *les projets compétitifs avec un partenaire industriel ne sont pas mentionnés pour raison de confidentialité Coord Part GMPA GMPA GMPA type de projet Acronyme Titre et/ou keywords coord/part partenaires Alias partenaires UP-Sy ANR EU Autres* EXECO Etude méta-transcriptomique et biochimique de l écosystème Coord MICALIS fromager : pour un contrôle accru de l EXpression d un ECOsystème alimentaire complexe FoodMicrobiome Cheese microbiota metagenomics and secondary metabolism Part SENSINMOUTH Etude et modélisation des mécanismes en bouche responsables de Part la dynamique de libération des stimuli sensoriels INCALIN Intégration des connaissances et méthodes de viabilité pour maîtriser la qualité des produits alimentaires Coord GENIAL Polytechnique, INRIA, ISC-PIF EcoMet Ecosystème fromager: étude fonctionnelle du Métabolisme du Coord MICALIS CEA-Saclay soufre DREAM FEDER Design and development of REAlistic food Models with wellcharacterised micro- and macro-structure and composition Evaluation et compréhension des aptitudes aromatiques de souches d affinage dans des fromages à pâte pressée non cuite part (coord WP) coord CAFE Computer-Aid Food processes for control Engineering part (coord WP) STAB-LAB Etude in situ et en temps réel du comportement biophysique de bactéries lactiques soumis à des stress de procédés coord GENIAL GENIAL SATIAROME Formulation d'un produit laitier à effet staiété part GENIAL ECODIGE Les flores de l écosystème fromager survivent-elle à leur digestion coord MICALIS et peuvent-elles avoir un effet immunomodulateur sur l hôte? Ecole Polytechnique, INRIA, ISC-PIF SOLEIL, PARIS Sud Orsay (lab chimie Physique, CLIO), ENS CACHAN LACTAFF qualité des fromages lactiques: locaux et maitrise de l'affinage part FROPACK Dynamique des communautés microbiennes des flores d'affinage et part évolution métabolomique de fromages de technologie pâte persillée soumises à un stress lié à l emballage *les projets compétitifs avec un partenaire industriel ne sont pas mentionnés pour raison de confidentialité

161 PNCA type de projet Acronyme Titre et/ou keywords coord/part partenaires partenaires Alias UPSa ANR PRONUTRIAL Effect of processing on nutritional quality of protein from meat products part BISENS Tailored biscuit with optimized satiety benefit part GMPA EU Autres* Chaire ANCA Aliment, Nutrition et Comportement Alimentaire coord GMPA PLEASIN (AIP Inra) food characteristics, self-choice of food, pleasure and intake in humans coord GMPA *les projets compétitifs avec un partenaire industriel ne sont pas mentionnés pour raison de confidentialité type de projet ANR Acronyme Titre et/ou keywords coord/part partenaires Alias partenaires UPSa HOLYRISK Scientific Uncertainty and Food Risk Regulation INRIA TANGERINE Non negative matrix factorization (NMF), food risk, consumption TelecomParisTech TelecomPa ristech RIBENUT Microbiological risks vs nutritonal benefits INRA-SQPOV MAP'OPT Equilibrium gas composition in modified atmosphere ADRIA Développement packaging and food quality EU OBELIX Endocrine Disruptors, Obesity, prenatal exposure VU University of Amsterdam Autres* Uncertainty Toolkit Uncertainty analyses, Bisphenol A, environnment, food Institut des Sciences de la Communication, CNRS *les projets compétitifs avec un partenaire industriel ne sont pas mentionnés pour raison de confidentialité Nutrition team of GRCTH type de projet Acronyme Titre et/ou keywords coord/part partenaires Alias partenaires UPSa ANR EU Autres* Ciproage citrulline part Ecophen nutrition, phenylketonuria part Homan enteral nutrition part Nutrinet santé epidemiology part UREN, CRNH Idf *les projets compétitifs avec un partenaire industriel ne sont pas mentionnés pour raison de confidentialité

162 Partenariats nationaux (ANR, ARC ) Intitulé ACV BIO : Analyse du cycle de vie des produits biologiques. 8 ALIMINFO : Alimentation et Information. Politiques alimentaires et d'information 3 ALISIRS : ALImentation dans la cohorte SIRS francilienne. Les déterminants socio- 4 Bourse régionale DIM-ASTREA - Agrosciences, territoires, écologie, alimentation. 2 Bourse régionale DIM-ASTREA - Agrosciences, territoires, écologie, alimentation. 2 Financement pour l'organisation du colloque "Sécurité sanitaire des aliments et organisation 2 DIM DAM DOM : Dimensions Durables de l'alimentation Domestique. 2 ELFE : Groupe thématique Alimentationnutrition, métabolisme et croissance 4 EUROPHIL : Les philanthropes en Europe et la vulnérabilité sociale, FOODPOL : Food Policies. 1 GDRI : Crises et mutations dans les campagnes européennes 9 Génèse et transmission des normes alimentaires en France au Xxème siècle. 1 GESALIM : Travaux sur l'impact de Régimes Alimentaires. 1 GOUV CONSO : Gouverner les conduites de consommation : les cas des politiques de lutte 3 LACCAVE : Long term impacts and adaptations to climate change in viticulture and enology. 5 Les inégalités sociales de nutrition en France : Evolution des achats d'aliments et de 1 Market Power in Verticallly related markets 7 MEDIALOG : Construction d un outil de médiation dialogique Consommateurs 6 MPinVRM : Market Power in Vertically Related Market 7 OCAD : Offrir et Consommer une Alimentation Durable. 7 OQALI : Mise en place de l'observatoire de la Qualité de l'alimentation 2 PAP-CPER 2 SAFEMED : Régulation sanitaire de l'offre alimentaire, accès aux marchés et concurrence 5 SOMEAT : Sécurité sanitaire des viandes issues de l'agriculture biologique Nombre Nom et prénom d'institu du responsable Type de financemen Co-contractants séparés par des virgules (ALIAS and UPSa labs in biold lett) OUEDRAOGO ANR BIO Intelligence Service, Synabio, Casino, Triballat, La Vie Claire, Arouna Pronatura et BIOCOOP SOLER Louis- ANR UMR 1215 GAEL, Université de Paris 13, INSERM, AgroParis Tech Georges LHUISSIER Anne ANR INSERM, CNRS, Région Ile de France, Ministère de la Recherche CAILLAVET France DIM - Domaine GOJARD Séverine DIM X X HAMMOUDI Abdelhakim AFD - Agence X GOJARD Séverine ADEME CSO (Sciences-po, CNRS) (Appel à TICHIT Christine U593 INSERM Bordeaux, U558 INSERM Toulouse, FLAVIC UMR 1129 INRA/ENESAD Dijon, UMR 1280 PHAN INRA Univ. Nantes, U780 INSERM, U690 INSERM, UMR CRNH U557 INSERM/INRA-UREN, UMR INSERM U476/INRA 1260 LHUISSIER Anne ANR CMH (ENS Paris - EHESS - CNRS) ETILE Fabrice Métaprogra mme DID'IT- BRUEGEL Martin CNRS Universités de Gerone, Albacete, Münster, Louvain, Gand, Lisbonne, Lund CRH (EHESS-CNRS) LHUISSIER Anne Privé : CSU (EHESS-CNRS), Université Toulouse Le Mirail NESTLE SOLER Louis- ADEME UMR1260 NORT Nutrition, Obésité et Risques Thrombotiques Georges GOJARD Séverine ANR CSO(Sciences-po, CNRS), CERTOP (Université Toulouse, CNRS) GIRAUD-HERAUD Eric Métaprogra mme ACCAF UMR 1287 EGFV, UMR 951 Innovation, UMR 6554 COSTEL, UE 1117 UVV, UMR 1131 SVQV, UMR 759 LEPSE, USC 1320 GAIA, UMR 1334 AGAP, UMR 1221 LISAH, UE 1057 DV, UMR 1048 SADAPT, UMR 1219 Œnologie, UE 0999 Pech- ROUGE, UMR 1230 SYSTEM, UE 1086 EUB, UMR 1083 Sciences for Oeunology, UMR 729 MISTEA, UMR 1110 MOISA, US 1116 AGROCLIM CAILLAVET France Privé : X et NICHELE FERRERO CHAMBOLLE ANR Claire Franco/Alle POITEVIN de ANR ADIV, INRA/LERECO, Laboratoire Dynalang-SEMIO, INC, Ecole Vétérinaire FONTGUYON Guy, de Lyon, INTERBEV BAZOCHE Pascale GREMAQ, Université de Berlin e CHAMBOLLE SOLER Louis- ANR INRA, BIO Intelligence Service, Danone, GREMAQ, GENIAL, GAEL, Nestlé, Georges NLPMM, UREN SOLER Louis- DGS et ANSES Georges DGAL SOLER Louis- DRRT- UMR GENIAL, UR Méta@risk et UMR UREN Georges MENRT HAMMOUDI ANR DEIAGRA, IAV, INAT, UAL, ENSA Abdelhakim SOLER Louis- ANR INRA-QuaPA (coord), ONIRIS-LABERCA, INRA-TOXALIM/AXIOM, INRA- Georges, SANS TOXALIM/TCMX, ANSES-Laboratoire de Fougères, ANSES, INRA-MET@RISK, Pierre INRA-Economie Publique, INRA-GENIAL, INRA-URA, IFIP, ITAVI, IDELE 14 SYDERET : Conception et transfert de systèmes LEROY Pascal, MAP/CEMA INRA UMR Santé Végétale, Cemagref UMR ITAP, ENITA UR Egérie, INRA décisionnels pour une réduction des 5 SOLER Louis- GREF UMR EGFV, INRA Innovation, INRA UEV, IFV, Chambres d'agriculture n 33, TIME : Time trends in the meal context: an ETILE Fabrice, Métaprogramme empirical analysis of activities occurring during 1 PLESSZ Marie VenirAuMonde : Conditions sociales de la GOJARD Séverine ANR CURAPP (CNRS/Université Picardie), naissance, structures familiales et prime 4 et TICHIT CITERES (CNRS/Université Tours), VDQA : Vins de Qualité à teneur réduite en SEBILLOTTE ANR - PNRA INRA UE Pech Rouge Alcool. 1 clementina ANR Franco Allemande (université de Claire Chambolle ANR Düsseldorf) CBVC = Competition and Bargaining ANR "DESIRABLE"= DESigning the Insect Sylvaine Poret ANR (GENIAL, Ynsect, LEGS, IPV, CEA, NuMéa, URA 83, SAS, Cemagref, EASM) biorefinery to contribute to a more (48 mois) sustainable agrifood industry ANR SOMEAT (voir envoyé ce matin) Pierre Sans ANR SOFI = Socio-cultural determinants of feeding practices in infancy Partenariats européens Intitulé PETER : Promoting European Traceability Excellence & Research 7 CO-EXTRA : GM's and non-gm's supply chains: their co-existence and tracability. 53 AGFOODTRADE : New Issues in Agricultural, Food and Bioenergy Trade. 12 TEAMPEST : Theorical Developments and Empirical Measurement of the External Costs of Pesticides. 9 EUROCOD- NORFISH : Norvegian Fish in European Market. 1 PIGCAS : Pig Castration 8 EADGENE : European Animal Disease Génomique Network of Excellence for Animal 100 S. Gojard Nombre Intitulé du d'institu laboratoire INRA-Laboratoire Méthodologies INRA-Laboratoire Méthodologies INRA UMR Economie Laboratoire Aristote de la "School of Département of Economics and Laboratoire SPA - Agrocampus unité Génétique et Diversité ALISS Etablisseme Nom et prénom du responsable scientifique dans l'unité ou l'équipe nt de interne INRA GREEN Raul Versailles INRA SOLER Louis-Georges, GREEN Raul versailles INRA - Paris CHAMBOLLE Claire Université de Thessaloniq University of Life INRA Rennes INRA Jouyen-Josas GIRAUD-HERAUD Eric COMBRIS Pierre OUEDRAOGO Arouna OUEDRAOGO Arouna

163 4- Organization chart and selected publications of ALIAS laboratories

164 Selected Micalis Publications Novo M, Bigey F, Beyne E, Galeote V, Gavory F, Mallet S, Cambon B, Legras JL, Wincker P, Casaregola S, Dequin S. Eukaryote-to-eukaryote gene transfer events revealed by the genome sequence of the wine yeast Saccharomyces cerevisiae EC1118. Proc Natl Acad Sci U S A Sep 22;106(38): Poncet S, Soret M, Mervelet P, Deutscher J, Noirot P. Transcriptional activator YesS is stimulated by histidine-phosphorylated HPr of the Bacillus subtilis phosphotransferase system. J Biol Chem Oct 9;284(41): Barinov A, Loux V, Hammani A, Nicolas P, Langella P, Ehrlich D, Maguin E, van de Guchte M. Prediction of surface exposed proteins in Streptococcus pyogenes, with a potential application to other Gram-positive bacteria. Proteomics Jan;9(1): Brinster S, Lamberet G, Staels B, Trieu-Cuot P, Gruss A, Poyart C. Type II fatty acid synthesis is not a suitable antibiotic target for Grampositive pathogens. Nature Mar 5;458(7234):83-6. Daou N, Buisson C, Gohar M, Vidic J, Bierne H, Kallassy M, Lereclus D, Nielsen-LeRoux C. IlsA, a unique surface protein of Bacillus cereus required for iron acquisition from heme, hemoglobin and ferritin. PLoS Pathog Nov;5(11):e Dessein R, Gironella M, Vignal C, Peyrin-Biroulet L, Sokol H, Secher T, Lacas-Gervais S, Gratadoux JJ, Lafont F, Dagorn JC, Ryffel B, Akira S, Langella P, Nùñez G, Sirard JC, Iovanna J, Simonet M, Chamaillard M. Toll-like receptor 2 is critical for induction of Reg3 beta expression and intestinal clearance of Yersinia pseudotuberculosis. Gut Jun;58(6):771-6.

165 Sokol H, Seksik P, Furet JP, Firmesse O, Nion-Larmurier I, Beaugerie L, Cosnes J, Corthier G, Marteau P, Doré J. Low counts of Faecalibacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis Aug;15(8): Tran SL, Guillemet E, Ngo-Camus M, Clybouw C, Puhar A, Moris A, Gohar M, Lereclus D, Ramarao N. Haemolysin II is a Bacillus cereus virulence factor that induces apoptosis of macrophages. Cell Microbiol Aug 23. doi: /j x. Chapot-Chartier MP, Vinogradov E, Sadovskaya I, Andre G, Mistou MY, Trieu-Cuot P, Furlan S, Bidnenko E, Courtin P, Péchoux C, Hols P, Dufrêne YF, Kulakauskas S. Cell surface of Lactococcus lactis is covered by a protective polysaccharide pellicle. J Biol Chem Apr 2;285(14): Fernandez A, Lechardeur D, Derré-Bobillot A, Couvé E, Gaudu P, Gruss A. Two coregulated efflux transporters modulate intracellular heme and protoporphyrin IX availability in Streptococcus agalactiae. PLoS Pathog Apr 22;6(4):e Lechardeur D, Fernandez A, Robert B, Gaudu P, Trieu-Cuot P, Lamberet G, Gruss A. The 2-Cys peroxiredoxin alkyl hydroperoxide reductase c binds heme and participates in its intracellular availability in Streptococcus agalactiae. J Biol Chem May 21;285(21): Touzain F, Denamur E, Médigue C, Barbe V, El Karoui M, Petit MA. Small variable segments constitute a major type of diversity of bacterial genomes at the species level. Genome Biol. 2010;11(4):R45. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR, Li J, Xu J, Li S, Li D, Cao J, Wang B, Liang H, Zheng H, Xie Y, Tap J, Lepage P, Bertalan M, Batto JM, Hansen T, Le Paslier D, Linneberg A, Nielsen HB, Pelletier E, Renault P, Sicheritz-Ponten T, Turner K, Zhu H, Yu C, Li S, Jian M, Zhou Y, Li Y, Zhang X, Li S, Qin N, Yang H, Wang J, Brunak S, Doré J, Guarner F, Kristiansen K, Pedersen O, Parkhill J, Weissenbach J; MetaHIT Consortium, Bork P, Ehrlich SD, Wang J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature Mar 4;464(7285): Rabot S, Membrez M, Bruneau A, Gérard P, Harach T, Moser M, Raymond F, Mansourian R, Chou CJ. Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism. FASEB J Aug 19. Tasse L, Bercovici J, Pizzut-Serin S, Robe P, Tap J, Klopp C, Cantarel BL, Coutinho PM, Henrissat B, Leclerc M, Doré J, Monsan P, Remaud- Simeon M, Potocki-Veronese G. Functional metagenomics to mine the human gut microbiome for dietary fiber catabolic enzymes. Genome Res Nov;20(11): Mondot S, Kang S, Furet JP, Aguirre de Carcer D, McSweeney C, Morrison M, Marteau P, Doré J, Leclerc M. Highlighting new phylogenetic specificities of Crohn's disease microbiota. Inflamm Bowel Dis Aug 18. Jers C, Pedersen MM, Paspaliari DK, Schütz W, Johnsson C, Soufi B, Macek B, Jensen PR, Mijakovic I. Bacillus subtilis BY-kinase PtkA controls enzyme activity and localization of its protein substrates. Mol Microbiol Jul;77(2): Bernard E, Rolain T, Courtin P, Guillot A, Langella P, Hols P, Chapot-Chartier MP. Characterization of O-Acetylation of N-Acetylglucosamine: A NOVEL STRUCTURAL VARIATION OF BACTERIAL PEPTIDOGLYCAN. J Biol Chem Jul 8;286(27): Rul F, Ben-Yahia L, Chegdani F, Wrzosek L, Thomas S, Noordine ML, Gitton C, Cherbuy C, Langella P, Thomas M. Impact of the metabolic activity of Streptococcus thermophilus on the colon epithelium of gnotobiotic rats. J Biol Chem Mar 25;286(12): Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, de Vos WM, Brunak S, Doré J; MetaHIT Consortium, Antolín M, Artiguenave F, Blottiere HM, Almeida M, Brechot C, Cara C, Chervaux C, Cultrone A, Delorme C, Denariaz G, Dervyn R, Foerstner KU, Friss C, van de Guchte M, Guedon E, Haimet F, Huber W, van Hylckama-Vlieg J, Jamet A, Juste C, Kaci G, Knol J, Lakhdari O, Layec S, Le Roux K, Maguin E, Mérieux A, Melo Minardi R, M'rini C, Muller J, Oozeer R, Parkhill J, Renault P, Rescigno M, Sanchez N, Sunagawa S, Torrejon A, Turner K, Vandemeulebrouck G, Varela E, Winogradsky Y, Zeller G, Weissenbach J, Ehrlich SD, Bork P. Enterotypes of the human gut microbiome. Nature May 12;473(7346): Benjdia A, Martens EC, Gordon JI, Berteau O. Sulfatases and a radical AdoMet enzyme are key for mucosal glycan foraging and fitness of a prominent human gut Bacteroides. J Biol Chem jul 22;286(29): Gloux K, Berteau O, El Oumami H, Béguet F, Leclerc M, Doré J. A metagenomic β-glucuronidase uncovers a core adaptive function of the human intestinal microbiome. Proc Natl Acad Sci U S A Mar 15;108 Suppl 1: Mondot S, Barreau F, Al Nabhani Z, Dussaillant M, Le Roux K, Doré J, Leclerc M, Hugot JP, Lepage P. Altered gut microbiota composition in immune-impaired Nod2-/- mice. Gut Aug 25. Domínguez-Escobar J, Chastanet A, Crevenna AH, Fromion V, Wedlich-Söldner R, Carballido-López R. Processive movement of MreBassociated cell wall biosynthetic complexes in bacteria. Science Jul 8;333(6039): Epub 2011 Jun 2. PubMed PMID: Buescher JM, Liebermeister W, Jules M, Uhr M, Muntel J, Botella E, Hessling B, Kleijn RJ, Le Chat L, Lecointe F, Mäder U, Nicolas P, Piersma S, Rügheimer F, Becher D, Bessieres P, Bidnenko E, Denham EL, Dervyn E, Devine KM, Doherty G, Drulhe S, Felicori L, Fogg MJ, Goelzer A, Hansen A, Harwood CR, Hecker M, Hubner S, Hultschig C, Jarmer H, Klipp E, Leduc A, Lewis P, Molina F, Noirot P, Peres S, Pigeonneau N, Pohl S, Rasmussen S, Rinn B, Schaffer M, Schnidder J, Schwikowski B, Van Dijl JM, Veiga P, Walsh S, Wilkinson AJ, Stelling J, Aymerich S, Sauer U. Global network reorganization during dynamic adaptations of Bacillus subtilis metabolism. Science Mar 2;335(6072): Dubois T, Faegri K, Perchat S, Lemy C, Buisson C, Nielsen-LeRoux C, Gohar M, Jacques P, Ramarao N, Kolstø AB, Lereclus D. Necrotrophism is a quorum-sensing-regulated lifestyle in Bacillus thuringiensis. PLoS Pathog. 2012;8(4):e

166 Houry A, Gohar M, Deschamps J, Tischenko E, Aymerich S, Gruss A, Briandet R. Bacterial swimmers that infiltrate and take over the biofilm matrix. Proc Natl Acad Sci U S A Aug 7;109(32): Le Roy T, Llopis M, Lepage P, Bruneau A, Rabot S, Bevilacqua C, Martin P, Philippe C, Walker F, Bado A, Perlemuter G, Cassard-Doulcier AM, Gérard P. Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice. Gut Nov 29. [Epub ahead of print] PubMed PMID: Lechardeur D, Cesselin B, Liebl U, Vos MH, Fernandez A, Brun C, Gruss A, Gaudu P. Discovery of intracellular heme-binding protein HrtR, which controls heme efflux by the conserved HrtB-HrtA transporter in Lactococcus lactis. J Biol Chem Feb 10;287(7): Lepage P, Leclerc MC, Joossens M, Mondot S, Blottière HM, Raes J, Ehrlich D, Doré J. A metagenomic insight into our gut's microbiome. Gut Jan;62(1): Mondot S, Barreau F, Al Nabhani Z, Dussaillant M, Le Roux K, Doré J, Leclerc M, Hugot JP, Lepage P. Altered gut microbiota composition in immune-impaired Nod2(-/-) mice. Gut Apr;61(4): Pierre S, Guillot A, Benjdia A, Sandström C, Langella P, Berteau O. Thiostrepton tryptophan methyltransferase expands the chemistry of radical SAM enzymes. Nat Chem Biol Dec;8(12): GENIAL Selected GENIAL publications Aka J.-P., Courtois F., Louarme L., Nicolas J., Billaud C. (2013). Modelling the interactions between free phenols, L-ascorbic acid, apple polyphenoloxidase and oxygen during a thermal treatment. Food Chemistry 138, Ammari F., Jouan-Rimbaud Bouveresse D., Boughanmi N., Rutledge D.N. (2012). Study of the heat stability of sunflower oil enriched in natural antioxidants by different analytical techniques and front face fluorescence spectroscopy combined with Independent Components Analysis. Talanta 99, Benkhelifa H., Alvarez G, Flick D. (2008). Development of a Scraper-Rheometer for Food Applications: rheological calibration. Journal of Food Engineering 85, Bosc V., Ferrari I. et Michon C. (2008). Adhesion to solid surfaces of gels of iota-carrageenan alone or in mixture with casein. Colloids and Surfaces A : Physicochem. Eng. Aspects., 331 (1-2), 2-7. Camel V., Ouethrani M., Coudray C., Philippe C., Rabot S. (2012). Semi-automated solid-phase extraction method for studying the biodegradation of ochratoxin A by human intestinal microbiota. Journal of Chromatography B, ,

167 Chantoiseau E., Plana-Fattori A., Doursat C., Flick D. (2012). Coupling fluid flow, heat transfer and thermal denaturation-aggregation of beta-lactoglobulin using an Eulerian/Lagrangian approach. Journal of Food Engineering 113, Chow Y.-N., Louarme L., Bonazzi C., Nicolas J., Billaud C. (2011). Apple polyphenoloxidase inactivation during heating in the presence of ascorbic acid and chlorogenic acid. Food Chemistry 129 (3), Deterre S., Rega B., Delarue J., Decloux M., Lebrun M., Giampaoli P. (2012). Identification of key aroma compounds from bitter orange (Citrus aurantium L.) products: essential oil and macerate distillate extract. Flavour and Fragrance Journal, 27 (1), Devic E., Guyot S., Daudin J.D.,Bonazzi C. (2010). Effect of Temperature and Cultivar on Polyphenol Retention and Mass Transfer during Osmotic Dehydration of Apples. Journal of Agricultural and Food Chemistry 58 (1), Ducept F., De Broucker T., Soulié J.M., Trystram G.,Cuvelier G. (2012). Influence of the mixing process on surimi seafood paste properties and structure. Journal of Food Engineering 108, Durand M., Meyer H., Benzerara O., Baschnagel J., Vitrac O. (2010). Molecular dynamics simulations of the chain dynamics in monodisperse oligomer melts and of the oligomer tracer diffusion in an entangled polymer matrix. Journal of Chemical Physics,132(19). Espinosa L, Simoneaux R., Renard C, Biau N, Cuvelier G. (2012).The significance of structural properties for the development of innovative apple puree textures. LWT - Food Science and Technology 49, Fang, X., Domenek S., Ducruet V., Rand M., Vitrac O. (2013). Diffusion of Aromatic Solutes in Aliphatic Polymers above Glass Transition Temperature. Macromolecules. Fehaili S., Courel M., Rega B. et Giampaoli P. (2010). An instrumented oven for the monitoring of thermal reactions during the baking of sponge cake. Journal of Food Engineering 101 (3), Guinault A., Sollogoub C., Ducruet V., Domenek S. (2012). Impact of crystallinity of poly(lactide) on helium and oxygen barrier properties. European Polymer Journal 48(4), Jouan-Rimbaud Bouveresse D., Climaco Pinto R., Schmidtke L.M., Locquet N., Rutledge D.N. (2011). Identification of significant factors by an extension of ANOVA-PCA based on multiblock analysis Chemometrics and Intelligent Laboratory Systems 106, Sagne C., Fargues C., Broyart B., Lameloise M.-L., Decloux M. (2009). Modelling permeation of volatile organic molecules through reverse osmosis spiralwound membranes. Journal of Membrane Science 330(1-2), This H. (2009). Molecular Gastronomy, a Scientific Look at Cooking. Accounts of Chemical Research 42 (5), Vanin F., Lucas T. et Trystram G. (2009). Crust formation and its role during bread baking. Trends in Food Science and Technology 20 (8), Veinand B., Godefroy C., Adam C. et Delarue J. (2011). Highlight of important product characteristics for consumers. Comparison of three sensory descriptive methods performed by consumers. Food Quality and Preference 22 (5), GMPA

168 Selected GMPA publications Deleris, I.; Saint-Eve, A.; Dakowski, F.; Semon, E.; Le Quere, J. L.; Guillemin, H.; Souchon, I. 2011, The dynamics of aroma release during consumption of candies of different structures, and relationship with temporal perception. Food Chemistry 127, (4), Doyennette, M., C. de Loubens, I. Deleris, I. Souchon and I. C. Trelea. Mechanisms explaining the role of viscosity and post-deglutitive pharyngeal residue on in vivo aroma release: A combined experimental and modeling study. Food Chemistry, (2): p Dupuy, A., V. Athes, J. Schenk, U. Jenelten and I. Souchon. Experimental and theoretical considerations on breakthrough pressure in membrane-based solvent extraction: Focus on citrus essential oil/hydro-alcoholic solvent systems with low interfacial tension. Journal of Membrane Science, (1-2): p Irlinger, F. and J. Mounier, Microbial interactions in cheese: implications for cheese quality and safety. Current Opinion in Biotechnology, : p Forquin, M. P., A. Hebert, Roux A., Aubert J., Proux C., Heilier J.F., Landaud S., Junot C., Bonnarme P., Martin-Verstraete I., Global Regulation of the Response to Sulfur Availability in the Cheese-Related Bacterium Brevibacterium aurantiacum. Applied and Environmental Microbiology, (4): p Mansour, S., J. Bailly, J. Delettre, and P. Bonnarme, A proteomic and transcriptomic view of amino acids catabolism in the yeast Yarrowia lipolytica. Proteomics, (20): p Monnet, C., V. Loux, J.F. Gibrat, H.E. Spinnler, V. Barbe, B. Vacherie, F. Gavory, E. Gourbeyre, P. Siguier, M. Chandler, R. Elleuch, F. Irlinger, and T. Vallaeys, The Arthrobacter arilaitensis Re117 Genome Sequence Reveals its Genetic Adaptation to the Surface of Cheese. PLoS ONE, (11): p. e Passot, S.; Cenard, S.; Douania, I.; Trelea, I. C.; Fonseca, F., Critical water activity and amorphous state for optimal preservation of lyophilised lactic acid bacteria. Food Chemistry 132, (4), Perrot, N., I. C. Trelea, C. Baudrit, G. Trystram and P. Bourgine. Modelling and analysis of complex food systems: state of the art and new trends. Trends in Food Science and Technology, (6): p Picque D., Leclercq-Perlat M.N., Guillemin H., Perret B., Cattenoz T., Provost J.J., Corrieu G., Camembert-type cheese ripening dynamics are changed by the properties of wrapping films, Journal of Dairy Science, (2): p Picque, D., H. Guillemin, P.S. Mirade, R. Didienne, R. Lavigne, B. Perret, M.C. Montel, and G. Corrieu, Effect of sequential ventilation on cheese ripening and energy consumption in pilot ripening rooms. International Dairy Journal, : p Sicard, M., C. Baudrit, M. N. Leclerc-Perlat, P. H. Wuillemin and N. Perrot. Expert knowledge integration to model complex food processes. Application on the camembert cheese ripening process. Expert Systems with Applications, (9): p Streit, F.; Corrieu, G.; Beal, C. 2010, Effect of Centrifugation Conditions on the Cryotolerance of Lactobacillus bulgaricus CFL1. Food and Bioprocess Technology 3, (1), PNCA

169 Selected PNCA publications Fromentin C, Tomé D, Nau F, Flet L, Luengo C, Azzout-Marniche D, Sanders P, Fromentin G, Gaudichon C. Dietary Proteins Contribute Little to Glucose Production Even Under Optimal Gluconeogenic Conditions in Healthy Humans. Diabetes Dec 28. In press. Poupin N, Huneau JF, Mariotti F, Tome D, Bos C, Fouillet H. Isotopic and modeling investigation of long-term protein turnover in rat tissues. Am J Physiol Regul Integr Comp Physiol Nov 7. In press Schwarz J, Tomé D, Baars A, Hooiveld GJ, Müller M. Dietary protein affects gene expression and prevents lipid accumulation in the liver in mice. PLoS One. 2012;7(10):e Rasoamanana R, Chaumontet C, Nadkarni N, Tomé D, Fromentin G, Darcel N. Dietary fibers solubilized in water or an oil emulsion induce satiation through CCK-mediated vagal signaling in mice. J Nutr Nov;142(11): Miner-Williams W, Deglaire A, Benamouzig R, Fuller MF, Tomé D, Moughan PJ. Endogenous proteins in terminal ileal digesta of adult subjects fed a casein-based diet. Am J Clin Nutr Sep;96(3): Mimoun S, Andriamihaja M, Chaumontet C, Atanasiu C, Benamouzig R, Blouin JM, Tomé D, Bouillaud F, Blachier F. Detoxification of H(2)S by differentiated colonic epithelial cells: implication of the sulfide oxidizing unit and of the cell respiratory capacity. Antioxid Redox Signal Jul 1;17(1):1-10. Poupin N, Bos C, Mariotti F, Huneau JF, Tomé D, Fouillet H. The nature of the dietary protein impacts the tissue-to-diet 15N discrimination factors in laboratory rats. PLoS One. 2011;6(11):e Guelzim N, Huneau JF, Mathé V, Quignard-Boulangé A, Martin PG, Tomé D, Hermier D. Consequences of PPAR(α) Invalidation on Glutathione Synthesis: Interactions with Dietary Fatty Acids. PPAR Res. 2011;2011: Malet A, Bournaud E, Lan A, Mikogami T, Tomé D, Blais A. Bovine lactoferrin improves bone status of ovariectomized mice via immune function modulation. Bone May 1;48(5): Chotechuang N, Azzout-Marniche D, Bos C, Chaumontet C, Gaudichon C, Tomé D. Down-regulation of the ubiquitin-proteasome proteolysis system by amino acids and insulin involves the adenosine monophosphate-activated protein kinase and mammalian target of rapamycin pathways in rat hepatocytes. Amino Acids Jul;41(2): Chevalier L, Bos C, Azzout-Marniche D, Dardevet D, Tomé D, Gaudichon C. Dietary protein regulates hepatic constitutive protein anabolism in rats in a dose-dependent manner and independently of energy nutrient composition. Am J Physiol Regul Integr Comp Physiol Dec;299(6):R Andriamihaja M, Davila AM, Eklou-Lawson M, Petit N, Delpal S, Allek F, Blais A, Delteil C, Tomé D, Blachier F. Colon luminal content and epithelial cell morphology are markedly modified in rats fed with a high-protein diet. Am J Physiol Gastrointest Liver Physiol Nov;299(5):G Potier M, Fromentin G, Lesdema A, Benamouzig R, Tomé D, Marsset-Baglieri A. The satiety effect of disguised liquid preloads administered acutely and differing only in their nutrient content tended to be weaker for lipids but did not differ between proteins and carbohydrates in human subjects. Br J Nutr Nov;104(9): Schwarz J, Burguet J, Rampin O, Fromentin G, Andrey P, Tomé D, Maurin Y, Darcel N. Three-dimensional macronutrient-associated Fos expression patterns in the mouse brainstem. PLoS One Feb 1;5(2):e8974. Fouillet H, Juillet B, Gaudichon C, Mariotti F, Tomé D, Bos C. Absorption kinetics are a key factor regulating postprandial protein metabolism in response to qualitative and quantitative variations in protein intake. Am J Physiol Regul Integr Comp Physiol Dec;297(6):R Chotechuang N, Azzout-Marniche D, Bos C, Chaumontet C, Gausserès N, Steiler T, Gaudichon C, Tomé D. mtor, AMPK, and GCN2 coordinate the adaptation of hepatic energy metabolic pathways in response to protein intake in the rat. Am J Physiol Endocrinol Metab Dec;297(6):E Magné J, Huneau JF, Delemasure S, Rochette L, Tomé D, Mariotti F. Whole-body basal nitric oxide production is impaired in postprandial endothelial dysfunction in healthy rats. Nitric Oxide Aug;21(1): Westerterp-Plantenga MS, Nieuwenhuizen A, Tomé D, Soenen S, Westerterp KR. Dietary protein, weight loss, and weight maintenance. Annu Rev Nutr. 2009;29: Nefti W, Chaumontet C, Fromentin G, Tomé D, Darcel N. A high-fat diet attenuates the central response to within-meal satiation signals and modifies the receptor expression of vagal afferents in mice. Am J Physiol Regul Integr Comp Physiol Jun;296(6):R Andriamihaja M, Chaumontet C, Tome D, Blachier F. Butyrate metabolism in human colon carcinoma cells: implications concerning its growth-inhibitory effect. J Cell Physiol Jan;218(1):58-65.

170 ALISS Articles in peer-reviewed journals indexed by international databases Selected ALISS publications Allain, M.L.; Chambolle, C., Anti-competitive effects of resale-below-cost laws. International Journal of Industrial Organization, 29 (43): Allais, O.; Bertail, P.; Nichèle, V., The effects of a fat tax on French households' purchases: a nutritional approach. American Journal of Agricultural Economics, 92 (1): Blanchard, P.; Huiban, J.P.; Sevestre, P.; Musolesi, A., Where there is a will, there is a way? Assessing the impact of obstacles to innovation Industrial and Corporate Change, First on line. Bougherara, D.; Combris, P., Eco-labelled food products: what are consumers paying for? European Review of Agricultural Economics, 36 (3): Chambolle, C.; Poret, S., When Fair trade contracts for some are profitable for others. European Review of Agricultural Economics, Forthcoming. Clarck, A.E.; Etile, F., Happy house: spousal weight and individual well-being. Journal of Health Economics, 30 (5): Combris, P.; Bazoche, P.; Giraud-Héraud, E.; Issanchou, S., Food choices: what do we learn from combining sensory and economic experiments? Food Quality and Preference, 20 (8): Dallongeville, J.; Dauchet, L.; De Mouzon, O.; Requillart, V.; Soler, L.G., Increasing fruit and vegetable consumption: a cost-effectiveness analysis of public policies. European Journal of Public Health, 21 (1): Darmon, N.; Caillavet, F.; Joly, C.; Maillot, M.; Drewnowski, A., Low-cost foods: how do they compare with their brand name equivalents? A french study. Public Health Nutrition, 12 (6): de Mouzon, R.; Requillart, V.; Soler, L.G.; Dallongeville, J., Are fruit and vegetable voucher policies cost-effective? European Review of Agricultural Economics, First online: -. Duvaleix-Treguer, S.; Hammoudi, A.; Rouached, L.; Soler, L.G., Firms' responses to nutritional policies. European Review of Agricultural Economics. Etile, F.; Jones, A.M., Schooling and smoking among the baby boomers - An evaluation of the impact of educational expansion in France. Journal of Health Economics, 30 (4): Ginon, E.; Lohéac, Y.; Martin, C.; Combris, P.; Issanchou, S., Effect of fibre information on consumer willingness to pay for French baguettes. Food Quality and Preference, 20 (5):

171 Giraud-Héraud, E.; Hammoudi, A.; Hoffmann, R.; Soler, L.G., Joint private safety standards and vertical relationships in food retailing. Journal of Economics and Management Strategy, 21 (1): Goglia, R.; Spiteri, M.; Menard, C.; Dumas, C.; Combris, P.; Labarbe, B.; Soler, L.G.; Volatier, J.L., Nutritional quality and labelling of ready-to-eat breakfast cereals: the contribution of the French observatory of food quality. European Journal of Clinical Nutrition, 64 (S3): S20-S25. Régnier, F.; Masullo, A., Obésité, goûts et consommation. Intégration des normes d'alimentation et appartenance sociale. Revue Française de Sociologie, 50 (4): Teyssier, S., Inequity and risk aversion in sequential public good games. Public Choice, 151 (1-2): Books Bruegel, M., A Cultural history of food in the age of empire ( ). Berg Publishers, Oxford ( GBR ). Gojard, S., Le métier de mère. Paris (FRA): Editions la Dispute (Corps, Santé, Société). Tichit, C.; Robette, N., Understanding the family composition of households in the Demographic and Health Surveys. Paris (FRA): Ceped - Centre Population et Développement (Les Clefs pour). Met@Risk Selected Met@Risk publications Albert I., E. Espié, H. de Valk, J.-B. Denis, A Bayesian evidence synthesis for estimating campylobacteriosis prevalence, Risk Analysis, 31(7): Bertail, P., S. Clémençon & J. Tressou, Statistical analysis of a dynamic model for food contaminant exposure with applications to dietary methylmercury contamination. Journal of Biological Dynamics, Volume 4, Issue 2, March 2010, pages Blanchemanche S., Marette S., Roosen J., Verger P., Rational choice regulation and risk communication. Uncertainty transfer from risk assessment to public, Health Risk & Society, Vol. 12, No. 3, pp Buche P., Couvert O., Dibie-Barthélemy J., Hignette G, Mettler E., Soler L., Flexible querying of Web data to simulate bacterial growth in food. International Journal of Food Microbiology, 28(4), (IF: 3.143) Crépet, A. & J. Tressou, Bayesian nonparametric model for clustering individual co-exposure to pesticides found in the French diet. Bayesian Analysis 6(1), Crépet, A., H. Harari-Kermadec & J. Tressou, Using Empirical Likelihood to Combine Data: Application to Food Risk Assessment. Biometrics 65(1), Dhanjal C., Blanchemanche S., Clémençon S., Rona-Tas A., Rossi F., Dissemination of Heath Information within Social Networks, In : Vedres B. (ed.), The Unexpected Link: Using Network Science to Tackle Social Problems, Oxford University Press Marette, S., Roosen, J., Blanchemanche, S., Feinblatt-Mélèze E., Functional Food, Uncertainty and Consumers' Choices: A Lab Experiment with Enriched Yogurts for Lowering Cholesterol, Food Policy, Volume 35, Issue 5, October 2010, Pages Marette S., Roosen J., Blanchemanche S., The Combination of lab and field experiments for benefit-cost analysis, Journal of Benefit - Cost Analysis, (2011), vol. 2, n 3. pp Marquez A, Paris A, Roussel B, Perez-Carreon J, Le Berre V, François J-M, Villa-Trevino S, Guéraud F. Proteasome activity deregulation in LEC rat hepatitis: following the insights of transcriptomic analysis. Omics 11(2007): Roosen J., Marette S., Blanchemanche S., Verger P., Does Health Information Matter for Modifying Consumption? A Field Experiment Measuring the Impact of Risk Information on Fish Consumption, Review of Agricultural Economics, vol. 31, n 1, pp

172 Roosen J., Bieberstein A., Marette S., Blanchemanche S., Vandermoere F., The effect of information choice and discussion on consumers Willingness-to-Pay for Nanotechnologies in Food, Journal of Agricutural and Resource Economics, 36, 2, Vandermoere, F., Blanchemanche, S., Bieberstein, A., Marette, S., & Roosen, J., The morality of attitudes toward nanotechnology: About God, techno-scientific progress, and interfering with nature, Journal of Nanoparticle Research, 12 (2). pp Vandermoere, F., Blanchemanche, S., Bieberstein, A., Marette, S., & Roosen, J., The public understanding of nanotechnology in the food domain: the hidden role of views on science, technology and nature, Public Understanding of Science, 20, Selected GRCTH Nutrition and Metabolism team publications Bahri Hicheri S, Naima Zerrouk N, Aussel C; Moinard, Crenn P, Curis E, Chaumeil JC, Cynober L, Sfar S. Citrulline: from metabolism to therapeutic use. Nutrition Sep 27. doi:pii: S (12) /j.nut [Epub ahead of print] Hanachi M, Melchior JC, Crenn P. Hypertransaminasemia in severely malnourished adult anorexia nervosa patients: risk factors and evolution under enteral nutrition. Clin Nutr Aug 31. doi:pii: S (12) /j.clnu [Epub ahead of print] Senesse P, Bachmann P, Bensadoun R.J, Besnard I, Bourdel-Marchasson I, Bouteloup C, Crenn P, Goldwasser F, Guérin O, Latino-Martel P, Meuric J, May-Levin F, Michallet M, Vasson M.P, Hébuterne X. SFNEP oncology nutrition guidelines. Nut Clin Metab 2012; 26: Crenn P, Bouteloup C, Michallet M, Senesse P. SFNEP oncology nutrition guidelines: Place of artificial nutrition in the management of cancer patients. Nut Clin Metab 2012; 26: Crenn P. SFNEP oncology nutrition guidelines: Appetite stimulants and anti-cachexia treatment. Nut Clin Metab 2012; 26: Melchior JC, Preaud E, Heurtebis J, Brami M, Duru G, Fontaine E, Hebuterne F, Lukacs B, Zazzo JF, Panis P, Nitenberg G. Clinical and economic impact of malnutrition per se on the postoperative course of colorectal cancer patients. Clin Nutr ;31: Mattar L, Pichard C, Godart N, Melchior JC. Can birth weight predict later body composition in anorexia nervosa? Eur J Clin Nutr. 2012;66:964-7 Hanachi M, Le Floch M, Crenn P. Clinical management of a patient with enterostoma. Nut Clin Metab 2012; 26: 82-8 Menard S, Lebreton C, Schuman S, Matysiak T, Dugave C, Bouhnik Y, Malamut G, Cellier C, Allez M, Crenn P, Schutzke J, Cerf Benssussan N. Paracellular and transcellular intestinal permeability in active celiac disease. Am J Pathol 2012; 180: Crenn P, Hanachi M, Neveux N, Cynober L. Circulating citrulline levels: a biomarker for intestinal functionality assessment. Ann Biol Clin. 2011;69: Crenn P. Recognizing and treating malnutrition in ambulatory practice. Nut Clin Metab 2011; 25: Mattar L, Godart N, Melchior JC, Falissard B, Kolta S, Ringuenet D, Vindreau C, Nordon C, Blanchet C, Pichard C. Underweight patients with anorexia nervosa: comparison of bioelectrical impedance analysis using five equations to dual X-ray absorptiometry. Clin Nutr. 2011;30: Mattar L, Godart N, Melchior JC, Pichard C. Anorexia nervosa and nutritional assessment: contribution of body composition measurements. Nutr Res Rev ; 8:1-7 Crenn P, Annane D. Intestinal functionality measurement in intensive care: Dosage of circulating citrulline. Reanimation 2010; 19: Crenn P, Cynober L. Effect of intestinal resections on arginine metabolism: practical implications for nutrition support. Curr Opin Clin Nutr Metab Care. 2010;13:65-9 Leibowitch J, Mathez D, de Truchis P, Perronne C, Melchior JC. Short cycles of antiretroviral drugs provide intermittent yet effective therapy: a pilot study in 48 patients with chronic HIV infection. FASEB J. 2010;24: Aslangul E, Assoumou L, Bittar R, Valantin MA, Kalmykova O, Peytavin G, Fiévet MH, Boccara F, Bonnefont-Rousselot D, Melchior JC, Giral P, Costagliola D. Rosuvastatin versus pravastatin in dyslipidemic HIV-1-infected patients receiving protease inhibitors: a randomized trial. AIDS. 2010;24:77-83 Melchior JC, Corcos M. Parenteral nutrition and anorexia nervosa: is it useful, is it ethical? J Adolesc Health. 2009;44:410-1 Crenn P, De Truchis P, Neveux N, Galpérine T, Cynober L, Melchior JC. Plasma citrulline is a biomarker of enterocyte mass and parenteral nutrition indication in HIV-infected patients. Am J Clin Nutr 2009; 90: Crenn P. The right to nutrition: A human right to promote and defend. Nut Clin Metab 2009; 23:

173 5- Presentation of ALIAS associated (not full partners) laboratories ALIAS associated partner n 1: Nutritional Epidemiology Research Unit (UREN) UREN: U1125 Inra / U557 Inserm / Cnam/ Paris 13 University Director: Serge Hercberg, MD, PhD; Pr of Nutrition University P13/Hôpital Avicenne - Objectives: 1) to gain a better, more comprehensive understanding of the nutrition-health relationships by identifying nutrition-related risk or protective factors involved in the etiology of various health outcomes, in particular chronic diseases (cancer, CVD, diabetes, obesity,, important bodily processes (aging, cognition, fertility,...), and the quality of life. 2) to shed light on the underlying mechanisms (biomarkers, intermediate endpoints,...) 3) to achieve a better understanding of the determinants of dietary behaviours and nutritional status (eg., social, economic, psychological, cultural, sensory, cognitive factors, ) - Structuration. Four complementary axes: - elaboration of methods in nutritional epidemiology (leader: Emmanuelle Kesse, CR1- INRA) - nutrition-chronic disease relationships (leader: Dr. Leopold Fezeu, MCF-CE UParis 13/INRA) - nutrition-physiopathological function relationships (leader: Emmanuelle Kesse, CR1- INRA) - determinants of dietary behaviours and nutritional status (leader: Sandrine Péneau, MCF UParis 13) These 4 axes take advantage of shared resources, such as databases associated with our cohorts, also computing facilities (computer server security system), food composition tables, biobank data, and many others. 23 tenured research scientists and university professors, which corresponds to 13 full-time equivalents; 3 post-doctoral fellows; 10 doctoral students; 14 technical and administrative staff affiliated with INSERM, INRA, University of Paris 13 and CNAM; 26 staff members (including dietitians, statisticians, and others) with fixed-term contracts. - Ressources (academic projects on-going) 2 Projects funded by the French National Research Agency (ANR); 2 funded by the French National Institute of Cancer; 3 funded by National Clinical research programmes; 2 European projects and 3 other collaborative academic projects - Production/appeal During the period , our scientific production has led to more than 370 publications in international peer-reviewed journals and more than 180 conference presentations. ALIAS associated partner n 2: GIS CRNH-IdF Created in 2003, the Human Nutrition Research Centre of Paris Ile de France (CRNH-IdF) gathers Hospitals, Universities, and Research Institutes in a shared scientific objective focusing human dietary behavior. This main topic includes the consequences of behavior on health (hormonal regulation, cardiovascular diseases, cancer, obesity, hypertension, diabetes, risk factors and metabolic and digestive diseases), and also the determining factors of behavior like food economy, socio-cultural background, structure of the meal and dietary typography. The CRNH-IdF is also involved in formation, social marketing, and evaluation of population nutritional status and nutritional education The CRNH-IdF combines complementary approaches including clinical and experimental investigations, epidemiology, physiology, genetics, economics, sociology and education sciences. The CRNH-IdF operates several large cohorts, including Suvimax, Sufolom3 and Nutrinet-Sante.

174 The CRNH-IdF is a GIS (groupement d interet scientifique) which includes nearly 200 permanent employees (PhD, MD, engineers, technicians and administrative staff), in 12 different units depending on 8 different administrations (see p2): 5 research units : UMR Inserm U557 /U1125 Inra/Cnam/Paris 13 (Pr S. Hercberg), UMR Inserm U872 team 7/UPMC Paris 6 (Pr K. Clément), UR Inra 1303 ALISS (Dr LG. Soler), USC 914 Inra/Agroparistech (Pr D. Tomé), EA 3412 Paris 13 (Pr JF. D'Ivernois); 1 Surveillance Unit in nutritional epidemiology :USEN InVS/Cnam/Paris 13 (S. Hercberg); 4 Clinical Departments - Endocrinology- Diabetology- Nutrition, Jean Verdier Hospital, AP-HP Bondy (Pr P. Valensi); dedicated in CRNH to cardiovascular risk factors (insulin resistance, HTA, etc) - Endocrinology, Avicenne Hospital in Bobigny (Pr G. Reach); dedicated in CRNH to patient compliance - Gastro-Entero-hepatology, Avicenne Hospital (Pr R. Benamouzig) ; dedicated in CRNH to digestive tract and hepathology - Nutrition, La Pitié-Salpétrière Hospital, in Paris (Pr A. Basdevant) ; dedicated in CRNH to obesity and adipose tissue - 2 specific human investigation platforms: - the Research Centre on Volunteers (CRV) in Avicenne (Pr R. Benamouzig), mainly dedicated to digestive functions & satiety - the Unit for ambulatory exploration and genomic exploration in La Pitié-Salpétrière (Pr JM. Oppert) mainly dedicated to obesity and adipose tissue phenotyping and genotyping. Several CRNH-IdF research teams (UMR Inserm U557 /U1125 Inra/Cnam/Paris 13, UR Inra 1303 ALISS, USC 914 Inra/Agroparistech) are involved in ALIAS, offering a high expertise in translational research. The CRNH-IdF will join ALIAS as an associated partner to offer its wide range of expertise and capacities for clinical investigations in nutrition. Moreover, the CRNH-IdF plays a significant role in the infrastructure project NUTRIPOLE, as leader of 4 WP. This project tends to group the 4 French CRNH in a common structure. If this project is accepted, the new structure will group on a national basis more than 400 scientists, 7-9 hospitals, 6 clinical investigation platforms, and associated omics. The 3 major scientific objective of NUTRIPOLE are: (i) the homogenization of human phenotyping investigations in all the centers for technics, methods, protocols, equipment, quality and monitoring concerns to build a high expertise multi-center group; (ii) the significant increase of the number of patients and/or healthy volunteers recruited in nutritional clinical investigations (within a single protocol and methodology) to open the way to large cohort phenotyping; (iii) to build a one-stop shop access to clinical research in nutrition for academia, industry and government agencies. ALIAS associated partner n 3: IHU ICAN (Pr Arnaud Basdevant, coord) and UMR872 INSERM UPMC (Pr. K. Clément) Hospitalo-Universitary Institute ICAN is hosted by the largest European hospital and run by Université Pierre-et-Marie-Curie the first ranked French university with leaders in international medical and scientific publications, and most particularly in translational research. The Pitié-Salpêtrière university hospital is a reference centre for medical and surgical care, clinical research and training in CMD. The clinical activity in cardio metabolism represents approx 22,000 hospitalisations and over consultations per year. Clinical recruitment is notable in terms of number and diversity of clinical disorders (from monogenic to common forms of the disease), bioresources and biological/imaging

175 investigations. Medical and paramedical staff consists of 800 professionals. Physicians and researchers at ICAN come together to combine advances in high throughput technologies (genomics, metagenomics, expression of genes, epigenetics, peptides, lipids and metabolites in tissues and body fluids), preclinical models (cellular, rodent, humanized mammals) and the investigation of tissue alteration (using cellular and molecular approaches and imaging) with advances in systems biology to provide a coherent platform for data integration and analysis. Within ICAN, several teams will be working on these projects including clinicians involved in patients recruitment and follow-up and research team such the INSERM/UPMC UMR 872 Nutriomic team working in the pathophysiology of obesity and related phenotypes. The objective is the identification of new biophenotypes, predictors, and shared pathways in Cardio Metabolic Diseases that could be targeted with new treatments. Major ambitions will the achievement of translational research to foster predictive technologies and new pathophysiological concepts into prevention and medical, interventional and surgical treatments. Within ICAN, clinical partners and investigators at the Human Nutrition Research Center (CRNH Ile de France) are key leaders in developing clinical investigation programs in the nutrition field. In this context ICAN partners will pursue and reinforce their strong collaboration with the labex ALIAS at INRA related to the relationships between food patterns, intestine function and cardiometabolic tissue alterations. Indeed, ALIAS includes a broad range of expertise covering the socio-economic aspects of food consumption, technology and food security and the impact of modulation of nutrition and eating behavior on health through the digestive and metabolic processes. The reinforcement of expertise within the labex ALIAS and deep links with ICAN partners will be essential since ICAN researchers will incorporate these environmental and biological dimensions into their translational approaches in patients suffering of cardiometabolic diseases. This includes diagnostic and therapeutic decisions which will be developed in the future. The privileged links between ICAN and ALIAS structure will contribute to offer a unique setting for academic and private sectors (food companies, pharmas inc. SMEs) whose supporters are already numerous in the cardiometabolic field. Main EU programs: EU consortia DIOGENES (6PCRD), HEPADIP (6PCRD), ADAPT (7PCRD), FLIP (7PCRD), HOPE (7PCRD), ALPHA (DG SANCO) Main ANR programs: ANR Rioma ( ) - Adipose tissue inflammation in CMD; ANR Adipotox ( ) - Pollutants and consequence on inflammatory processes; ANR MicroObes ( ) - Gut Microbiota in obesity and weight loss (coord: J. Doré, Micalis, coordinator unit of ALIAS); ANR Alia ( ) - Study the contribution of intestine in metabolic disease ; ANR ELIANE (PNRA ) - Environmental Links to physical Activity, Nutrition and health, a multidisciplinary project on spatio-social factors associated with individual lifestyle patterns in French adults and children 5 selected publications : Hooton H,, Clément K. PLoS One. 2012;7(7):e IF 4,1 Dalmas E, Clément K, Guerre-Millo M. Trends Immunol Jul;32(7): IF 9,5 S Gandotra, C Le Dour, W Bottomley, et al. N Eng J Med 2010, 364:740-8 IF 47 Ratziu V, Charlotte F, Bernhardt C, Giral P, et al. l. Hepatology 2010;51: IF 10.8 Achard C, Courtillot C, Lahuna O, et al. N Engl J Med 2009;361: IF 47 Furet JP, Kong LC, et al. Diabetes 2010, 59(12): IF 8.5 ALIAS associated partner n 4 : Microorganisms, biomolécules and intestinal physiopathologie (Director : Pr. Germain Trugnan) Affiliation (s) : UPMC/INSERM/CNRS/ENS Nom du responsable : Germain Trugnan

176 Adresse : UPMC ; ERL INSERM U 1057/UMR , rue Chaligny PARIS germain.trugnan@upmc.fr La thématique centrale de l équipe se concentre sur les modalités et les conséquences du dialogue entre microorganismes et cellules épithéliales intestinales humaines. Nous développons une démarche intégrative et translationnelle allant de la biologie fondamentale à la clinique humaine. Nous disposons pour cela d un large éventail d expertises reconnues que nous mettons au service d un projet resserré : biologie des cellules épithéliales digestives, imagerie cellulaire, lipidomique et biophysique des membranes, protéomique, physiopathologie digestive, microbiologie, virologie cellulaire et moléculaire, gastroentérologie clinique. Deux aspects particuliers de ce dialogue ont été choisis pour leurs intérêts fondamentaux et leurs retombées cliniques potentielles. Nous nous intéressons d une part à des microorganismes non pathogènes, les bactéries du microbiote intestinal, aux mécanismes de leur dialogue avec les cellules épithéliales intestinales et aux conséquences d une dysbiose dans le contexte des maladies inflammatoires chroniques de l intestin (MICI). Nous nous intéressons d autre part à des microorganismes pathogènes, les rotavirus, au rôle joué par l épithélium intestinal dans leur assemblage et leur propagation et surtout aux conséquences de ces connaissances pour le développement de stratégies thérapeutiques antivirales innovantes. Effectif de chercheurs (EPST), enseignants-chercheurs (H-U, U) : 1 chercheur et 10 enseignantschercheurs Five selected publications : Duboc H, Rajca S, Rainteau D, Benarous D, Maubert MA, Quervain E, Thomas G, Barbu V, Humbert L, Despras G, Bridonneau C, Dumetz F, Grill JP, Masliah J, Beaugerie L, Cosnes J, Chazouillères O, Poupon R, Wolf C, Mallet JM, Langella P, Trugnan G, Sokol H, Seksik P. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut Sep 19. [Epub ahead of print] This is a Micalis-U1057 co-publication Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology May;140(6): Usefulness of co-treatment with immunomodulators in patients with inflammatory bowel disease treated with scheduled infliximab maintenance therapy. Sokol H, Seksik P, Carrat F, Nion-Larmurier I, Vienne A, Beaugerie L, Cosnes J. Gut Oct;59(10): Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Beaugerie L, Brousse N, Bouvier AM, Colombel JF, Lémann M, Cosnes J, Hébuterne X, Cortot A, Bouhnik Y, Gendre JP, Simon T, Maynadié M, Hermine O, Faivre J, Carrat F; CESAME Study Group. Lancet Nov 7;374(9701): Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez- Humarán LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottière HM, Doré J, Marteau P, Seksik P, Langella P. Proc Natl Acad Sci U S A Oct 28;105(43): This is a Micalis-U1057 co-publication

177 6- Comments received by ANR and Idex in previous calls / pre-selection phase Avis ANR février 2012:

178 FCS, le 8/12/2012 : La proposition s appuie sur un pôle déjà crée en Pour ce genre d initiative, un des critères importants pour l Idex est le caractère structurant du projet. Hors dans la version actuelle cet aspect ne semble pas satisfaisant, dans la mesure où les seuls partenaires de l UPSa impliqués sont l INRA et AgroParis-Tech. Le projet doit considérer des ouvertures possibles et la création au sein de l Idex de passerelles avec d autres partenaires. Par ailleurs, et comme il a été précisé dans le message de cadrage général envoyé le 03/12/2012, il faudra clairement identifier les objectifs et les résultats attendus. Préciser également, en fonction de ces objectifs, comment les équipes vont s organiser. Aussi, dans un sujet avec un intérêt sociétal clair, il semble important de mentionner si des partenaires industriels sont impliqués, quel rôle ils joueront, ainsi que la dimension à l international du projet.

179 IDEX Paris-Saclay APPEL A PROJET RECHERCHE IDEX 2013 Titre du Projet : Biotechnologies et Chimie bio-sourcée et bio-inspirée Type de projet : réseau de recherche interdisciplinaire Responsable du projet : Nom : Pernodet Prénom : Jean-Luc Fonction : Chercheur (DR2 CNRS) Etablissement/laboratoire : Univ. Paris-Sud/CNRS UMR8621 Institut de Génétique et Microbiologie Courriel : jean-luc.pernodet@igmors.u-psud.fr Tél : Interdisciplinary network: Biotechnologies, Bio-based and Bio-inspired Chemistry Project Summary This initiative aims to strengthen and structure the research community within the perimeter of the Paris-Saclay campus to develop interdisciplinary projects in the field of biotechnology, bio-based and bio-inspired chemistry. This community, which comprises about 700 persons, could respond to major challenges in the field of environment, energy, food and health through three main themes: 1) the exploration of microbial and plant metabolisms and their understanding to develop novel biological systems or bio-inspired chemical systems; 2) the utilization of these systems for health, food and industry, including the production of synthons, of commodities for the industry, of bio-fuels and bio-energy; 3) the valorization of biomass, industrial byproducts and CO 2, contributing to a circular economy of carbon. The amount of the support requested is 893 k. This funding will be used to supplement other institutional funding and provide leverage to structure the community and foster interdisciplinary collaborations between research groups. A steering committee, associating academic scientists and representatives from industry, will be in charge of this network. AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 1

180 Context and participants Biotechnology and chemistry can contribute answers to several of the major issues highlighted by the Idex project group, particularly in the fields of environment, energy, food and health. Within the Paris-Saclay perimeter, many teams are conducting research related to these issues. At the request of the Idex project group, a working group of fifteen people (biologists and chemists from University Paris-Sud, University Versailles-Saint-Quentin, CNRS, INRA, CEA, Ecole Centrale Paris, Agro- Paris-Tech...) was set up to make proposals for structuring the community of biologist and chemists. The working group sent a questionnaire to teams within the Paris-Saclay perimeter. The analysis of the answers (more than 80 teams responded) identified three themes that have the potential to structure the community: 1) the exploration of microbial and plant metabolisms and their understanding to develop novel biological systems or bio-inspired chemical systems; 2) the utilization of these systems for health, food and industry, including the production of synthons, of commodities for the industry, of bio-fuels and bio-energy; 3) the valorization of biomass, industrial byproducts and CO 2, contributing to a circular economy of carbon. About seventy teams, representing more than 700 persons, biologists and chemists, but also biophysicists and bioinformaticians, have already declared their interest for this network and these three themes. The diversity of the expertise of these teams covers a wide spectrum and goes from basic research to applied approaches and development. Thus, the projects will benefit from these complementary skills. Different teams, involved in various stages, could cover the entire project. It will be necessary to include in these projects economists and sociologists, essential in this type of work to estimate the impact of the development of new production processes. It should be noted that these projects will naturally lead to methodological developments (e.g. in genetics, chemistry...) that will find a broader application area. Our objective is to build a network for interdisciplinary scientific animation within Paris-Saclay, in order to structure and strengthen the research community. This network should continue its activities and evolve also beyond the end of the project in 2016, while maintaining a flexible structure. Some research units located in Evry, which were not involved in the earlier phases of elaboration of this project (e.g. the Institute of Systems & Synthetic Biology; will be able to join the program given the associated partner-status of the Evry University. Our network should also promote interactions with French industrial and pre-industrial platforms (see below). AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 2

181 Themes covered by the project. Theme 1. Exploration of microbial and plant metabolisms and their understanding to develop novel biological systems or bio-inspired chemical systems. Several teams of microbiologists and plant biologists study in collaboration with chemists and/or biophysicists the metabolisms of microorganisms and plants, remarkable for their great diversity. The system biology approaches, implemented by some teams, combine the study of metabolism and its regulation with partial or complete modeling of the systems studied; predictions resulting from this modeling are then used to propose rational rather than empirical modifications of these systems for a specific purpose. These novel metabolic engineering strategies will contribute to the development of synthetic biology and may lead to new biological systems with improved or novel biosynthetic capabilities. The understanding of metabolic reactions at the molecular level is a source of inspiration for chemists attempting, for example to reproduce the activity of enzymes using systems obtained by chemical synthesis. This approach, complementary to biosynthetic approaches, can lead to the production of the same compounds by new chemical systems less expensive and easier to handle than the corresponding biological systems. Thirty-five teams (about 400 persons, including about 260 permanent staff members) are interested in this theme (a team can be interested by more than one theme). Theme 2. Utilization of these systems for health, food and industry The biological or chemical systems elaborated in theme 1 will be used to develop tools for: - the production of synthons, of commodities for industry, of molecular platform molecules such as lipids, proteins (peptides) or saccharides from plant or microbial biomass or from waste, pollutants or industrial by-products; - the development of methods for their synthesis or eco-friendly and efficient processes for the valorization of these precursors. These tools will be used for various applications with a high societal impact potential: - the production of compounds of biological interest, such as bioactive compounds, inhibitors, modulators, plant growth promoters, molecular probes (for instance for imaging). These molecules will be screened for possible applications to health issues (e.g. antitumoral, antibacterial, antiviral, antifungal, drugs for degenerative diseases, probiotics, vaccines); - the production of bio-fuels, of bio-energy, the development of conversion tools for renewable energy or tools for renewable energy storage (non-carbon fuels or obtained from atmospheric CO 2 ); - the production of biopolymers, eco-compatible or biodegradable polymers; AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 3

182 - the valorization of these tools for food industry (food conservation, preservation of nutritional properties,...) and food security (prevention / detection, cleaning, surface treatment,...). Thirty-three teams (about 400 persons, including about 250 permanent staff members) are interested in this theme (a team can be interested by more than one theme). Theme 3. Valorization of biomass, industrial byproducts and CO 2, for a circular carbon economy. This theme is centered on the concept (in the broad sense) of agro-refineries (pre-conditioning) and of bio-refineries (transformation). The objective is to make the best out of whole plant biomass as a renewable source of products and services (food, materials, synthons, energy). This concept also requires the selection of simple and eco-compatible processes for the sake of overall efficiency in the use of renewable resources. Among the possible processes of transformation, several types can be considered: biological, chemical, thermo-chemical, physical (including pre-treatment and post-treatment). This theme, which represents only one part of the whole chain going from the field to the finished product, is closely articulated with themes 1 and 2: - choice of production methods to produce biomass that is easier to transform, - choice of production methods to produce a biomass with stronger potential - selection of microorganisms for the production of molecules of interest, - overcoming some bottlenecks encountered in white biotechnology. Bio-inspired is a not only a direct reference to many chemical processes mimicking life (e.g. photocatalytic synthesis), but also a reference to solutions derived from the living world for the replacement of molecules and polymers derived from petrochemicals. One can think for example of smart products/materials, self-repairing, self-adapting or simply easily recyclable materials. Economists will be associated with this project to conduct systemic socio-economic analyzes necessary to identify and evaluate the different ways of coupling relevant processes, from the point of economics, social use and sustainability. Eleven teams (about 230 persons) are interested in this theme (a team can be interested by more than one theme). Objectives. The majority of the teams associated with this project are already structured within a Labex (e. g. SPS, LERMIT, BASC, CHARMMMAT, LAPSIS) or are in the process of building a new institute (e.g. I2BC). The purpose of this proposal is to build a network for interdisciplinary scientific animation within the Paris-Saclay perimeter. This network should evolve and continue its activities after 2016, AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 4

183 but should stay as a network and another type of structure is not planned. The objectives of this network are the following: - to strengthen and structure, in the perimeter of Paris-Saclay, a community of researchers in the field of microbial/plant biotechnologies and bio-inspired/eco-compatible chemistry; - to promote cooperation (e.g. to combine life science, basic science and engineering through modeling approaches) and the emergence of innovative projects within this community; - to promote interactions of this research community with researchers in social sciences (economics, law, ethics, sociology...); - to attract students by responding to their concerns for the environment and to allow them to have regular contacts with research laboratories and internships in laboratories right from the onset of their studies; - to develop innovation and links with the industrial and pre-industrial platforms (e.g. B.R.I. 1, PIVERT 2 ); - to identify centers of excellence worldwide in this field and to establish perennial links with these centers. Proposed actions The purpose of the proposed actions is to encourage interdisciplinary collaborations, since multidisciplinary approaches are essential to respond to challenges in the fields of environment, energy, food and health and to develop the projects presented above. It will also be essential to develop collaborations with new disciplines and acquire new skills as soon as a research project reaches the stage of technological development. The funding requested will be used to supplement other institutional funding and provide leverage to reach the objectives stated above and foster collaborations. The proposed actions are listed below. The costs and the breakdown of the costs over the period are presented in table 1. 1 The innovation hub B.R.I. (Bioraffinerie Recherches et Innovations) is an open hub in the field of biorefining, and represents a global benchmark in innovation centers. B.R.I. brings together the biorefineries of Bazancourt- Pomacle (Cristal Union, Cristanol, Chamtor, etc.), the R&D centre ARD, as well as the French engineering schools Ecole Centrale Paris, AgroParisTech and Reims Management School. 2 P.I.V.E.R.T.(Picardie Innovations Végétales Enseignement et Recherches Technologiques) is a center of excellence for research, innovation, experimentation and formation in the domain of chemistry applied to oleaginous plants (rape, sunflower, etc ). Localised in Compiègne, it will bring together more than 150 researchers, engineers and academic staff working in different research units and pre-industrial platforms over the next decade. AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 5

184 1. Training workshops and thematic schools. Training workshops and thematic schools will be organized for scientists (academic and industrial) on transverse topics (e.g. green chemistry, biodiversity...). These workshops and schools will gather scientists from different disciplines and origins (academy and industry). During these sessions, presentations will be given by scientific leaders, and brain-storm sessions focused on multidisciplinary problem solving will be organized. Workshops on ethics, law, intellectual property, and economics will also be organized for scientists (academic and industrial) to improve their awareness of these topics. Courses and training workshops will be organized for personnel from industry. These courses and workshops will be built in close collaboration with industry, to take into account their training needs. These courses not only will strengthen the interaction with industry but also provide an additional source of funding. A medium-term objective is to cover the cost of these workshops and thematic schools with the fees requested from participants, but support will be necessary to initiate these initiatives (80 k for 3 years). 2. L and M1 students internships. The project will provide funding (1.5 to 2 k per trainee, depending on the length of the internship) to L and M1 students for short term internships in participant s laboratories on topics related to the three themes described above. In the french system, only trainees that stay longer than 40 working days are entitled to receive financial support for the full period of their internship. As a result, laboratories are reluctant to prolonge internships beyond this period. The project funding will therefore create the possibilty for motivated students to extend their mandatory internship or engage in a voluntary intership, for instance during the summer holidays.. The selection will be done on the scientific project and on the student s CV. The estimated cost of this action for is 66 k. 3. M2 students internships. A support (5 k for the trainee s financial gratification and bench fees) will be given to selected multidisciplinary projects involving two teams and one M2 student. The selection will be done on the scientific project and on the student s CV. The estimated cost of this action for is 150 k. 4. Participation of a Paris-Saclay team to the igem competition. The International Genetically Engineered Machine competition (igem, is the premiere undergraduate Synthetic Biology competition. Student teams receive a kit of biological parts at the beginning of the summer from the Registry of Standard Biological Parts. Working at their AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 6

185 own schools over the summer, they use these parts and new parts of their own design to build biological systems and operate them in living cells. This project design and competition format is an exceptionally motivating and effective teaching method and contributes to attract students to biotechnology and synthetic biology. A Paris-Saclay igem team was created in 2012 and participated in the 2012 competition. Our objective is to guarantee that each year, a Paris-Saclay team will have the possibility to develop its project and to participate in the competition. The support requested will be used to cover the costs of the experiments and the travel expenses for the team to the European jamboree, and hopefully to the final jamboree in Boston. The estimated cost of this action for is 75 k. A long term objective is to organize a future igem European jamboree in Paris-Saclay. 5. Multidisciplinary tandems of Ph.D. students or post-docs In order to show the benefits of multidisciplinary approaches to scientists earlier in their carrier, tandems of Ph.D or post-docs will be organized on complementary subjects from different disciplines, already financed by their respective laboratories. These tandems should collaborate for at least one year, aiming at producing, in addition to their specific work, a collaborative multidisciplinary piece of work which should lead to a common publication or congress communication. The supported tandems will be selected on the interdisciplinarity of their scientific project and on the CVs of the tandem s partners. The financial incentive (about 4 k per tandem) will be granted in the form of additional funding which could be used for instance to cover the cost of additional training of the Ph.Ds/post-docs or to support their participation in a scientific meeting. The results obtained by these multidisciplinary tandems will be presented during the restitution meeting and the best projects will be awarded a prize. The cost of this action is 120 k for three years. 6. Fostering international collaborations and the exchange of scientists. Laboratories involved in this project are aware and have used the existing possibilities to support the stay of foreign scientists in Paris-Saclay laboratories or the stay of Paris-Saclay scientists in foreign laboratories for periods ranging from one month to one year (e.g. visiting Professor, Chair Blaise Pascal, France-MIT exchange, Programs Hubert Curien managed by Campus France, cooperation programs from CNRS). The teams will continue to apply for these types of support, but the calls for them are annual, meaning that these exchanges have to be planned a long time in advance. Our objective is to set up a flexible and responsive system to support the exchange of scientists, permanent staff, as well as Ph. D. students or post-docs. The requested funding could be used to send a Paris-Saclay scientist in a foreign laboratory or to welcome a foreign scientist in a Paris-Saclay laboratory, either to initiate collaboration or when an expertise, not available in Paris- Saclay but available in the foreign laboratory, is urgently needed. The funding could also be used to AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 7

186 extent a stay already supported by another source of funding or to cover in part the expenses linked to mobility. The estimated costs of these actions is 120 k for three years. To increase the possibilities of exchange of permanent staff without increasing the financial cost, a system of reciprocal exchange between the University of Paris-Saclay and foreign institutions might be established, scientists from Paris-Saclay going abroad and exchanging their positions with foreign scientists coming to Paris-Saclay. All these actions will increase the international visibility of Paris- Saclay in the field of biotechnologies and bio-based/bio-inspired chemistry and will allow identifying foreign centers of excellence in this field with which perennial links could be established. 7. Support for the demonstration of the proof of concept. We plan to implement a flexible and responsive funding system to support the demonstration of the proof of concept linked to a funding application, or the filing of a patent application, or before valorization. The funding will be used to cover the operating costs linked to the experiments necessary for this proof of concept; it could also help to establish new collaborations, as the demonstration of the proof of concept may require skills that are not present in the team from which the project originated. The institutional services in charge of the valorization of research results should be involved in the evaluation of the projects applying for this type of support. This type of support was a major request of the teams and 240 k will be devoted to this action over the three years. 8. Communication. About 70 teams have already declared their interest for this initiative and for the three themes proposed. The first objective of the actions of communication will be to increase this number, by creating a web site and organizing meetings to inform all teams from Paris-Saclay about the various possibilities of support that the interdisciplinary network Biotechnologies/Bio-based and Bioinspired Chemistry might provide. It will be also be necessary to involve economists in our network. Communication directed towards industries will have the objective to inform companies about the expertise available in Paris-Saclay laboratories and about the collaboration opportunities. A total of 30 k should be devoted to communication during the three years. 9. Restitution meetings Two restitution meetings will be organized before the end of The teams that received support from the network will present their results during these meeting. These meeting will be free and open to all scientists from Paris-Saclay and to people from industry. The cost of these two meeting is estimated to 12 k. AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 8

187 Network governance A Steering Committee will be in charge of the governance of this network. It will be composed of 12 academic researchers from Universities and Research Organisms, representing the various scientific forces involved in this initiative, and which have already been identified within the Idex perimeter (see annex 1 and annex 2), as well as 6 members representing industrial and professional organizations (professional associations or federations, pôles de compétitivité, these members have yet to be identified). One representative of this committee will be in charge of relationships and information exchange with the Paris-Saclay Idex. The Steering Committee will meet on a regular basis (at least three meetings per year), and will be responsible for the establishment of new calls for proposals, project selection, project monitoring and review, as well as general network organization and animation. Evaluation committees will be called when needed, depending on the specific actions, with a will to maintain light and reactive structures whenever possible. On a yearly basis, a General Assembly will be organized, in order to favor exchange with the teams involved in the project. It should be noted that the network s perimeter will be maintained open, including research groups which have already been identified, but also accepting the association of new groups. All research groups from Paris-Saclay and partners of Paris-Saclay (e. g. Evry) could answer the calls for proposals from the network, as long as they are within the network s scientific boundaries. AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 9

188 Table 1. Proposed actions and estimated costs. Action N description 1 Training workshops and thematic schools cost Cost for Deliverables Action directed towards 3 years (for some actions, the number of students scientists industry projects supported per year is given for 2014 and 2015, it might be lower in 2013) 20 k 30 k 30 k 80 k Organization of 3 to 6 workshops, courses or thematic schools during the 3 years 2 L and M1 student internships 18 k 24 k 24 k 66 k Support for students per year 3 M2 student internships 75 k 75 k 150 k Support for about 15 students (30 teams) per year 4 Paris-Saclay igem team 25 k 25 k 25 k 75 k Participation of a team to igem each year 5 Multidisciplinary tandems of 24 k 48 k 48 k 120 k Support for about 12 Ph.D. students or post-docs tandems (24 teams) each 6 Exchange of Ph. D students and scientists with foreign laboratories 7 Demonstration of the proof of concept year 24 k 48 k 48 k 120 k Support for about 12 exchanges per year 48 k 96 k 96 k 240 k Support 2-3 projects each year 8 Communication 14 k 8 k 8 k 30 k web site, communication to all Paris-Saclay teams on the possibilities of support 9 Restitution meeting 6 k 6 k 12 k Organization of two Total 173 k 360 k 360 k 893 k meetings during the 3 years AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 10

189 Annex 1: list of the research groups which have already declared their interest for the network and are interested by one or several of the three themes of the project. Name of the P.I. Organism Name of the team Staff S Aymerich INRA APT Régulation Génétique et Biofilms chez les Bacillacées 11 G Trystram APT Ingénierie procédés Aliments 106 L Morin UPS CNRS Biodiversité des protistes 3 C SOLA UPS CNRS Infection Génétique Evolution des Pathogènes Emergents 5 MJ Virolle UPS CNRS Métabolisme Energétique des Streptomyces IGM 5 C. Rameau INRA APT Contrôle de la Ramification des Plantes 5 J D. Brion UPS Conception et synthèse de molécules d intérêt thérapeutiques 13 C. Dugave CEA Conception, modélisation et ingénierie d agents d imagerie 9 C. Conesa CEA Régulation Nucléaire et Stress 8 V. Fromion INRA Biologie des Systèmes 11.5 B Figadère UPS Chatenay Pharmacognosie, chimie des substances naturelles 32 F. Chauvat CEA Plasticité des Fonctions et des Interactions Cellulaires 9 B. Crousse UPS CNRS Molécules fluorées et chimie médicinale 9 D. Debieu INRA Antifongiques mode d action et résistance 10 L. Kuras CNRS Transcriptionnelle et ubiquitylation chez la levure 3 L.Tchertanov ENS Cachan Bioinformatique, Modélisation et Dynamique Moléculaire 12 Marsolier-Kergoat CEA Laboratoire du métabolisme de l'adn et réponses aux génotoxiques 10 MH Lebrun INRA Evolution et Génomique des Interactions Plantes-Pathogènes 7 M.Paternostre CNRS CEA Assemblages supramoléculaire/nanotubes peptidiques 4 Champomier Verges INRA Flore Lactique et Ecosystème Carné 6 W. Leibl CEA Photocatalyse et Biohydrogène 20 P. Cuniasse CEA Modélisation et Ingénierie Moléculaire 13 S. Un CEA Hyperfréquences, métalloprotéines et système de spin 3 G. Dujardin CNRS Biogenèse et foncti des complexes respiratoires mitochondriaux 6 N. Bonnefoy CNRS Traduction des ARN mitochondriaux chez la levure S. pombe 6 AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 11

190 Name of the P.I. Organism Name of the team Staff M. le Maire CNRS CEA Protéines Membranaires 18 A.Delahodde CNRS Fonctions et Dysfonctions des Mitochondries 7 J Labarre CEA Dynamique des réseaux biologiques 7 M. Delaforge CEA Stress Oxydant et Détoxication 14.5 P. Berthault CEA CNRS Structure & Dynamique par Résonance 7 S. Hermann UP Orsay Ribosomes et Physiologie Mitochondriale 5 M. Viaud INRA Analyse Fonctionnelle du Génome de Botrytis 8 V. Dive CEA Rôle fonctionnel des métalloprotéases à zinc 15 M. Caroff UP Orsay Structure et Activités des Endotoxines 7 C. Carles CEA Mécanistique et régulation des ARN polymérases 4 H. Hirt INRA CNRS Signalisation et Protéomique, 14 T.Chardot INRA APT Dynamique et Structure des Corps Lipidiques 14 D. Mengin-Lecreulx UPS CNRS Enveloppes Bactériennes et Antibiotiques 7 M.Gondry CEA Enzymologie et Biosynthèse Peptidique Non Ribosomale 6 H. Höfte INRA APT Paroi végétale 23 E. Spinnler INRA APT Ingénierie d'élaboration des bio-produits par voie biotechnologique 18 A.Guyonwarch UPS CNRS Physiologie et Métabolisme des Corynebactéries 8 T. Bouchez CEMAGREF Laboratoire de microbiologie des bioprocédés 15 L. Lepiniec INRA APT Développement et maturation de la graine 13 P. Guerche INRA APT Homéostasie Lipides/protéines de la graine d'arabidopsis 4 P.Noirot INRA Intégration fonctionnelle des processus cellulaires 24 JM. Nicaud INRA APT Biologie Intégrative du Métabolisme Lipidique Microbien 15 A. Ivancich CNRS Metalloprotéines et Radicaux Protéiques 1 P. Perré Ecole Centrale Laboratoire de Génie des Procédés et Matériaux 51 P-H Ducrot INRA APT Lignines et tanins; structures, assemblages et valorisation 16 AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 12

191 Name of the P.I. Organism Name of the team Staff C. Mougin INRA Physicochimie et Ecotoxicologie des Sols d Agrosystèmes Contaminés 24 M. BuBow CNRS U Paris-Sud Laboratoire de Génomique et Biodiversité Microbienne des Biofilms 7 A Marinetti CNRS Production par voies biologiques et/ou chimiques 10 J Xie CNRS ENS Cachan Synthèse et valorisation de biomolécules fonctionnelles 7 D Prim CNRS-U Versailles St Quentin Ecochimie, Catalyse, Héterochimie Organique 23 C Kouklovsky CNRS Procédés et Substances Naturelles 16 A. Aukauloo CNRS UPsud CEA Photosynthèse Artificielle/Chimie Inorganique 13 JP Mahy CNRS UPsud Chimie Biorganique et Bioinorganique 15 B. Vauzeilles CNRS Upsud Glycochimie et Systèmes Photoactifs à l'interface Chimie-Biologie 7 R. Rodriguez CNRS Molecular Medicine Program 7 M. Malacria CNRS Chimie organométallique de synthèse moléculaire et macromoléculaire 8 JM Beau CNRS U. P-Sud Laboratoire de Synthèse de Biomolécules/Biomolécules, sucres, glycoconjugués, organomét. 17 P Martin INRA Jouy Lait, Génome & Santé, Génétique animale et Biologie intégrative (GABI) 11 JL Pernodet UPS CNRS Microbiologie Moléculaire des Actinomycètes 11 J Ouazzani CNRS Institut de Chimie des Substances Naturelles 8 JD Faure INRA Différenciation et polarité cellulaire 7 G. Mouille INRA Plateau Technique Spécifique de Chimie du Végétal 7 G. Tcherkez CNRS Plateforme Métabolisme-Métabolome 7 P. Langella INRA Interactions des bactéries commensales et probiotiques avec l hôte 29 J. Pelta CNRS Macromolécules Polymères aux Interfaces 29 O'Connel INRA Analyse fonctionnelle du génome de Colletotrichum 6 AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 13

192 Annex 2: members of the working party Biotechnologies and Bio-based and Bio-inspired Chemistry. This working party could constitute a basis for composing the Steering Committee in which at least one representative of Evry should be included. AUKAULOO Ally, ICMMO, Univ. Paris-Sud AYMERICH Stéphane, MICALIS, INRA BANSE Frédéric, ICMMO, Univ. Paris-Sud GROGNET Jean-Marc, ibitec-s, CEA HOFTE Herman, IJBP, INRA LEPINIEC Loïc, IJPB, INRA NICAUD,Jean-Marc, MICALIS, INRA PERNODET Jean-Luc, IGM, Univ. Paris-Sud PERRE Patrick, Ecole Centrale Paris PRIM Damien, Univ. Versailles-Saint-Quentin SPINNLER Henry-Eric, Agro-Paris-Tech VAUZEILLES Boris, ICMMO, Univ. Paris-Sud et ICSN, CNRS AAP Idex 2013 Interdisciplinary network: Biotechnologies/Bio-based and Bio-inspired Chemistry 14

193 IDEX Paris-Saclay APPEL A PROJET RECHERCHE IDEX 2013 Titre du projet : Physique and Ingénierie pour la Médecine - recherche intégrative en imagerie TEP-IRM et ses applications médicales : PIM Research Project: Physics and Engineering in Medicine: Integrative research in PET-MR imaging and its medical applications Coordinator: Irène Buvat, Senior Scientist (DR2 CNRS), head of the Quantification in Molecular Imaging team, Imaging and Modeling in Neurobiology and Cancerology (IMNC) lab, UMR 8165 CNRS - Paris Sud University - Paris Diderot University. Mail: Building 440, Orsay Campus, Orsay Cedex Phone: ; Cell phone: buvat@imnc.in2p3.fr Outline Summary 2 1. Introduction: why a PET-MRI project for a Physics and Engineering in Medicine consortium? 3 2. Scientific project Methodological developments prompted by the PET-MRI technology Design and evaluation of multimodal PET-MRI probes Advanced MRI combined with PET imaging Quantitative PET-MRI MRI-guided PET image reconstruction PET-MRI image segmentation Multiparametric tumor imaging Extracting brain PET-MRI joint structures for statistical analysis Breakthrough applications for PET-MR imaging Making a difference in specific oncologic applications A revolutionary approach for biologically guided radiation therapy? A new insight into the central nervous system sensitivity to drugs and psychiatric disorders? Training actions Dissemination Project management Partners Coordination Budget Conclusion Bibliography Appendix Teams participating to the project and expertise brought by each team CEA-LIST CEA-SHFJ 25 CEA - Service Hospitalier Frédéric Joliot CEA-Neurospin IGR and Radiotherapy department IMNC INSERM-U IC-CPO IMT IR4M IRCIV Complete CV of the coordinator Glossary Suggested experts 38 1

194 PIM: Physics and Engineering in Medicine: Integrative research in PET-MR imaging and its medical applications Summary The objective of the Physics and Engineering for Medicine (PIM in French) is to transfer the tremendous research resources in physics and engineering of the Paris Saclay Campus (PSC) to the Medicine application field. A first step towards this goal is to create a unique cooperative research and training environment in PSC that would contribute to the development of advanced medical imaging and therapy techniques based on the variety and competitiveness of local expertise in physics, engineering, information processing and biomedical research. Federating the efforts of a dozen of local labs or research institutes involved in physics or information processing related to medical applications is very challenging. Still, the current trends towards multimodality medical imaging (meaning combining different medical imaging techniques to get a better description of a disease) and integration of imaging and therapy (meaning using imaging to plan or monitor therapy) offers a unique opportunity to demonstrate that the PSC strategy to create a cooperative campus is perfectly in line with the growth of multidisciplinary research in the medical field. This PIM project builds on the novel Integrated Positron Emission Tomography Magnetic Resonance Imaging (PET-MRI) medical imaging facility obtained through the Investments for the Future national policy ( France Life Imaging funded project (FLI)) that will be installed in CEA-Service Hospitalier Frédéric Joliot (CEA-SHFJ) in This cutting-edge equipment appeared as an ideal opportunity to demonstrate that the local concentration in PSC of research task force in physics, engineering, information processing and medical fields is a considerable asset to address challenging research projects that only a cooperation between labs of different specialties can complete. The integration of MRI and PET can actually be viewed as the combination of far more than two imaging modalities, given that each in itself can provide a very broad spectrum of anatomical, functional and molecular information. By combining PET and MRI, biological properties of cells such as hypoxia, apoptosis, proliferation, expression of peptide or protein on the cell membrane, can be analyzed simultaneously with microvascularization, the presence of reporter probes or even the mechanical tissue properties. The combination of PET and MRI therefore opens new avenues in the molecular investigation of physiopathological processes and diseases, to advance in the field of personalized medicine, where the aim is to identify the specific profile of a disease in each and every patient, to select the best possible treatment accordingly. The integration of PET and MRI in a common imaging device raises two issues: first, it creates a new need for methods or even concepts appropriate to deal with joint PET-MRI data so as to understand, utilize, and make the best of this new type of information. Second, it prompts the question of which research or clinical investigation will best take advantage of this multiparamatric characterization. Given the strong and long experience in PET, MRI, PET/MRI, clinical research, radiation therapy and information processing of the research PSC teams, we propose to answer these questions in two respects: first, we will develop methodological approaches to optimize this unique combination of complementary imaging modalities and second, we will explore the value of PET-MRI in innovative applications for which simultaneous exploration of different molecular phenomena could bring a breakthrough. These include specific oncology applications, high-end radiation treatment that would benefit from a precise biology-based delineation of target regions, and advanced neuroimaging to better understand the central nervous system, mental disorders and addictions. Our ambition is to play a key role in the development and dissemination of PET-MRI and in the identification of both research and clinical applications for which it will make a big difference. All along the project, research will be tighly associated with training, based on the large involvement of the actors in training activities. PSC might therefore become one of the first French or even European universities offering PET-MRI training by experts in the field together with providing internship opportunities in a PET-MRI facility. The alignment of this project with other recent initiatives, such as Investments for the Future and the IDEX strategy, associated with the acquired support of our institutions and of several companies in the field, suggest that through PIM, PSC will make a decisive step towards being recognized worldwide as a key player in the transfer of physics and information technology to healthcare. On the long term, based on the experience acquired through this PET-MRI focused project, it is expected that new actors (research labs and engineer schools) will join the consortium, considerably enlarging the scope of PIM. In particular, PIM will likely later extend to many other advanced medical imaging modalities, other biomedical applications, and other innovative therapeutic strategies. A PIM Institute is foreseen to structure a broader community of PSC scientists involved in complementary fields. By acting as one of the pioneer centers in the field of PET-MRI, the PIM project targets a national and international visibility with many original scientific and medical outcome, including a significant impact on guidelines and future practice of PET-MRI in other French facilities and beyond. This project is also expected to attract talented researchers eager to work in the extremely stimulating scientific environment that PSC provides. 2

195 1. Introduction: why a PET-MRI project for a Physics and Engineering in Medicine consortium? - Motivation for the project. This PIM project finds its roots in the willingness to transfer the world-class research resources in physics and engineering of the Paris Saclay Campus (PSC) to the Medicine application field. To achieve this goal, it was decided to create a unique cooperative research and training environment in PSC that would contribute to the development of advanced medical imaging and therapy techniques based on the variety and competitiveness of local expertise in physics, engineering, and biomedical research. A first initiative in that direction was submitted as part of the Labex I French call in 2010, under the lead of Jacques Bittoun, to structure most PSC actors involved in Medical Physics and in its applications. Although the proposal did not get funded, the cooperative work performed at that time brought research scientists from different fields closer and stimulated many discussions. The deadlock that was then identified is that the physics field and associated application field are extremely large. Therefore, federating the efforts of a dozen of local labs or research institutes towards focused objectives is very challenging. Still, we realized that the current trends towards multimodality multifunctional imaging and integration of imaging and therapy gave us a unique opportunity to demonstrate that the PSC strategy to create a cooperative campus is perfectly in line with the growth of multidisciplinary research in the medical field. - Trigger event. Soon after, in 2011, the Investments for the Future national policy gave us a new opportunity to pursue our efforts towards integrating research in physics and engineering for medical applications. Through the France Life Imaging project (FLI project), we obtained fundings for setting an integrated Positron Emission Tomography Magnetic Resonance Imaging (PET-MRI) medical imaging facility in CEA-Service Hospitalier Frédéric Joliot (CEA-SHFJ) in This opportunity then appeared as the ideal setting to demonstrate that the local concentration in PSC of research task force in physics, engineering, information processing and medical fields is a considerable asset to address leading-edge research projects that only a cooperation between labs of different specialties can complete. We then decided to refocus our initial Labex project onto a PET-MRI project, as a seed action towards creating a PIM institute with international outreach. Indeed, as described below, the new PET-MRI technology considerably expands imaging frontiers but also issues many challenges to researchers, in term of how best take advantage of this technology. - Context: multimodality in vivo molecular imaging - an intrinsically multidisciplinary area shaping personalized medicine. Medical imaging modalities, such as Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Single Photon Computed Emission Tomography (SPECT), Computed Tomography (CT) or Ultrasound imaging (US) have their own unique advantages. It is now well recognized that imaging modalities are synergistic, and that combining information from imaging modalities add value above that of individual modalities. Well-established demonstrations are the success of PET/CT in the clinics (Bockisch et al 2009, Delbeke et al 2009), which has refined the fields of oncology, surgical planning and radiation therapy, and the increasing development of devices supporting several imaging modalities, such as a PET/SPECT/CT clinical system (Mediso Medical Systems) and the recent advent of PET/MR clinical systems (Vaska et al 2013). In that context, the integration of MRI and PET can be viewed as the combination of more than two imaging modalities, given that each in itself provides a very broad spectrum of information. MRI, including diffusionweighted (DW) MRI, dynamic contrast enhanced (DCE) MRI, dynamic susceptibility contrast (DSC) MRI, blood oxygen level-dependent effect (BOLD) imaging, fluorine-19 MR measurements of oxygen-sensitive compounds, and the measurement of lactate, among others, provides structural information on tumor vasculature and physiology at a millimetric spatial resolution together with unique functional information (Kircher et al 2012b). PET can accurately measure local concentrations of a large variety of radioactive molecular targets of interest with unsurpassed sensitivity (nano to pico molar). Specific tracers can be used to visualize biological properties of cells such as hypoxia (using [ 18 F]fluoromisonidazole ([ 18 F]FMISO) for instance), apoptosis (Annexin V labeled with fluorine-18), proliferation (using 3 -deoxy-3 -[ 18 F]fluorothymidine ([ 18 F]FLT)), expression of peptide or protein on the cell membrane, etc (Pantaleo et al 2008, Holland et al 2012, Zimmer et al 2012). The combination of PET and MRI therefore opens new avenues in the molecular investigation of physiopathological processes and diseases, to advance in the field of personalized medicine, where the aim is to identify the specific profile of a disease in each and every patient, so as to make sure he/she receives the best possible treatment. - A prime environment for a timely PET-MRI project. Although PET and MRI have been around for decades, the integration of both to refine diagnosis and assist in patient management has been slow. First, making the best of PET or MRI requires a very specific expertise, which has often been developed so far in different departments of hospitals and research institutes. Second, combining MRI and PET acquired in different departments requires dedicated tools that are not widely available yet. It is foreseen that the recent advent of commercial PET-MRI integrated systems will deeply change the practice of medical imaging for research, patient diagnosis, treatment planning and patient monitoring, similar to the breakthrough brought by PET-CT imaging systems in the 2000 s. Yet, the major areas in which PET-MRI will revolutionize research and/or clinical practice remains to be identified (von Schulthess et al 2013). Given the strong and long experience in PET, MRI, PET/MRI, clinical research, radiation therapy of the research PSC teams (Appendix 9.1), the purpose of our project is to identify these areas in two respects: first, by developing methodological approaches to optimize this unique combination of complementary imaging modalities that will be available thanks to the installation in 2014 of a PET-MRI imaging system at the CEA-SHFJ facility in Orsay and second, by exploring the value of PET-MRI in innovative applications for which simultaneous exploration of different molecular phenomena could bring a breakthrough. 3

196 - National and international competitiveness. In France, in addition to the CEA-SHFJ PET-MRI system, only one other simultaneous PET-MRI installation is currently planned in Lyon (Rhône-Alpes Region). Our project has several original features with respect to the Lyon s project. Our project is mostly centered on physics, engineering and information processing to disseminate into the medical field. This approach will be complementary to the Lyon s project where the machine will be installed in a medical environment. CEA-SHFJ performs imaging research on primates, which might be a considerable asset to design and evaluate new PET- MRI imaging probes and protocols with the aim to translate them to the clinics. Our consortium includes advanced radiation therapy departments (IC-CPO and IGR) and national experts in the field of dosimetry (CEA-LIST) that will make it possible to explore PET-MRI in the context of treatment planning. Our consortium also benefits from the unparalleled experience in MRI and high-field MRI of the CEA-Neurospin lab. It also has a strong experience in the physics of high-end PET systems (CEA-SHFJ among the pioneers in time-offlight PET in the 80 s) and in PET image quantification (IMNC) and in a > 20 years experience in PET and MRI imaging, including original tracer developments, in particular for neuropsychiatric studies, an area where simultaneous PET-MRI might bring a definite breakthrough given the importance of simultaneous co-localization of neuropsychological processes. Another asset is the > 30 years experience in medical image processing of the teams of Institut Mines-Télécom (IMT), a French leading academic actor in the field of information technologies. In addition, in the framework of the FLI funded project, a large-scale research infrastructure aiming at establishing a coordinated and harmonized network of biomedical imaging in France, there will be a significant interaction between the two projects to share experience and accelerate PET-MRI developments. Worldwide, PET-MRI projects are also in their infancy, with only a dozen of simultaneous PET-MRI systems (Siemens) planned in Europe, and another dozen in North-America. A proposal for a European project (EUFICIO- NETs) has already been submitted to the FP7-HEALTH-2013-INNOVATION-1 program by IGR and CEA-SHFJ to cooperate with the University Medical Center of Groningen (NL) and the German Cancer Research on the improvement of therapeutic interventions in tumors by developing and validating PET-MR imaging techniques. Through the EUFICIO proposal, but also by joining other European collaborative and training actions such as the COST TD1007 ( we plan to start entering the European network of PET-MRI facilities and expertise. By acting as one of the pioneer centers in the field of PET-MRI, the PIM project aims at a national and international visibility with many original scientific and medical outcomes, with a significant impact on guidelines and future practice of PET-MRI in other French facilities and beyond. It is also expected that this project will attract talented researchers eager to work in the extremely stimulating scientific environment that PSC provides. 2. Scientific project 2.1. Methodological developments prompted by the PET-MRI technology PET/MRI is a highly innovative technology allowing for multimolecular imaging. The technology is not mature yet and many methodological developments are needed to make the best of it. Our project therefore includes a series of methodological developments that all aim first at transferring the best of what one can achieve on standalone PET and MRI scanners into an integrated PET-MRI system, and second, at taking advantage of the coupling of the modalities to enhance the informational content provided by each one and to invent new concepts of multiparametric imaging. The corresponding subprojects are briefly described below, and results expected by February 2016, when the project outcome will first be evaluated, are underlined Design and evaluation of multimodal PET-MRI probes (CEA-SHFJ, IR4M) In the past 10 years, a variety of innovative MRI approaches have been proposed for the non-invasive assessment of molecular or cellular events (Kircher et al 2012a). However, while MRI is highly specific for molecular identification (with spectroscopy), it has to cope with its inherent low sensitivity, a drawback that could be overcome by the use of exogeneous probes concentrating a large number of magnetic nuclei or contrast agent. The most promising approaches to date are based on the use of nano-objects, such as 19 F-enriched nanoparticles (Ruiz-Cabello et al 2011), superparamagnetic iron oxides nanoparticules (Laurent el al 2011) and cryptophane cages encapsulating hyperpolarized 129 Xe (Tarentula et al 2010). Unlike MRI, PET is highly sensitive and quantitative but of lower spatial resolution than MRI, based on the administration of a tracer dose of a radioactive (carbon-11 of fluorine-18-labelled) probe. Designing from a molecular point of view a single PET-MRI multimodal probe would combine the complementary advantages of both modalities in terms of imaging. Validation of such approaches will be performed at a preclinical stage first, on in-house available separate PET and MRI systems (µpet/ct versus 1.5T MRI), then on an integrated PET/MRI system. The use of iron oxide particles precoated with streptavidin moieties will offer a unique opportunity for labeling those nano-objects with the short-lived positron-emitter fluorine-18 (T 1/2: min) using a newly developed biotinylated [ 18 F]reagent Advanced MRI combined with PET imaging (IR4M, IGR) Sor far, research on integrated PET-MRI has mostly focused on coupling functional PET with anatomical MRI. Still, it is well agreed that the most promising aspect of integrated PET-MRI lies in the combination of PET with functional and molecular MRI. Strength of the PIM consortium in this regard is that it includes groups working at the cutting edge of MRI technology. We will therefore pursue our efforts to explore and develop novel MRI techniques that are not available on PET-MRI systems yet. These techniques will be implemented on the PET- MRI scanner installed in CEA-SHFJ to study their value in combination with PET. 4

197 Quantitation of tissue biomechanical properties (IR4M, IGR) MR-Elastography (MRE) allows to detect the tissue motion in the human body and to follow its response to a mechanical stress in order to reveal, as tactile palpation does, the local mechanical properties of peripheral organs (eg liver (Huwart et al 2006, Yin et al 2007), or breast (Sinkus et al 2000, Plewes et al 2000)) as well as remote organs (eg heart (Robert et al 2009) or brain (Green et al 2008, Kruse et al 2008, Sack et al 2009)) that cannot be reached by the medical doctor's hand. Mechanical properties depend on tissue structure, biological conditions and potential diseases like cancer. In collaboration with Beaujon Hospital and IGR, IR4M has studied breast elastography to support the discrimination between benign and malignant tumors (Kruse et al 2007). At Beaujon Hospital, MRE is developed to study liver cancer, fibrosis, and cirrhosis (Robert et al 2009). In the brain, the elasticity of large tumors (38 to 75 mm diameter) was correlated to tissue consistency evaluated at surgery (Xu et al 2007). In a patient with a temporal glioma, the mean elasticity modulus in tumoral tissue has been measured 30% higher than in the corresponding region of the healthy hemisphere (Uffmann et al 2007). However, the difficulty to introduce mechanical waves in the brain through the skull and the cerebrospinal fluid has limited the quantitation of the viscoelastic moduli so far. Recently, IR4M has developed an original device to circumvent these limitations by guiding pressure waves through the subject's buccal cavity (Maître et al 2010, Maître et al 2011). Through the extracted viscoelastic moduli, MRE aims at providing new quantitative biomarkers on the biomechanical state of the tissue. By 2016, the aim will be to implement MRE on the PET-MRI system installed at CEA-SHFJ, and to include data collected from MRE, either at the tumor level or at the voxel level, in tumor profiling ( 2.1.6), possibly in Biology- Guided Radiation Therapy (BGRT, 2.2.2) and also to monitor tumor evolution over therapies Multimodal and multicompartimental assement of tumor (IR4M-IRCIV, CEA-SHFJ) New drugs such as thyrosine kinase induce different degrees of destruction of three tumoral compartiments: vascular, cellular and interstitium. The sequences and the links of the different steps of destruction need to be better understood in order to improve the action against the resistance mechanisms. The combination of functional (hemodynamic) and metabolic imaging by different modalities is required to investigate these complex processes. We will study different compartimental models involving contrast agents of different molecular weights (Leach et al 2012) in order to assess the vascular space. The hemodynamic response will be simultaneously followed by [ 15 O]water based on 4D non-parametric Bayesian (NPB) reconstruction ( 2.1.4). The cellular and interstitial spaces will be investigated combining diffusion MRI and metabolic characterisation with different PET tracers specific of angiogenesis and apoptosis (Jones et al 2012). This will be performed in association with ongoing IR4M projects performed in close collaboration with the Integrated Research Center Institute in Villejuif (IRCIV) that is already linked with IR4M: i) preclinical studies on complementarity between DCE-MRI and DCE- US to assess microvascularisation at each step of tumoral angiogenesis; ii) Computational Fluid Dynamic (CFD) modelling of contrast agents (intra and extra vascular) in microvascular network; and finally iii) development of realistic phantoms to model tumor microvascularisation in DCE-US (Lassau et al 2012) and DCE-MRI experimental conditions Quantitative PET-MRI If visual interpretation of PET and MRI images remains essential, estimation of parameters (aka quantification) reflecting the observed function or structure from the image is often required to facilitate classification, therapeutic management and patient monitoring. The combination of PET with MRI raises new challenges in terms of image quantification that will need to be addressed to establish the quantitative accuracy achieved on these machines. Three aspects will be carefully investigated: PET attenuation correction, respiratory motion correction, and conversion of MRI signal into tissue elemental composition PET attenuation correction on PET/MRI systems (CEA-SHFJ, IMNC, IR4M) Attenuation correction is mandatory in PET to retrieve accurate activity estimate, hence tracer concentration, from the detected signal. PET requires attenuation correction based on electron density of tissues being imaged. In PET-CT, the Hounsfield units (HU) from the CT image are converted into linear attenuation coefficients for the 511 kev photons of PET. Unlike CT, MRI does not provide information about the electron density of the tissues, and cannot be used directly to derive attenuation coefficients. New strategies are being developed to deduce attenuation coefficients from MRI scans (Bezrukov et al 2013). These include deriving the attenuation coefficient map from anatomical atlases, segmenting MRI images obtained with specific sequences, a combination of these two approaches, or exploiting PET emission data and MR anatomical information from to compute the attenuation maps. A major issue is the difficulty to image bone with MRI. Bone mostly contains proton with reduced mobility and relaxation times are extremely short resulting in a complete signal loss for all standard imaging sequences (spin echo and gradient echo). IR4M researchers have a long standing experience in bone imaging (Remy et al 1998, Antoniadis et al 1999, Choel et al 2004, Last et al 2005, Benoit et al 2009) and are currently transferring original ultrashort Echo-Time (UTE) sequence previously implemented at 4.7T (Kusmia et al 2012) on the 1.5T MR scanner in SHFJ for various applications. We will first assess the accuracy of the method implemented on our PET-MRI scanner, by comparing quantification of images obtained from a PET-MRI with that obtained from a PET-CT scanner in phantoms and patients. If quantitative accuracy does not appear to be sufficient for the targeted quantitative studies ( 2.2), we will evaluate bone MRI with UTE sequences for attenuation correction. In vivo MRI bone imaging will be performed for various applications to estimate the needed sequence parameters to bring a significant improvement in PET-MRI reconstructions. Validation of attenuation correction will be one of the first studies performed on the machine, so that PET-MRI patient scan features can be compared to PET-CT patient data in all research studies. Dealing with attenuation will also require revisiting a number of applicationdedicated coils, so as to reduce their metal content that enhances the attenuation issue in PET (MacDonald et al 5

198 2012) PET-MR motion correction (CEA-SHFJ, IMNC, IR4M) Motion, especially respiratory and cardiac motions, introduces artifacts and quantitative biases in PET images. This issue of patient motion is enforced in high spatial and temporal resolution imaging, such as provided by PET- MRI. Simultaneous PET-MRI is very appealing for motion compensation, since techniques such as multiple navigator echoes or MR tagging can be used to measure 3-dimensional (3D) motion fields, which can then be incorporated into the iterative PET reconstruction to obtain motion-corrected PET images (Ouyang et al 2013). Yet, corresponding PET-MRI acquisition protocols remain to be optimized as the duration of the MRI tagged acquisition prevents from acquiring other relevant MRI data simultaneously with the PET scan. Motion correction strategies will be implemented and/or validated in the PET-MRI machine installed at the CEA-SHFJ, for protocols significantly penalized by organ motions. 4D PET reconstruction will be favored to account for motion, based on previous experience (Grotus et al 2009) and on anticipated research in the field of image reconstruction ( 2.1.4). The MR-based motion correction will be included in NPB PET-MRI reconstruction ( 2.1.4) and evaluated with simultaneous functional MRI and PET acquisitions (see neuropsychiatric applications in 2.2.3) Conversion of MRI into tissue elemental composition (CEA-LIST, IC-CPO) Tissue composition is an important factor in treatment dose planning. When treatment plans are derived from CT images, HU provide an indicator of tissue densities, and these densities are taken into account for the planning, either by assigning a tissue type to a tissue density, or using the Schneider method (Schneider et al 2000). In MRI, neither tissue density nor tissue composition is directly available. A comprehensive study is therefore needed to differentiate different tissue compositions based on various MRI sequences, so as to properly account for tissue composition in Monte Carlo (MC) dose calculation (Vanderstraeten et al 2007). CEA-LIST has the expertise to tackle that problem (Le Loirec et al 2012) and provide solutions that will be implemented when calculating treatment plans from PET-MRI data (cf 2.2.2). Short-term results include implementation and/or evaluation of the accuracy of a PET-MRI attenuation correction and of a PET-MRI motion correction schemes on our PET-MRI machine. A strategy to deduce material composition from MRI data for dosimetry purpose will also be developed; this task will be initiated on separate PET and MR scanners MRI-guided PET image reconstruction (CEA-LIST, CEA-SHFJ, CEA-Neurospin, INSERM U1000) Since 2008, CEA-LIST and CEA-SHFJ work together on the application of NPB methods for PET image reconstruction (ESTEBAN project, Barat et al 2007). Classical statistical image reconstruction algorithms like expectation maximization maximum likelihood (EM-ML) or maximum a posteriori (MAP) algorithms are based on a deterministic approach: the image voxel intensities are estimated by minimization of a cost function including a data fidelity term (negative log-likelihood) and, for MAP, a penalty term (regularization). In ESTEBAN, image reconstruction is considered as a statistical inference problem, where the signal to be reconstructed is treated as a random probability measure. As a consequence, the whole emission probability distribution is reconstructed, unlike in EM-ML or MAP where only one point (the emission value that minimizes the cost function) is estimated, and credible intervals or the standard deviation of the distribution can be derived as quantitative measurements of the uncertainty. Being non-parametric, the method offers a highly flexible framework for the definition of a priori laws and can account for weak hypotheses. This approach is particularly robust to small sample sizes and it is expected that NPB might a significant reduction in injected dose or acquisition duration (Fall et al 2011). The NPB reconstruction algorithm has been extended to the 4D case (space + time) by including time in the model (Fall et al 2011). The tracer pharmacokinetics and its input function are estimated in a probabilistic framework, and functional volumes with their associated uncertainty are estimated simultaneously. The NPB algorithm has been implemented and validated for two PET scanners: one dedicated to whole-body imaging in oncology and the other to brain imaging (Fall et al 2011). A hybrid PET-MRI system provides complementary anatomical, physiological, metabolic, and function information that are spatially and temporally correlated. These multimodality data obtained during a single study should enhance the clinical evaluation of several neurological and oncological pathologies, and facilitate therapeutic monitoring. Yet, the best way to combine these multimodal data is still unknown. Rather than a simple juxtaposition of modalities, the optimal use of a PET-MRI system for a better characterization of the disease might require the integration of various physiological parameters at the voxel level. CEA-LIST and CEA-SHFJ propose to contribute to this task by applying their expertise in NPB methods in 4D imaging. In a first step, we propose to include in the 3D and 4D PET NPB reconstructions the possibility to share common structures with anatomical T1 and T2 MRI. This approach relies on a hierarchical clustering that is already used in the 4D NPB reconstruction, consisting in associating several spatial components with a common kinetics. For a joint PET-MRI reconstruction, a Bayesian nonparametric regression model (Dirichlet Process Generalized Linear Model) can be used to segment MR images. This technique allows for a structuring of the MR image in spatial clusters that can be shared with a PET NPB reconstruction. In a second step, an additional clustering level will be considered for the inclusion of other type of MR information, in particular using functional MRI data. New hierarchical structures will thus be shared between functional MRI and PET. Sharing anatomical, functional and metabolic structures may contribute to reduce discrepancies observed when estimating parameters separately from both modalities (e.g. cerebral perfusion). In addition, this hierarchical 6

199 modeling enabled by PET-MRI systems may open new opportunities to visualize and interpret PET-MRI data. Indeed, based on the shared modeling, anatomical, functional and metabolic information could be gathered in a consistent probabilistic way, leading to a phase space distribution representation (in the manner of enhanced or hyperspectral imaging). This distribution, combined with its uncertainty provided by the Bayesian approach, may also reveal relevant for a more biologically guided radiotherapy treatment planning ( 2.2.2). By beginning of 2016, we expect completing the development and implementation of hierarchical NPB PET-MRI reconstruction software tools. The demonstration of the relevance of hierarchical structured approach for simultaneous PET-functional MRI in pharmacology studies of central nervous system drugs and in neuropsychiatry ( 2.2.3) is also planned. In the long term, molecular and functional multiparametric distribution estimation software tools, based on hierarchical structured analysis described above and Bayesian posterior uncertainty, will be developed and validated PET-MRI image segmentation (IMT, IMNC) In many applications, image segmentation is required at some point of the analysis, for instance when assessing the texture of a tumor (either in PET or in MRI), when defining the gross tumor volume or the biological tumor volume for treatment planning in radiotherapy, or when calculating kinetic parameters in brain studies. In PET, segmentation is always challenging due to the limited spatial resolution in PET images (from 2 to 8 mm depending on the PET system from scanner dedicated to brain research to whole-body clinical scanners). Assisting PET image segmentation by incorporating MR images presenting a high spatial resolution (~1 mm for anatomical MRI) is therefore appealing. Methods have already been developed to take advantage of high resolution images in PET segmentation tasks (e.g., Shidahara et al 2009, Bousse et al 2012). A possible strategy consists of deriving an initial tumor localization from PET data, which is then used to constrain a deformable model for accurately segmenting the tumor in high resolution images (Rouchdy et al 2011, Wojak 2010, Wojak et al. 2010). The latter scheme allows for many refinements such as performing tumor segmentation into parts by combining deformable models and fuzzy sets (Khotanlou et al, 2009), or jointly exploiting the information contained in multi-protocol MRI scans using multi-phase and multi-channel level set techniques (Israel-Jost et al 2008).The limitations of these methods are currently twofold: first, most of them are relatively sensitive to the spatial registration accuracy between the images, second the management of possible mismatches between information provided by the two imaging modalities remains an issue. Several aspects will be investigated to move forward in that research. Since 2006, IMT-Télécom ParisTech has performed seminal work on structural knowledge modeling (such as fuzzy spatial relations embedded in a graph (Bloch 2006) or ontological representation (Hudelot et al. 2008)) with the aim of guiding segmentation and recognition of structures in images, based on the fact that in both normal and pathological contexts, spatial relations are much more stable than shape information that is highly prone to individual variability. Sequential (Colliot et al. 2006, Fouquier et al. 2012) and global (Nempont 2009) constraint satisfaction schemes have been elaborated, yielding promising results on tumoral MR data. Building on these works, we will investigate the use of structural knowledge and spatial reasoning for modeling and understanding the structure and evolution of tumors within their anatomical context from PET-MRI data. Research will be carried out along two directions: (1) performing tumor segmentation using novel deformable tumoral organ models incorporating weak constraints on tumor location; (2) assessing the impact of a tumor on adjacent structures thanks to a description of image content jointly in qualitative and quantitative terms. To comply with the foreseeable variety of PET-MRI protocols, which will likely comprise multiple MR acquisitions delivering data with potentially different dimensions (eg T2+functional MRI) and statistics (eg T2+DCE-MRI), a unified and versatile framework for measuring similarity/discrepancy in multimodal multi-channel contexts is required. IMT-Télécom SudParis has previously developed region-based segmentation schemes using information-theoretic similarity measures in the level set framework (Rougon et al 2006). Recently, novel high-dimensional geometric entropic estimators have been identified (Hamrouni-Chtourou 2012), paving the way for multi-feature multi-channel statistical segmentation schemes that will be developed in this project. For specific anatomical territories investigated via multi-protocol MRI (eg abdominal and thoracic regions undergoing cardio-respiratory motion), technological constraints are likely to limit the applicability of motion correction within reconstruction ( ) to a subset of MR data. Hence, MR-based retrospective registration will be needed for aligning the remaining MR images. In addition, multimodal nonrigid registration will remain a need in longitudinal PET-MRI studies and radiotherapy planning. Depending on the PET-MRI protocol, various alignment strategies will be investigated based on IMT previous experience: (1) landmark-based: developments will rely on a nonlinear registration method developed by IMT-Télécom ParisTech, combining a breathing model with constraints on structure interfaces and tumors, which was shown to yield physiologically consistent results for PET-CT (Chambon et al. 2011, Moreno et al. 2008); (2) voxel-based: relying on a versatile multimodal highdimensional statistical registration model developed by IMT-Télécom SudParis (Hamrouni et al 2011). An option to deal with the uncertainties associated with the real match between the structural or functional edges present in the images to be combined is to propagate the uncertainties associated to these edges in the subsequent quantification task so as to associate an uncertainty to the measured parameters. The IMNC group will investigate this option, with the aim to take advantage of priors derived from MRI images to segment PET images while providing a standard deviation associated with the parameters derived from the PET region. 7

200 Short term results include the development, implementation and validation of PET-MRI segmentation approaches, as well as the demonstration of the quantitative impact of using MRI-guided PET segmentation in PET image quantification Multiparametric tumor imaging (IMNC, IMT, IR4M) Context and Methods Tumor physiopathology cannot be captured by a single modality, let alone by a single image-derived parameter. Depending on the cancer type, diagnosis or prognosis is best achieved using a given modality or biomarker. IMNC has a broad expertise in assessing the role of different parameters to characterize tumor lesions and/or early response to therapy in PET, including the Standardized Uptake Values (SUVs), metabolic volume, total lesion glycolysis, metabolic glucose rate or texture indices (Tylski et al 2010, Hapdey et al 2011, Buvat et al 2012, Maisonobe et al 2013, Soussan et al 2013). IMNC has also largely studied the entanglement of metabolic activity measurement with metabolic volume estimation caused by partial volume effect, contributing to develop and assess partial volume correction methods (Soret et al 2006, Soret et al 2007a, Soret et al 2007b, Hutton et al 2012, Maisonobe et al 2013). The availability of MR data to complement PET is an opportunity to revisit lesion characterization by providing a more complete picture of tumor features in terms of metabolic activity, metabolic volume, microvascularisation, perfusion, hypoxia, cellular density, cell death, growth factor expression, neoangiogenesis, and heterogeneity in various respects. For instance, combining DW-MRI and [ 18 F]FLT-PET may allow for determining the overall proliferative capacity for a tissue region; co-analyzing DCE-MRI and [ 18 F]FMISO- PET may result in elucidating the spatio-temporal relationship between angiogenesis and hypoxia in vivo. However, in spite of the steady increase in quality and variety of quantitative imaging biomarkers, data from different modalities have not been effectively integrated to provide a comprehensive assessment of tumor status. Developing tools for mining information from the measured parameters is thus mandatory to enable a more accurate quantification / decision than the one based on a single value or parameter map. Such tools, which do not currently exist for PET-MRI, will be designed at the lesion scale, where a tumor is described by a few global parameters for each modality, and at the voxel scale, where a tumor is analyzed locally across modalities Lesion scale : multiparametric tumor characterization We will elaborate on the idea of profiling tumors using feature vectors instead of scalar values, and performing multivariate data analysis in higher dimensional feature spaces to classify lesions and predict/assess tumor response to treatment. This requires solving two coupled issues: (1) variable selection, ie identifying a relevant information subspace from the feature-vectors derived from each modality; (2) optimal decision ie accurately classifying individual tumors or tumor response in the reduced-dimension feature space. Approaches such as Principal Component Analysis, Independent Component Analysis or non-linear variants of these, in particular Support Vector Machines (Sahbi et al. 2011, Aldea 2009), will be studied. Large-size databases needed for building relevant training and test samples for these techniques will be collected by the Nuclear Medicine Departments (IGR, SHFJ) involved in the project. Because the optimal information to characterize lesion or assess tumor response is expected to highly depend on the lesion type and therapy, research will aim at developing a generic methodology instantiable to a variety of pathological and clinical contexts. It will rely on IMNC previous work on index comparison via simple statistical approaches (Maisonobe et al 2013, Soussan et al 2013), which will be extended to vector classification using more sophisticated multivariate analysis. The methodology will be illustrated on a few protocols for which combining PET- and MR-derived indices is expected to improve tumor classification or tumor response assessment ( 2.2.1) Voxel scale : multiparametric tumor imaging Beyond comparing two values (before and after/during treatment) as suggested by the EORTC (European Organization for Research and Treatment of Cancer) or PERCIST (PET Response Criteria in Solid Tumors) standard recommendations (Young et al 1999, Wahl et al 2009), IMNC has worked on parametric imaging methods taking full advantage of image information to assess tumor response. In particular, IMNC developed a Gaussian Mixture Model (GMM) approach to characterize local changes between two registered PET images using a feature space combining inter-image differences and baseline scan values. The resulting parametric image depicts regions where metabolic activity has increased, decreased, or remained stable (Necib et al 2011). These images, which clearly reveal tumor heterogeneity including necrosis and resistant areas (Maisonobe et al 2012a), may also be used for radiotherapy treatment planning. Several strategies for extending this technique to MRI will be studied. Following Galban et al (2011), two parametric images, respectively describing PET and MR data changes, will be co-analyzed to determine if the joint change in metabolic activity and in some relevant MR feature improves treatment assessment. GMM-based classification in a feature space combining PET and MR image initial values and inter-image differences (possibly for several PET and/or MR data types) will be also investigated. To characterize tumor response in longitudinal studies involving more than two scans, the factor analysis method described in (Necib et al 2008, Maisonobe et al 2012b) will be extended to jointly process PET-MR data acquired before and during treatment. Data normalization and spatial resolution inconsistency will be addressed. Normalization will be first achieved empirically, weighting PET and MR data similarly unless prior information suggests another choice. Alternatively, the direct image comparison approach based on midway histogram equalization and statistical change detection, developed by IMT-Télécom ParisTech to extract tumor growth areas in longitudinal anatomical MR studies (Angelini et al 2012), will be extended to diffusion MRI and PET, taking into account noise and data properties all along the processing chain. Spatial resolution inconsistency will be addressed using multiresolution techniques (eg wavelet analysis). 8

201 By February 2016, we will develop and implement a general methodology for selecting and combining local parameters derived from PET and MR images, to improve tumor classification, prognosis, and tumor response assessment. We also expect to demonstrate the relevance and usefulness of this methodology on specific PET- MR cancer imaging protocols ( 2.2.1). We will also extend parametric imaging methods initially developed for PET or MR only to make them appropriate for the effectiveness of treatment between two PET-MR scans or more. Again, the added value of the parametric imaging methods on specific PET-MRI cancer imaging protocols will be studied on specific PET-MR cancer imaging protocols ( 2.2.1). These works will also contribute to identifying the PET-MR imaging protocols (including information processing) most appropriate to refine diagnosis or prognosis in various cancer types Extracting brain PET-MRI joint structures for statistical analysis (CEA-Neurospin, CEA-LIST, CEA- SHFJ, INSERM U1000) Many applications of joint PET-MRI image will require statistical analysis of these images, across subjects for group studies in clinical research, and longitudinally on a single subject in clinical practice. This statistical analysis might be challenging due to the number of parameters to investigate and associated issues: the small number of available samples compared to the large size of the multi-modal images and the possibly low Signal-to-Noise (SNR) of the functional images (be they MR or PET images). To obtain an acceptable compromise between sensitivity and specificity when performing inference, it is thus essential to account for the structure of multi-modal images: not only do the two modalities share information, but also this information is best captured by considering image patterns that match the underlying physiopathology rather than voxels. Indeed, a voxel-level statistical analysis is plagued by fundamental limitations such as multiple comparisons or the curse of dimensionality. Taking into account the image structure in the statistical analysis is typically performed by means of a dictionary learning procedure: different spatio-temporal components are identified based on a linear mixing model together with a prior on the components of interest. Standard priors include sparsity, smoothness or being piecewise constant in the temporal or spatial domain. With respect to alternative approaches (clustering, independent component analysis), sparse dictionary learning has some key advantages: 1) unlike clustering, it makes it possible to obtain overlapping components; 2) it performs all estimation procedures by minimizing a single criterion instead of multiple inconsistent steps; each step of the alternate optimization is a convex problem, which benefits to the stability of the solution; 3) it can be implemented using online versions, hence with reduced memory and computational costs (Mairal et al 2010); 4) it is straightforwardly extended to multiple datasets (including multiple subjects or multiple modalities) with adaptive constraints on the kind of similarity imposed on spatial and functional components. This setting has been used successfully on resting-state functional MRI (Varoquaux et al 2011). The Parietal group has developed with many partners a public library that implements this approach ( and has the ability to enhance it with fine-tuned priors and penalties to accommodate the constraints of the data. For instance, complex structures can be recovered more easily by using hierarchical spatial penalties that encode multi-scale priors on the regions of interest (Michel et al 2011, Jenatton et al 2012). Importantly, these approaches will be adapted to extract structures jointly from PET and MRI without imposing exact correspondence: a structure may be present in one modality and not the other. For this purpose, we will draw from the expertise of the Parietal group in resting-state data analysis (Varoquaux et al 2011), as in this unguided experimental paradigm matching of functional structures across time points and subjects is no guaranteed. More recently, evidence has increased that a single discriminative or statistical model based on fixed segmentation of the image would not be optimal in terms of performance, and that detection sensitivity and accuracy can be improved by using a judicious combination of spatial modeling, data randomization and sparse model fitting or statistical test (Varoquaux et al 2012, Bühlmann et al 2012). The Parietal group has set up such a framework for functional MRI data analysis (Varoquaux et al 2012) but this can be used as well in many other settings, such as the detection of hyper/hypo-signals, the classification of images, or the detection of outliers. We will perform segmentation of structures jointly in the two modalities ( 2.2.1) and use these for statistical and classification analysis in clinical studies. We will rely on state-of-the-art implementations of dictionary learning using efficient estimation (online learning) and tunable criteria (the penalties of the analysis models). In particular, we will focus on understanding the functional impact of psychiatric disorders ( 2.2.3). For this purpose, joint analysis brings strong benefits as PET gives access to quantitative brain metabolism parameters while functional MRI has a good spatial resolution that will enable to relate the functional differences to specific brain structures. Within three years, we will design methods for the joint statistical analysis of multi-subject or longitudinal datasets of PET-functional MRI volumes. We will also start using these methods for clinical studies of brain pathologies ( 2.2.3) using the PET-MRI scanner Breakthrough applications for PET-MR imaging Up to now, most work has been dedicated to solving the technical issues associated with PET-MRI and although PET-MRI systems are now a reality, there is still a lot of room for technical and methodological improvements as described above. The huge task of defining in which research and clinical applications PET-MRI may be superior to PET-CT has hardly begun. Any statements on the clinical utility of PET/MR are thus speculative at the moment. Our project aims at identifying such research and clinical applications for which PET-MRI might be a definite asset, focusing on the domains in which the medical scientists of the PSC are worldrecognized leaders. The areas of cancer and brain imaging that we will investigate through the eye of PET-MRI 9

202 are full of unsolved issues and therefore bear a large potential to evidence the far-reaching applications for which PET-MRI will become a major player, with a possible large impact on public heathcare in the future Making a difference in specific oncologic applications (CEA-SHFJ, IGR, IR4M-IRCIV, IMNC) Although hybrid PET-CT has become a key player in tumor staging and assessment of therapy response in numerous oncology applications, significant clinical data are beginning to accumulate which suggest that there are some situations where MRI may have an advantage over CT combined with PET. It is not uncommon today for oncology patients to have a PET/CT and an MR scan providing complementary diagnostic data. In addition, MRI offers an alternative morphological imaging approach avoiding additional radiation exposure in pediatric patients. To clarify the role of PET/MR in the management of cancer patients, and act as a pilot center for identifying the added value of PET/MRI compared to PET/CT, we identified a number of applications where PET/CT or MRI alone have definite limitations. We will study the value of PET/MRI for these applications listed below, considering PET with anatomical MRI, but also investigating the combination of PET with functional MR. These investigations will directly benefit from all methodological developments described in 2.1, in terms of protocol optimization and quantification methodology Phase I evaluation of anti-angiogenic treatments for personalized medicine Over the past six years, targeted therapy (O'Connor et al. 2012) with tyrosine kinase inhibitors (TKIs), vascular endothelial growth factor (VEGF) inhibitors, and mammalian Target Of Rapamycin (mtor) inhibitors have become the standard of care for a variety of malignancies, including renal cell carcinoma (RCC), gastro-intestinal stromal tumours (GIST), colo-rectal cancer, breast cancer and hepatocellular carcinomas (HCC). These targeted therapies complicate the evaluation of tumor responses, which are frequently underestimated. For instance, despite significant clinical improvement, the radiological response rate using the classical RECIST criteria demonstrated only 15% partial response and 70% stable disease in metastatic RCC. Thus, traditional evaluations based on tumor size criteria are no longer effective, as necrosis may occur without reduction in tumour size. The goal of functional and metabolic imaging (La thangue et al 2011, Provenzale 2007) in Phase I trials is to provide adapted tools to monitor patients with early tumor response surrogate markers both in MRI (Leach et al 2012) (eg, blood flow, blood volume, K trans) and in PET (eg, tracers targeting VEGFR2, Platelet-Derived Growth Factor Receptors (PDGFR), Integrins and mtor receptors) (Mitrasinovic 2012). This work will be performed in close collaboration with IRCIV, and with SITEP/IGR ( which is the first clinical research facility in Europe in terms of recruitment of patients in phase I trials (600 patients per year) Head and neck cancer MRI is considered as the modality of choice for imaging head and neck tumors because it provides excellent soft tissue contrast that is useful for differentiating masses from neighboring tissues. The choice of therapy for these tumors mainly depends on tumor location, the invasion of adjacent structures and on the presence of metastases. However, [ 18 F]FDG-PET has proved useful for the detection of cervical lymph node metastases in comparison with both CT and MRI. Because MRI and PET/CT are currently used for primary staging and restaging in these patients, a combined PET/MRI appears to be an excellent alternative for imaging these malignancies. For the detection of the primary tumor in patients with suspected head and neck squamous cell carcinoma, the sensitivity of PET/MRI images was 100% in a prospective study (Nakamoto et al 2009) and promising results in the initial staging of head and neck tumours have recently been reported (Platzek et al 2013). We will thus investigate the role that PET/MRI might play in the management of patients with head and neck tumors, especially in the context of tumor staging Hepatocellular carcinoma For the detection of small primary hepatocellular carcinoma (HCC < 2 cm), the soft-tissue contrast of liver MRI is clearly greater than that of PET and CT especially when liver-specific contrast medium is used, yielding a HCC detection sensitivity around 85%. In contrast, the sensitivity of [ 18 F]FDG-PET for detecting HCC is between 50 and 70%, mostly because well-differentiated HCC has a high rate of gluconeogenesis comparable with normal liver tissue, resulting in similar uptake of [ 18 F]FDG. Among PET tracers, [ 18 F]fluorocholine is more sensitive than [ 18 F]FDG for detecting well-differentiated HCC. The sensitivity of [ 18 F]FDG-PET/CT was significantly better in less differentiated HCC and for detection of distant metastases. Lymph node and distant metastases occur predominantly in poorly differentiated or highly aggressive undifferentiated HCCs and thus are frequently [ 18 F]FDG-avid. A prospective study found that PET in combination with morphologic imaging detected more lymph node metastases than did stand-alone CT and MRI. For HCC patients, the major advantage of PET/MRI scanners in the diagnostic algorithm is therefore to have a single examination compared to sequential MRI acquisitions for evaluation of primary tumor extent together with a PET/CT for whole-body staging performed with [ 18 F]FDG or [ 18 F]fluorocholine (Buchbender et al 2012, Talbot et al 2010). We will therefore investigate whether a hybrid PET- MR scan would indeed be more valuable than a [ 11 C]choline-PET/CT scan followed by a complementary MRI scan. We also intend to demonstrate at least a similar diagnostic accuracy, and possibly better performance, in the detection and localization in patients with chronic liver disease and suspected liver nodules Prostate cancer Anatomical and functional imaging modalities contribute to the succeeding stages of prostate cancer management and combined PET/MRI data might provide substantial advances. Merged PET/MRI might guide biopsy for cancer diagnosis and help to predict tumour aggressiveness. Lymph node staging and detection of recurrences might also benefit from simultaneous PET/MRI techniques, including diffusion-weighted MR, 10

203 especially for small volume metastases. Bone staging would be enhanced, combining PET results to MRI, to improve bone lesions diagnostic accuracy. DCE-MRI and MR spectroscopy might also benefit from the association to PET molecular information to detect local recurrence (Park et al 2012, Fortuin et al 2012, Beer et al 2011) PET-MRI in malignant lymphoma Due to the increased glucose metabolism of most lymphoma subtypes, PET with [ 18 F]FDG has become an established modality for lymphoma staging. Furthermore, therapy monitoring in lymphoma patients helps identify non-responders, who may benefit from aggressive therapy. On the other hand, several studies have shown the good diagnostic accuracy of whole-body MRI including Diffusion-Weighted Imaging (DWI) in lymphoma patients when evaluating the apparent diffusion coefficient (ADC) values. An integrated PET/MRI protocol incorporating DWI should therefore provide added value in primary lymphoma staging and follow-up. As lymphoma occurs in young patients and repeated PET scans are needed for assessing the response to treatment, the reduced radiation exposure is an important advantage of PET/MR for this indication (Platzek et al 2012, Punwani et al 2012) Brain MRE in patients with glioma Brain MRE ( ) will be assessed on healthy subjects and patients with glioma. The clinical protocol will be performed on 1.5 and 3 T MRI scanners at CEA-SHFJ and Bicêtre Hospital before being implemented on the PET-MRI system. Patients will be recruited at IGR. A first atlas of shear elasticity and viscosity of human brain in healthy subjects will be established from full brain MRE on 24 subjects. Reproducibility study will be carried and viscoelastic moduli will be determined according to the subjects' age and sex. Brain MRE of 24 patients with glioma will be compared to outcomes on healthy subjects and to independent gradations of the tumors. The 3D reconstruction of the viscoelastic maps from the acquired MRE data will involve new approaches currently developed at IR4M and Beaujon to account for the structural and mechanical anisotropy and heterogeneity of the brain tissue. Diffusion tensor imaging (DTI) will be used to guide a hexagonal-based reconstruction and the extracted mechanical parameters will be studied for their added value to PET data. MRE will then be implemented onto the PET-MRI system and the extracted data will be compared to results previously obtained on the 1.5 and 3T MRI systems Paediatric applications In paediatric oncology, [ 18 F]FDG-PET and MRI represent the most powerful functional and morphological imaging modalities. A recent study showed that MRI is the method of choice during primary diagnosis while [ 18 F]FDG-PET is more important during follow-up or in multifocal disease. Then, paediatric tumours that require both PET and MR imaging may be more adequately evaluated by combined PET/MRI (Mueller et al 2012, Pfuger et al 2012). We therefore also plan to investigate the role of PET/MRI in young patients. The collaboration with CEA-LIST in the framework of that project will also make it possible to precisely quantify the dosimetric advantage of replacing protocols involving PET/CT by protocols involving PET/MR for those patients. Indeed, the MRI-guided PET image reconstruction method proposed in could allow for a decrease of the activity injected for PET acquisition and the PET-MRI based treatment planning could also reduce the total dose needed to obtain the same degree of tumor cell damages A revolutionary approach for biologically guided radiation therapy? (IGR, IC-CPO, IMNC, CEA-LIST) Objectives and methods The main goal of current treatment techniques such as intensity modulated radiation therapy (IMRT), stereotaxic arc therapy, and proton therapy, is to improve the local control of the tumor by increasing the dose to the tumor while reducing the dose to sensitive organs, hence reducing toxicity. While sophisticated devices are now available to deliver the dose very precisely in 3D or even 4D space, a major issue that currently remains unsolved is where the dose should be deposited to optimize the treatment outcome. Dose planning is currently mostly performed based on the patient's anatomical data provided by CT and/or MRI, ie accounting for the geometry of the tumor only. Yet, there is currently a growing interest in shaping the dose to the biologically active functional tumor volume, to also account for the tumor metabolic activity and to its relative sensitivity to radiation. This has been performed so far using PET-CT images, showing that biologically guided radiation therapy (BGRT) has the potential to improve the local control of the tumor (Vanderstraeten et al 2006a, Vanderstraeten et al 2006b, Mac Manus et al 2009, Tsien et al 2012). Compared to PET-CT, the new hybrid PET-MRI systems currently available have many additional features: MRI provides a better soft tissue contrast compared to the CT image, MRE regionally probes the biomechanical state of the probed tissue, and functional MRI coupled with PET enables the joint assessment of several functional/metabolic/molecular tumor features that might be extremely useful to better delineate the biologically active tumor region to be targeted. In addition, having a precise picture of the functional MR signal coregistered with the PET signal thanks to a PET-MRI system might be crucial for BGRT, where a posteriori registration of images acquired at different time on different systems would be sub-optimal. This is all the more true to precisely delineate sub-regions in a heterogeneous tumor, like hypoxic areas, or regions presenting high metabolic heterogeneities (Szeto et al 2009). PET-MRI might thus appear as a revolutionary approach to BGRT, providing an exquisite combination of details regarding the biological structure of the tumor to yield a biologically-based treatment plan for radiotherapy, either photon or proton-based. 11

204 A strength of our PIM consortium is that it gathers all expertise to address this challenge, including expertise in PET and MR image quantification and image segmentation, treatment planning, measurement and control of the clinical dose, both in conventional radiotherapy and protontherapy. We therefore propose to take advantage of the use the co-registered functional regions identified on PET-MRI images to define the functional sub-volumes that will be used to plan treatment in radiotherapy and conform the dose distributions to these plans. This task will rely on methodological tasks described in 2.1. Based on a functional multiparametric biological region delineation, the tools used in conventional optimization routine will be used to increase the dose in the target areas of the tumor that show a higher metabolic activity or are highly radiation resistant. Monte Carlo (MC) methods will be used to calculate the dose distributions in the patient images of the patient corresponding to the biologically-based treatment plan. The advantage of using MC methods during this step is to avoid approximations performed in conventional Treatment Planning Systems (TPS), and to account for the different tissue composition that MRI can identify to estimate the energy deposition, hence the dose, more accurately. This task will require specific methodological developments to convert MRI signal (as a function of the sequence used) into tissue composition ( ). The demonstration of the usefulness of deriving biological treatment plan from PET/MR includes two steps. First, the conformity of the dose delivery to a biological treatment plan has to be checked. We suggest to complete this task based on measurements performed using dosimetric gels and experimental means (two medical accelerators, a treatment planning system, dosimetry tools and computational resources) from the CEA-LIST and upcoming DOSEO platform. Measurements will be made in the exact configuration of the treatment plan, to visualize and verify that the implementation of the treatment agrees with the prescription from a geometric and a dosimetric point of view. As a second step, the impact of biologically-based treatment plans compared with anatomically-based treatment plan will be assessed in collaboration with clinical experts from the IGR and the IC-CPO. The changes induced by accounting for the biology of the tumor will be quantified, using methods similar to those previously reported reported (Low and Dempsey 2003, Petit et al 2009, Madani et al 2011). The gain in local control of the tumor and reduction in toxicity will require longitudinal studies, that will be made possible thanks to the IGR and IC-CPO partnerships, although results will not be available by 2016 due to the insufficient follow-up of the treated patients. Models for predicting outcomes, such as EUD (equivalent uniform dose) to estimate the gain in local control of the tumor (Steward et al 2007) may also be developed by CEA-LIST to validate the interest of the BGRT in collaboration with clinical experts Practical proof of concept: Brain tumors treated with the Novalis Tx radiosurgery machine In brain tumors, treatment planning and the evaluation of local response to therapy are usually based on conventional MRI and CT. Although these investigations display the brain anatomy with high accuracy, contrast enhancement, hypo- or hyperintensity on T2-/flair-MRI are not tumor specific. Many recent studies strongly suggested that an important part of active tumor tissue can also be located in the areas within non-enhanced or iso-intense appearance (Galban et al 2011). Moreover, after surgery and just before adjuvant radiation (also after radiation or chemotherapy), treatment-related changes, such as blood-brain-barrier (BBB) disturbance with enhancement or vasogenic edema are visible, but cannot be clearly differentiated from viable tumor tissue. New concepts such as pseudo-progression or pseudo-remission were introduced for brain gliomas, underscoring the fact that conventional MRI is insufficient for the visualization of tumor tissue after therapy. Advanced MRI methods such as diffusion/perfusion MRI and MRE are promising for evaluating the (peri)tumoral microvasculature and cell density as well as the mechanical properties at the tissue level, before and after treatment (Dhermain et al 2010, van der Heide et al 2012). Yet, histopathological data validating the sensitivity and specificity are scarce. Hence, routine integration of diffusion / perfusion MRI and MRE in radiation treatment planning should be considered premature. MRI spectroscopy is a true metabolic exploration at the cell level, but this approach remains relatively laborious, with a rather low spatial resolution. Therefore, there is an urgent need for implementing new and practical imaging approaches to increase accuracy and specificity in tumor delineation for high precision radiotherapy. In that context, imaging the biological and molecular characteristics of tumor tissue by PET is extremely appealing. Various types of radiotracers may be used in brain tumors to optimize tumor delineation and to image the tumor microenvironments. Amino acid (AA) - PET (eg [ 11 C]methionine ([ 11 C]MET)and 2[ 18 F]fluoroethyl-Ltyrosine ([ 18 F]FET)) could be used for delineating in brain gliomas, metastases and benign cranial tumors such as meningiomas and glomus tumors. The higher sensitivity / specificity of AA-PET in the grading of gliomas in comparison to CT and MRI was strongly suggested (Grosu et al 2005). It is also anticipated that the ability to image the tumor microenvironment in vivo through PET imaging of hypoxia will provide useful prognostic information regarding factors that influence response to treatment (Yamamoto 2012b). Major determinants of tumor hypoxia include the structure and functionality of tumor vasculature and the degree of angiogenesis. By combining DSC-MRI providing vasculature/perfusion information with [ 18 F]FMISO-PET imaging demonstrating hypoxia, new insights into the relationship between tumor hypoxia and vasculature can be expected (Kawai et al 2011). It is obvious that accurate co-registration of PET and MRI images, as provided by combined PET-MR imaging system, will be essential for such investigations. We will therefore investigate the combination of DSC-MRI and [ 18 F]FMISO-PET first in the pre-treatment evaluation of tumor grading and hypoxic areas, then planning for heterogenous radiation therapy and finally monitoring treatment response of selected high-grade brain tumors, mostly because of their intrinsic heterogeneity, at the radiological and biological level. Selected patients referred to the radiation therapy department of IGR will be presented to the weekly brain tumor board for stereotactic hypo-fractionated image- 12

205 guided irradiation. Irradiation will be performed using the Brainlab IMRT software under a Novalis TX LINAC, a noninvasive stereotactic radiosurgery machine. Importantly, the conventional anatomical gross target volume (GTV) will be first created, strictly following the available EORTC guidelines on the basis of a separate diagnostic MRI data set only and then compared with the biological target volume delineated from PET-MRI hybrid imaging. A hypothesis is that biologically active areas will be more predictive for sites of recurrence than anatomical enhanced regions, opening a perspective for a real biologically-guided escalated dose scheme, using IMRT and simultaneous integrated boost Fine tuning of treatment plans in protontherapy Proton therapy is considered as one of the most conformal approaches nowadays in radiation therapy. The question of where to hit to kill tumor cells is therefore of utmost importance in protontherapy. PSC will be the only French campus where PET-MRI imaging will be available next to a protontherapy center. The IC-CPO team has long been interested in the issue of selective irradiation for improving local control of radioresistant tumors, in particular chordomas. IC-CPO is the first to have published recently on the usefulness of conventional imaging (MRI/CT scan) and [ 18 F]FMISO-PET/CT in chordomas (Mammar et al 2012). The impact of the methodological developments presented in will therefore be carefully investigated in the context of protontherapy. We will study two issues more specifically: - The conversion of MRI into tissue elemental composition ( ) is even more important with proton beams compared to photon beams, where a precise range of the particles is used to protect distal organs and to reduce the integral dose. We will investigate whether MRI, using appropriate sequences, allows one to reduce the uncertainty associated with tissue elemental composition based only on the CT, to what extent, and with which consequences on the treatment plans, in particular on the safety margins that are systematically applied to account for these uncertainties. The impact of a better identification of the tissue composition on the deformation of the Bragg peak and on the superposition of the pencil beams in presence of complex tissues inhomogeneities will be investigated. These studies will be based on real patient treatment plans, and will involve MC based models of calculations. To that end, we will use and compare two simulation platforms: (1) The GATE MC simulation platform (Jan et al 2011), which development is led by IMNC and CEA-SHFJ, and which is currently the only platform enabling simulation of radiotherapy treatments, including protontherapy, and imaging in the same framework. This platform will also make it possible to investigate other aspects introducing uncertainties in treatment delivery, including organ motion, that can be accounted for in GATE. (2) The second platform has been developed by the CEA-LIST in the framework of the PROUESSE ANR project (ANR -09-COSI : Proton therapy: development and validation of a simulation tool and accurate and rapid Monte Carlo simulation for dose deposition). A fast MC code, called PROUESSE, has been developed in order to improve usability of MC simulations for clinical applications, in collaboration with several teams, especially CEA-LIST and IC-CPO. This code incorporates toolkits and a comprehensive architecture for passive proton therapy simulations, patient handling or voxel s calculations, and dose scoring. Users import DICOM-RT/ION and a Hounsfield units conversion is performed automatically. Beam inputs can come either from parameterized sources or phase space files. Output includes 3D dose and/or phase space files. The interest of the fast PROUESSE code is that it can be used for daily clinical applications in complex patient voxelized geometries. - A second study that will be carried out to start with is to evaluate and quantify the incidence of new approaches of BGRT on the planning of treatments with proton beams, in particular for those locations treated at the protontherapy center in Orsay, in particular skull base chordomas (Fuji et al 2011, Nguyen et al 2008, Rutz et al 2007, Igaki et al 2004). Despite the progress of neuronavigation and microsurgery and the advent of hadron therapy, local control of skull base chordomas remains poor, on the order of 75% and 54% at 5 and 10 years respectively (Munzenrider et al 1999). These tumors, characterized by very slow growth, show different components on the MRI and CT scan. Our preliminary study has demonstrated a high hypoxic cell population as an explanation for this high relapse rate (Mammar et al, 2012). [ 18 F]FMISO, a fluorinated analogue of misonidazole, which undergoes reduction after penetrating the cancerous cell, allows visualization of hypoxic zones. Hypoxia induces an aggressive phenotype, an increasing metastatic potential contributing to tumor progression, and resistance to ionizing radiation and cytotoxic agents. These characteristics are linked to the induction of a certain number of biological changes, including tumor angiogenesis, mutation of p53, glucose cellular metabolism dysfunction (Prekeges et al 1991, Brown et al 1999, Teicher et al 1994). Boost radiotherapy, oriented by conventional imaging (CT scan/mri) and guided by [ 18 F]FMISO-PET, would allow targeting of these hypoxic zones, increasing the dose in an adequate and intelligent manner and improving local control while reducing complications. Functional and metabolic MRI are able to detect metabolic and functional abnormalities beyond the tumor volume seen on conventional MRI, assess early response to treatment, and delineate the regions of high risks for treatment failure (Cao et al 2006). During this year at CPO, it will be possible to deliver a proton with modulated intensity (IMPT) that will allow dose distributions to be shaped in three dimensions and thus have higher dose conformality to the biological target volume detected by PET/MRI device. Another important advantage of IMPT treatments is the decreased production of neutrons and integrale dose. These advances will benefit many pediatric patients. By 2016, we will develop a method to derive tissue elemental composition from MRI sequences and will study the impact of such a definition on uncertainties affecting treatment plans in protontherapy. We also aim at the proof of concept of defining biological target regions and associated dose-painting based on PET/MR imaging for highgrade gliomas and for chordomas. In the preoperative setting, we will perform PET/MR imaging to compare functional 3D tumor mapping to the effective molecular patterns of the tumor data. The practical implementation of 13

206 biological target delineation based on combined DSC-MR / [ 18 F]FMISO-PET for treatment in brain tumor patients treated by the Novalis TX radiosurgery machine will be achieved. The impact of using PET/MRI to define the treatment plan in protontherapy in chordomas will also be determined. On the long run, we expect to demonstrate the gain in local control of the tumor and toxicity reduction for several tumor types, both in conventional radiotherapy and in protontherapy. By working closely with companies developing Treatment Planning Systems (Dosisoft, IBA), we will aim at implementing methods to account for PET/MR biological information in TPS A new insight into the central nervous system sensitivity to drugs and psychiatric disorders? (INSERM U1000, CEA-SHFJ, CEA-Neurospin) Central Nervous System (CNS) pharmacology Among various applications, MRI-guided PET image reconstruction could be advantageously applied to pharmacology studies of central nervous system (CNS) drugs such as the ones performed at the CEA-SHFJ. Indeed, pharmacokinetic-pharmacodynamic (PK-PD) modeling aims at describing the mathematical relationship between pharmacokinetic parameters such as the administered dose, plasma concentration kinetics and the effect of a drug. In the coming studies, instant effect might be estimated using functional MRI and correlated with simultaneous determination of plasma and brain kinetics that will be obtained using PET imaging. Brain PK of numerous CNS compounds has been studied by PET imaging experiments and CEA-SHFJ has been involved in this field for years. Drugs may be isotopically labeled in house (CEA-SHFJ radiochemistry unit) with a positron-emitter such as carbon-11 and/or fluorine-18, thus leading to radiotracers showing the same distribution as the corresponding parent compound (in some cases, analogs of drugs may also be labeled with for example fluorine-18 permitting non-invasive CNS explorations). The use of a radiolabelled drug will therefore permit to quantitatively measure its concentration in selected brain areas by PET. Information on receptor occupancy by a drug on a specific pharmacological target can also be measured by PET. This requires target-selective (already developed or not) PET radioligands and suitable mathematical modeling that is now available to study various brain receptors. Simultaneous functional MRI and PET acquisitions should allow for concurrent brain PK and neuronal activation measurements, in particular for neuro-psychiatric treatments and drugs-of abuse. This could also provide key information in early drug development to optimize the posology of the tested drug. Indeed, it has been shown that functional MRI can be used to quantitatively estimate the pharmacodynamic effect of CNS drugs. This holds for opiates (Khalil-Mahani et al 2013) and nicotine (Yamamoto et al 2012a) under optimized experimental conditions. Receptor occupancy by opiates and nicotine can be simultaneously estimated using validated [ 11 C]carfentanyl (Weerts et al 2012) and [ 18 F]fluoro-A (Zanotti-Fregonara et al 2012) PET protocols. We have already shown that these compounds have to undergo complex interaction with transporters expressed at the blood-brain barrier (BBB) to reach their pharmacological target, thus affecting their brain kinetics (Tournier et al 2011, Cisternino et al 2012). Simultaneous PET-MRI acquisition will therefore be performed in nonhuman primates to study the influence of these transport systems on opiates and nicotine brain kinetics from PET data and provide concurrent information on their consequences on drug response. Also, MRI protocols using the contrast agent Gd-DTPA is the actual gold standard to non-invasively evidence BBB disruption in vivo (Kaur et al 2011). It has also been shown that preclinical MRI can monitor the effects of a given drug on brain perfusion (Ciobanu et al 2012). Thus, concurrent PET-MRI acquisition will be investigated to evidence a transient BBB disruption and study the pharmacokinetic impact of experimental BBB disruption or variation in brain perfusion on some PET radioligands. By 2016, we plan to attest the feasibility of PK plasma/pk brain/pd studies using an integrative PET-MRI system in non-human primates and this in order to to prepare clinical translation. We will also combine MRI and PET to measure the influence of BBB disruption or variation in brain perfusion on selected PET radiotracers kinetics, and use these findings to refine PET kinetic modeling Mental disorders and addictions Because psychiatric disorders such as alcohol and substance-use disorders, anxiety, depression, or psychoses, are among the first disabling conditions in the high-income countries, and are still rising (depression is projected to become the first cause of disability by 2030), objective information is needed on the early effects of their treatments. While the psychopharmacologic drugs and the substances-of-abuse are generally known to modulate brain neurotransmission, it remains unclear how their action on their molecular targets relate with changes in regional cerebral activity implementing the cognitive alterations underlying the symptoms of addiction and psychiatric dimensions. A methodology assessing this relation would be useful for monitoring the mechanisms underlying, e.g. patients s response to treatments. Elucidating the relationships between the molecular targets of drugs and their effects on the brain regions implementing the cognitive functions, a direct application in humans of the sub-project above, remains a challenge due to the limitation in the synchronicity of imaging acquisition between molecular, functional, and structural modalities. We propose to validate the proof of concept that this limit can be overcome using the new PET-MRI integrated system within CEA-SHFJ, focussing on specific brain molecular site, brain region, and cognitive function studied within INSERM U1000. Dopamine neurotransmission can be impaired by substance dependence, and modulated by drugs such as antipsychotics or some antidepressants. Using PET, we previously reported the changes in dopamine transporter radioligand binding to the striatum and extrastriatal regions, in substance-dependent 14

207 patients (e.g. Leroy et al 2007, 2012). Also, using functional MRI in adolescents at-risk for addiction, we recently measured the changes in striatal activation in response to reward anticipation (e.g., Schneider et al 2012), a circumscribed cognitive function. Impairment in this cognitive function is central to the reinforcement-related psychopathology relevant to dependence and affective conditions. Still, the relationship between the dopamine transport and the impairments in reward system functioning remains unknown. Thus, we hypothesize the pharmacokinetics of the radioligand specific binding relates to the striatal activation during a task tapping the reward system. As an initial application, we therefore aim to measure the changes between the variations in radioligand binding to the dopamine sites and the regional activation in patients as compared to healthy controls. To start with, we will focus on the striatum and basal ganglia since these structures are central to the brain and readily segmented, less variable and less susceptible to reconstruction artefacts and partial volume effects than the cortex. Also, the striata are a target for a number of validated PET-radioligands, and their activation in reward function is well documented with functional MRI. In addition, the brain cellular and molecular underpinning of this function is among the best documented in animal models relevant to the pharmacology of addictions and mental disorders. The study will be designed as a cross-sectional comparison of patient versus healthy control groups. Patients will be included in a stabilized and treated state fulfilling international DSM-5 diagnostic inclusion criteria. An amendment for the new PET-MRI system will be required in a protocol that has already all administrative approvals (including promoter, ethics CPP-IdF7 and ANSM approvals) for separate PET and MRI in human controls and patients with mental disorders. PET images will be acquired to determine the specific binding of [ 11 C]PE2I, a radioligand targeting the central dopamine reuptake sites. Acquisition of BOLD functional MRI images will be acquired during a reward task. Both PET and functional MRI methods and associated statistical analyses with voxel-based or region-of-interest approaches have already been applied on-site but using sequential PET and functional MRI image acquisitions at SHFJ (Leroy et al., 2012, 2007; Artiges, et al 2011). Using the new PET- MRI system, acquisitions will be performed separately during the initial period of technical validation of the machine, and compared to the results already obtained on previous PET and MRI systems used by the INSERM U1000 researchers. The MRI-guided PET image reconstruction will be performed by the CEA- SHFJ team ( 2.1.4) while extraction of joint PET-MRI imaging structures for further statistical analysis will be performed in collaboration with the CEA-Neurospin team ( 2.1.7). After determination of the image kinetics in both modalities from the new PET-MRI system, the functional MRI task stimulation procedure will be adapted within INSERM U1000 for synchronous acquisition with PET data according to the radioligand kinetics within the brain regions of interest. By February 2016, we expect completion of acquisition and analysis of data in PET and functional MRI separate modalities in a set of participants, and validation of the new PET-functional MRI results by comparison to the data available within INSERM U1000. Detailed operating procedures for implementation of synchronous PET - functional MRI (fmri) acquisitions in brain studies will be defined. On the longer term, a methodology for synchronous PET-functional MRI assessment of dopamine system and cognitive functioning will be developed and its clinical relevance for assessing treated patients will be demonstrated. Biomarkers most appropriate in PET-fMRI investigation for addiction and mental disorders will be identified. 3. Training actions PET-MRI will require developing new types of training programs adapted to this intrinsic multidisciplinary research tool and the required multidisciplinary profiles of the participants. Most participants to the PIM project are strongly involved in training activities, the list of which is provided below. This project will be an ideal opportunity for many students to learn and develop skills in advanced medical imaging and radiotherapy, by accessing the state-of-theart instruments and technologies in the field, and by participating to the research that will shape the clinical practice of the future. The training activities belonging to the local engineering schools and to Paris-Sud University both in science and medicine will therefore be rationalized into an integrated approach. Actions will be performed to integrate PET-MRI training programs at the interface of the future School of Engineering and School of Medicine, in close collaboration with the PSC Engineering and System Sciences Consortium (CSIS) action, the School of Medicine of Paris Saclay University, the Medical Physics Master of Paris-Sud University, and the INSTN (www-instn.cea.fr). Two persons will be more specifically in charged of this task: Marie Poirier-Quinot and Vincent Lebon who are currently in charge of teaching medical imaging in the Medical Physics Master (headed by Jacques Bittoun). This PIM project is a great opportunity to refocus existing master programs on multimodal imaging and to reorganize the training offer in medical imaging. Discussions are on their way to merge the current EMMI master (European Master in Molecular Imaging) with the Medical Physics Master, leading to a new Medical Imaging Master2 degree. The educational program of this Master2 will explicitely include training on multimodal imaging: PET/MRI, PET/CT, MRI/EEG, EEG/MEG, MRI/US... The partners of this IDEX project who are partly involved in the current EMMI and Medical Physics Masters will actively contribute to multimodal imaging training. The educational program will be adapted to the different backgrounds of the students (Biology, Health sciences and Physics) by the mean of knowledge update modules (i.e. Physics update for biologists, Biology update for physicists... ). In return, the Master2 will provide all IDEX partners with students mastering a wide range of the imaging techniques as well as imaging applications to life science. 15

208 List of training activities in which members of the consortium are currently significantly involved: - EMMI: European Master in Molecular Imaging 1 ( - Institut Mines-Télécom engineering school ( - Master BME-Paris / ParisTech/ Paris Descartes ( - Master IMA - Télécom ParisTech / UPMC (perso.telecom-paristech.fr/~bloch/p6image/ima-prog.html) - Medical Physics Master of Paris-Sud University ( ml) - Diplôme de Qualification en Physique Radiologique et Médicale (www-instn.cea.fr/-dqprm-physiquemedicale-.html) - Institut de Formation Supérieure Biomédicale ( - DES de Médecine Nucléaire (www-instn.cea.fr/-des-de-medecine-nucleaire-.html) - Ecole des Neurosciences de Paris ( 4. Dissemination Dissemination and animation actions towards the scientific (physics and imaging science) [Sci] and medical [Med] communities will be organized with the objectives of raising interest, stimulating research and confronting approaches/best practices in PET-MRI imaging. These actions might include: At the national level: [Sci-Med] Creation of a topical Working Group on PET-MRI within the joint CNRS-INSERM Research Network STIC-Santé 2 (Information and Communication Technology for Healthcare). [Med] Organization of a special session on medical applications of PET-MRI during the annual Journées Françaises de Radiologie congress 3 of the French Radiology Society 4 (SFR). [Med] At a longer term: Organization of an INSERM Training Workshop 5 on clinical PET-MRI. At the international level: [Sci] Organization of a special session on PET-MRI image processing in a forthcoming edition of the IEEE International Symposium of Biomedical Imaging (ISBI) 6. [Sci-Med] At a longer term: Organization of an interdisciplinary European Summer School, involving speakers from the various PET-MRI centers in Europe. Joined dissemination actions with the France Life Imaging (FLI) 7 funded project will also be performed, as most PIM actors are also involved in the FLI project. At least one PIM workshop will be organized by February 2016, to present the range of research activities performed as part of this project, attract new collaborators, and share experience. 5. Project management 5.1. Partners Nine partners will participate to the PIM project, gathering the various expertise required to achieve the goals of the project. Many of these teams have already worked together within various national or European projects, but no project has gathered all teams together so far. This project should therefore foster joint research between labs of physics, dosimetry, medical imaging, information processing, medical institutes and medical research groups, with the long-term goal of building a center of excellence in medical physics able to address the most difficult issues while being always concerned by the translational aspect of its research for improving healthcare. A larger number of research or medical groups is expected to join in a second phase of the project. Table 1 lists the nine teams, together with the manpower brought by each team to the PET-MRI project. The total size of each team is also given to show the long-term task force that could be later involved in a PIM institute. A more detailed description of each partner is provided in Appendix 9.1, including a short CV of the team leader(s), and 10 publications representative of the team expertise for the project. The links and complementarity of the teams for this PET-MRI project are described in Figure 1. This Figure shows the role and expertise of each team in the research project, as well as the main interactions that are expected between partners, both regarding methodological developments and breakthrough applications. 1 EMMI is an international program dedicated to in vivo molecular imaging. Courses are held in English at a group of European partner Institutions: INSTN (FR), and the Universities of Paris Sud 11 (FR), Antwerp (BE), Crete (GR) and Turin (IT). 2 stic-sante.org 3 jfr.radiologie.fr 4 Société Française de Radiologie ( 5 extranet.inserm.fr/colloques-seminaires/ateliers-de-formation its.aviesan.fr/document.php?pagendx=319 16

209 Partners Lab headcount Manpower (FTE) (Lab and teams) CEA-LIST (LM2S and LNHB) Research scientists and Physicians Research scientists and Physicians 30 3 CEA-SHFJ 17 6 CEA-Neurospin (Parietal and Uniact) IGR - Radiotherapy Department 20 4 IMNC - UMR 8165, CNRS - Paris-Sud University (QIM) 20 2 INSERM U Institut Curie (Centre de Protonthérapie d Orsay) Institut Mines-Télécom (IMT) (Télécom ParisTech and Télécom SudParis) IR4M, UMR 8081, CNRS - Paris-Sud University IRCIV Total Table 1: Lab and teams participating to the PIM project, lab headcounts (including teams that are not involved in the project) and team manpower directly involved in the project. Figure 1: Schematical description of the role of the different teams participating to the project, their field of expertise (PET or MRI top) and of their implication regarding methodological developments (top) and applications (bottom). All teams involved in methodological research also directly take part of applicative research, due to the problem-driven nature of most methodological developments. 8 Permanent staff involved in medical imaging activities. 17

210 5.2. Coordination The PIM project will be managed by a steering committee (SC) headed by Irène Buvat who will act as the project Principal Coordinator. The SC will be responsible for the optimal project implementation, reporting to IDEX, and interactions with present and future actors of the project. The SC will consist of: - one representative of each of the 9 participating teams, - one representative of the PET-MRI scanner manufacturer, - one representative of each institution the participating teams depend on (CNRS, INSERM, CEA, Paris Sud University), - one person in charge of training actions, - one person in charge of dissemination and public relation activities including liaison with the France Life Imaging project. The SC will meet at least every 2 months and more frequently if needed. The SC will be assisted by an international advisory board (AD) that will attend the SC meeting at least once a year. This AD will be composed of 3 world-class specialists in the field: - a PET expert, - an MR expert - an information processing expert, and will participate to strategic meetings where scientific and management orientations will be discussed. In addition to optimizing the project implementation, especially in terms of (1) resource sharing and usage and (2) validation of the research topics addressed as part of the PIM project, and based on this first experience of a multidisciplinary research effort around the PET-MRI facility, the SC will also actively work on the structuration of this PIM initiative towards a PIM institute, to include a larger number of teams in a next step. A proposal in that direction will be prepared so as to be discussed during the short-term evaluation of this PIM project (February 2016). 6. Budget The requested budget aims at triggering the first cooperative actions towards the future PIM institute, by supporting PET-MRI research involving at least two of the 9 teams participating to the project. We therefore ask for the funding of 7 PhD scholarships, in addition to short-term contracts (post-doc, research assistant, engineers), as follows: Manpower: PhD scholarship, post-doc and short term contracts: 1620 k in total - 7 PhD scholarships for three years, 40 k per year per student: 840 k. - 5 two-year term contract for research scientists, 60 k per year per researcher: 600 k. - 1 clinical research assistant for three years, 60 k per year: 180 k. A non-exhaustive list of collaborative research projects anticipated within the PIM consortium, under an implementation model associating at least two teams, is presented in Table 2: Project title Partners Related tasks Essential methodological development in multimodal probes IR4M, CEA-SHFJ MRE development and implementation on the PET-MRI system IR4M, CEA-SHFJ Quantitative accuracy in integrated PET-MRI against standalone PET and standalone MRI for brain and cancer applications Bayesian nonparametric space-time joined reconstruction for simultaneous PET/fMRI co-modalities with applications to neuropsychiatrics Parametric PET-MRI imaging for predicting and assessing tumor response in PET Dictionary learning for the joint segmentation of PET and MRI images and application to the comparison of populations Dosimetric evaluation of PET-MRI BGRT for paedratic applications Implementation of DSC-MRI and [ 18 F]FMISO-PET BGRT for brain tumors using stereotactic methods and Monte Carlo dose calculations Simultaneous determination of receptor occupancy by CNS drugs using PET imaging and subsequent neuropharmacological effect measured using fmri: preclinical validation Validation of synchronous PET-fMRI for psychiatry and psychopharmacology Table 2: Collaborative research projects anticipated within the PIM consortium. CEA-SHFJ, IMNC CEA-SHFJ, CEA-LIST IMNC, IMT, CEA-SHFJ, IR4M- IRCIV CEA-Neurospin, CEA-SHFJ, CEA-LIST CEA-LIST, CEA- SHFJ, IC-CPO and/or IGR CEA-LIST, IGR IMT, IMNC CEA-SHFJ, CEA-Neurospin INSERM U1000, CEA- SHFJ, CEA-Neurospin

211 Operating costs: 480 k The rest of the budget will be devoted to a participation of the operating costs up to 480, including: Access to the medical accelerator of CEA-LIST to validate the conformity of dose delivery for PET-MRI based treatment plan before clinical validation. Operating costs of 30 k, corresponding to three weeks of operation. PET-MRI scans: 2 k / scan including radiotracer and scan operation Computational resources (PCs, workstation, software) Travel expenses, especially for networking with other experienced PET-MRI facilities (Germany, Universoty College London) Workshops organization A total budget of 2 M is therefore requested for this PIM project. Our project is supported by our funding institutions, namely: CEA CNRS INSERM Institut Curie Institut Gustave Roussy Institut Mines Télécom Integrated Research Cancer Institute in Villejuif Paris Sud University Supporting letters by each institution will be sent to the IDEX committee shortly after January 16 th 2013, in agreement with Patrico Leboeuf, in charge of the coordination of this IDEX call for proposals. In addition, a number of companies we already collaborate with on related topics, also strongly support the PIM project, including Brucker, Dosisoft, Guerbet, IBA. 7. Conclusion This PIM project is a seed action for structuring a top-level PSC research activity in physics and engineering for enhanced medicine. By focusing on developing a pioneered PET-MRI activity in PSC, including both methodological developments and medical applications, PIM will give PSC the opportunity to actively participate to the discovery of breathrough applications for PET-MRI and of novel knowledge in physiopathology, with the ultimate aim to improve patient management and healthcare. The actors involved in the presented PET-MRI project gather worldwide-recognized expertise in MRI (IR4M, CEA- Neurospin), PET (CEA-SHFJ, IMNC), advanced radiation therapy and proton therapy (IGR, IC-CPO), clinical expertise and translational research (CEA-SHFJ, IGR, IR4M-IRCIV), dosimetry (CEA-LIST) and information processing for medical purpose (IMT, CEA-LIST, CEA-SHFJ, IMNC, IR4M, CEA-Neurospin), ensuring that challenges associated with the PET-MRI technology will be efficiently addressed and that new methodological and applicative concepts will emerge. Part of the research described in this project can be started immediately, based on the standalone PET and MRI scanners already used daily in the current research of the participants. This will allow us to initiate our copperative actions before the PET-MRI scanner is installed in CEA-SHFJ, so as to demonstrate the impact of our structuring effort by the short-term evaluation of our project in February All along the project, research will be tighly associated with training, based on the already large involvement of the actors in training activities. PSC might therefore become one of the first universities offering PET-MRI training by experts in the field together with providing internship opportunities in a PET-MRI facility. The alignment of this project with other recent initiatives, such as Investments for the Future and the IDEX strategy, associated with the acquired support of our institutions and several companies in the field, suggest that through PIM, PSC will make a decisive step towards being recognized worldwide as a key player in the transfer of physics and information technology to healthcare. On the long term, and based on the experience acquired through this PET-MRI focused project, it is expected that new actors (research labs and engineer schools) will join the consortium, considerably enlarging the scope of PIM. In particular, PIM will later extend to many other advanced medical imaging modalities, other biomedical applications, and other innovative therapeutic strategies. This is already agreed on by all current PIM actors to be the long term objective of PIM. 8. Bibliography Aldea E. Apprentissage de données structurées pour l'interprétation d'images. PhD Thesis Télécom ParisTech, 2009E053, Angelini E, Delon J, Bah AB, Capelle L, Mandonnet E. Differential MRI analysis for quantification of low grade glioma growth. Medical Image Analysis. 16: , Antoniadis T, Scarpelli JP, Ruaud JP, Gonord P, Guillot G. Bone labelling on micro-magnetic resonance images. Med Image Anal. 3: , Artiges E, Leroy C, Pepin A, de Beaurepaire R, Gruel N, Galinowski A, Karila L, Trichard C, Martinot JL. Striatal and extrastriatal dopamine transporter in schizophrenia: a high resolution PET study. Biological Psychiatry. 69: 257S,

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217 9. Appendix 9.1. Teams participating to the project and expertise brought by each team The nine (9) teams included in the PIM project are listed below, with a brief summary of expertise and 10 publications illustrating their expertise in domain related to the proposed project CEA-LIST Contact: Bénédicte Poumarède: benedicte.poumarede@cea.fr (simulation), Eric Barat: eric.barat@cea.fr (signal and image processing), Valentin Blideanu : valentin.blideanu@cea.fr (metrology). The CEA-LIST is an active long-standing player in the technology, metrology and training in radiotherapy. Its highly complementary range of skills (nuclear physics, Monte Carlo simulations, dose metrology, development of sensors, etc) makes the CEA-LIST a unique research organization to address the scientific problems raised by health issues in radiotherapy. CEA-LIST leads R&D activities in radiotherapy technologies and associated medical imaging, including: The development of simulation codes for application to the field of radiotherapy and medical imaging. An expertise in non-parametric Bayesian methods for statistical signal and image processing, The development of instrumentation for dosimetry like diamond or OSL detectors. The development of software for patient safety. The metrology of ionizing radiation: the national metrology laboratory for ionizing radiation (LNHB) develops the absorbed dose and radioactivity standards, especially for medical applications. CEA-LIST has a number of collaborations with key companies in the field, such as ELEKTA or DOSISOFT. In this context, the CEA-LIST is currently creating a reference platform named DOSEO devoted to the development of radiotherapy and associated imaging technologies. Its activities will focus on innovation applied to various steps of the radiotherapy workflow, academic education and users training, increased control of the treatment delivery (metrology, quality control), tests / demonstration of industrial products. The DOSEO platform will be at the crossroad between universities and research institutes, clinics, users, industry, metrology labs, quality control institutions and regulatory agencies. Located within the CEA Saclay research center, DOSEO will include 2 bunkers equipped with 2 medical accelerators, one scanner, parallelized computers, as well as room for meetings and education, offices, and a conventional lab. Bénédicte Poumarède, obtained her PhD in nuclear physics (Toulouse University) in 1995, and then managed some projects in EADS company between 1995 and She joined CEA in 2002 as a researcher in the sensor signal and technology research department. During this period, she developed skills in project management dedicated to radiotherapy. Since 2011, she is the head of the simulation, validation and systems lab in CEA CEA and manages the DOSEO platform project. Recent publications representative of the expertise in the field: - Habib B, Poumarède B, Tola F, Barthe J. Evaluation of PENFAST - a fast Monte Carlo code for dose calculations in photon and electron radiotherapy treatment planning, Phys Med. 26: 17-25, Tola F, Poumarède B, Habib B, Gmar M. Optimisation of Monte Carlo codes PENELOPE 2006 and PENFAST by parallelization and reduction variance implementation. Proceeding, Second European Workshop on Monte Carlo Treatment Planning, October 2009, Cardiff, United Kingdom Barat E, Comtat C, Dautremer T, Montagu T, Fall MD, Mohammad-Djafari A, Trébossen R. Nonparametric bayesian spatial reconstruction for positron emission tomography, 2009, September, 10th International meeting on fully three-dimensional image reconstruction in radiology and nuclear medecine, Pékin, Chine, pp Fall MD, Barat E, Comtat C, Dautremer T, Montagu T, Stute S, Continuous Space-Time Reconstruction in 4D PET. IEEE Medical Imaging Conference Proceedings , Fall MD, Barat E, Comtat C, Dautremer T, Montagu T, Mohammad-Djafari A. A discrete-continuous Bayesian Model for Emission Tomography, Proceedings of the 2011 IEEE International Conference on Image Processing , Lazaro-Ponthus D, Guérin L, Batalla A, Frisson T, Sarrut D. Commissioning of PENELOPE and GATE Monte Carlo models for 6 and 18 MV photon beams from the Siemens Artiste linac, 11th Biennal ESTR0, London UK,. S515, Le Loirec C, Garcia-Hernandez J C, Bonniaud G, Poumarède B and Lazaro D Dosimetric verification of PenSSaRT, a new Monte Carlo dose calculation system based on PENELOPE and dedicated to patient-specific treatment quality control in radiotherapy, MCTP 2012, Sevilla (15-18 May 2012).Proceedings , Lazaro D, Barat E, Le Loirec C, Dautremer T, Montagu T, Guérin L, Batalla A. Denoising techniques combined to Monte Carlo simulations for the prediction of high-resolution portal images in radiotherapy treatment verification. Phys Med Biol, in press, CEA-SHFJ CEA - Service Hospitalier Frédéric Joliot Contacts: Badia Ourkia Helal (head of the Department) badia-ourkia.helal@cea.fr; Claude Comtat (physics) claude.comtat@cea.fr; Nicolas Tournier (pharmacology) nicolas.tournier@cea.fr; Frédéric Dollé (radiochemistry) frederic.dolle@cea.fr 25

218 The CEA - Service Hospitalier Frédéric Joliot (CEA-SHFJ) is a department of preclinical and clinical research in molecular and functional imaging associated with a clinical nuclear medicine facility, with a day-hospital area dedicated to clinical research. It is one of Europe s pioneering centers in the field of molecular imaging by PET with a strong expertise in the development of novel molecular probes and methodologies in pharmacology and physics for imaging both simple and complex pharmacological targets and biological processes. The technical platform gathers high-performance equipment dedicated to molecular and functional imaging, including six PET scanners, one MRI, a cyclotron for the production of positrons emitters and a laboratory to produce radiopharmaceutical molecules. The SHFJ is composed of three methodological research groups and hosts the research team in medical MRI of the IR4M laboratory and the unit INSERM U1000 of neuroimaging in psychiatry. The biomedical physics group is involved in methodological developments in data acquisition modeling, signal and image processing. It has a well-established expertise in statistical image reconstruction algorithms for PET. The group has also a long experience regarding the implementation of reconstruction algorithms on various PET scanners and their evaluation for real clinical data. Since 2008, it gained an expertise in nonparametric Bayesian methods for the reconstruction of PET images. The group has also a more than thirty-year experience in installing and running prototypal PET scanners. The pharmacology group is involved in central nervous system PET radioligand development in tight collaboration with the radiochemistry unit that develops and synthetizes in-house original radiolabeled ligands. Members of this team acquired expertise in PET tracers pharmacokinetic, including metabolism, transport by carrier-mediated systems through biological membranes as well as selectivity and affinity toward their pharmacological target. This group also develops mathematical models and acquisition protocols that allow for accurate PET quantification to measure receptor availability or affinity for a specific PET ligand. This may include study of the arterial input function with radiometabolite quantification using radio-hplc and LC-MS analysis for drug determination in plasma during PET protocols. Main pharmacological developments are performed in non-human primates (baboons) and some protocols led to successful clinical application. The pharmacology group is also involved in studying CNS drug kinetics, with a particular interest in drugs-of-abuse. The radiochemistry group designs, develops and prepares new labeled molecules (radiopharmaceuticals) carrying mainly carbon-11 or fluorine-18 for applications in oncology and neurosciences. This activity includes the implementation of efficient organic syntheses in order to prepare and supply the precursors needed for the labeling part on the one side and the target non-labeled molecules (as reference compounds) on the other side. This activity is fully integrated with in-house research programs in the field of oncology and neurosciences and is often also linked with external (academic or industrial) partnerships. Badia Ourkia Helal is an Endocrinologist and Nuclear Medicine specialist, MD, who head the Department of Nuclear Medicine of Antoine Béclère Hospital (Assistance Publique, Hopitaux de Paris) from 1997 to She has been recently (2012) appointed as the head of the Department of Nuclear Medicine of CEA-SHFJ. She is also an assistant professor of biophysics at the Paris Sud University since 1990, is an active member of the French thyroid research group which elaborated guidelines for the management of thyroid nodules (1995, 2011) and of differentiated thyroid cancer (2008). Her main research interest includes oncology in general, and thyroid cancer in particular, and general nuclear medicine. Recent publications representative of the expertise in the field: - Sureau FC, Reader AJ, Comtat C, Leroy C, Ribeiro MJ, Buvat I, Trébossen R. Impact of image-space resolution modeling for studies with the High-Resolution Research Tomograph. J Nucl Med. 49: , Bataille F, Comtat C, Jan S, Sureau FC, Trébossen R. Brain PET partial-volume compensation using blurred anatomical labels. IEEE Trans Nucl Sci. 54: , Leroy C, Comtat C, Trébossen R, Syrota A, Martinot JL, Ribeiro MJ. Assessment of 11C-PE2I binding to the neuronal dopamine transporter in humans with the High-Spatial-Resolution PET scanner HRRT. J Nucl Med. 48: , Ribeiro MJ, de Lonlay P, Delzescaux T, Boddaert N, Jaubert F, Bourgeois S, Dollé F, Nihoul-Fékété C, Syrota A, Brunelle F. Characterization of hyperinsulinism in infancy assessed with PET and 18F-fluoro-L-DOPA. J Nucl Med 46: , Helal BO, Merlet P, Toubert ME, Franc B, Schvartz C, Gauthier-Koelesnikov H, Prigent A, Syrota A. Clinical impact of 18F- FDG PET in thyroid carcinoma patients with elevated thyroglobulin levels and negative 131I scanning results after therapy. J Nucl Med. 42: , Peyronneau MA, Saba W, Goutal S, Damont A, Dollé F, Kassiou M, Bottlaender M, Valette H. Metabolism and quantification of [18F]DPA-714, a new TSPO Positron Emission Tomography radioligand. Drug Metab Dispos. 41:122-31, Tournier N, Cisternino S, Peyronneau MA, Goutal S, Dolle F, Scherrmann JM, Bottlaender M, Saba W, Valette H. Discrepancies in the P-glycoprotein-mediated transport of 18F-MPPF: a pharmacokinetic study in mice and non-human primates. Pharm Res. 29: , Tournier N, Declèves X, Saubaméa B, Scherrmann JM, Cisternino S. Opioid transport by ATP-binding cassette transporters at the blood-brain barrier: implications for neuropsychopharmacology. Curr Pharm Des. 17: , Roeda D, Kuhnast B, Damont A, Dollé F. Synthesis of fluorine-18-labelled TSPO ligands for imaging neuroinflammation with Positron Emission Tomography. J Fluor Chem. 134: , Cerutti E, Viale A, Damont A, Dollé F, Aime S. Synthesis and testing of a p-h2 hyperpolarized 13C probe based on the pyrazolo[1,5-a]pyrimidineacetamide DPA-713, a MRI-vector to target the peripheral benzodiazepine receptors. Magn Reson Chem. 49: , Kuhnast B, Dollé F. The challenge of labeling macromolecules with fluorine-18: Three decades of research. Curr Radiopharm. 3: ,

219 CEA-Neurospin Contact: Philippe Ciuciu, (Parietal), Michel Bottlaender (Uniact) CEA - NeuroSpin is a neuroimaging center focusing on MRI at ultra-high field (UHF) which hosts fellows from various institutions, including CEA, INSERM and INRIA. The institute consists of several complementary laboratories covering physics, image processing, neurocognitive sciences and the investigation of specific pathologies. Members include 130 (permanent and non-permanent) researchers, 34 PhD students and 6 technicians. The LRMN lab is mainly involved on MRI methodology on preclinical (7 T and T) and clinical magnets (3T, 7T and 11.7 T). They have strong experience in RF pulse design, MR sequences, MRI hardware, reconstruction algorithms and compressed sensing for MRI applications. MRI (anatomical, functional and diffusion-weighted) data analysis is split in several labs depending on the modality. This project mostly concerns the Parietal and UNIACT teams. Parietal ( is an INRIA-CEA team situated on the Neurospin neuroimaging platform, that is involved in neuroimaging data reconstruction and processing (coregistration, statistics and learning approaches for functional imaging: fmri, MEG). Parietal comprises two INRIA permanent researchers : Bertrand Thirion and Gaël Varoquaux, and one CEA researcher, Philippe Ciuciu, about 15 people overall. Parietal is involved in research programs such as atlas learning, the analysis of brain functional connectivity, application of high-dimensional classification tools for diagnosis purpose and for the study of brain function, solution of many neuroimaging inverse problems (MRI reconstruction, MEG), multi-fractal analysis of brain signal and computational modeling of vision. Parietal is involved in the development of many scientific Python sofwtare (scikit learn, Mayavi, nipy). UNIACT is one of the Neurospin laboratories that develops clinical and translational neuroimaging research protocols using the Neurospin platform. The Unit is also in charge of all the MRI acquisition procedures of Neurospin. UNIACT consists of 3 permanent CEA MD-PhD researchers, about 20 people overall. UNIACT includes 4 research teams focused on different fields: neuro-pediatrics, neuropsychiatry, neuromodulation and neurology-pharmacology the lattest being mostly involved in the present project. This team is involved, in close collaboration with specialized clinical teams, in several research programs of multi-modal imaging in neurodegenerative diseases mainly Alzheimer and Parkinson diseases and in multiple sclerosis. These clinical protocols aim to identify and characterize biomarkers to help physiopathological understanding and earlier diagnosis of the diseases and to provide surrogate markers for further therapeutic trials. Philippe Ciuciu (39 years old, IEEE Senior member 10, CEA) received the engineering degree from ESIEA Paris and DEA degree in automatic control and signal processing from the Université Paris-Sud, Orsay, France, both in He then obtained his PhD in signal processing from the same university in After a one-year postdoctoral position in the Life Science Division of CEA, he has been hired by the same institute to develop statistical methods for fmri data analysis. Since 2007, Dr Ciuciu has been with the NeuroSpin centre dedicated to ultra-high field MRI and applications to neurosciences. Guest editor to the IEEE JSTSP journal, he organized several special sessions in international conferences (IEEE ICASSP'06, MICCAI'09, IEEE ISBI'11) and has served as regular reviewer for 14 international top-ranked journals. In 2012, he has been elected as member of the BISP technical committee of the IEEE ISBI conference. Dr Ciuciu has published 25 refereed journal papers, 2 book chapters, more than 60 conference papers and is holding 1 MRI-related pending patent. Michel Bottlaender obtained a Medical Degree in 1991 (University of Strasbourg; France). He then obtained his PhD in Biochemistry and Pharmacology in 1994 in University Paris XI. After a one-year post-doctoral position at the Royal Free Hospital School of Medicine (London; UK) in the Molecular Neurobiology Unit (Pr. E.A. Barnard), he has been hired by CEA, Life Science Division to develop, at the SHFJ, new radiopharmaceutical for PET imaging. Since 1997, Dr Bottlaender headed the Neuro-Imaging and Pharmacology team at SHFJ, and is in charge of the research in pharmacology and preclinical and clinical development of new radiotracers for PET. In 2010 he joint NeuroSpin, CEA where he is currently in charge of the Neurology and Pharmacology team. He develops several clinical protocols in multimodal imaging (PET and MRI) in the field of Alzheimer disease and Multiple Sclerosis in close collaboration with Neurologist of Assistance Publique Hôpitaux de Paris Hospitals. Recent publications representative of the expertise in the field: - Chaari L, Vincent T, Forbes F, Dojat M, Ciuciu P. Fast joint detection-estimation of evoked brain activity in event-related fmri using a variational approach. IEEE Trans Med Imaging. In press Risser L, Vincent T, Forbes F, Idier J, Ciuciu P. Min-max extrapolation scheme for fast estimation of 3D Potts field partition functions. Application to the joint detection estimation of brain activity in fmri. J Sign Proc Sys. 65: , Chaari L, Pesquet JC, Benazza-Benyahia A, Ciuciu P. A wavelet-based regularized reconstruction algorithm for SENSE parallel MRI with applications to neuroimaging. Medical Image Analysis. 15 : , de Souza LC., Corlier F., Habert M-O., Uspenskaya O., Maroy R., Lamari F., Chupin M., Lehéricy S., Colliot O., Hahn-Barma V., Samri D., Dubois B., Bottlaender M., Sarazin M. Similar beta-amyloid burden in posterior cortical atrophy and Alzheimer s disease. Brain. 134: , Stankoff B., Freeman L., Aigrot M-S., Chardain A., Dollé F., Williams A., Galanaud D., Armand L., Lehericy S., Lubetzki C., Zalc B., Bottlaender M. Imaging of central nervous system myelin by Positron Emission Tomography in Multiple sclerosis using [ 11 C]Methyl-2-(4-methylaminophenyl)-6-hydroxybenzothiazole. Annals Neurol. 69: ,

220 - Tournier N., Valette H., Peyronneau M-A., Saba W., Goutal S., Kunhast B., Dolle F., Scherrmann J-M., Cisternino S., Bottlaender M. Transport of selected PET radiotracers by human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2): an in vitro screening. J Nucl Med. 52: , Vincent T, Risser L, Ciuciu P. Spatially adaptive mixture modeling for analysis of within subject fmri time series. IEEE Trans Med Imaging. 29: , Bottlaender M., Valette H., Delforge J., Guenther I., Saba W., Dollé F., Curet O., George P., and Grégoire M-C. In Vivo Quantification of Monoamine Oxidase-A in baboon brain: A PET study using [ 11 C]befloxatone and the multi-injection approach. J Cereb Blood Flow Metab. 30: , Valette H., Xiao Y., Peyronneau M-A., Damont A-L., Kozikowski AP., Wei Z-L., Kassiou M., Kellar K., Dolle F., and Bottlaender M. 18 F-ZW-104: A new Radioligand for Imaging Neuronal Nicotine Acetylcholine Receptors. In vitro Binding Properties and PET Studies in Baboons. J Nucl Med. 50: , Rabrait C, Ciuciu P, Ribés A, Poupon C, Leroux P, Lebon V, Dehaene-Lambertz G, Le Bihan D, Lethimonnier F. High temporal resolution functional MRI using parallel echo volume imaging. J Magn Res Imaging. 27: , Picard F, Bruel D, Servent D, Saba W, Fruchart-Gaillard C, Schollhorn-Peyronneau MA, Roumenov D, Brodtkorb E, Zuberi S, Gambardella A, Steinborn B, Hufnagel A, Valette H, Bottlaender M. Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study. Brain. 129: , IGR and Radiotherapy department Contact : Eric Deutsch : deutsch@igr.fr; Frédéric Dhermain: frederic.dhermain@igr.fr The clinical radiation therapy activities at IGR are distributed through the clinical department of radiotherapy and the radiation physics unit. More than 3000 patients are treated each year by 6 linear accelerators or brachytherapy. A broad range of RT service is delivered in daily practice from treatment planning (4-D CTscanning, Image-Guided Radiation Therapy/ IGRT) to treatment delivering such as 3-D conformal external beam radiation, Intensity-Modulated Radiation Therapy (IMRT), partial breast irradiation, high and pulsed dose rate brachytherapy. IGR is in the process of making substantial investments in two of the most advanced linear accelerators that will allow us to deliver high precision RT (cranial and extracranial Stereotactic Radiation Therapy). The radiation therapy department headed by Pr Deutsch is composed of 10 faculty radiation oncologists, 3 PUPH, 1CCA, 14 medical residents. The physics unit headed by Dr Lefkopoulos is composed of 8 faculty and professional staff, 13 fellows and graduate students. The team has been pioneering safety in the field of radiation therapy since metrology and quality control procedures have been developed at IGR. These procedures are now widely used at the national and European level. Furthermore, a radiobiology lab (head Pr Deutsch, 2 PUPH, 1 CR INSERM, 3 postdocs, 6 PhDs, 3 Technicians) related to the IGR Radiation Therapy Department plays a key role in our Department and aims at transferring the most advanced and innovative research in biology and physics into clinical applications in order to improve outcome both in terms of cancer control and normal tissue toxcity. In summary, the department has a three-part mission of excellence in patient care, translational and basic research, education of medical students and residents and has developed expertise in most of the field of radiation oncology. Eric Deutsch is full professor at Paris-Sud and head of the radiation oncology department of IGR. His activity is focused on the biological improvement of the therapeutic ratio of radiotherapy using biological modifiers. He leads a preclinical research lab of more than 25 FTEs within the INSERM 1030 molecular radiotherapy unit and has a clinical activity focused on the transfer of novel drug-radiotherapy approaches into the clinic. His clinical research activity is fully integrated within IGR s phase I unit. He is currently PI of phase I/II trials evaluating novel drug-radiotherapy combinations such as PARP inhibitors, EGFR inhibitors, antiviral agents for the treatment of HPV related malignancies. He is strongly committed to education (board member of the doctoral school of oncology) in the fields of radiation biology and radiation therapy. He is a board member of the excellence network of laboratories LABEX LERMIT aiming at developing novel pharmacological approaches. Eric Deutsch is also medical director of IGR&D, IGR s technological and transfer office. Recent publications representative of the expertise in the field: - Dhermain F, Hau P, Lanfermann H, Jacobs AH, van den Bent MJ. Advanced MRI and PET imaging for assessment of treatment response in patients with gliomas. Lancet Neurol. 9: , Dhermain F. Role of perfusion, vascular permeability and anatomic MR imaging in radiation therapy for gliomas. Bull Cancer. 97: 753-8, Dhermain F, Saliou G, Parker F, Page P, Hoang-Xuan K, Lacroix C, Tournay E, Bourhis J, Ducreux D. Microvascular leakage and contrast enhancement as prognostic factors for recurrence in unfavorable low-grade gliomas. J Neurooncol. 97: 81-8, Dhermain F, Ducreux D, Bidault F, Bruna A, Parker F, Roujeau T, Beaudré A, Armand JP, Haie-Meder C. Apport des nouvelles techniques d imagerie à la planification radiothérapique des patients porteurs de glioblastome polymorphe. Bull Cancer. 92: , Isambert A, Dhermain F, Bidault F, et al. Evaluation of an atlas-based automatic segmentation software for the delineation of brain organs at risk in a radiation therapy clinical context. Radiother Oncol. 12: , Haddy N, Mousannif A, Tukenova M, Guibout C, Grill J, Dhermain F et al. Relationship between the brain radiation dose for the treatment of childhood cancer and the risk of long-term cerebrovascular mortality. Brain. 134: , Meyzer C, Dhermain F, Ducreux D, Habrand JL, Varlet P, Sainte-Rose C, Dufour C, Grill J. A case report of pseudoprogression followed by complete remission after proton-beam irradiation for a low-grade glioma in a teenager: the value of dynamic contrast-enhanced MRI. Radiat Oncol. 5: 9, IMNC Contact: Irène Buvat buvat@imnc.in2p3.fr 28

221 The Imaging and Modelling in Neurobiology in Cancerology lab is a CNRS Paris Sud University Paris Diderot University lab dedicated to instrumentation and methodology research in biomedical imaging, mostly involved in nuclear (scintigraphic) imaging and optical imaging. This lab includes 5 research teams ( The PIM project concerns the Quantification in Molecular Imaging (QIM) team of IMNC. QIM specialized in quantitative SPECT and PET imaging including Monte Carlo simulation of the imaging process, tomographic reconstruction, corrections, and estimation of parameters from PET and SPECT images and has a worldwide recognized experience in this field. An originality of this team is that SPECT and PET quantification is addressed from the very basic aspects (Monte Carlo simulation of the whole imaging process including realistic numerical description of patient features) up to clinical studies with long-lasting collaborations with Nuclear Medicine Departments. The application field is mostly focused on cancer imaging but the group has also a strong experience in brain and cardiac SPECT and PET. The team is the leader of OpenGATE international collaboration, which develops and maintains the GATE software for Monte Carlo simulation in imaging and radiotherapy ( that has become the most used simulation software worldwide for SPECT and PET applications. Irène Buvat, leader of QIM, is currently the spokesperson of OpenGATE, while Sébastien Jan, working jointly for CEA-SHFJ and QIM, is the technical coordinator of this international collaboration. QIM has or had a number of collaborations with key companies in the field, such as General Electrics Healthcare, Siemens, Philips Medical Systems, Dosisoft, Guerbet, and Biospace. Irène Buvat received her Ph.D. degree in particle and nuclear physics from Paris Sud University, France, in During her thesis, she oriented her career towards applications of Nuclear Physics for Medical Imaging. She spent one year as a post-doc at University College London, UK, working on Single Photon Emission Computed Tomography (SPECT) and two years at the National Institutes of Health, Bethesda, USA, specializing in Positron Emission Tomography (PET). In 1995, she entered the French CNRS (Centre National de la Recherche Scientifique) and is currently the head of a Quantification in Molecular Imaging team of the Imaging and Modelling in Neurobiology and Cancerology CNRS lab in Orsay, France. Her research activities focus on developing corrections and tomographic reconstruction methods in PET and SPECT to improving quantification PET and SPECT images. Her methodological approach is based on the use of Monte Carlo simulations to investigate all details of the forward imaging process so as to identify key aspects to be considered when developing quantification methods. She is currently the spokesperson of the worldwide OpenGATE collaboration developing the GATE Monte Carlo simulation tool dedicated to Monte Carlo simulations in emission and transmission tomography and radiotherapy. Irène Buvat is also largely involved into making quantification in SPECT and PET a clinical reality. She contributed to a number of studies demonstrating the clinical values of sophisticated quantification to improve image interpretation, and obtained a large number of research contracts with the major companies in the field. She has authored or co-authored more than 90 peer-reviewed articles and co-edited the Handbook for particle detection and imaging (Springer Verlag, 2011). Irène Buvat is also greatly involved in teaching medical physics in several French Universities (Nantes, Lyon, Paris Sud). She is an associate editor of IEEE Transactions on Medical Imaging and of IEEE Transactions on Nuclear Science and serves on the Editorial Board of the Journal of Nuclear Medicine and on the Advisory Editorial Board of Physics in Medicine and Biology. Recent publications representative of the expertise in the field: - Buvat I, Necib H, Garcia C, Wagner A, Vanderlinden B, Emonts P, Hendlisz A, Flamen P. Lesion-based detection of early chemosensitivity using serial static FDG PET-CT in metastatic colorectal cancer. Eur J Nucl Med Mol Imaging. 39: , Erlandsson K, Buvat I, Pretoruis PH, Thomas BA, Hutton BF. A review of partial volume correction techniques for emission tomography and their applications in neurology, cardiology and oncology. Phys Med Biol. 57: R119-R159, Grotus N, Reader AJ, Stute S, Rosenwald JC, Giraud P, Buvat I. Fully 4D list-mode reconstruction applied to respiratory-gated PET scans. Phys Med Biol. 54: , Hapdey S, Buvat I, Carson JM, Carrasquillo JA, Whatley M, Bacharach SL. Searching for alternatives to full kinetic analysis in 18F-FDG PET: an extension of the Simplified Kinetic Analysis method. J Nucl Med. 52: , Maisonobe JA, Garcia CA, Necib H, Vanderlinden B, Hendlisz A, Flamen P, Buvat I. Comparison of PET metabolic indices for the early assessment of tumor response in metastatic colorectal cancer patients treated by polychemotherapy. Eur J Nucl Med Mol Imaging. 40: , Necib H, Garcia C, Wagner A, Vanderlinden B, Emonts P, Hendlisz A, Flamen P, Buvat I. Detection and characterization of tumor changes in FDG PET patient monitoring using parametric imaging. J Nucl Med. 52: , Nioche C, Soret M, Gontier E, Lahutte M, Dutertre G, Dulou R, Capelle L, Guillevin R, Foehrenbach H, Buvat I. Evaluation of quantitative criteria for glioma grading with static and dynamic 18F-FDopa PET/CT. Clin Nucl Med. in press Soret M, Bacharach SL, Buvat I. Partial volume effect in PET tumor imaging. J Nucl Med. 48: , 2007a. - Soussan M, Chouahnia K, Maisonobe JA, Boubaya M, Eder V, Morère JF, Buvat I. Prognostic implications of volume-based measurements on FDG-PET/CT in stage III non-small-cell lung cancer after induction chemotherapy. Eur J Nucl Med Mol Imaging. in press, Tylski P, Stute S, Grotus N, Doyeux K, Hapdey S, Gardin I, Vanderlinden B, Buvat I. Comparative assessment of methods for estimating tumor volume and Standardized Uptake Value in FDG PET. J Nucl Med. 51: , INSERM-U1000 INSERM, Paris Sud University, Paris Descartes University (Neuroimaging & Psychiatry). Contact: Jean-Luc Martinot jean-luc.martinot@cea.fr and Eric Artiges eric.artiges@cea.fr. 29

222 The INSERM Unit 1000 ( based within the institute of biomedical imaging of the CEA at SHFJ works in close collaboration with the psychiatry dept. in the Orsay hospital, and associates members in the Paris Sud university clinical department for addiction and psychiatric disorders within Paul Brousse hospital, Villejuif. Ongoing collaborative researches on addiction or psychiatric conditions associate other recruiting university departments within the Assistance Publique - Hôpitaux de Paris (eg, Corentin-Celton Hospital, the Adolescent Medicine dept. in Cochin Hospital, the child and adolescent psychopathology dept. in Salpêtrière Hospital) and some departments within the regional psychiatric hospital Barthelemy-Durand in Essonne. This group conducts research in adults or in children and adolescents since the 90s, using psychometry and behavioural assessments coupled with brain imaging techniques. Within the INSERM U1000 unit, two permanent INSERM researchers (MD, PhD) will be involved part-time in the present project (JL Martinot, E Artiges), bringing expertise in psychiatry neuroimaging using PET and fmri. Notably, they contributed to the validation of, and developed clinical applications for brain psychopharmacology and psychiatry studies with four different PET scanners in SHFJ (leti TTV 01 and 02, HR+ and HRRT Siemens scanners). They developed applications to psychiatry for four MRI systems (1,5 Tesla General Electrics and Philips in SHFJ, 3 Teslas Siemens in Neurospin and ICM Paris). They have a large experience for analysis and interpretation of PET images using radioligands for brain dopamine, serotonin and MAO-A systems, desoxyglucose metabolism, as well as functional MRI and anatomical MRI. Claire Leroy, a research engineer thoroughly experienced in acquiring and processing brain PET dopamine transporter images will be part of the study team. In addition, Christian Trichard, MD, PhD, will be involved in the present study as a clinician, and as he is experienced in PET radioligand data interpretation. Jean-Luc Martinot obtained a Medical Degree (Paris7 University) followed by laureate to resident internship (Internat des Hôpitaux de Paris) leading to the certification both in adult and in child & adolescent psychiatry, through a training in most University departments of the Paris area, in clinical psychopathology and biological psychiatry depts. He was awarded a research fellowship grant at the Atomic Energy Commission (CEA) department of medical research in Orsay where he trained in brain imaging and set up investigations on mental disorders that he pursued as Assistant Professor in Assistance Publique Hôpitaux de Paris Hospitals. The initial research findings in both pathophysiology and psychopharmacology motivated his tenure position as INSERM Chargé de Recherche (CR1). An accreditation to research direction (HDR) in neuroimaging was followed by a tenure position as INSERM Director of Research (DR1), and the creation of the research unit that he currently leads ( Dr Martinot is the coordinator of investigations involving brain imaging in mental disorders, notably a European research network for translational neuroimaging methodology in mental disorders (ERANET Neuron). He is the vice-president of the European psychiatric assocuation (Neuroimaging section), a board member of the European College of Neurospychopharmacology, and a member of the MILDT scientific council (prime minister mission against addictions). His main activities include PET and MRI in patients with affective disorders, schizophrenia, or addictions, and in vivo catecholamine determinations during antidepressant or antipsychotic treatments, and functional brain imaging during brain stimulation treatments. Eric Artiges obtained a Medical Degree (Paris 6 University) wit a specialization in psychiatry in He defended a PhD thesis in Life science entitled Cerebral activations during cognitive tasks in healthy subjects and patients with schizophrenia: PET studies with H 2 15 O in 2000 (Paris 6 University) and obtained his Accreditation to Research Direction from Paris 11 University on Neuroimaging and psychiatric disorders: a pathway towards multimodality in He joined INSERM U1000 in 2001 where he currently acts as a research scientist specialized in brain imaging (PET and MRI) to study mental disorders (schizophrenia, affective disorders, or addictions). He is also currently the head of the psychiatry department of Orsay Hospital. Recent publications representative of the expertise in the field: - Whelan R, et al., the IMAGEN Consortium. Adolescent impulsivity phenotypes characterized by distinct brain networks. Nature Neuroscience. 15: 920-5, Stacey D, et al., the IMAGEN Consortium. RASGRF2 regulates alcohol-induced reinforcement by influencing mesolimbic dopamine neuron activity and dopamine release. Proc Natl Acad Sci U S A. 109: , Paillère Martinot ML, Martinot JL, Ringuenet D, Galinowski A, Gallarda T, Bellivier F, Lefaucheur JP, Lemaitre H, Artiges E. Baseline brain metabolism in resistant depression and response to transcranial magnetic stimulation. Neuropsychopharmacology. 36:2710-9, Houenou J, Wessa M, Douaud G, Leboyer M, Chanraud S, Perrin M, Poupon C, Martinot JL, Paillere-Martinot ML. Increased white matter connectivity in euthymic bipolar patients: diffusion tensor tractography between the subgenual cingulate and the amygdalo-hippocampal complex. Molecular Psychiatry. 12: , Wessa M, Houenou J, Paillère-Martinot ML, Berthoz S, Artiges E, Leboyer M, Martinot JL. Fronto-striatal overactivation in euthymic bipolar patients during an emotional go/nogo task. Am J Psychiatry. 164: , Chanraud S, Reynaud M, Wessa M, Penttilä J, Kostogianni N, Cachia A, Artiges E, Delain F, Perrin M, Aubin HJ, Cointepas Y, Martelli C, Martinot JL. Diffusion tensor tractography in mesencephalic bundles: relation to mental flexibility in detoxified alcoholdependent subjects. Neuropsychopharmacology. 34: , Kédia G, Berthoz S, Wessa M, Hilton D, Martinot JL. An agent harms a victim: a functional magnetic resonance imaging study on specific moral emotions. J Cogn Neuroscience 20: , Chanraud S, Martelli C, Delain F, Kostogianni N, Douaud G, Aubin HJ, Reynaud M, Martinot JL. Brain morphometry and cognitive performance in detoxified alcohol-dependents with preserved psychosocial functioning. Neuropsychopharmacology 32: , Leroy C, Comtat C, Trébossen R, Syrota A, Martinot JL, Ribeiro MJ. Assessment of 11C-PE2I binding to the neuronal dopamine transporter in humans with the high-spatial-resolution PET scanner HRRT. J Nucl Med. 48: ,

223 - Dehaene S, Artiges E, Naccache L, Martelli C, Viard A, Schürhoff F, Recasens C, Paillère-Martinot ML Leboyer M, Martinot JL. Conscious and subliminal conflics in normal subjects and patients with schizophrenia : the role of the anterior cingulate. Proc Natl Acad Sci U S A. 100: , IC-CPO Contact: Alejandro Mazal, alejandro.mazal@curie.net The expertise of the team in the Centre de Protontherapy d Orsay and, more general, in the Institut Curie (IC) in the field concerned by the PIM PET-MRI project is based on more than 20 years of use of protons in radiation therapy in both clinical applications and research and development. The Medical Physics Department of the Department of Oncologic Radiotherapy of Curie Institute has a long experience on treatment planning and quality assurance on three clinical sites (Paris, Saint Cloud and Orsay) treating with state of the art approaches (IMRT and IGRT with linacs and tomotherapy as well as with protons). The proximity in Orsay between the proposed future PET-MRI facility and the protontherapy center facilitates the direct interaction of the participating teams. As an exemple of existing cooperations in the field we can mention the project Prouesse (Development and validation of a Monte Carlo based modelisation and simulation tool for proton therapy) in the frame of ANR Cosinus having as participants CEA-List, I.Curie, Dosisoft, Centre Antoine Lacassagne, CEA Irfu, et le laboratoire CNDRI de l INSA Lyon. Alejandro Mazal was born in Argentina in He first studied engineering followed by medical physics in Buenos Aires, where he have also worked at the National Academy of Medicine. In 1985 he moved to Paris. At the Universities of Toulouse and Paris he took a master and PhD degree in medical physics (dealing with stereotactic radiation therapy) and then got a permanent position at Curie Institut under the direction of Jean Claude Rosenwald. In 1990 he participated to the protontherapy project in Orsay, where he was appointed as technical director covering the medical physics and engineering fields for about 8 years. He took some sabbaticals in US, at Indiana University Cyclotron Facility and at Massachusetts General Hospital & Harvard Medical School as invited scientist. In 2005 he has been in charge of the call for bids for the new protontherapy project in Orsay as the project director, in 2008 he was named head of medical physics at Curie Institute and in 2010 he has been elected as Chairman of the Particle Therapy Cooperative Group (PTCOG). Recent publications representative of the expertise in the field: - Mazal A: Proton beams in radiotherapy. In: Handbook of radiotherapy physics. Theory and practice. Chapter 46, pp Ed P.Mayles, A.Nahum, J.CRosenwald. Taylor & Francis, Engelsman N., Mazal A, Jaffray D.A.: Patient positioning and setup verification for planning and treatment. In : Proton and Charged Particle Radiotherapy Ed.T.F.De Laney, H.M.Kooy. Chap 7, pp.57-69, Lippincott, Williams & Wilkins, Grotus N, Reader AJ, Stute S, Rosenwald JC, Giraud P, Buvat I. Fully 4D list-mode reconstruction applied to respiratory-gated PET scans. Phys Med Biol. 54: , Fournier-Bidoz N, Kirova Y, Campana F, El Barouky J, Zefkili S, Dendale R, Bollet MA, Mazal A, Fourquet A.: Technique alternatives for breast radiation oncology: Conventional radiation therapy to tomotherapy. J Med Phys. 34:149-52, Mazal A, Habrand JL, Delacroix S, Datchary J, Dendale R, Desjardins L, Ferrand R, Malka V, Fourquet A.: [Protontherapy: basis, indications and new technologies]. Bull Cancer. 97:831-46, El Barouky Jad, Fournier-Bidoz Nathalie, Mazal Alejandro, Fares Georges Rosenwald Jean-Claude: Practical use of Gafchromic( ) EBT films in electron beams for in-phantom dose distribution measurements and monitor units verification. Phys Med. 27:81-8, Francois P, Boissard P, Berger L, Mazal A. In vivo dose verification from back projection of a transit dose measurement on the central axis of photon beams. Phys Med. 27:1-10, De Almeida CE, Fournier-Bidoz N, Massabeau C, Mazal A, Canary PC, Kuroki IR, Campana F, Fourquet A, Kirova YM. Potential benefits of using cardiac gated images to reduce the dose to the left anterior descending coronary during radiotherapy of left breast and internal mammary nodes. Cancer Radiother. 16:44-51, Fournier-Bidoz N, Kirova YM, Campana F, Dendale R, Fourquet A. Simplified field-in-field technique for a large-scale implementation in breast radiation treatment. Med Dosim. 37:131-7, Kirova YM, Menard J, Chargari C, Mazal A, Kirov K: Case study thoracic radiotherapy in an elderly patient with pacemaker: The issue of pacing leads. Med Dosim. 37: 192-4, IMT Contact: Nicolas Rougon nicolas.rougon@telecom-sudparis.eu The Institut Mines-Télécom (IMT) is a leading public organization in the field of information sciences and technologies with an internationally-recognized experience in image processing and understanding for digital health, in close collaboration with medical teams and close interaction with the medical industry through the Télécom & Digital Society Carnot Institute. Télécom ParisTech and Télécom SudParis, the two Télécom components of IMT contributing to University Paris-Saclay, are federated in this project. Télécom ParisTech has significant expertise in multimodal image processing for the segmentation of tumors (brain, lung, lymph nodes), involving dedicated tools for normalizing and standardizing the image signal with respect to multimodal spatial uncertainty, inter-patient variability, and variation in longitudinal scanning conditions. It has also a strong competence in segmenting and recognizing anatomical structures, both in normal and pathological contexts, based on the modeling of anatomical knowledge, in particular spatial relations between structures resulting in merging image processing and interpretation with spatial reasoning approaches. Télécom SudParis has expertise in multimodal image processing for non-contrast and contrast-enhanced thoracic imaging (lung, heart), including denoising, enhancement, multi-feature/view nonrigid registration, anatomo-pathological segmentation, 31

224 deformation modeling and analysis, and high-dimensional classification. Current industrial collaborations involve Philips Healthcare Research, General Electric Healthcare, Siemens Healthcare, Air Liquide, GlaxoSmithKline, Dosisoft, EOS Imaging, ImagineEyes, Intrasense, Segami, Orange Labs and PSA. Nicolas Rougon received an Engineer degree in Telecommunications and a Ph.D. in Signal and Image Processing from Télécom ParisTech in 1989 and 1993, respectively. During his thesis, he was with Philips Healthcare, working on 3D Ultrasound image processing. After a one-year post-doctoral period in the Ophthalmology Service at APHP-Hôtel Dieu, he joined the Signal & Image Processing Department at Télécom SudParis as an Associate Professor. In 1999, he co-created the Advanced Research and TEchniques for Multidimensional Imaging Systems (ARTEMIS) Department at Télécom SudParis, serving as adjunct Head until 2007 before leaving for a one-year sabbatical at the Center for Mathematics and their Applications (CMLA) of ENS Cachan. During this period, he also served as an Adjunct Scientific Head of the CNRS ISIS (Information- Signal-Images-viSion) Research Network in charge with computer vision activities, and as an Associate Editor of IEEE Transactions on Image Processing. Since 2001, he has been coordinating at Télécom SudParis a research program on multimodal cardiac imaging in close partnership with APHP, with the objective of developing image analysis methods for quantitative computer-aided diagnosis and functional modeling of the heart, with current emphasis on cardiac MRI and CT. Recent publications representative of the expertise in the field: - Fouquier G, Atif J, Bloch I. Sequential model-based segmentation and recognition of image structures driven by visual features and spatial relations. Computer Vision and Image Understanding. 116: , Angelini E, Delon J, Bah AB, Capelle L, Mandonnet E. Differential MRI analysis for quantification of low grade glioma growth. Medical Image Analysis. 16: , Ius T, Angelini E, Schotten MT, Mandonnet E, Duffau H. Evidence for potentials and limitations of brain plasticity using an atlas of functional resectability of WHO grade II gliomas. NeuroImage. 56: , Chambon S, Moreno A, Santhanam A, Rolland J, Bloch I. MARIO : Modélisation de l'anatomie normale et pathologique pour le Recalage non linéaire entre Images TDM et TEP en Oncologie. Traitement du Signal. 28: , Aldea E, Bloch I. Toward a better integration of spatial relations in learning with graphical models. In: Briand H, Guillet F, Ritschard G, Zighed D. Advances in Knowledge Discovery and Management (Springer), 77-94, Bloch I. Knowledge-driven recognition and segmentation of internal brain structures in 3D MRI. In Computional Surgery and Dual Training (Garbey M, Lee Bass B, Collet C, de Mathelin M, Tran-Son-Tay R, Eds), Springer-Verlag, 75-90, Hamrouni S, Rougon N, Prêteux F. Multi-feature statistical nonrigid registration using high-dimensional generalized information measures. 14 th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2011), Toronto, Canada. Lecture Notes in Computer Science. 6891: , Hamrouni S, Rougon N, Prêteux F. Groupwise registration of cardiac perfusion MRI sequences using normalized mutual information in high dimension. SPIE Medical Imaging 2011: Image Processing. 7962:796208:1-12, Khotanlou H, Colliot O, Atif J, Bloch I. 3D brain tumor segmentation in MRI using fuzzy classification, symmetry analysis and spatially constrained deformable models. Fuzzy Sets and Systems. 160: , Hudelot C, Atif J, Bloch I. Fuzzy spatial relation ontology for image interpretation. Fuzzy Sets and Systems 159: , IR4M IRCIV Contacts: Luc Darrasse (luc.darrasse@u-psud.fr), director of the lab; Xavier Maître (xavier.maitre@u-psud.fr), resp. of team 1; Ludovic de Rochefort (ludovic.de-rochefort@u-psud.fr), resp. team 2; Nathalie Lassau (Nathalie.lassau@igr.fr), resp. team 3 and adj. director of the lab. The lab "Imagerie par Résonance Magnétique Médicale et Multi-Modalités (IR4M)", formerly named U2R2M, performs a unique development in MRI instrumentation and methodology in France under the joint gouvernance of Université Paris-Sud and CNRS (UMR8081 label). Since 2009 the imaging research team at IGR (EA4040 label) joined the IR4M project, so MRI/MRS is now combined with ultrasound and optical imaging. This configuration interfaces Physics, Engineering, Biology, Pharmacology, Chemistry, and Medicine, and holds translational research from fundamental studies to preclinical and clinical applications. IR4M main asset relies on a strong methodology focus aiming at new applications over the whole medical application range, covering cancer, neurobiology, musculoskeletal, respiratory and cardiovascular systems, guided intervention and therapy monitoring. IR4M is based on three multidisciplinary teams totalizing 50 researchers, engineers, and technicians: (team 1) "Methodological and instrumental developments", (team 2) "Structure and Function", (team 3) "Multimodal imaging in oncology". IR4M is spread over 3 sites: (1) the Faculty of Sciences in the Orsay Campus, (2) CIERM, a clinical MRI facility at SHFJ site at Orsay Hospital, (3) IGR in Villejuif. This multi-site feature is driven by the need to maintain tight links between physicists in a rich scientific environment and clinicians in an hospital environment (6 medical doctors do their research in two of the IR4M teams). A full overview of the IR4M research themes is available on the web site The IR4M activities rely on a large multimodality in vivo imaging platform, which combines 3 preclinical MRI units at different magnetic field strengths (0.1, 4.7, and 7 T), a 1.5 T clinical scanner entirely dedicated to instrumental and clinical research (Philips Achieva at CIERM), 3 ultrasound machines with 3D capabilities (Toshiba, Visualsonics), and in vivo optical imaging with Cell Vizio fiber confocal (Maunakea) and small-animal fluorescence (Xenogen) equipments. The platform is open to external users, which helps to develop advanced instrumentation, methods and applications in relation with a number of industrial, life science and medical partners. The platform is partially supported by University Paris-Sud as shared research equipments since it welcomes a dozen of teams from Science, Medicine, and Pharmacy faculties. 32

225 Paris-Sud 11 University, the Institut National de la Santé et de la Recherche Médicale (INSERM), the Centre National de la Recherche Scientifique (CNRS) and the Institut de Cancérologie Gustave Roussy (IGR) have agreed to found a new federated research structure at the Institut de Cancérologie Gustave Roussy called the "Integrated Research Cancer Institute in Villejuif", shortened to IRCIV. The agreement was signed on February 27th, 2009 at the Institut Gustave Roussy by all partners. This federated structure, composed of Constituent Units, unites cancer research teams certified by the Paris-Sud 11 University (via the Paris-Sud, Medicine UFR), Inserm and the CNRS which already have facilities at IGR in close proximity to its technical platforms. Headed by Pr Eric Solary, the IRCIV should make it possible to widen the scope for the action of the Constituent Units that are under the supervision of different partners and seek to identify synergies between these facilities. IR4M-UMR 8081 is one of the lab integrated in IRCIV in Dr. Luc Darasse is a CNRS full-time Senior Researcher. He graduated in engineering from ENSAM (Paris) in 1978, and obtained his PhD degree and his habilitation from University of Paris-Sud in 1984 and 1994 respectively. His interdisciplinary research has been mainly focused on specialized instrumentation and methodology for advanced medical MR applications, and more specifically since 1995, high-temperaturesuperconductive RF coils and hyperpolarized helium-3 MRI both with international acknowledgement. As a result of his research activities in low-field MRI, he created the French start-up Magnetech in 1987 (Escanglon Award from the Société Française de Physique in 1991). He is the director of IR4M since 2010, the founder-director of Imagiv (CNRS GDR3271 Imageries in vivo), a CNRS extramural research facility set-up with a nationwide partnership of about 100 teams, since 2009, and the leader of the national workpackage Instrumentation and innovative technologies of France Life Imaging. Recent publications representative of the expertise in the field: - Lassau N, Chapotot L, Benatsou B, Vilgrain V, Kind M, Lacroix J, Cuinet M, Taieb S, Aziza R, Sarran A, Labbe C, Gallix B, Lucidarme O, Ptak Y, Rocher L, Caquot LM, Chagnon S, Marion D, Luciani A, Uzan-Augui J, Koscielny S. Standardization of dynamic contrast-enhanced ultrasound for the evaluation of antiangiogenic therapies: the French multicenter Support for Innovative and Expensive Techniques Study. Invest Radiol. 47: 711-6, Lassau N, Cosgrove D, Armand JP. Early evaluation of targeted drugs using dynamic contrast-enhanced ultrasonography for personalized medicine. Future Oncol. 8: , Katabathina VS, Lassau N, Pedrosa I, Ng CS, Prasad SR. Evaluation of treatment response in patients with metastatic renal cell carcinoma: role of state-of-the-art cross-sectional imaging. Curr Urol Rep. 13: 70-81, Moss R, Grosse T, Marchant I, Lassau N, Gueyffier F, Thomas SR. Virtual patients and sensitivity analysis of the Guyton model of blood pressure regulation: towards individualized models of whole-body physiology. PLoS Comput Biol. 8, Maître X, Darrasse L, Sinkus R, Louis B. Apparatus and method for generating mechanical waves into living bodies, system and method for mapping an organ or tissue and system and method for characterising the mechanical properties of said organ or tissue. European patent n , Paris-Sud University, CNRS, 17/08/ de Rochefort L, Liu T, Kressler B, Liu J, Spinc le P, Lebon V, Wu JL, Wang Y. Quantitative Susceptibility Map Reconstruction from MR Phase Data Using Bayesian Regularization: Validation and Application to Brain Imaging. Magn Res Med. 63: , Horcajada P, Chalati T, Serre C, Gillet B, Sebrie C, Baati T, Eubank JF, Heurtaux D, Clayette P, Kreuz C, Chang JS, Hwang YK, Marsaud V, Bories PN, Cynober L, Gil S, Ferey G, Couvreur P, Gref R. Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging. Nature Materials 9: , Kalouche I, Crepin J, Abdelmoumen S, Mitton D, Guillot G, Gagey O. Mechanical properties of glenoid cancellous bone. Clin Biomech 25: , Smirnov P, Poirier-Quinot M, Wilhelm C, Lavergne E, Ginefri JC, Combadiere B, Clement O, Darrasse L, Gazeau F. In vivo single cell detection of tumor-infiltrating lymphocytes with a 1.5 Tesla MRI system. Magn Reson Med. 60: , de Rochefort L, Vial L, Fodil R, Maitre X, Louis B, Isabey D, Caillibotte G, Thiriet M, Bittoun J, Durand E, Sbirlea-Apiou G. In vitro validation of computational fluid dynamic simulation in human proximal airways with hyperpolarized 3He magnetic resonance phase-contrast velocimetry. J Appl Physiol. 102: ,

226 9.2. Complete CV of the coordinator Irène Buvat Director of Research, CNRS Born 21 july 1966 in Désertines (03, France) Married, 3 children French citizenship Home address: Work address: 30 rue de la source perdue, Gif sur Yvette, France Imaging and Modeling in Neurobiology and Cancerology (IMNC) UMR 8165 CNRS Paris 7 University Paris 11 University, Building 440, Orsay Campus Orsay Cedex, France University degrees Accreditation as research supervisor (Habilitation Diploma). Paris 6 University PhD in Physics, Paris Sud University, Orsay. With honours cum laude: Scatter correction in scintigraphic imaging IFSBM Degree (Institut de Formation Supérieure Biomédicale, R. Monier), Paris Sud University Certificate of advanced graduate studies (DEA) in "Nuclear and Particle Physics Paris Sud University, Orsay Magistère in Physics, Ecole Normale Supérieure d Ulm, Paris. Research Activities Imaging and Modeling in Neurobiology and Cancerology laboratory, CNRS joint laboratory UMR 8165 Paris 7 University Paris 11 University. Head of the "Quantification in Molecular Imaging" team Inserm U678, University Hospital Pitié-Salpêtrière, Paris. Head of the "In vivo Imaging of perfusion and molecular exchanges" team Inserm U494, University Hospital Pitié-Salpêtrière, Paris. Head of the "Quantitative imaging of radio tracers in oncology and neurology" team Inserm U66, and then Inserm U494, University Hospital Pitié-Salpêtrière, Paris. CNRS Researcher: Enhanced quantification in SPECT and PET Department of Nuclear Medicine, National Institutes of Health, Bethesda MD, USA. Visiting scientist position: Improving quantification in cardiac PET cardiac Department of Medical Physics and Bio-Engineering, University College London. Visiting scientist position: Improving quantification in SPECT. Supervision of 18 PhD students and 20 MSc students since Most significant achievements - Co-initiator in 2001 and leader since 2005 of the OpenGATE collaboration (17 international laboratories, among which UCLA, the University of Massachusetts Medical School, Forschungszentrum-Juelich, Memorial Sloan-Kettering Cancer Center) aiming at developing the Monte Carlo simulation software GATE for modeling emission tomography, computed tomography and radiation therapy. Since 2007, this simulation software has become the most widely used throughout the world in the field of emission tomography ( to design new detectors, acquisition protocols, and data processing methods. - Significant contributions to improved quantification in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) medical imaging. Scientific production since 1992 (full list at - Peer-reviewed journals: 86, h-factor=23 - Invited conferences in international symposia: 10 (of which 2 at the Society of Nuclear Medicine meetings in 2009 and 2010) - Invited conferences at national symposia: 11 - Proceedings of peer-reviewed conferences: 41 - Communications at conferences and symposium: 91-1 book Handbook of particle detection and imaging (Springer Verlag, 1249 pages, 2011) and 7 book chapters - Software: 2 (GATE : and pixies : 34

227 - 1 patent (Patent N A method for the decomposition of scintigraphic images in total and scattered components. Inventors : I. Buvat, H. Benali, J.P. Bazin and R. Di Paola. INSERM and Sopha Médical. 1993) Grants (full list at A total of 2892 k awarded by: - French Cancer National Institutes (INCA) (105 k , 107 k ) - MEDICEN cluster for innovative therapies and advanced technologies in healthcare (133 k , 90 k , 187 k ) - EC FP7 (148 k ) - French National Research Agency (ANR) (320 k ) - Dosisoft company (120 k ) - Philips (120 k ) - Foreign Affair ministry and British Council (10 k ) - CPS-Siemens Knoxville (92 k$ ) - French Research Ministry (400 k , 150 k ) - GE Healthcare (400 k , 150 k ) - SMVI company (360 k ) Main administrative responsibilities (full list at - Elected member of the IEEE Medical and Imaging Science Council since Chair of the award committee of the IEEE Medical and Imaging Science Council since Member of the conseil scientifique de l IN2P3 CNRS since Member of the steering committee of the French GDR (Research group) Stic Santé since Member of the steering committee of the French GDR MI2B since Organizer of 5 GATE workshops during the IEEE Medical Imaging Conferences (2006, 2008, 2008, 2011, 2012) in San Diego, Dresden, Orlando, Valencia - Organizer of short courses during the IEEE Medical Imaging Conferences 2008 in Dresden - Leader of the National working group Quantification in Nuclear Medicine since 1999 ( Reviewing - Associate editor of IEEE Transactions on Nuclear Science and IEEE Transactions on Medical Imaging - Board member of Journal of Nuclear Medicine - International Advisory Board member of Physics in Medicine and Biology - Reviewers for Medical Physics, European Journal of Nuclear Medicine and Molecular Imaging - Member of 37 PhD thesis committees (reviewer in 21) and of 4 Habilitations (reviewer in 3) - Reviewer of research project for the French National Research Agency (ANR every year since 2005), French AERES (2009, 2010), French Cancer National Institute (INCA ) - Consulting for the IAEA agency ( ) and for the CERN (2007, 2009) Teaching activities (full list at - Medical Physics at Master 2 level: 25 hours/year at University Paris 11, 12 hours/year at Nantes University, 14 hours/year at Lyon University. - Medical Physics for Medical Doctors (DES of Nuclear Medicine): 14 hour/year at National Institutes of Nuclear Science and Technologies (INSTN, Saclay) Awards , Prime d excellence scientifique allocated by the CNRS (French National Center of Scientific Research) , Citations Prize from the Institute of Physics (UK) for the largest number of citations of a paper published between 2004 and 2008, for the paper "GATE": a simulation toolkit for SPECT and PET", Phys Med Biol 2004, vol 49: , CNRS bronze medal. 35

228 9.3. Glossary 3D three dimensions (space) 4D four dimensions (space + time) AA Amino Acid AD Advisory Board ADC Apparent Diffusion Coefficient ANSM Agence Nationale de Sécurité du Médicament et des produits de santé BBB Blood-Brain-Barrier BGRT Biology Guided Radiation Therapy BOLD Blood Oxygen Level-Dependent CEA Commissariat à L Energie Atomique et aux Energies Alternatives CFD Computational Fluid Dynamic CNRS Centre National de la Recherche Scientifique CNS Central Nervous System CPP Comité de Protection des Personnes CT Computed Tomography DCE Dynamic Contrast Enhanced DSC Dynamic Susceptibility Contrast DTI Diffusion-Tensor Imaging DTPA Diethylene Triamine Pentaacetic Acid DW Diffusion-Weighted DWI Diffusion-Weighted Imaging EEG ElectroEncephaloGram EMMI European Master in Molecular Imaging EM-ML Expectation Maximization Maximum Likelihood EORTC European Organization for Research and Treatment of Cancer EUD Equivalent Uniform Dose FDG 2-Fluoro-2-Deoxy-Glucose FET 2-FluoroEthylTyrosine FLI France Life Imaging FLT 3 -Deoxy-3 -Fluoro-Thymidine FMISO Fluoromisonidazole fmri functional Magnetic Resonance Imaging, usually referring to brain function GATE Geant4 Application for Emission Tomography GIST Gastro-Intestinal Stromal Tumours GMM Gaussian Mixture Model GTV Gross Target Volume HCC HepatoCellular Carcinoma HU Hounsfield Unit IC-CPO Institut Curie Centre de Protonthérapie d Orsay IDEX Initiative D'EXcellence IGR Institut Gustave Roussy IMNC Imaging and Modelling in Neurobiology and Cancerology team IMPT Intensity Modulated proton Therapy IMRT Intensity Modulated Radiation Therapy IMT Institut Mines Télécom INRIA Institut National de Recherche en Informatique et en Automatique INSERM Institut National de la Santé Et de la Recherche Médicale INSTN Institut National des Sciences et Techniques Nucléaires IPS IDEX Paris-Saclay IR4M Imagerie par Résonance Magnétique Médicale et Multi-Modalités IRCIV Integrated Research Center Institute in Villejuif IRM Imagerie par Résonance Magnétique (nucléaire) Labex LABoratoire d Excellence LIST Laboratoire d'intégration des Systèmes et des Technologies MAP Maximum A Posteriori MC Monte Carlo MEG MagnetoEncephaloGram MET Methionine MR Magnetic Resonance MRE Magnetic Resonance Elastography MRI Magnetic Resonance Imaging mtor mammalian Target Of Rapamycin NPB Non-Parametric Bayesian PD PharmacoDynamic PDGFR Platelet-Derived Growth Factor Receptors PERCIST PET Response Criteria in Solid Tumors PET Positron Emission Tomography PIM Physique et Ingénierie pour la Médecine (english version : Physics and Engineering for Medicine) PK PharmacoKinetic PSC Paris-Saclay Campus 36

229 PSU QIM RCC RECIST SC SHFJ SITEP SNR SPECT SUV TEP TKI TPS U1000 US UTE VEGF Paris Sud University Quantification in Molecular Imaging team Renal Cell Carcinoma Response Evaluation Criteria In Solid Tumors Steering Committee Service Hospitalier Frédéric Joliot Service Innovations Thérapeutiques Précoces (linked to IGR) Signal-to-Noise Ratio Single Photon Computed Emission Tomography Standardized Uptake Value Tomographie par Emission de Positons Tyrosine Kinase Inhibitor Treatment Planning System Unité 1000 (INSERM codification of research team) Ultrasound Imaging Ultrashort Echo-Time Vascular Endothelial Growth Factor 37

230 9.4. Suggested experts For obvious conflict of interest reasons, we ask for our project not been evaluated by French colleagues. Below is a suggestion of knowledgeable international experts in alphabetic order, together with their specific area of expertise. Silvio Aimé, Professor, Head of the Molecular Imaging Center of the University of Torino, Turin, Italie. Expertise: MRI, contrast agents for molecular imaging applications Silvio.aime@unito.it Brian Hutton, Professor, Director of Research in nuclear medicine physics, University College London. Expertise: medical physics applied in nuclear medicine, Single Photon Emission Tomography, Positron Emission Tomography b.hutton@ucl.ac.uk Sébastien Ourselin, Senior Scientist, Deputy Director of the Centre for Medical Image Computing (CMIC) and Professor of Medical Image Computing, Centre for Medical Image Computing - University College London Expertise: PET/MRI at University College London s.ourselin@cs.ucl.ac.uk Tomáš Paus, Senior Scientist, Professor of Psychology and Psychiatry, University of Toronto. Expertise: expert in mapping the human brain in health and disease using a variety of tools, including Positron Emission Tomography, Magnetic Resonance Imaging, electroencephalography, and transcranial magnetic stimulation tpaus@research.baycrest.org Uwe Pietrzyk, Professor, Institut für Neurowissenschaften und Medizin / INM-4, Forschungszentrum Jülich GmbH Expertise: PET/MRI, brain imaging u.pietrzyk@fz-juelich.de Kamil Urgubil, Director of the Center for Magnetic Resonance Research Professor of medicine, neurosciences, and radiology. University of Minnesota, Departments of Radiology, Neurosciences, and Medicine Exertise: Imaging sciences, brain sciences, Magnetic resonance research kamil@cmrr.umn.edu Sybille Ziegler, Professor, Chair for Computer Aided Medical Procedures & Augmented Reality, University of Münich Expertise: PET instrumentation, integrated PET/MR imaging s.ziegler@lrz.tum.de 38

231 Interactions between Science, Innovation, and Society (ISIS) IDEX Paris- Saclay APPEL A PROJET RECHERCHE IDEX 2013 Project Name : Interactions between Science, Innovation, and Society (ISIS) Project Type : Social Sciences Project ISIS Coordinators : Christian BESSY (Chargé de recherche CNRS en économie, directeur adjoint de l IDHE- Cachan) christian.bessy@idhe.ens- cachan.fr Christian LICOPPE (Professeur de sociologie des technologies d information et de communication, directeur adjoint du LTCI) christian.licoppe@telecom- paristech.fr Jérôme PÉLISSE (Maître de conférences en sociologie, chaire d excellence CNRS , Directeur du PRINTEMPS) jerome.pelisse@uvsq.fr 0

232 Table of contents 1. Origins of the project Partners of the project Positionning Summary of the project ISIS s National and International Ambition Established Partnerships and Existing Links to National and International Actors ISIS s impact on teaching Governance: «Executive Comittee» and «Scientific Committee» Presentation of the scientific project... 4 INTRODUCTION... 4 WP 1: Quantification, modeling and metrology... 6 WP 2: Innovation, entrepreneurship and market development WP 3: Norms and Regulations of scientific work WP4: Law and Justice, Science and Technology ANNEXES Funding Justification References Partners CESDIP (Centre de Recherches Sociologiques sur le Droit et les Institutions Pénales) CRG (Centre de recherche en gestion) DANTE (Laboratoire de Droit des Affaires et Nouvelles Technologies) EST (équipe GHDSO) GREGHEC (Innovation & Entrepreneurship - Society and Organizations) IDHE- Cachan (Institutions et dynamiques historiques de l économie) ISP- CACHAN (Institut des Sciences Sociales du Politique) LSQ (laboratoire de sociologie quantitative) LTCI (Laboratoire Traitement et Communication de l Information) PESOR (Pilotage Économique et Social des Organisations) PRINTEMPS (Laboratoire Professions, Institutions, Temporalités ) STEF (ENS Cachan) Summary partners, staff and financial contributions

233 1. Origins of the project The ISIS (Interactions Science, Innovation, Society) is the result of a merger between two Labex projects in social sciences (6S and LISI). Even though these projects were well evaluated, they were not funded. Given the evolution of the IDEX partnerships, a new perimeter is suggested. Indeed, 4 new research centers joined the preexisting teams: GHDSO- EST and PESOR from Université Paris Sud, DANTE from UVSQ, and IDHE from Université d Évry (Histoire Economique Sociale et des Techniques). These teams will considerably enhance the interdisciplinary aspect of the project through their expertise in history, law and business administration. 2. Partners of the project CESDIP (UVSQ- CNRS- Ministère de la Justice) CRG (Polytechnique CNRS) DANTE (UVSQ) GHDSO (équipe de EST - Université Paris Sud) IDHE Cachan and Evry (ENS Cachan Université d Evry- CNRS) ISP Cachan (ENS Cachan- CNRS) LSQ (équipe du CREST- GENES) LTCI (Télécom ParisTech - CNRS) PESOR (Université Paris Sud) PRINTEMPS (UVSQ- CNRS) GREGHEC (HEC CNRS) STEF (ENS Cachan/IFE) 3. Positionning 3.1. Summary of the project Knowledge production is the complex result of a combination of scientific activities, social constraints and law that in turn orients the organization and government of activities, as well as the regulation of social life. By combining the approaches and competencies of researchers from different disciplines: sociology, economics, business administration, law, education and history, the consortium s goal is to examine the way measurements, organizational models, scientific results, norms and regulations circulate, are debated in public arenas, are interpreted and implemented in different areas, and also to shed light on their social and economic implications. In this attempt, objects such as the construction of socio- economic categories and indicators, clusters, open innovation, interactions between laboratory life, education and industry, as well as the use of science in the judicial sphere will be examined ISIS s National and International Ambition ISIS s ambition is to develop and structure social sciences research and education in Saclay by relying on researchers domains of excellence and on the exceptional scientific environment of the area. By integrating different disciplines in common research operations (sociology, history, law, education, business administration and economics), the project aims to structure a cluster of research and education in social sciences that will have both a national and an international attractiveness in the following domains: 2

234 - Use of quantification in social sciences but also in firms and public administrations. Here our research operations will be complementary to those of Labex ECODEC. - Processes of innovation and entrepreneurship relying on scientific developments. - Analysis of scientific work as well as its norms and regulations. - Interactions between «law and justice» and «sciences and technologies». The project will be developed in two phases until 2019: During the phase, the goal is to structure research in the social sciences. More precisely, Saclay partners will be gathered to work together on complementary objects with the aim of renewing the domains of science, innovation, technology and knowledge. As such, the research operations presented in this project rely on well recognized competencies (awarded ANR funding, European Coordination action or other types of institutional grants) that are extended and articulated in a way that gives coherence to the collective goal. Our interaction with national partners (such as IFRIS- Institut Francilien recherche, Innovation, Société located in Marne- la- Vallée) will ensure that our research orientations have by 2016 a real added value both for involved organizations and for national partners. During the phase, international reputation will be our main goal. We intend to transform Université de Saclay s social sciences into a world class program. Internal and external funding will be applied for in order to attract competitive international researchers in our domains but also to develop international research and educational programs and partnerships Established Partnerships and Existing Links to National and International Actors Our project will benefit from universities and schools facilities and grants as well as from the national initiatives to which some of the involved researchers participate. Île- de- France s Domaines d Intérêt Majeur (DIM) will be one of them. Indeed, the IS²IT (Innovation, sciences, techniques, société directed by P.B. Joly) and GESTES (Groupe d Étude sur le Travail et la Souffrance au Travail, co- directed by M. Gollac and J. Pélisse) are DIMs with consequent budgets (700 to 800k Euros per year) that offer access to PhD, Post- doctoral or Scientific event funding. Besides, they give access to a network of researchers on which our group can rely to have fruitful scientific discussions and enhance its attractiveness. A partnership is also being negotiated with the IFRIS. The goal is to develop an internationally renowned Ile- de- France based scientific group specialized in questions related to interactions between science, innovation and society. ISIS also intends to further develop partnerships with the private sector. Here, we can already rely on the existing network of some of the teams involved in this project (GREGHEC, SnO, PESOR ). Indeed, our exchanges include research contracts as well as training and educational funding partnerships. These will be further deepened in order to expand the existing network. Last but not least, researchers involved in this project have different research networks on the international academic scene. By merging seminars, and organizing international joint conferences, our goal is to strengthen and widen our networks ISIS s impact on teaching Our efforts to structure the research milieu will be coupled with the inception of two new Masters Programs - - the Master of Quantitative Methods in Social Sciences, and the Master of Science and Society Studies - - that involve a large number of partner research centers. Research will moreover 3

235 influence educational goals through different channels. First, a wide range of case studies will be developed in this project. These can become supports for teaching. Second, our continous efforts towards research complementarities will help define a coherent educational and training strategy. Furthermore, two summer schools will be organized. First, an annual summer school on Innovation and Entrepreneurship is planned in this project (WP2). Second, partners involved in this project will participate in an international summer school that will be hosted at Saclay in Finally, the numerous seminars, workshops and conferences that will be organized by the involved partners in this project will be open to Saclay s students, researchers, professors as well as private actors and public administrations. They will constitute an occasion to develop knowledge, discuss and debate various topics ranging from quantification to the use of science in the judicial sphere. Thus the knowledge developed in this project will also allow for providing training for firms (in management, for instance) or public administrations (policy- makers, police or judicial bodies, for instance) Governance: «Executive Comittee» and «Scientific Committee» The ISIS light governance will rely on a single, wide coverage (one member per contributing organization), decision committee, called the ISIS Scientific Committee (ISC) which will convene at least three times a year. The day- to- day operations, supervision, and ISIS outside representation, will be managed by a three- member ISIS Executive Committee, representing ENS Cachan, UVSQ and Télécom ParisTech (i.e. the actual coordinators of the project). The ISIS Executive Committee will prepare issues to be decided upon by the ISC, such as budget allocation, expenses, new project kick- offs, former projects closures, workshops, PhD & post- doc financing, etc. The ISC will also collect the inputs from ISIS members about potential projects to be launched, and will evaluate ongoing projects once a year. 4. Presentation of the scientific project INTRODUCTION Knowledge production is the complex result of a combination of scientific activities, social constraints and law that in turn orientates the organization and government of activities, as well as the regulation of social life. Scientists, experts, public organizations and others participate to this endeavor in a deliberative or in an involuntary way. They thereby introduce new indicators and categories thought as democratic, organizational forms deemed as efficient, regulation systems designed to bring cohesion in social activities, or scientific results that can be transformed into facts in decision making. Recently, a large set of artifacts has been introduced and this project aims to examine some of them. The selection of the following topics reflects the areas of research in which the consortium is recognized as or aims to become a leading actor on a longer term both on the national and international level. The consortium s goal is to examine the way measurements, organizational models, scientific results and regulations circulate, are debated in public arenas (Chateauraynaud 2011), interpreted and implemented in different areas, and to shed light on their social and performance implications. Quantifying and categorizing the social and economic activities or governing with numbers 4

236 (Desrosières 2008) and benchmarks have probably become the main concern of policy- makers. In parallel, organizational models such as clusters (Porter 1998) or open innovation (Chesbrough 2003) are believed to bring efficiency to the business world. In the scientific sphere, new funding schemes and law (Silbey, Husing, 2011), performance indicators, mergers and partnerships are introduced to regulate knowledge production. The knowledge hereby produced is itself mobilized by experts in the judicial sphere (Dumoulin, 2007; Pélisse, 2012). However, the construction, circulation and reception of these artifacts as well as their appropriateness to reach their goals, that is, a more democratic, efficient or integrated system is still to be examined. Each of the four axis of research presented in this project aims to contribute to the debate on the circulation, the social reception, the effectiveness, and the implications of a range of artifacts. In particular, the first axis will contribute to developing quantitative research while proposing a reflection about the way metrologies and categorizations are used in different disciplines, organizations and countries. The second axis examines organizational models that aim to enhance innovation in the business sphere. In extension, the third axis focuses on the way new forms of regulating and norming science affect knowledge production and circulation in academic, industrial and educational spheres. Last but not least, the fourth axis aims to shed light on the way experts use scientific results in the judicial system and the way justice but also the definition of human being can be reshaped by science. These axes will be examined by combining approaches and competencies of researchers from different disciplines: sociology, economics, business administration, law, education and history. A common concern is the focus on mechanisms of artifacts creation and circulation. These can include mediations (norms, cognitive artifacts, technical equipment) or intermediaries (go- between) enabling coordination among different logics of action and communities. 5

237 WP 1: QUANTIFICATION, MODELING AND METROLOGY This WP primarily brings together CESDIP, the IDHE at Cachan, the LSQ, PRINTEMPS and the SnO, but also involves researchers from LCTI and the CRG. Drawing on a tradition of research on quantification, both from the viewpoint of its construction, and from that of its social uses, ISIS will promote the use of databases, will open new fronts in quantitative research, seeking to spread a reflexive data culture in the social sciences (Desrosières, 2008), thus encouraging a confrontation between scientists who study the same social processes and realities using different methodologies. ISIS will benefit from cutting- edge equipment such as EQUIPEX CASD (a secured remote data center, permitting access to individual or sensitive data to which several partners participate and contribute funds), and DIM- SHS (social surveys center). ISIS will also rely on the on- going creation of a specialized Master on Quantification in social sciences at Paris Saclay. It will moreover also seek a rapprochement with other sciences that use quantification for the problematization and causal inference, such as the sciences and technologies analyzed below in WPs 2 and 3. Three research projects will be conducted during the period. The first two will be completed in 2016, whereas the third one is meant to be deployed over the entire period. The years constitute boot years to establish the conditions for the completion of these studies. The first project will be devoted to the Comparison of strategies of quantification in the social sciences. The second project deals with the categorizations of the occupational space in Europe. The third project focuses on metrology and governance, in cooperation with the three other streams or axis of the overall project. WP 1.1: Comparing measurement and quantification strategies in the social sciences A growing number of researchers routinely resort to increasingly sophisticated quantitative methods. This, as expected, has raised several criticisms (on compositional effects, on the use of causality concepts, on the influence of unobserved variables...). Refusing to view statistics as a mere tool for social sciences, Michael Sobel (2000) rightly described an interplay between statistics and social sciences, and pointed out that it was a fruitful phenomenon, simultaneously urging researchers in social sciences to take advantage of the latest research in statistics and econometrics. In Saclay, there is a confrontation between observational and statistical techniques versus simulation techniques. Indeed, while social scientists most often use census or survey data, experts in complex systems modeling favor simulation or agent- based modeling (on the usefulness of the combination of both methods, see Bruch and Mare, 2006). We therefore plan to investigate the construction of variables and nomenclatures, and the development of devices to collect information (e.g., surveys or experiments) that help to bridge the gap between learned conceptions and ordinary judgments. Some devices, especially large- scale ones, are formatted not only by the scientific debate, but also by political and societal issues (Monso and Thévenot, 2010). Variables are seldom comparable to concepts, and many methods have difficulty addressing this issue. This is the moment when the issue of interpretation and of the gap between what figures suggest and what we say about them really emerges. We wish therefore to create modeling experiments by using a combination of various methods to explore common objects or data, which will lead us to compare not only the results, but also their potential interpretations, as well as researchers activities. We will 6

238 particularly focus on the intrinsic capabilities of different types of modeling in order to describe regularities and structures, or to support causal analysis (Goldthorpe, 2001; Spirtes, Glymour and Scheines, 2000; Durand and Vaara, 2009). To make circulation and discussion possible between the different projects, teams and research centers mobilized on this axis, we will merge the three research seminars in quantitative studies (CREST s sociology seminar, the seminar on reflexive Quantitativism at ENS Cachan, and PRINTEMPS s seminar on quantitative sociology and the sociology of quantification). A specific attention will be devoted to the reception of regression analysis methods in French social sciences, through the constitution of a database collecting methods used in the articles published in the main academic social sciences journals since Our project will then consist in one international seminar on this question of quantification at the level of Saclay. SnO already received the first workshop organized with ASQ s editorial board (June 2010), and has been part of European initiatives such as OTREG seminars and European Theory Development Workshops in cooperation with the Academy of Management Review. Furthermore, a Summer school for PhD students will be organized in by CESDIP (F. Vesentini), together with PRINTEMPS, 2 Belgian research units (Louvain, Liège) and one Canadian center (Univ. of Montreal). A third year will take place in UVSQ (25 to 30 PhD Students for 5 days). Aim: Making Saclay a renowned national and international cluster for research and education on quantification in the social sciences. Operations: a common seminar ( ); an international Conference (2014); a Summer School. Involved researchers: J. Deauvieau (PRINTEMPS), C. Dumoulin (PRINTEMPS), I. Fréchon (PRINTEMPS), N. Robette (PRINTEMPS), O. Samuel (PRINTEMPS), C. Bessy (IDHE), H. Harari- Kermadec (IDHE), A. Perdoncin (IDHE), T. de Saint- Pol (IDHE), R. Durand (SnO), D. Goux (LSQ), M. Gollac (LSQ), L. Wolff (LSQ). Funding granted until now: Summer School ( ): (different partners, incl. 3 x CESDIP). Requested Funding: A 6 months post- doc position for the organization of the international conference ( ). - Travel expenses, invitations, accommodation ( ) - Summer School: for the year 2015 in UVSQ. Scientific results: learning actions (seminars + Summer School) + 1 edited book on soc. sc. jnls in France. WP1.2: Categorizations of the occupational space in Europe This project deals with the categorizations of the occupational space at the European level. It will continue several comparative researches on statistical institutions such as Eurostat, financed so far by an ANR ( ). 7

239 The first question deals with ordinary categorizations of social space (Boltanski and Thévenot, 1983). 30 years ago in France, and at the end of 2000 in Europe, studies on ordinary categorizations were conducted, relying on an imaginative empirical procedure: subjects were invited to comment on and sort cards depicting individuals according to their putative social similarity. A project aiming at generalizing this card game study has been submitted by the LSQ (Cécile Brousse) for the period, based on a sample of 1500 individuals an unprecedented sample size for this type of experimental surveys. In a second phase, the links between scientific and lay practices of categorization will be studied in different new domains (categorizations related to gender, delinquency, suspicion regarding past or present criminal activities ). The second question is concerned with the statistical categorizations of the occupational space. The goal here is to study the history and uses of occupational classifications in various countries: Belgium, Germany, France and Great- Britain. National classifications are based on different social experiences and on histories of labor. We want to understand the modes of description of the occupational world through the prism of statistical production in the countries mentioned. Is there a specific classification? What are the uses of these classifications? How have they evolved since statistical harmonization has been required at the European level? What are the links between the statistization of the occupational world and the institutional forms of work? The third question aims at a study using statistical data from European surveys (in particular the SILC- EUROSTAT survey). The point here is to use the statistical harmonization as a resource for the study of the European social space. Most social stratification theories are framed within national spaces (Wright, Goldthorpe, Esping- Andersen, Bourdieu). Our goal is to study how much the different regions of the European social space (defined by income- diploma proximity) are organized around socio- occupational groups. Our goal is thus to articulate a sociology of the quantification of the European occupational space (projects 1 and 2) with a quantitative sociology dealing with the same question (projet 3). Aim: To deal with the current discussions on common occupational classifications at the European level. This is a contribution to the proper way to describe social structures in Europe and to sketch the relationships between lay and professional categorizations. Involved Researchers: C. Brousse (LSQ), J. Deauvieau (PRINTEMPS), C. Dumoulin (PRINTEMPS), M. Gollac (LSQ), C. Ollivier (PRINTEMPS Girsef, Belgique), I. Petev (LSQ), T. Razafindranovona (LSQ), L. Thévenot (LSQ), L. de Verdalle (PRINTEMPS), F. Jobard (CESDIP), F. Vesentini (CESDIP). Funding granted until now: ANR ( ): Requested funding and grants ( ): 1/ DIME- SHS: access to DIME- SHS resources devoted to the 1500 units sample. 2/ IDEX Paris Saclay: : Travel expenses: Card games, tablet computers and documentation: Research engineer (12 months full job): Scientific results (until 2016): Submission to different French and non- French academic journals. 8

240 WP 1.3: Metrology and governance Today rating agencies, professional reviewers and evaluators, or NGOs that establish rankings driven by environmental or social practices, strongly contribute to classify, evaluate, and allocate resources and power. Governance through norms (Thévenot, 2009) has emerged as a new method for managing state- related issues. Further, standardized indicators have become available in various fields such as cultural industries, service provision or security (Chiapello, 2009; Zauberman, 2009). Current governance modes are based on the worship of transparency and accountability (Guthrie and Durand, 2008; Espeland and Sauder, 2007). Capitalizing on Salais's work (2010), we will investigate indicator- based policies in such fields as social rights, psychosocial risks, and crime. We will also conduct further research on the roles played by quantification experts in corporate or public management, by studying the constraints associated with the professionalization of their trade, along with associated ethical aspects (link with axe 3 about the norms of scientific work). WP 1.3.1: The metrology of work via the studies of psychosocial risks In the field of labor research, two project members have, at the request of France's Ministry of Labor, set up and led a group of experts tasked with monitoring workplace psycho- social risks. This project is a unique opportunity to observe (1) how the issue of health at the workplace is construed by different actors, (2) how arguments justifying or criticizing quantification and indicators are being built and deployed (Clot, 2010; Dejours, 2010), (3) and various conflicting outlooks on the way they should be used and on the relations between quantification, management, and criticisms. One original research on this topic will be conducted by analyzing how the psychosocial risks are measured, and with what sort of tools, by consulting firms, by union s observatories, by the government or by other actors. It will analyze the interests and skills of the "encoders", and of users how the figures are used by companies or branches, how policies might be built on them, how they might help the judges to make their decisions? This research will be based on a large regional network (more than 200 scholars in Ile de France GESTES, Groupe d études sur le travail et la souffrance au travail, directed by two scholars involved in this project see which gives postdoctoral and PhD grants and other fundings on this topic. Moreover, parts of the questions submitted to the sampled population in the Ile- de- France penal metrology surveys (WP 1.3.2) are related to feelings of insecurity, and will give us a larger base to contextualise the data on perceived vulnerability (Robert and Pottier, 1997). Also, IDHE s research members (Mias et al., 2013) participate in a research on women s exposition to reprotoxic substances and prevention issues (ANSES research). Aim: Analyzing how the psychosocial risks are measured, and on what sort of tools these measures are based. Involved Researchers: L. Wolff (LSQ), M. Gollac (LSQ, co- director of GESTES), J. Pélisse (PRINTEMPS, co- director of GESTES), J. Kubiak (PRINTEMPS), A. Mias (IDHE). Funding granted until now: ANSES ( ): Requested funding in : 1/ Request submitted to GESTES: a postdoctoral ( ) or a PhD ( ) position 2/ Request submitted to IDEX Paris Saclay : Travel expenses: Documentation:

241 WP 1.3.2: Penal metrology In this field, a variety of quantification tools are now available: statistics of criminal justice agencies, other public statistics, specific population surveys (victimisation) or conducted in intersecting domains (public health ). For analysing such a complex field, our strategy is to organise within an Academic Observatory a confrontation between the major quantification tools and time series in use at LSQ or accessible through CASD (public transportation, household budgets, employment, national population census, national accounting). Through a dedicated project financed (ANR- CRIMINSEC- 07- BLANC- 0026) and the coordination of a European Coordination action from the FP6 (CRIMPREV ), the CESDIP has already conducted secondary analysis of all the insecurity and victimisation surveys (national, regional, local) available in France at the time. Our Observatory would be operated along two principles: i) long term observation of crime data ii) comparison of crime data from a variety of sources: institutional data and surveys, and sensitive nominative databases like the criminal records database and samples from the national census (échantillon démographique permanent - EDP). A long- term cooperation between CESDIP, LSQ and PRINTEMPS will serve this aim. In a first step, the Observatory structure would make its products available to a wider academic community, in particular by way of a web site. In a second step, at junction of projects 2 & 3, we will develop a CESDIP- LSQ s common project on the consequence of a criminal record for the employment outcomes of males in France. Two research designs could be implemented, each one based on what has been suggested so far in project 1 and project 2. We will either work on longitudinal survey data (samples from INSEE s national census (EDP) and samples from the criminal records database hold by the Ministry of Justice. This project would bring together researchers from CESDIP and LSQ. Criminal records are sensitive statistics, but apart from the fact that CESDIP is part of the Ministry of Justice, discussions are currently conducted in order to locate this database at CASD. We will choose an audit methodology or a testing methodology, in which the employment audit involves sending matched pairs of individuals ( testers ) to apply for real job openings in order to see whether employers respond differently to applicants on a basis of selected characteristics, including information on a criminal curriculum. This methodology builds a bridge to the next action (1.3.3). Aim: This operation, linked with the operations presented in axis 4, will contribute to make Saclay a large pole of sociology of law and justice, dedicated notably to quantitative research. Involved Researchers: J. Deauviau (LSQ), M. Gollac (LSQ), F. Jobard (CESDIP, and CASD scientific board s member), Ph. Robert (CESDIP), F. Vesentini (CESDIP), R. Zauberman (CESDIP). Funding granted until now: ANR : CESDIP : 1) The salary of one full- time engineer in statistics (F. Jouwahri) 128K / 3 years. 2) 50% of the salary of one half- time assistant- engineer in documentation and web (J.- Ch. Le Pellec) 9K /yr. Requested Funding ( ): : Two post- doctoral positions (2 x ); setting up and maintenance of an Internet observatory ( ); computer equipment (5 000 ) Expected Scientific Results: Creation of an academic observatory of quantification of crime ( ), a website 10

242 WP 1.3.3: The assessment of organizations and the use of performance indicators Research on the role of performance quantification within public or corporate organizations, and the ways in which actors produce it or use it will be conducted during the period ( ).This type of research has for instance been examined by SnO s researchers (Durand, Rao and Monin, 2007; Durand and Jourdan 2012) who investigated how market structures and macro- level institutions influence organizational efficiency, particularly on strategic decision- making using quantitative sociology (like the uses of panels at the micro- economic level). In the future, a cross- referenced database about the evaluations of international corporations carried out by rating agencies with various rationales (i.e. financial, humanitarian, or professional rationales) will be built. Research will also be conducted on the impact of the assessments made by rating agencies on the behavior of the actors, in particular in R&D activities or in the academic field (link with axe 3), through a collaboration between HEC, IDHE, DANTE, CESDIP and PRINTEMPS. Another object of study is the role of categorization in international contexts in mediated markets, i.e. markets in which intermediaries evaluate market players. For instance, when multiple guides or raters evaluate the same firms across territories, do these ratings converge? What is the impact of this convergence or divergence on their performance and their decisions? The first steps of a study on these questions have been undertaken at SnO, with a joint work by R. Durand and L. Paolella. The topic is corporate lawyers and how professional guides class and rank firms depending on their practices (i.e. categories of service). This project will be pursued by cross fertilization with the work of Christian Bessy on new organizational forms of corporate lawyers in France (Bessy, 2012). The research on raters and ratings will further be extend through reviving research designs in criminal justice, in which judges are asked to analyze fictitious criminal cases, and to give sentences on cases for which the variables of the defendant, the victim or the situation are changed. Marie- Emma Boursier (legal scholar, DANTE) and Anthony Amicelle (political scientist, CESDIP) would work on it in order to shed light on how crucial players in the criminal justice system (public players like judges and magistrates or private ones like compliance officers) have, or don t have, ratings on individuals, curricula, etc (Amicelle, Favarel- Garrigues, 2012). Carole Gayet- Viaud (CESDIP) will deploy this method in order to trace the difference between a misdemeanor and a crime, an anti- social behavior and a criminal action. This method is similar to one of the methodologies evoked in the penal metrology action (3.2) which also makes use of tests. Aim: Contribution to Saclay s pole of sociology of law and economic sociology, together with quantitative research. Involved Researchers: A. Amicelle (CESDIP), Marie- Emma Boursier (DANTE), Christian Bessy (IDHE), R. Durand (SnO), Carole Gayet- Viaud (CESDIP). Requested funding ( ): for the organization of interdisciplinary seminars on rating and indicators. 11

243 WP 2: INNOVATION, ENTREPRENEURSHIP AND MARKET DEVELOPMENT Innovation has always been a key driver to business development but the last decades have witnessed an abrupt break with the past: from what was basically a weapon for growth, limited to the most enterprising, innovation has become a condition of survival in saturated global markets, providing a strategic alternative to price wars. Contemporary forms of innovation are getting more and more complex, mixing up technological, economic, social, organisational aspects in an attempt to meet contemporary challenges (Benghozi et al. 2010; Midler et al. 2012). The objective of this axe is to support an interdisciplinary perspective focusing on the variety of collaborative practices involving a large number of potential actors (engineers, marketing departments, architects, artists, users, etc.), with different languages, tools and organizational forms. The challenge for these groups is to transform fuzzy concepts into objects and services adding value and values. This WP will take advantage of its location to develop research on and within the innovation processes in a close relationship with other involved actors. It takes advantage of existing research and educating collaborations in the past on the theme of innovation and entrepreneurship (PIMREP, 2010) (master program involving Ecole Polytechnique, HEC and TelecomParisTech, Chairs Ecole Polytechnique- HEC and Ecole Polytechnique- TelecomParis, etc). Specific efforts will be devoted to the promotion of cross- discipline research. Such initiative will help to foster the dialogue with all the Saclay s actors of innovation: innovators, firms, public authorities, civil society. The research program focuses on the relations between innovation management, entrepreneurship and market development, in both mature industries and high technology start- ups: it renews classical approaches by taking seriously the collective nature of innovation and the specificity of entrepreneurship in high technology contexts. The perspective mainly focuses on issues related to the traditional definition of innovation and entrepreneurship, i.e. economic and firms growth and market development thanks to the development of new products or service provisions. It approaches the question of innovation and entrepreneurship (I&E) within the firm, i.e. the micro- dynamics of activities (organisational design, management of creation processes and entrepreneurship, users practices) on the one hand, and the innovation in/as the firm s strategy (business models, structuring of markets and value chain), on the other. Besides, the project will also focus on others forms of entrepreneurial and organizational creativity that make society and markets evolve (megaprojects, financing, new forms of contracts, hierarchy, etc.). Innovation issues have generally been studied by distinct disciplines (strategic management, theory of organization, sociology and entrepreneurship). To understand the new forms of innovation requires a dialogue between them. More specifically, the program will focus on three main research operations and a pedagogical one. WP2.1: Innovation and coordination in high technology environments The first perspective is about R&D ecosystems in high technology environments (clustering, geographical externalities, open innovation, platforms structure) (Chesbrough, 2003; Iansiti et al. 2004; Gawer, 2009; Adner et al. 2010; Dougherty et al., 2011; Brousseau et al. 2011). This part of the program will study the deployment of I&E in a global business, confronted with market contexts 12

244 characterized by radically different usage and regulatory conditions. Actually, open innovation based strategies target specific organizational structure able to support a large number of contributors; to implement new forms of contracts and partnerships, to design new form of local proximity. Such dynamics have been, moreover, reinforced by the development of Information and communication technologies providing radically new means for innovation and market developments (Abecassis & Benghozi 2011). The following research actions will be undertaken to address these issues: (i) Characterization of industrial partnerships in open innovation ecosystems, (ii) Architecture of production and distribution platforms, (iii) New cooperative practices in the management of open innovation, (iv) The management of mega technological projects and the risks they present (v) Design and role of management tools in innovation project and (vi) The legal infrastructure of such cooperation, specifically as regards competition and intellectual property law requirements. These actions have already been launched through researches using different methodologies. One is the) characterization of the emerging digital ecosystems specificities through the identification of new forms of partnerships and of innovative processes overlapping on the infrastructures, the devices and the content (PJ Benghozi and E. Salvador). A second methodology consists in the exploitation of spatial data (Marie Le Pellec, CNES, CRG; Arnaud Saint Martin, Printemps). A third one is based on the measurement of innovation in territories by focusing on the characteristics of intangibles assets (Bounfour, Edvinsson, 2005). Five Phd students are examining these issues within different industries: three PhDs in electric mobility and new associated services (Felix von Pechmann, Renault, CRG ; VEDECOM, Telecom Paristech) and two PhDs on alternative mobility projects and European rail transport (Julia Heildermeier and Hervé Champin, IDHE Cachan) A seminar will be organized in addressing these issues across these fields and others. Indeed, each of these fields represents a very specific landscape. A PhD will be launched. Aim: exploring new forms of R&D organization using different empirical methodologies Involved researchers: This operation will involve the following members among others of the network: K. Dahlin, A. Masini and S. Jouini (HEC); P.J. Benghozi, F. Charue- Duboc, S. Lenfle, C. Midler and H. Dumez (Ecole Polytechnique); Tommaso Pardi, Isabel da Costa (IDHE), R. Maniak and V. Fernandez (LTCI); Ahmed Bounfour, Sandra Charreire- Petit and Florence Durieux (PESOR); M. Chagny, V.L. Benabou, M. Clément- Fontaine (DANTE); M. Le Pellec (CRG); A. Saint Martin (Printemps). Funding granted until now: several PhDs initiated Requested funding: a third of a post doc (each year) + 10K for the seminar + 10K for fieldwork missions Expected Scientific Results: publications, a workshop to debate on the researches engaged in the first perspective and a seminar innovation and society WP2.2: Entrepreneuship and start- ups In the innovation networks that emerge in high technology environment, entrepreneurship and start- ups play a crucial role and present specificities. For instance, academic spin- offs, acting as mediators between science and industry, engage in a wide range of partnerships with established firms and improve the innovative performance of their partners (Mindruta, 2008; Phelps et al. 2010; 2011). Therefore, a second line of research will investigate key issues relating to new ventures founding, development and growth, collaborations between incumbents and start- ups, specificities of entrepreneurship. The objective is to enhance our understanding of the factors that foster the 13

245 founding of new ventures (Astebro 2011; Yong et al. 2010), to study the development of a learning dynamics within innovative start- ups (Ben Mahmoud- Jouini et al. 2010), to investigate the factors that hamper growth dynamics in start- ups and innovative ventures, to examine how collaborations with high- tech start- ups impact the innovative performance of partner firms. The following research actions will be undertaken to address these issues: (i) Dynamic cartography of high technology start up and research spin off, (ii) Economic of start up: strategy, organization, life circle, growth, (iii) Venture capitalist and incumbent strategies vis à vis high tech start up, (iv) Specificities of social entrepreneurship, (v) Evaluation of business plans and management of performance through indicators and (vi) Repartition of value and ownership of intellectual innovation. These issues will be addressed through the database formed by startups hosted within the incubators of Saclay cluster: HEC Challenge plus 1, Ecole Polytechnique, Telecom- Paris and Incuballiance. Hence, raw data exists but needs further modelization in order to be exploitable. A quantitative and a qualitative methodology will be adopted to analyze trajectories of launch and growth of these start- ups as well as collaborations with incumbents through corporate venturing. Another field of research is the project that has been undertaken by the centre of entrepreneurship of HEC (Invivo start- up, up/start- up- In- Vitro) since 2011 matching innovators (researchers, etc) with HEC alumni that bring managerial and entrepreneurship competencies. This represents a rich field of experimentation and research. Some actions have already been launched through PhDs (Julie Fabbri, CRG; Isabelle Micaelli, HEC; Navid Bazzazian, HEC; Anisa Shyti, HEC) and other PhDs will be launched in the period Besides, IDHE launched a study on Optics Valley s entrepreneurs and start- ups. The study aims at understanding entrepreneurs trajectories and work as well as their relationship to the territory s actors (Andrey Indukaev, PhD), while trying to analyze indicators of their performance from different perspectives (Sabine Sépari and Hugo Harari- Kermadec, IDHE). Aim: a better understanding of the factors that foster the founding of new ventures and the dynamics of collective learning anchored in territories Involved researchers: F. Hoos, G. Di Stefano, D. Mindruta, K. Yong, S. Sommers, C. Phelps and E. Krieger (HEC), R. Maniak (LTCI), C. Midler, R. Beaume, F. Charue- Duboc (CRG), and Sabine Sépari, Andrey Indukaev, Hugo Harari- Kermadec (IDHE); V.L. Benabou, M. Clément- Fontaine (DANTE). Funding granted until now: several PhDs initiated, the study of Optics Valley and the experimentations launched at HEC entrepreneurship center Requested Funding: a third of a post doc (each year) + 10 K for fieldwork Expected Scientific results: publications, a database of the startups on the cluster, PhDs WP2.3: Industrial organizations from a historical perspective The third operation follows a historical perspective of industrial innovation. The Study of industrial and techno- scientists innovations during the 19th and 20th centuries needs to be revisited from a usage perspective. In fact, technical objects have been examined as inventions and innovations shedding light on periods that start with their adoption and end with their diffusion. The aim here is to examine their use starting from the prescription (conception and production) phase to their 1 HEC Challenge+ program (25 years old) is dedicated to innovative entrepreneurial projects with substantial growth potential. It welcomes 30 projects per year. It has trained over 380 projects with a success rate (company set up and crossing the 5- year markt) of over 70%. 4 companies are listed in the stock market and twenty have been sold. 14

246 appropriation by users in a workspace. The objective is to examine specifically, hydraulic and machinery technologies. Documents produced by study desks inside firms offer a promising historical material for the study of both design (projection, calculations, prescribed organization procedures) and implementation phases. This study will rely on archives identified by researchers in a set of firms. Restitution through the 3D modeling technology will be developed during the period of this project. Aim: Understanding organization and use of technical objects with 3D modeling methodology and historical work. Involved researchers: Jean- Louis Loubet, Nicolas Hatzfeld, Serge Benoît, Alain P. Michel, Florent Le Bot (IDHE Cachan and Evry). Required funding: 5K for documentations and archival missions Expected results: publications. A 3D video WP 2.4: Valorization The research program will be associated with the development of an educational operation. Its objective is to create a teaching platform on innovation and entrepreneurship, which will elaborate best practices for curricula on innovation through international comparisons, and to increase, therefore the scale of I&E activities on the Saclay Campus. The three following actions will be undertaken. A seminar in 2015 will gather instructors, incubators staff and start- ups and researchers in order to produce a kit for coaches and evaluators of innovative ventures targeting incubators and venture capitalists. It will rely on the network of Saclay Cluster incubators such as HEC, Ecole Polytechnique, Incuballiance, TelecomParisTech. An international summer school on entrepreneurship involving researchers and Phd Students will be organized in A previous edition was organized in 2011 by T. Astebro and C. Phelps (HEC). This edition will involve all Saclay Cluster and beyond. Involved Research fellows: Among other members of the network, the following researchers will be involved: P. Détrie, F. Iselin and S. Jouini (HEC); C. Midler and R. Beaume (Ecole Polytechnique). Obtained grants and funding: Funding of the PIMREP initiative by ParisTech Required funding: a third of post doc (each year) and 15K for the summer school organization Expected scientific results: a teaching program on entrepreneurship 15

247 WP 3: NORMS AND REGULATIONS OF SCIENTIFIC WORK The aim of this work package is to bring together different disciplines with diverse approaches in order to understand how norms and regulations emerge and how they influence scientific work, practices, contents and their circulation, by examining the interaction among different spheres (educational, research, industrial). More specifically, the aim here is to combine approaches coming from the disciplines of sociology, history, economics and education encompassing studies on objects such as policy, work, law, laboratories, curricula, journals, schools, careers or professional networks in a way that will allow us to understand the emergence, evolution, deviance from or contestation of the norms and regulations of scientific contents and practices, while acknowledging that different spheres of knowledge do interact. Our starting point is thus the shared belief that science and technology studies artificially split studied objects. First, a separation between levels of analysis can be observed. While some STS studies have dealt with the organizational and institutional mutations that have deeply altered the way in which science is regulated and linked to social and economic issues (Gibbons et al., 1994; Jasanoff, 2007; Etzkowitz and Leydesdorff, 1997 and 2000), others have focused on scientific practice per se, that is, on the experiments conducted by researchers who are grappling with objects and instruments whose characteristics govern the knowledge produced (Latour, 1989). Surprisingly enough, this micro- sociological point of view has only marginally contributed to the debate on changing regimes of knowledge production (Gibbons, 1994; Pestre, 2003). Second, micro- level studies did not take into account the results streaming from other approaches. In particular, they have been constructed without any sound dialogue with the sociology of law, work, labor and professional identities. As J. Wajcman (2006) and Doing (2004 and 2008) recently emphasized, this is the reason why, to a large extent, the joint work conducted by researchers interested in labor and researchers interested in science is a promising perspective, but has not yet come of age. Third, by separating public policy studies, academic laboratory studies, curricula studies and industrial research, scholars have underestimated the links among these spheres. Indeed, evidence from our previous studies shows that the transformation of academic researchers practices and work cannot be perceived independently from their educational activity or their interaction with industrial partners (Fages and Albe, 2007), and that transformations in laboratory life can t be seized without reference to public policies (Jouvenet, 2011), or that transformations in industrial researchers work cannot be understood without understanding transformations in academic researchers work and vice- versa (Younès 2013). Moreover, the recent intervention of labor unions in the area of R&D in large firms and public research policies is likely to change existing laboratory arrangements (Béthoux, da Costa, Didry, ongoing study). Taken altogether, these results show that studies on the emergence, transgression or evolution of norms should be revisited in a way that takes into account the interactions between the different spheres. We therefore intend to examine norms and regulations by shedding light on their characteristics, the deviance of local norms from those prescribed by policy- makers, their contestation, as well as their emergence and evolution, when interactions among education, industry, academic research, policy tools, law and labor relations are taken into account. 16

248 WP 3.1.: The evolution of norms and regulations of industrial research in perspective The goal of this operation is to understand the way in whichthe organization of knowledge production in firms has evolved during the recent years and to compare these changes with the transformations that occurred in other scientific spheres. We intend to confront our results with the studies of research teams that can increase our knowledge about the topic. While studies on industrial researchers work have mainly been examined at the IDHE and the CRG, academic researchers work has mostly been studied at the PRINTEMPS. The goal here is to combine these different competencies. WP : Understanding change in large firms Two sets of studies have recently contributed to the understanding of change in enterprises. First, the contribution of the project funded by an ANR and hosted at the IDHE- Cachan (TRAVCHER), The work of scientists, has helped to understand the current conditions of knowledge production in large firms by showing that the science- industry relations, as well as the increasing externalization of research towards suppliers, have considerably shifted the activities of some researchers towards network management. Also, a large range of functions inside the firm seem to influence researchers work (marketing, sales, production, development ) in a context of restructuring. Secondly, studies on managerial processes conducted on a longer time span show that these processes have evolved during the past decades. Marketing functions increasingly influence research orientations (Charue- Duboc and Midler, 2002) even if the balance between market and science concerns has shifted over time (Gastaldi and Midler, 2005). How have these changes affected research in industrial laboratories? In order to answer this question, we will organize a conference on the theme, and complete our knowledge by a future operation to be explored. WP : Capturing the transformation of scientific work in firms Indeed, given that both organizational and community belonging affect the professional oportunities of researchers (David and Foray, 2002; Bessy, 2009), we consider that the study of researchers careers can be a good indicator of the way the industrial and the academic organization of research has recently evolved. Empirically, we will use a combination of quantitative data (bibliometric and contracts) and biographic interviews. Starting with large French firms located in Saclay and belonging to research- intensive industries (such as telecommunications equipment, automobile and pharmaceutical industries), we aim to construct a database that will include researchers publications and patents. The analysis of this data will enable an identification of the way researchers expand their domains of expertise, change the position of authorship (from first to last author for instance), or stop publishing at one point of their careers. Biographic interviews help explain the factors and mechanisms of these changes. Are they due to commercial pressures, shifts in the interest of the scientific community of reference, financial pressures, or other factors? In order to construct a database and conduct interviews in at least one firm, a post- doctoral fellow will be recruited. WP : Capturing the transformation of scientific work in academic research centers In parallel, the PRINTEMPS team will conduct a comparable operation in academic laboratories. Based on its experience in laboratory studies, the goal here is to compare the work of industrial 17

249 researchers to that of the technical staff of academic laboratories. While researchers work has been studied during the last years by Morgan Jouvenet (cf. bibliography), the aim here is to include a new invisible category in laboratories: the technical staff that surrounds, supports and accompanies the research and the researchers (Doing, 2004). Bridges could be built to a further UVSQ research centre in management (LAREQUOI), specifically regarding works done by Pascal Corbel (Corbel 2011). WP : How law affects scientific work Interviews in both of these domains will also be the occasion to gather work contracts in order to construct a database similar to the one developed by Bessy (2009) and examine how law affects mobility of researchers and the distribution of property rights. In addition, a joint operation between the IDHE and CECOGI (a team that will join the École Normale Supérieure de Cachan) will focus on the emergence of property right conventions in different branches of the economy. On the longer run ( ), the aim is to conduct international comparisons in firms, curricula and academic laboratories in order to shed light on the way institutions in different countries affected scientific work in these organizations. Aims: The goal of this operation is to understand the way the organization of knowledge production in firms evolved through the last years and to compare these changes with transformations that occurred in other scientific spheres. Involved Researchers: IDHE (C. Didry, A. Mias, P. Boisard, A. Jobert, D. Younès, Z. Yi, Ch. Bessy and É. Béthoux), PRINTEMPS (J. Pélisse, M. Jouvenet, V. Tocut and A. Saint- Martin). Partnering team: CECOGI which particularly works on intellectual property issue in emergent sciences and technologies, P. Corbel (LAREQUOI, UVSQ). Funding granted untill now: ANR TRAVCHER ( ): One PhD (ENS- Cachan): One PhD (UVSQ): Requested funding (95,000 ): One post- doctoral position ( ) to assist the IDHE team in the study of careers, and the organization of a seminar (5 000 ) and an international conference ( ). The PRINTEMPS laboratory will ask for the mutation (détachement) of an Ingénieur de recherche (V. Tocut, a technical staff specialized in microelectronic, working currently in the Linear Accelerator Laboratory LAL and finalizing a process of conversion in the sociology of professions) in order to conduct the research on academic researchers (30,000 ). Expected scientific results: Case studies on scientific work. Organization of seminars and an international conference. Publications. WP 3.2.: Emergence and evolution of norms and regulations and the impact of clusterization on science Clusterization is here understood as the process of increasing proximities between research education and industry. It takes two forms: the decrease of geographical distances as well as the convergence of practices around instruments, projects, trainings and professionalization paths. When resulting from public policy initiatives, this process is coupled with a facilitation effort for technological transfers towards industry. If the plateau de Saclay is not yet the most cited case in this domain, the current endeavors are meant to bring the desired convergence. This part of the work package aims at analyzing the social conditions of this evolution and at comparing them with international cases using a reflexive quantitative as well as a qualitative method. It will thus both 18

250 contribute to the first axis on the construction of categories, and to the science- education- industry debate that will be captured in this work package. While the STEF laboratory has already gathered quantitative data on recent evolutions on the topic, partners now intend to focus on case studies in order to shed light on the process of clusterization in a way that will allow an analysis of the mechanisms of change, reorganization, transformation or reproduction of research and teaching practices induced by the geographical, institutional, economic, social and cognitive reorganization of academic and industrial territories. These case studies are all related: the first is the École Normale Supérieure de Cachan taken as a hub of education- research- industry relations, the second, is joint research structures that include laboratories from this school and the third is joint Masters programs in which the school participates. We argue that nanosciences and nanotechnologies, because of their particular national and transnational governance in the organization of this domain, as well as because of their weight in Saclay, constitute a particularly interesting case when the impact of clusterization on research and teaching practices is to be examined (Marcovich and Shinn, 2011; Sa, 2010; Thurs, 2007). The study will include a historical approach, and a change in progress approach. WP : Studying the evolution of norms and regulation at the ENS- Cachan First, an exploratory study conducted by an ENS- Cachan team (that includes members of IDHE and STEF) on the history (starting 1912) and protohistory of the school (going back to its origins in 1880) showed the relevance of this case in order to examine the evolution of the concept of applied science with its implications on the dynamics between education, research and science- industry relations. Deepening this study will then allow us to explicit the mechanisms of the emergence and evolution of the norms and regulations of scientific content and practices that led to the transformation of the ENS de Cacahn from a technical school to a Saclay partner on three domains: science- industry relations, academic research and education. In our forthcoming study, we intend to put a special emphasis on the evolution of nanosciences in comparison to other disciplines. Here, we will study the evolution of science- industry relations (through contracts and interviews), the evolution of practices and contents of research and curricula as well as the circulation of knowledge among the three spheres. In addition to researchers participation, this first part of the study will also rely on the participation of students from the Social Sciences Department at the ENS Cachan. This operation will be coordinated by Caroline Vincensini (IDHE), head of the social sciences department, Florent Le Bot (IDHE Evry), Elisabeth Chatel (IDHE Cachan) and Virginie Albe (STEF). WP : Ethnographic studies of joint Masters Programs and of joint technological platforms Taking into account the results of the first operation, and following the approach of Fages and Albe s study on the curricula strategies in the creation of specific Masters degrees in «nano», as well as Morgan Jouvenet s claim on the necessity to examine the impact of policy tools supporting new organizational forms of research that include multidisciplinary research, laboratory mergers or public- private partnerships (Matthieu, Jouvenet and Vinck, 2013), the STEF and the PRINTEMPS teams will conduct ethnographic studies in order to shed light on the mechanisms of knowledge circulation during the ongoing clusterization phase at Saclay. We will examine platforms of experimental teaching as well as technological platforms (such as NanoInnov and NanoMed) linking 19

251 researchers to local industrial actors. In particular, we will follow actors from different institutions intervening in the new Masters programs in order to describe the kind of interactions they have with each other, with their research colleagues, and with industrial actors, and in order to examine the way in which these interactions shape their teaching and research practices and contents. In addition, a PhD candidate has started a research on the professional integration of graduates from ENS- Cachan, CELSA, and an engineering school from the Saclay plateau. This PhD will allow a better understanding of the job market characteristics and the links between education and industry. Working sessions assembling researchers working on this topic in France and in other countries (for instance, A. Rip s team at the University of Twente), as well as a conference on scientific clusters will be organized. On the long- run ( ), we would like to compare this case with other initiatives implemented in France with similar organizational forms (in particular Grenoble) or introduced in other countries in nanosciences and nanotechnology. We also intend to conduct comparisons with other disciplines going through similar initiatives in the Saclay area. Aims: Capture the emergence and evolution of norms and regulations in changing environments. A particular attention to the process of clusterization will be given. Involved Researchers: from STEF laboratory (V. Albe and V. Fages), the IDHE Cachan and Évry (F. Le Bot, C. Vincensini, E. Chatel, Ch. Bessy), and PRINTEMPS (A. Saint- Martin, M. Jouvenet). Funding granted until now: The ENS- Cachan funded to conduct research, organize a conference and a publication on its history. It will also contribute through its students to the field work. Requested funding ( ): Two post- doctoral positions ( x 2) to work jointly with the PRINTEMPS team and the STEF team on ethnographies. They will also contribute to the coordination of joint seminars that gathers all the teams implied in this part of the work package (IDHE, STEF, PRINTEMPS), and to the organization of an international conference on the theme. Missions (documentations, travel ): Organization of seminars and a conference: Expected Scientific results: case studies on technology platforms and joint Masters program. Case study on ENS Cachan. Organization of seminars and an international conference. Publications. WP 3.3.: When norms and regulations are bypassed, controversed or contested The norms and regulations of scientific work can be bypassed, controversed or contested. This part of the project examines both contemporary and historical deviant cases, ongoing controversies around existing norms and regulations, and forms of organized contestation in this domain. WP : Transgressing norms in education Indeed, long term historical and sociohistorical studies have criticized the birth of science and scientific work s mode 2 regime that supposedly arose in the years 1950 (Shinn, 2002; Gingras, 2003; Pestre, 2003a). According to the tenants of the mode 2 regime, this scheme replaced a system in which a split between the academic world and society meant that no interactions between science and industry existed. Instead, scholars who examined the circulation and transmission of scientific knowledge in France showed that this classical histographical construction depended on objects, and sometimes, implicit methodological choices: a top- level history that examines policies and national prescriptions and that is limited to mostly Parisian academic and scientific elites and their institutions. By changing the perspective, these studies focused on mechanisms of circulation and transmission of scientific knowledge in the academic milieus as well as in a larger sphere that 20

252 encompasses the split in the history of sciences between, on the one side, a traditional academic sphere and, on the other, technical and professional spheres (for studies on scientific and technical education see Grossetti, 1994; Grelon and Grossetti, 1996; Rollet, 2007; d Enfert and Fonteneau, 2011; for the study of scientific and technical journals see Bret, Chatzis and Pérez, 2008; Nabonnand and Rollet, 2011; d Enfert, 2008). They could therefore show that deviant cases existed. In this part of the work package, we will first contribute to these history studies by examining deviant cases of local supply and local systems of scientific and technical education during the 19 th and 20 th centuries, examine the circulation of sciences by and through scientific journals during the same period, and analyze recent fraud cases both in the industry and academic worlds. The interest of studying local supply and local systems of scientific and technical education has been underlined by Michel Grossetti (1994) and Jean- Michel Chapoulie (2010) and has been reviewed by Laurent Rollet (2009). It will be reinvested in order to study the realities of local configurations when it comes to scientific and technical education in the 19 th and 20 th centuries. Starting from our study on national prescriptions on curricula and practices during the 19 th and 20 th centuries (Gispert, Hulin and Robic, 2007), we have shown that the norm was to separate educational filières by attributing to them differentiated scientific curricula. We now intend to select a number of local case studies in order to evaluate the effectiveness of these prescriptions and analyze transgressions. These cases will be further compared to the Ecole Normal Supérieure de Cachan case mentioned in WP 3.2. This operation will rely on archival work in regions, once the selected cases will have been defined. Since this operation is of common interest to researchers working on the history of ENS- Cachan and the GHDSO, the national seminar Local supply and local systems of scientific and technical education launched by the GHDSO in 2013 will be open to this consortium. WP : The circulation of sciences by and through scientific journals The second operation will focus on the circulation of sciences by and through scientific journals with the aim to show mechanisms of specialization and characterize norms and publics (19 th and 20 th centuries). An emerging field of research on scientific and technical periodicals beyond the most famous academic journals which have already be studied pays particular attention to long term journals specialization processes and their scientific and technical readership (Bret, Chatzis and Pérez, 2008; Gispert, 2011). Our goal is to analyze the norms of scientific production and activity that these publications promote, depending on their editorial project and targeted readership. In this attempt, we will construct corpuses of scholarly press, scientific and technical journals as well as industrial and commercial local press. The construction of different categories of actors and readerships will precede the realization of databases that will reveal the diversity of scientists productions and activities and the diversity of competing or coexisting norms, depending on the periodicals and their specialization. A special attention could be devoted here to the non- institutionalization process of criminology in France (a government order was taken in Feb and deleted six months later). WP : Discourses of Scientific Deviance 21

253 The third research perspective that allows for capturing deviance and for characterizing dominant scientific norms, focus on the issue of scientific deviance. Problems linked to scientific fraud are regularly debated and they may give rise to heated exchanges between scientists (Goodstein, 2010). Both in the industry and in the academic fields these issues have taken an increasingly important place. Recently, Diederik Stapel, a social psychologist at the University of Tillberg recognized falsifying the results of his experiments for 20 years, in order to fit the expectations of the system. By focusing on conflicts, deviances, transgressions, controversies and scandals, it becomes possible to elicit the norms of a social world and the role played by law and legal professionals (Bessy and Chateauraynaud, 1995). Our goal is to construct a database with the coverage of all these cases. While the media extensively covers industrial cases, we also intend to develop a partnership with the observatory of fraud located in HEC Switzerland 2. A textual analysis will be conducted in order to extract different registers structuring the discourses. The study will be carried out both by Jérôme Pélisse (PRINTEMPS) and Christian Bessy (IDHE). The École Normale Supérieure de Cachan will fund a PhD candidate to work on this topic. WP : Controversies on norms and regulations of scientific work Studies on changing regimes of scientific production have recently focused on either explaining the rationale behind the transformations or on their expected effects on scientific production. However, in the social sphere, these changes are not to be taken for granted. Rather, they are leading to public controversies on what the role of science should be and how it should be organized, funded and evaluated (Vinck et al., 2007). It is then particularly interesting to explore these controversies in order to shed light on the different logics at play. In this attempt, we will construct a database to gather media coverage, union press releases, research associations communications on the topic, etc A textual analysis will be conducted in order to extract competing argumentations. Depending on the results, further research operations could be conducted. These can include the constitution of social movements opposing changes, for instance. The research will be conducted by Morgan Jouvenet (PRINTEMPS) in collaboration with Matthieu Hubert (affiliated researcher to PACTE, Grenoble). While studies of controversies usually focus on argumentation, we intend to compare argumentative logics to changes that we observe in laboratories (in previous WPs). WP : Contestation of scientific norms and regulations Moreover, Elodie Béthoux, Isabel da Costa, Annette Jobert, Pierre Boisard and Claude Didry (IDHE) have been following the evolution of labor union debates and activities in the domain of industrial research, especially in multinational firms. Indeed, during the last years, trade unions have been concerned with R&D and investment decreasing budgets, particularly in times of restructuring. Finding ways to reverse this trend has therefore become one of their targets. Understanding how trade unions decided to intervene in this domain, what types of actions they are developing to reach their goals, and how these affect or not the firms decisions should therefore be examined. This will be done through the analysis of trade union documents, transnational negotiations, and interviews in order to understand the repertoires of trade union arguments and how they change. 2 Link to their webpage : 22

254 Aim of WP 3.3: to examine contemporary and historical cases that allow capturing the characteristics of norms and regulations, their justification, deviance, bypassing, and forms of contestation around them. Involved researchers: from the GHDSO- EST (R. d Enfert, V. Fonteneau, H. Gispert, L. Alfonsi, D. Berdah, A. Jacq, J. Robinet, N. Verdier), PRINTEMPS (J. Pélisse, M. Jouvenet), and IDHE (Ch. Bessy, É. Béthoux, I. da Costa, A. Jobert, P. Boisard and C. Didry). Partner: M. Hubert (affiliated researcher to PACTE, Grenoble). Funding granted till now: Two ongoing PhDs (ENS- Cachan and Université Paris- Sud): The ENS Cachan will fund a PhD on the theme of scientific deviance. Requested funding ( ): One post- doctoral position to work on contestation issues ( ). Missions (transport, hotels for regional archives ), documentation : 3 x ( ). Organization of a national seminar ( Local supply and local systems of scientific and technical education ): x 3. Total: Expected Scientific Results: case studies and Publications. Last but not least, this work project, will not only facilitate cooperation among researchers of this subgroup, it will also contribute to other WP through a wide number of results. As such, studies on industrial research and clusterization will contribute to WP2, research on norms and regulations that include metrics and categories can be discussed with scholars working in WP1, analysis of intellectual property rights, researchers contracts and inter- organizational contracts will contribute to the studies on law in WP4. 23

255 WP4: LAW AND JUSTICE, SCIENCE AND TECHNOLOGY Science and law are two dominant forms of truth discourse in contemporaneous societies. Ssocial sciences have put the stress on these two objects with a strong interest for their crossings. In particular, Science & Technology Studies have launched and developed a research program at the crossroads of sociology of science and sociology of law. The chapter wrote by Sheila Jasanoff in The Handbook of Science and Technology Studies clearly shows the perspectives opened by the idea of coproduction between science and society when it is applied to the analysis of science and law (also Jasanoff, 2004 and 2011). Expertise in courts has been one of the favorite domains of research. The question of the role of sciences and technology, and more specifically of varied kinds of expertise in judicial practices and sentencing has generated many different types of groundbreaking research. Some researchers focus on a single case (Jasanoff, 1998), others deal with matters such as forensic activities (Timmermans, 2007) or laboratories in genetics (Renard, 2008; Dufresne and Robert, 2012). The history of the uses of DNA in criminal justice has been written by sociologists of science (Lynch, Cole, McNally and Jordan, 2008), but we do not know so much about the uses of neurosciences in law and justice though some studies exist (Rafter, 2008; Freeman and Goodenough, 2010; Larrieu, 2011). The reception of science in/by courts puts into play more general issues concerning the reliance on mundane understandings of science (Lynch and McNally, 2005). Researches on judicial expertise are an important part of STS research, but socio- historical studies (Dumoulin, 2007) and the sociology of professions (Dumoulin, 2007; Pélisse, 2012) have brought many kinds of technical experts to the fore, like architects, economists, psychiatrists, interpreters or translators. Apart from this, law and justice are also relying on the extensive use of various technologies (and particularly information and communication technologies or ICT), to get the (judicial) job done at different levels of the civil and criminal processes (police work, making of the judicial file, legal reasoning, administration of proof, sentencing s. Dumoulin and Licoppe, 2011; Kaminski et al., in press 2013). Our partners cooperate to the program «Cyberjustice», an international research that has been launched by the University of Montreal ( Home/Home), and on virtual hearings and video- recording of police interrogations to the Digital Society Institute project. Moreover, a network has been created by some researchers who are involved in these hybrid objects (Law, Sciences & Techniques Network, which the DANTE is member of. Four main actions are proposed over the period They are chosen for their likelihood to cross- fertilize different research experiences and to allow the development of bilateral collaborations. While the program for focuses on what science and technology do to law and justice, the perspectives for should be more oriented toward what law and justice do to science and technology an aspect which would have been partly addressed in the third project (for example with the action on scientific fraud or the other one on patents). 24

256 WP 4.1: Research on CCTV as a new method of production of proofs The state of the art (Dumoulin, Germain and Douillet, 2010) has shown that some unexpected uses of CCTV have not been sufficiently investigated. If studies successfully describe the practical activities of the CCTV operators in concrete settings (Le Goff and Malochet, 2011) or CCTV s broader influence on police work (Neyland, 2011), the use of CCTV as a source for admissible evidence is still a blind spot in the literature (Jobard and Schulze Icking, 2004). This form of CCTV is able to provide an empirical basis to assess and discuss surveillance studies core assumptions. A specific research will focus on the way CCTV pictures may be relied on, or contested, as evidence in criminal process and courtrooms. Our first goal is to produce data documenting the actual uses of CCTV: how are pictures available? Under what conditions are they deemed good enough to be used as evidence? Are they really used or not? To charge and convict a defendant or to discharge him? As a sole element of proof, or as a complement to more receivable forms of proof. These questions have seldom been raised in the literature although they could reshape the direction of the research on CCTV, and more empirical and well- documented inquiries are clearly required. One aim of this action is to contribute to the theoretical and empirical displacement of surveillance studies debates from the administration of surveillance to the discussion of the ways in which CCTV s images are used as evidence in judicial settings context of making evidence is at stake. To study these new uses of CCTV and its consequences on criminal process, we request the funding for a postdoctoral position for 18 months ( ). The postdoctoral student would be hosted by ISP with a monitoring committee including researchers from CESDIP and LCTI. Aims: analyzing the use of images as proofs and evaluating the impact of this technology on penal processes. Involved researchers: L. Dumoulin (ISP), T. Le Goff (CESDIP), C. Licoppe (LCTI) Funding granted till now: a grant by the INHES ( ) ; a regional grant (Région Rhône- Alpes) for a seminar on the state- of- art of CCTV issues. Requested funding : Expected scientific results (2019): publications and case studies. WP 4.2: Exploratory research on electronic monitoring: a micro- sociological approach Electronic monitoring or tracking is linked to the transfer of the penalty from the prison to everyday social spaces. It involves non- professional agents and institutions in the surveillance at a distance. In this perspective, ethnographic approaches are particularly relevant to understand how penalty is transformed, who are the new actors involved, how space and sociality in everyday spaces are reshaped by electronic monitoring, and become contested sites. Space, place and proximity are experienced and used for action in a different way, which become empirically available to fine grained ethnographic approaches, while offenders representations of this kind of sanction are researchable with interviews and focus groups (Troshynski, Lee and Dourish, 2011). Researchers from ISP and CESDIP have produced research on electronic monitoring, specifically the reshaping of some judicial decisions with respect to the availability of this type of control (as a control measure mesure de sûreté - for parole offenders for example s. Pitoun and Lévy, 2004 at CESDIP, Dumoulin, 2011, and more broadly Devresse, 2011; Nellis, Beyens and Kaminski, 2012) This work could be articulated to the existing competences existing in LTCI regarding micro- sociological approaches (involving distributed cognition, activity theory and ethnomethodology). 25

257 Two actions will be undertaken within this frame. We plan first to realize a one year long ethnographic research concerning the implementation of electronic monitoring/tracking. A group of electronic monitored offenders would be followed by a researcher from the installation of the bracelet to the ending of the monitoring. The research design also includes ethnographic observations in the relevant sites (parole officers, prison warders, offenders) but above all in the coordination centers where the operators monitor offenders location and may act upon that basis. We also aim to describe the interactions and mutual accountability of participants at this nexus of devices and software, watchers and offenders, place and sociality. For this operation, we need a funding for a post- doc position for one year. In parallel, we propose to launch a multi- disciplinary workshop (or colloquium) on electronic monitoring, which will give the opportunity to valorize our project as an important site of excellence for the SHS research on technology and penal justice. Aims: Analyzing the electronic bracelet using a new approach. Involved researchers: A. Kensey (CESDIP), R. Lévy (CESDIP), L. Dumoulin (ISP), Ch. Licoppe (LCTI). Granted funding until now: a grant from GIP Mission de recherche Droit et justice ; a grant for the Rhône- Alpes Région to facilitate franco- brasilian academic events on supervision and new technologies. Requested funding : : one year post- doc ( ) and the organization of an international conference ( ) Expected scientific results (2019): articles and a multidisciplinary conference. WP 4.3: Research on neurosciences and law To fuel the debate on the ethical questions relating to the societal impact of the discoveries made by neurosciences and of their technical spin- offs, we propose to pay special attention to the growing reception of neuroscience in criminal law and criminal justice. Neurosciences impinge questions of law in two main domains: the ability of neurosciences to predict criminal behaviour (and then, to regulate it); the ability of neurosciences to give an accurate picture of the moral or ethical abilities of the persons, and from there to re- structure or re- define core notions such as individual responsibility. The contribution is relevant to what is now coming to be called neurojustice or neurolaw. Neurosciences in law is a thorny theme in France today (CAS, 2009; RFS, 2010). CESDIP's involvement in societal debates on the possible introduction of criminology in France (Mucchielli, 2009), as well as its researches on the history of forensic sciences, like phrenology (a proto- neuroscience), or of criminology (Piazza, 2011), provide a strong base to explore the contested links between neurosciences and law. Our project combines here in a distinctive way the sociology of law and the sociology of science and technology. CESDIP has an easy access to the bureau and agencies that participate in producing prospective for the ministry of Justice. Moreover, the existence and the proximity of the Saclay's NeuroSpin platform (5 laboratories) offer an easy access to the scientists in the field. We plan to launch later a qualitative research about their positioning in this field and the relationship between them and end users such as the ministry of Interior, the ministry of Justice, the customs services, the prison services, etc. The research would also explore more deeply the new tensions which occur in this field with respect to the «science/society», and try to understand the conditions of emergence of a networked assemblage between neurosciences researchers and judicial administrations and scientists, as well as to identify all the translations and intéressement processes involved, within a STS perspective. It will be based on the detachment of Pierre Piazza (a political 26

258 scientist who devote his works to the history of forensics and criminology) to the CNRS ( Accueil en délégation ) for two years and will require a budget only for research expenses (5 000 per year). Aims: Creating the first scientific location for the study of a possible introduction of neurojustice/neurolaw in France Involved researchers: Fabien Jobard (CESDIP), Morgan Jouvenet (PRINTEMPS), Pierre Piazza (CESDIP). Requested funding : (travel expenses on the field, international workshop) WP 4.4: Around expertise in courts The last domain of research deals more generally with the issue of the use of expert knowledge in courts, an activity which is by definition at the juncture between scientific knowledge and judicial process. Expertise is part of many controversies: concerning psychiatrists; economists; scientists specialized in the climate, the agro- alimentary, health and safety or the nuclear issues. But it takes a specific dimension when it is referred to in the courtroom, and is a key site with respect to the interactions between sciences, societies and law. Our purpose here is to capitalize on the multiple competences of our laboratories to build a network of excellence associating the researchers who have already done significant researches on this topic. This aim could be achieved by launching a seminar drawn to define where are the main gaps in the existing research, on which researchers in Saclay could develop a larger scale collaborative project (for instance for funding by the ANR). This exploratory seminar would bring together doctoral students who are actually working on expertise (R. Juston on forensic expertise, PRINTEMPS; J. Boirot on psychiatric expertise in Europe, CESDIP; A. Leroy on psychiatric expertise, ISP); researchers who have already developed extensive studies of expertise in judicial settings (L. Dumoulin, A. Gozhia, J. Pélisse); foreign colleagues with a recognized expertise (notably B. Renard, researcher in Louvain - Belgium). This seminar (requested budget ) could give birth to both to intermediate collaborative operations (collective academic book, seminar of research) and to the construction of a large scale collaborative project on expertise in the courtroom before Based on a 6 months postdoc ( euros), a special focus will be made on the question of the «cost» of the expertise as a potential threat on the independance of the expert and, moreover as a potential criterion to choose private litigation proceedings (mediation, arbitration) versus public service of justice. Aims: develop knowledge on judicial expertise as a heuristic activity where science and law meet. Involved researchers: J. Boirot (CESDIP), L. Dumoulin (ISP), F. Jobard (CESDIP), R. Juston (PRINTEMPS), A. Leroy (ISP), C. Licoppe (LCTI), J. Pélisse (PRINTEMPS), A. Gozhia (DANTE), N. Reboul- Maupin (DANTE), M. Court de Fontmichel (DANTE). Granted funding untill now: PhD grants (R. Juston, DIM IS²IT A. Leroy, allocation ENAP ) Requested funding : (6 months postdoc + missions and organizations of the seminar). In summary, this fourth axis which emerged from the fusion of the Labex 6S and LISI is particularly rich in perspectives. It promises the realization of excellent research and the development and reinforcement of cooperation between researchers belonging to constituent laboratories (CESDIP, DANTE, ISP, LTCI and PRINTEMPS) from different institutions within the Saclay perimeter. This is the reason why the presented operations aim to capitalize several well- established traditions of research 27

259 but also to go forward and to create synergies in order to build new collaborative projects. This is an ongoing process, open to the adjunction of colleagues from these other laboratories or other disciplines, especially legal scholars from Paris Sud in a near future. A transverse action which exemplifies its collective force and its potential impact on public policies and professionals will be the launching of a test formation seminar for magistrates and police officers on the social implications of science in police and judicial process (budget: ). ANNEXES 28

260 Funding Justification By Working Project, the funding Justification could be presenting in the following table : Postdoc/ingenieur Missions, documentation Sum and equipment WP 1 Quantification, modeling and metrology WP2 Innovation, Entrepreneurship and Market Development WP3 Norms and regulations of scientific work WP4 Law and Justice, Science and Technology To fund all its activities, ISIS needs approximatively per year. During 3 years : ISIS will provide funding to initiate four research programs, including postdoc, missions and equipment. Additional funding could be secured from ANR, ERC, PCRD programs, DIM IS²IT, DIM GESTES, etc. ISIS supports two Master s degree programs and organizes two international Summer school (WP 1.1 and WP 2.4 both in 2015). Postdoc Research ingenieur (1.1.) (1.3.2) (1.3.2) (2.1) (2.2) (2.4) (3.1) (3.2) (3.2) (3.3) (4.1) (4.1) (4.2) (4.4) (1.2) (1.3.2) (3.1) (1.3.2) (3.1) (1.3.2) Missions (seminar, field research, documentation, invitation of foreign scholars...) Equipment (CASD access, database) 5000 (1.1) 8000 (1.2) (1.3.1) 5000 (1.3.3) 7000 (2.1) (3.2) (3.3) 3000 (4.4) 5000 (1.2) 5000 (1.3.2) 5000 (1.1) 5000 (1.3.3) 7000 (2.1) 5000 (2.3) 5000 (3.1) 4000 (3.2) (3.3) 5000 (4.3) 2000 (4.4) (1.1) 6000 (2.1) (2.4) (3.1) (3.2) (3.3) (4.2) 5000 (4.3) Summer school (1.1) (2.4) Valorisation Governance / administration Total 252 ke 410,5 ke 312,5 ke 29

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266 Pélisse J., (dir.), coll. Charrier E., Larchet K., Protais C., 2009, Des chiffres, des maux et des lettres. Une sociologie des experts judiciaires, Paris, La Découverte, Collection «Recherche», Série «Territoires du Politique». Pélisse J., (dir.), Protais C., Larchet K., Charrier E., 2012, Des Chiffres, des maux et des lettres : une sociologie de l expertise judiciaire en économie, psychiatrie et traduction, Paris, Colin. Pestre D., 1992, Physique et physiciens en France, , Paris, Éditions des Archives Contemporaines- EAC. Pestre D., 2003a, Science, argent et politique, Paris, Editions Quae. Pestre D., 2003b, Regimes of Knowledge Production in Society: Towards a More Political and Social Reading, Minerva, 41, 3, Pestre D., 2006, Introduction aux science studies, Paris, La Découverte. Phelps C., Basu S., Kotha S., 2011, Towards Understanding who Makes Corporate Venture Capital Investments and Why, Journal of Business Venturing (forthcoming). Phelps C., Yang H., Steensma K., 2010, Learning from What Others have Learned from You: the Effects of Knowledge Spillovers on Originating Firms, Academy of Management Journal, 53, 2, PIMREP, 2010, Former à l innovation à ParisTech, effervescences et perspectives, livre- blanc- pimrep- pdf- d Porter M., 1998, Competitive Advantage of Nations, Free Press. Rafter N., 2008, The Criminal Brain: Understanding Biological Theories of Crime, New York, New York University Press. Ramirez C., 2009, Constructing the Governable Small Practitioner: the Changing Nature of Professional Bodies and the Management of Professional Accountants Identities in the UK, Accounting Organizations and Society, 34, Raynaud D., 2003, Sociologie des controverses scientifiques, Paris, Presses Universitaires de France. Renard B., 2008, Ce que l'adn fait faire à la justice : sociologie des traductions dans l'identification par analyse génétique en justice pénale, thèse de doctorat en criminologie soutenue à l Université Catholique de Louvain. Rosental C., 2007, Les capitalistes de la science. Enquête sur les démonstrateurs de la Silicon Valley et de la NASA, Paris, CNRS Éditions. Rothaermel F.T., Deeds D.L., 2004, Exploration and Exploitation Alliances in Biotechnology: a System of New Product Development, Strategic Management Journal, 25, 3, Salais R., 2010, Usages et mésusages de l argument statistique: le pilotage des politiques publiques par la performance, Revue Française des Affaires Sociales, 1-2, Saxenian A., 1994, Regional Advantage. Culture and Competition in Silicon Valley and Route 128, Cambridge- London, Harvard University Press. Shinn T., Ragouet P., 2005, Controverses sur la science. Pour une sociologie transversaliste de l activité scientifique, Paris, Raisons d Agir. Silbey S.S., Huising R., 2011, Governing the Gap: Forging Safe Science through Relational Regulation, Regulation & Governance, Sobel M., 2000, Causal Inference in the Social Sciences, Journal of the American statistical Association, 95, 450, Spirtes P., Glymour C., Scheines R., 2000, Prediction, Causation and Search, Cambridge, The MIT Press. Teece D., 2000, Managing Intellectual Capital: Organizational, Strategic, and Policy Dimensions, Oxford, Oxford University Press. 35

267 Teece D., 2008, The Transfer and Licensing of Know- How and Intellectual Property: Understanding the Multinational Enterprise in the Modern World, World Scientific Publishing. Thévenot L., 2009, Governing Life by Standards. A View from Engagements, Social Studies of Science, 39, 5, Timmermans S., 2007, Postmortem. How Medical Examiners Explain Suspicious Deaths, Chicago, University of Chicago Press. Tushman M.L., O'Reilly C.A.I., 1996, Ambidextrous Organizations: Managing Evolutionary and Revolutionary Change, California Management Review, 38, 4, Vinck D., 1999, Les objets intermédiaires dans les réseaux de coopération scientifique. Contribution à la prise en compte des objets dans les dynamiques sociales, Revue Française de Sociologie, XL, 2, Vinck D., 2007, Sciences et société, Paris, Armand Colin. Vinck D., 2009, De l objet intermédiaire à l objet- frontière, Revue d Anthropologie des Connaissances, 1, Vinck D., 2009, Les Nanotechnologies, Paris, Le Cavalier Bleu, Collection «Idées Reçues». Vinck D., Gallice P., Jouvenet M., Zarama G., 2007, Dynamique technologique controversée et débat démocratique. Le cas des micro et nanotechnologies, in Goujon P., Lavelle S., (dir.), Technique, communication et société : à la recherche d un modèle de gouvernance, Namur, Presses Universitaires de Namur, Vinck D., Hubert M., Jouvenet M., Zarama G., 2006, Culture de la différence et pratiques de l'articulation entre chercheurs en micro- et nanotechnologies, in Leresche J.P., Benninghoff M., Crettaz von Roten F., Merz M., (dir.), La fabrique des sciences. Des institutions aux pratiques, Lausanne, Presses Polytechniques et Universitaires Romandes, Wajcman J., 2006, New Connections: Social Studies of Science and Technology and Studies of Work, Work, Employment and Society, 20, 4, Wu L., 2000, Some Comments on «Sequences Analysis and Optimal Matching Methods in Sociology: Review and Prospects», Sociological Methods and Research, 29, 1, Yong K., Pettit N.C., Spataro E., 2010, Holding your Place: Reactions to the Prospect of Status Gains and Losses, Journal of Experimental Social Psychology, 46, 2, Younès D., 2013, Entre concurrence et cooperation. La place des équipes de recherche académique dans l économie locale, in Aust J., Crespy C., (dir.), Les mutations des politiques de recherche : entre Etat, marché et professions, Paris, Editions des Archives Contemporaines. Zauberman R., 2009, Les enquêtes de délinquance et de déviance autoreportées en Europe. État des savoirs et bilan des usages, Paris, l Harmattan, Collection «Logiques Sociales». 36

268 Partners CESDIP (Centre de Recherches Sociologiques sur le Droit et les Institutions Pénales) UMR 8183 Min. Justice, CNRS and University of Versailles- Saint- Quentin- en- Yvelines CESDIP was created by government order n under the triple supervision of CNRS, the Ministry of Justice and the University of Versailles- Saint- Quentin- en- Yvelines (UVSQ). Its main research area is the sociology of institution and penal law, of police and gendarmerie, of deviance and crime, and crime prevention. Thanks to its international structure GERN (European research Group on Normativities), which federates around 40 research centers in 12 countries of the EU, and implemented the CrimPrev (FP6) program between 2006 and 2009, CESDIP is at the forefront of European academic research in these domains. In the past years, CESDIP s members have received prestigious prizes for excellence in their publications : the Howard Society Prize was granted to F. Jobard in 2010, the Hermann Diederiks prize to E. Blanchard in 2008, J the second young author prize of Sociologie du Travail to J. Gauthier. Ph. Robert, an emeritus researcher with CNRS, received two honoris causa doctorates (Universities of Liège and Macerata). Further, since 2000, 8 researchers recruited by the CNRS have chosen CESDIP as their laboratory, which is a strong indicator of CESDIP s excellence in the French academic milieu. Over the period, CESDIP published 67 articles in peer- reviewed scientific journals, 26 books, collective books or thematic issues. Numerous CESDIP articles were published in France s most prestigious journals of social sciences (Genèses, Histoire & Mesure, RFS, RFSP, Politix, Vingtième Siècle ) and in major international journals (British Journal of Criminology, British Journal of Sociology, Criminologie - Montreal, Déviance & Société Bern, Howard Journal, International Journal on Violence Schools, International Review of Victimology, Journal of Ethnic and Migration Studies, Journal European Public Policy, Revista de Estudos de Conflito e Control Social, Social Research, Studi Sulla Questione Criminale, Terrorism & Political Violence ). CESDIP s team consists in 10 CNRS research fellows (incl. 1 emer.), 12 university members (incl. 2 emer.), 16 research fellows of other administrations and authorities (Min. Justice, Région Île- de- France, Gendarmerie nationale, post- docs ), 21 PhD students, 6 administrative staff members (4 CNRS + 2 Min. Justice) = 65 fellows. Higher Education: CESDIP is the laboratory of the Master 2 of Political Science Department UVSQ. CESDIP is partner of 2 Summer Schools: - one lead by Frédéric Vesentini on quantitative studies (s. Axis 1) (Quantitative Studies, UVSQ, Leuwen, Montreal), - one lead by Jacques de Maillard (GERN Summer School, with Universities of Ghent, Porto, Leeds and Sheffield). CESDIP contribution to our project consists in: - 17 involved research fellows: o Axe 1: Fabien Jobard (CNRS), Renée Zauberman (CNRS), Philippe Robert (CNRS), Frédéric Vesentini (CNRS), Bruno Aubusson de Cavarlay (CNRS), Fadoua Jouwahri 37

269 - - - o (IE CDD), Kathia Barbier (doctorante UVSQ), Matthieu de Castelbajac (doctorant UVSQ), Bénédicte Féry (doctorante UVSQ), Fadoua Jouwahri (CNRS), Jean- Christophe Le Pellec (CESDIP) gayet, amicel Axe 4: Fabien Jobard (CNRS), René Lévy (CNRS), Pierre Piazza (U. Cergy), Tanguy Le Goff (IAU- IdF), Annie Kensey (Min. Justice), Jennifer Boirot (doctorante UVSQ) The salary of one full- time engineer in statistics (F. Jouwahri) 128K / 3 years. The salary of one half- time assistant- engineer in documentation and web (J.- Ch. Le Pellec) 17K / yr. Summer School F. Vesentini : / 3 yrs. Table on status and involved researchers (n=17) CNRS CR CNRS DR Univ. Prof Univ. MdC Ingénieurs Post- doc Doctorants Autres Bibliographie Aubusson de Cavarlay B., 2009, Comparisons between Victimisation or Self- Reported Crime Surveys and Official Statistics in France, in Robert Ph., (ed.), Comparing Crime Data in Europe. Official Crime Statistics and Survey Based Data, Brussels, VUB Press, Jobard F., Lévy R., Lamberth J., Névanen S., 2012, Measuring appareance- based discrimination. An analysis of identity checks in Paris, Population- E, 67, 3, Lévy R., Mayer M., Haverkamp R., 2003, Will Electronic Monitoring have a Future in Europe?, Freiburg- im- Breisgau, Edition Iuscrim, Piazza P., Laniel L., 2008, The INES Biometric Card and the Politics of National Identity Assignment in France, in Benett C., Lyon D., (eds.), Playing the Identity Card. Surveillance, Security and Identification in Global Perspective, London- New- York, Routledge. Robert Ph., Zauberman R., et al., 2010, The Victim s Decision to Report Offenses to the Police in France : Stating Losses or Expressing Attitudes, International Review of Victimology, 17,

270 CRG (Centre de recherche en gestion) École Polytechnique- CNRS Discipline: management, economics, psychology & sociology. Date of Creation: 1972, 1981 first research unit to be CNRS affiliated in management discipline. Since 2004, CRG is the management component of UMR 7176 PREG (Pole de Recherche en Economie et Gestion). Staff: 10 Permanent researchers, 14 associated researchers, 25 PhD students, and 1 post doctorate student, 3 research engineers and 5 administrative staff. Research themes: for 40 years, the CRG as played a leading role in the development of French management academic community as the recognition of management research in professional environment. Its research identity can be define by (i) a large and deep scope of theoretic investigations in social and human disciplines (from organization theory, economics, clinical psychology to sociology of work or situated action theory), and (ii) a problem oriented and collaborative research approach deeply rooted in the contemporary strategic questions of private as public organizations. This identity is highly recognized in the international academic community of Management Sciences, as an emblematic case of relevant research strategy. Ongoing CRG research is structured through 5 programs: (i) Innovation- based Competition & Design Systems Dynamics; (ii) Business strategies, market structure and regulation policies; (iii) Economic effects and organizational impact of the development of information and communication technologies and Internet. (iv) The Territorial Dynamics and New Organizational Configuration; (v) Multicultural management approaches Academic publications and academic developments: CRG researchers published on the period 125 articles in peer- reviewed journals (78 in English), 28 Books, Edited books or special issues of journals, 107 chapters into collective books, 21 doctoral thesis or HDR, 297 communications in academic conferences. Awards: 2012, best research book (FNEGE Fondation nationale pour l enseignement de la gestion et European Foundation for Management Development); 2011: Syntec prize; 2010: the AREA thesis prize was awarded to CRG doctorate; 2008 best research paper, HEC foundation; 2007 Stephan Shrader Best Paper Award Finalist, division technology and innovation management Academy Of Management, and Academy of Management Best Paper Proceedings, Editorial activities: Researchers serve as reviewers or editors in top international journals and are members of executive committees in many academic associations. PJ Benghozi, H. Dumez and C. Midler are members of AERES evaluation committees. PJ Benghozi is former president of the French Management Society (SFM), former president of the Economics and Management Section (37) of the National Committee for Scientific Research, former member of the Scientific Council, Paris Dauphine University. Interaction with firms: Interaction with professional environments, applying problem- based approaches, has always been one of the research methodologies favored by the CRG. This explains the density of exchanges with professional milieu (both private and public) in a variety of forms: research partnerships; Cifre grants; teaching and research chairs (3 chairs at present with Orange, Renault, Valéo, Safran, Seb, Air Liquide). C. Midler is a Cercle de l Entreprise member, the think tank of the French Institut de l Entreprise. The École de Paris du Management, founded in 1993 by Michel Berry, former CRG director, and supported by the CRG since then, is a forum for discussion 39

271 between management researchers and practitioners within the framework of permanent seminars and conferences. Education: The CRG is responsible for management doctorate training at École Polytechnique. CRG researchers are highly involved in national training programs for the best doctoral candidates in the discipline: CEFAG & CDEG. The CRG has a longstanding involvement in 5 Masters programs, in partnership with universities and major engineering as business schools : Projet Innovation Conception, Industrie des Réseaux et Économie Numérique, Gestion et Dynamique des Organisations, Management des organisations et politiques publiques, Ingénierie de l'innovation Technologique. CRG contribution to the project 3S: The CRG research programs will be heavily involved in axe 2, but will also contribute to other axes. CRG will bring its expertise on the different themes as its deep and diversified empirical connections in professional environment. On the methodological side, CRG will bring its deeply rooted expertise in cooperative research within innovation projects and more specifically in emblematic innovative projects as electric mobility or the Innovation Lab that will be developed in the Saclay environment. Researchers involved in the project DR CNRS Pr MCF Ingénieur de recherche Doctorants Permanent researchers : Romain Beaume (Fellow Ecole polytechnique) Pierre- Jean Benghozi (Directeur de Recherche CNRS) Florence Charue- Duboc (Directeur de Recherche CNRS) Hervé Dumez (Directeur de Recherche CNRS) Alain Jeunemaître (Directeur de Recherche CNRS) Christophe Midler (Directeur de Recherche CNRS) 2 Research Associates Sylvain Lenfle (maître de Conférence - Université de Cergy- Pontoise) Rémi Maniak (maître de Conférence - Télécom ParisTech) 8 PhD students Bo Chen Julie Fabbri Julie Hardouin Nathalie Herberth Marie Le Pellec Felix von Pechmann Romaric Servajean Thorsten Sobe 40

272 DANTE (Laboratoire de Droit des Affaires et Nouvelles Technologies) EA 4498 (Université de Versailles- Saint- Quentin- en- Yvelines) The Research Unit of Business Law and New Technologies (DANTE) created in 1997 is formed by all the faculty members of private law as well as legal historians. Besides these tenured graduated academics, it includes many researchers. Doctors, PhD students and practitioners with a rich and recognized research and publishing background and who have chosen to join the laboratory because of its influence in France and internationally. With more than a hundred members, the laboratory DANTE leads many projects, either through events and transversal publications or inside the teams that form this structure, in conjunction with an attractive Masters courses offering. The Unit researches as well as the Masters degrees are mainly directed toward the business and the law applicable to it, in France, Europe and internationally. Alongside the traditional strengths such the new technologies (Team Law and Technology - Intellectual property laws and New technologies of the information and the communication) and the law of contracts and competition (Team Contracts and market), there are two other teams specialized in Law arbitration and Attractiveness of business law. Very active in the collective research programs, the DANTE has obtained several research contracts (in particular contracts ANR Lise and Prosody and contract with the GIP- Justice) in partnership with other french or foreign universities and institutions. Most of them have a multidisciplinary approach, involving, amongst others, computer, sociologists, economists... CR CNRS Pr Maître de conférences Ingénieur de recherche Post- Doctorant Doctorants Liste nominative des chercheurs de chaque laboratoire impliqués dans le projet, en indiquant leur discipline, leur statut, l'axe (ou les axes éventuellement) dans lequel ils vont mettre en œuvre le projet : V.L. Benabou, Professeur, (Intellectual property laws and New technologies of the information and the communication - droit de la propriété intellectuelle et des nouvelles technologies de l'information et de la communication) - Axis 2 M. Chagny, Professeur (droit de la concurrence - Competition law) - Axis 2 M.E. Boursier, Maître de conférences (droit pénal - Criminal law) Axis 1 M. Clément- Fontaine, Maître de conférences- HDR (Intellectual property laws and New technologies of the information and the communication - droit de la propriété intellectuelle et des nouvelles technologies de l'information et de la communication)- Axis 2 et 3 M. de Fontmichel, Maître de conférences (Business law - droit des affaires) - Axis 4 N. Reboul Maubin, Maître de conférences- HDR (Private law - droit privé) - Axis 4 B. Rutherford Iglesias, Ingénieur de recherche - Axis 4 Bibliographie - Projet ANR LISE (ANR- 07- SESU ) «Dommage et technique» , piloté par l INRIA, avec Supelec, LORIA, Université de Caen, DANTE. 41

273 - Projet CCP- Prosodie (ANR- AA- PPPP- 00) «Les communautés de pratique en ligne» , piloté par l'institut Télécom Bretagne, avec Institut Mines Télécom, Univ. Nice- Sophia Antipolis, UVSQ, Université technologique de Compiègne, INRIA (LORIA), DANTE. - Ouvrage: Manuel de Droit pénal des affaires internationales, contrat d édition en cours, Lextenso Editions Benabou V.L., 2011, The Chase (P2P), in Stamatoudi I., (dir.), Copyright Enforcement in the Cyberspace, Brussels, Kluwer. Clément- Fontaine M., 2013, Les communautés épistémiques en ligne, Revue Internationale de Droit d'auteur (RIDA) (à paraître). 42

274 EST (équipe GHDSO) Université Paris Sud EST «Études sur les sciences et les techniques» is a research unit of the University Paris Sud (EA 1610). The researches carried out in the unit are devoted to the transmission and circulation of scientific knowledge from an historical point of view, either didactical or ethical. Within EST, the GHDSO group conducts researches on social and cultural history of sciences and technology. More precisely, the group focuses on Scientific and technical knowledge, Actors, Places and Publics in nineteenth and twentieth century France through three main entries : history of scientific and technical teaching, history of scientific periodicals and their publics, sciences in society since World War Two. CR CNRS Pr MCF Ingénieur de recherche Post- doctorant Doctorants Liste nominative des 7 chercheurs pour l axe 3 : Liliane Alfonsi, MCF, histoire des sciences et des techniques Delphine Berdah, MCF, histoire des sciences et des techniques Renaud d Enfert, MCF, histoire des sciences et des techniques Virginie Fonteneau, MCF, histoire des sciences et des techniques, Hélène Gispert, PR, histoire des sciences et des techniques Annick Jacq, CR CNRS, biologie, histoire de la biologie Jacques Robinet, doctorant contractuel, histoire des sciences Norbert Verdier, MCF, histoire des sciences et des techniques Publications GHDSO d'enfert R., Fonteneau V., (dir.), 2011, Espaces de l'enseignement scientifique et technique Acteurs, savoirs, institutions, XVII e - XX e siècles, Paris, Hermann. d Enfert R., 2008, Une revue «scientifique et industrielle» militante : L enseignement professionnel, , in Bret, Chatzis, Perez, Gispert H., (dir.), 2011, Quels publics, pour quelles mathématiques?, Rencontre du CIRM mrs.fr/liste_rencontre/programmes/resumesgispert.pdf. Gispert H., Hulin N., Robic M.C., (dir.), 2007, Science et enseignement. L exemple de la grande réforme des programmes du lycée au début du XX e siècle, Paris, Vuibert/INRP. Verdier N., 2013 (accepté à paraître), Éditer puis vendre des mathématiques avec la maison Bachelier ( ), Revue d Histoire des Mathématiques. Verdier N., 2012, Panthéons, journaux et salons à Berlin, Londres ou Paris : fabriquer des réseaux de sociabilité savante, in Thoizet É., Wanlin N., Weber A.G., Panthéons littéraires et savants XIX e - XX e siècles, Amiens, Artois Presses Université,

275 GREGHEC (Innovation & Entrepreneurship - Society and Organizations) HEC- CNRS GREGHEC, awarded top grades from AERES in March 2009 (the unit's overall rating was A+), was founded in 2004 and was granted UMR (2959) status in As HEC's academic research center, it is composed of select faculty members (those who are directly involved in research activities) and of PhD students. GREGHEC takes part to the ISIS project through two research teams: Society and Organization (SnO) and Innovation and Entrepreneurship (I&E) Innovation & Entrepreneurship team presentation The I&E team is a multidisciplinary research group (management disciplines, economics, law, psychology) created in It counts 25 members (assistant, associate and full professor) and 10 doctoral students (25% of GREGHEC resources). Research themes: (i) management of innovation and entrepreneurship (12 researchers), (ii) growth strategies (5), (iii) corporate ecological and social responsibility (4), (iv) economics and innovation (4), (v) organizational structure, learning and performance (5). More precisely, the subjects addressed are: (i) how particular situations lead to choosing alliances over other modes of growth, complementarity of partners knowledge specifically between firms and university scientist researchers, (ii) creativity and idea generation management, (iii) creative Industries management such as Design, (iv) management of highly uncertain projects, (v) innovation through business models especially in emerging economies, (vi) the conditions under which firms form relationships with and learn from external sources of knowledge and how they translate this learning into technical innovations, (vii) exploration management, (viii) technological innovation, (ix) entrepreneurs motivation and the economic effects of entrepreneurship, (x) the strategic logic and the value creation mechanism of Private Equity investments and venture Capital (the provision in a dynamic agency model, the comparison of the VC success in USA and Europe). Academic publications : Researchers have since 2006 published: (i) 100 articles in peer reviewed journal of which 43 in journals such as Academy of Management Journal, Journal of Marketing, Management Sciences, Organization Sciences, Strategic Management Journal, Journal of Management Studies, Journal of Product Innovation Management, Organization Studies, Research Policy ), (ii) 9 books and (iii) 56 books chapters. Editorial activity : Researchers serve as reviewers or editors in top international journals and are members of executive committees in many academic associations (see vitae). Their work was acknowledged many times through awards (Best conference papers, Best doctoral dissertation, Syntec Management Consulting best article. T. Astebro is listed in top 3.0 th percentile of downloaded working papers at Social Science Research Network ( International Orientation: 60% of GREGHEC members are strongly embedded in international context (education, previous professional experience, citizenship ). 48 PHD degree from HEC work outside of France. GREGHEC members production is embedded in an international context: 70 articles (on 110) published in peer reviewed journals are with international co- authors. 96 articles are published in international journals. 40 chapters are in international books. Exploitation of results: 7 chairs and centres associated with innovation are sponsored by companies : (i) Innovation & Globalization (Orange), (ii) Innovation Management in Aeronautics, Aerospace, Defense and Security (SAFRAN), (iii) New Business Models in Energy Chair (EDF), (iv) Innovation & Entrepreneuriat (Paris Chamber of Commerce), (v) Digital Innovation for 44

276 Business (Free - Meetic - Pixmania Group - PriceMinister - vente- privee.com), (vi) Google@hec, (vii) Private Equity Observatory- Buyout Center. Researchers working on entrepreneurship can rely on the centre of entrepreneurship and on HEC startup in which two affiliate professors are involved and that represent a rich field for experimentation and research. Higher education: Several education programs address innovation & entrepreneurship and are taught by team members: electives in master program and MBA, master degree (Project, Innovation and design in collaboration with École Polytechnique and TelecomParistech), specialized master degree (Entrepreneurship, Project management, New Technologies with TelecomParisTech), major in Exec.MBA, lessons at the incubator and tutoring for company creation, certificates (100 hours specialization) in Innovation Management in Aeronautics and in digital business. HEC offers several programs for entrepreneurs. A program for entrepreneurs on management skills and entrepreneurship (Challenge+) for 36 entrepreneurs on average per year (400 alumni, 250 launched a high tech venture). They created jobs (10 staff on average). The average turnover is 2K. HEC incubator has been hosting 60 ventures since its creation in 2007 (Master degree, MBA and alumni). On top of the permanent faculty, 6 affiliate professors are highly involved in the teaching of entrepreneurship and innovation in various programs. Since 2006, 60 doctoral dissertations were defended. 150 HEC PhDs are currently active in education and research. Contribution to ISIS: I&E team will bring its skills in strategic management, new product development, entrepreneurship and economics, its strong relationships with firms and its high involvement in the international research community. ISIS will build on the strong relationship with the CRG already consisting of a common seminar in innovation management and a common master degree in innovation. Most importantly, it will bring an innovative field of experimentation through Challenge plus and the Entrepreneurship Center and its involvement in several incubators. I&E team will contribute to axe 2 and to a less extent to axe 3. Table indicating the status and number of involved professors and researchers in ISIS CR CNRS Full Professor Associate Assitant professors Affiliate professors Doctorants Paris, Thomas Phelps, Corey Détrie, Jean- Pierre Astebro, Thomas Jouini, Sihem Pacheco Almeida, Gonzalo Sommer, Svenja Dahlin, Kristina Di Stefano, Giada de Hoos, Florian Mindruta, Denisa Yong, Kevyn Iselin, Frédéric Bazzazian, Navid Krieger, Etienne Shyti, Anisa Micaelli, Isabelle Society and Organizations presentation The Centre for research on Society and Organizations (SnO) has been built around various competences, with a view to tackling the challenges posed by society to organizations, and those posed by organizations to society. SnO is an inter- disciplinary research center within the HEC Paris School of Management which aims to examine society- related issues that organizations face, 45

277 organizational issues within society, and the recursive relationship between the two. These issues are brought to light within the context of the increasing legitimacy of management as a discipline and the critique that current socio- economic models are inadequate to address these contemporary issues. By focusing on the societal role of management as a discipline, SnO aims to contribute towards a furtherance of our understanding of the socio- economic context in which we are embedded, as well as the organizations that are shaped by and are shaping this context. Society can be understood as the broad interactional space in which ties between individuals and groups of individuals are formed, developed and disintegrated. This social space is a locus of interactions, exchanges and conflicts within a community of people characterized by shared rules, norms and values. An Organization, on the other hand, can be defined as a structured group of actors, whose action is coordinated, interdependent and based on formal and informal rules. The primary purpose of an organization can be oriented towards economic (profit), institutional, moral and political motives, or towards a combination of these. Thus, organizations encompass public and private companies, professional associations, non- governmental organizations, regulatory agencies and even virtual communities, to name some. Given that organizational boundaries appear more and more blurred and fuzzy, the investigation of such provides us with a key research challenge. The objective of SnO is to develop research projects, to present rigorous empirical results and to promote analytical models designed to further our understanding of various contemporary issues. Our approach combines a broad range of methods (both quantitative and qualitative) tailored to the phenomena under study and uses theoretical lenses coming from various disciplines including: economics, sociology, psychology, philosophy and history in combination with our management focus. SnO is sponsored by the HEC Foundation. Table indicating the status and number of involved professors and researchers in ISIS Pr MCF Doctorants Name Status Discipline Fields of Interest DURAND Rodolphe QUELIN Bertrand RAMIREZ Carlos ARJALIES Diane- Laure KREMP Pierre- Antoine Professor Strategy and Business Policy Competitive advantage/conformity Professor Strategy and Business Policy Economics of Organization, PPP Associate professor Accounting and Management Control Assistant professor Accounting and Management Control Norms and soft laws Non- Financial Performance Measurement Systems. Assistant professor Strategy and Business Policy Sociology of Organizations MANI Dalhia Assistant professor Strategy and Business Policy Economic Sociology. MEHRPOUYA Afshin Assistant professor Accounting and Management Control Socially responsible investments. 46

278 CLEMENTE Marco JACQUEMINET Anne KIVLENIECE Ilze PAOLELLA Lionel TOUBOUL SAMUEL PhD student Strategic Management Institutional Theory PhD student Strategic Management Corporate Social Responsibility PhD student Strategic Management Public- private interorganizational arrangements PhD student Strategic Management Categories PhD student Strategic Management Corporate Social Responsibility Two foreign affiliate assistant professor, from Bocconi (Italy) and Ivey (Canada), are too involved in the project : - - Julien Jourdan (general management, specialized on management and technology institutional theory) Jean- Philippe Vergne (general management, specialized on organizational and industry evolution). Publications Astebro T., Thompson P., 2011, Entrepreneurs: Jacks of All Trades or Hobos?, Research Policy, 40, 5, Midler C., Ben Mahmoud- Jouini S., Maniak R., 2012, Le management des innovations de rupture : nouveaux enjeux, nouvelles pratiques, Paris, Éditions de l École Polytechnique. Mindruta D., 2008, Value Creation in University- Firm Research Collaborations: A Matching Approach, London, Academy of Management Best Papers Proceedings. Paris T., Veltz P., 2010, L'économie de la connaissance et ses territoires, Paris, Hermann. Phelps C., Yang H., Steensma K., 2010, Learning from what Others have Learned from You: The Effects of Knowledge Spillovers on Originating Firms, Academy of Management Journal, 53, 2, Sommer S., Loch C.H., Dong J., 2009, Managing Complexity and Unforeseeable Uncertainty in Startup Companies: an Empirical Study, Organization Science, 20, 1,

279 IDHE- Cachan (Institutions et dynamiques historiques de l économie) UMR 8533, École Normale Supérieure de Cachan Université d Evry CNRS) The IDHE- Cachan is a mixed unit of the CNRS and the ENS- Cachan. It is directed by Claude Didry (Directeur de recherche, CNRS) and was rated A+ by the AERES in November It gathers researchers from different disciplines: Till 2008, the main themes researched in this laboratory were «work and labor dynamics», «firms, products and territories», «financial institutions and markets» and «knowledge and law of public interventions». For the forthcoming period, the IDHE will introduce a new theme which it already started developing since its last evaluation: «knowledge, capabilities and innovation». IDHE (Institutions and Historical Dynamics of Economics) was set up in It is a joint research center involving CNRS, ENS Cachan, Université d Évry and Universities of Paris 1, 8 and 10. It brings together academics and CNRS researchers from different disciplines: economics, sociology, law, history and business administration. It is composed of 64 members and 160 doctoral students. Its scope is interdisciplinary research in Human and Social Sciences. It operates from five sites in Paris and its région: Université d Évry, Université Paris 1 Panthéon- Sorbonne, Université Paris 8- Vincennes Saint- Denis, Université Paris Ouest- Nanterre- La Défense and ENS Cachan. In this project, only IDHE's ENS Cachan (located on ENS Cachan's campus, please consult cachan.fr) and Université d Évry will be involved as partners. The first research team is composed of 13 researchers and professors, 3 post- doctoral researchers, 7 associate researchers, 3 research assistants and engineers, and 10 doctoral students. IDHE's scientific project mobilizes different disciplines around five trans- disciplinary research areas: 1) Work, wage systems, and employment dynamics ; 2) Businesses, products and territories ; 3) Institutions and financial markets ; 4) Knowledge, law, and public policies; and 5) knowledge, capabilities and innovation. IDHE's ENS Cachan arm focuses on three of the five areas sanctioned by the five- year research program currently under way within IDHE. The Cachan team more particularly specializes in six areas: 1) Sociology of labor relations; 2) Economic sociology; 3) Sociology of the entrepreneur; 4) Economics of conventions; 5) work and innovation; and 6) Economic history. IDHE, awarded excellent ratings by AERES in 2009 (Overall rating was A+), is a partner of EQUIPEX CASD (Center for Secure Acess to Data) which is coordinated by ENSAE in partnership with HEC and the École Polytechnique, and the DIM IS2IT, Innovation, sciences, techniques, société. Two researchers belonging to IDHE Cachan's arm were awarded the CNRS bronze medal: Claude Didry in 1997 and Pierre- Paul Zalio in Besides, Pierre- Paul Zalio was named a member of the Institut Universitaire de France (IUF) in Concerning Higher Education, the members of IDHE are involved in teaching activities in the ENS- Cachan in two departments (Social- Sciences, Economics and Business administration) which are implicated in different Masters. Several members participate to the conception of a new master on quantification in social- sciences at the level of Paris Saclay University. IDHE Cachan leads an integrated European program that is part of the 6th FP (Framework Program for Research and Technological Development), entitled CAPRIGHT «Resources, rights and capabilities: in search of social foundations for Europe» ( ) and also co- ordinates two research projects funded by France's Agence Nationale pour la Recherche (ANR, National Agency for Research), entitled «Social support for entrepreneurship» and «Production of knowledge: portrait of the researcher as a salaried worker». 48

280 IDHE- Cachan s contribution to the ISIS project is mainly centered on WP 3 but also on WP 1 and 2. IDHE- Evry s contribution is centered on WP2, but researchers will also contribute to WP3. Surname First Position Domain Partner Organization Contribution name or in the company project BESSY Christian CR Economics IDHE ENS Cachan Coordinator, WP1, 3 DIDRY Claude DR Sociology IDHE ENS Cachan WP3 BOISARD Pierre CR Sociology IDHE ENS Cachan WP3 MIAS Arnaud MCF Sociology IDHE ENS Cachan WP1, 3 BETHOUX Elodie MCF Sociologie IDHE ENS Cachan WP3 Da COSTA Isabel CR Economics IDHE ENS Cachan WP2, 3 HARARI Hugo MCF Busin. admin. IDHE ENS Cachan WP1, 2 JOBERT Annette DR Sociology IDHE ENS Cachan WP3 PARDI Tommaso CR Sociology IDHE ENS Cachan WP2, 3 SÉPARI Sabine MCF Busin. admin. IDHE ENS Cachan WP2 VINCENSINI Caroline MCF Economics IDHE ENS Cachan WP3 YOUNES Dima Post- doc Sociology IDHE ENS Cachan WP3 CHAMPIN Hervé PhD Sociology IDHE ENS Cachan WP2 HILDERMEIER Julia PhD Sociology IDHE ENS Cachan WP2 PERDONCIN Anton PhD Sociology IDHE ENS Cachan WP1 INDUKAEV Andrey PhD Sociology IDHE ENS Cachan WP2 VIEGAS Stéphanie PhD Sociology IDHE ENS- Cachan WP3 LOUBET J.- Louis PU Histoire IDHE Univ. d Évry WP2 LE BOT Florent PRAG Histoire IDHE Univ. d Évry WP2, 3 HATZFELD Nicolas PU Histoire IDHE Univ. d Évry WP 2 BENOÎT Serge MCF Histoire IDHE Univ. d Évry WP 2 MICHEL Alain P. MCF Histoire IDHE Univ. d Évry WP2 Publications Bessy C., Brousseau E., 1998, Licensing of Technology: Various Contracts for Diverse Transactions, International Review of Law and Economics, 18, Didry C., Jobert A., 2010, L entreprise en restructuration, Rennes, Presses Universitaires de Rennes, Collection «Économie et Société». Pardi T., Jullien B., 2012, In the Name of Consumer: The Social Construction of Innovation in the European Automobile Industry and its Political Consequences, European Review of Industrial Economics and Policy. Béthoux E., Didry C., Mias A., 2007, What Codes of Conduct Tell Us: Corporate Social Responsibility and the Nature of the Multinational Corporation, Corporate Governance: an International Review, 15, 1, Younès D., 2012, Why is Intersectoral Cooperation Difficult to Maintain? Insights from French Cluster Policy, Environment and Planning C, 30, 5, Co- Publications Bessy C., Delpeuch T., Pélisse J., (dir.), 2011, Droit et régulations des activités économiques : perspectives sociologiques et institutionnalistes, Paris, LGDJ- Lextenso Éditions. Number of involved researchers: DR, CR et MCF: 11 (École Normale Supérieure de Cachan) and 5 (Université d Évry) Post- doc: 1 PhD students: 5 49

281 ISP- CACHAN (Institut des Sciences Sociales du Politique) UMR 7220 Ens Cachan - CNRS ISP, which was evaluated by AERES in 2008 and obtained an A+ grade, was created in 2006 through the merging of LASP (Paris 10) and of GAPP (ENS Cachan). Its main research areas are democracy, public policy and sociology of law. Its staff includes political scientists, sociologists and historians, operating from two sites University Paris 10 Nanterre, and ENS Cachan. ISP focuses on four main priorities two of which are included in our research project, and mainly involve ENS Cachan researchers. ENS Cachan s ISP team is widely acknowledged, both at a national and international level, as a leading research team in the sociology of law and justice, as exemplified by the quality of its publications (in the best journals of social sciences in their field : British Journal of Criminology, Déviance et Société, Droit et Cultures, Droit et Société, L Année Sociologique ), by its role as a founding member of several networks (including Droit et Société Network), by the intellectual debates it has contributed to launching, as well as by its training programs focusing on the methodology of research. The laboratory includes several leading researchers in the field of the sociology of law and justice such as Benoit Bastard, Jacques Commaille, Laurence Dumoulin, Patrice Duran or Claire de Galembert. Their research activities are articulated around two priorities: 1) Norms and political regulation; and 2) Public action and political power. It contributed to training many researchers who have also become key players in the sociology of law and justice, and with whom it maintains fruitful collaborations (at University Paris 13, EHESS, and ENS- Ulm, for example). The scientific quality and energy of the ENS Cachan team can be appraised by such indicators as (1) the originality and the diversity of obtained results (over the period : 30 articles in national and international peer- reviewed scientific journals, 13 books, collective books or thematic issues), and (2) the fact that, both nationally and internationally, specialists of law as well as specialists of political science and of sociology have shown great interest in these results. These results can be summarized in three subsets: 1) Production and implementation of legal devices; 2) Transformations of the public policies of justice and 3) Expertise and new technologies (Concerning topics that will constitute the core of this project, the ENS Cachan team can boast results dealing with the place of experts in the processes of elaboration of public decisions, as well as with new technologies (Information and Communication Technologies, and monitoring technologies). Besides, together with the IDHE, the ISP has been involved in the setting up of a specialized technical infrastructure: the Emile Durkheim research library of social sciences, on the site of Cachan. The laboratory supports the quantitative processing of data collected through investigations; it houses in its premises the journal Droit et Société which is acknowledged as one of the top- ranked journals in social sciences. Members of ISP are involved in several masters: Master of Sociology (ENS Cachan) but also Masters of Political Science (IEP Grenoble) and Masters of Law (Paris 2, Grenoble ). They are involved in the training of judges (Ecole Nationale de la Magistrature), lawyers and social workers. ENS Cachan's ISP research group involved in the project DR CNRS CR CNRS PhD Students ISP contribution to this project consists in 3 research fellows in axe 4: Benoit Bastard (CNRS), Laurence Dumoulin (CNRS), Aude Leroy (doctorante ENAP- ISP, ENS Cachan). 50

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283 LSQ (laboratoire de sociologie quantitative) CREST- LSQ, GRECSTA, UMR ENSAE- PARISTECH Research topics at the LSQ- CREST include social structures and individual behavior; integration and discrimination; sociology of quantification and methodological issues of quantification. Most research efforts at LSQ make use of quantitative methods, generally combined with qualitative methods. LSQ researchers belong to diverse theoretical schools, such as methodological individualism, constructivistic structuralism and pragmatic sociology of action. They are used to confronting their points of view, their methods and their results, either during the seminars organized by the laboratory, or whilst jointly conducting empirical research. All LSQ researchers value methodological rigour, which makes it possible to share and discuss ideas in a fruitful fashion. LSQ researchers have published numerous books, along with numerous research articles in leading French and international journals such as Actes de la Recherche en Sciences Sociales, American Sociological Review, Économie et Statistique, European Sociological Review, Revue Française de Sociologie, Social Studies of Science, Sociologie, Sociologie du Travail. LSQ is in charge of CREST's sociology seminar. LSQ is a partner of the EQUIPEX DIME- SHS ( Données, Infrastructures, Méthodes d'enquêtes en Sciences humaines et sociales co- ordinated by Sciences- Po) and the GENES is a partner of EQUIPEX CASD, an infrastructure project that is aimed at developing a center for secure remote access to confidential data (CASD), which will be made available for French researchers in social sciences and economics. CASD will provide secure access to highly detailed individual data, making it possible to process highly detailed data. Members of the LSQ who are involved in the project Status Status at LSQ Number DR CNRS Associate member 1 CR CNRS Associate member 3 CR Sciences Po Associate member 1 MCF Associate member 1 Admin. INSEE Full time member 3 Admin. INSEE Associate member 4 Post doc Associate member 1 Name Christian name Status Status at LSQ Action BODIER Marceline Admin. INSEE Associate member 1.3 BUGEJA Fanny MCF Associate member 1.2 BROUSSE Cécile Admin. INSEE Associate member 1.2 COULANGEON Philippe DR CNRS Associate member 1.1 DUVAL Julien CR CNRS Associate member 1.1 GODECHOT Olivier CR CNRS Associate member 1.1 GOLLAC Michel Admin. INSEE Full time member 1.3 GOUX Dominique Admin. INSEE Full time member 1.1 LESNARD Laurent CR CNRS Associate member 1.1 MERON Monique Admin. INSEE Associate member 1.2 PETEV Ivaylo Post doc Associate member 1.1, 1.2 SAFI Mirna CR Sc-Po Associate member 1.1 STEHLÉ Juliette Admin. INSEE Associate member 1.1 THÉVENOT Laurent Admin. INSEE Full time member

284 Publications Godechot O., 2011, La formation des relations académiques au sein de l'ehess, Histoire & Mesure, 26, 2, Godechot O., 2011, How did the Neoclassical Paradigm Conquer a Multi- disciplinary Research Institution?, Revue de la Régulation, 10. Godechot O., Louvet A., 2010, Academic Inbreeding: An Evaluation, La Vie des Idées, 24 pages. Gollac M., (dir.), 2012, Mesurer les facteurs psychosociaux de risque au travail pour les maîtriser, rapport pour le ministre du Travail, de l Emploi et de la Santé. Thevenot L., 2011, Conventions for Measuring and Questioning Policies. The Case of 50 Years of Policies Evaluations through a Statistical Survey, Historical Social Research, Special issue edited by Rainer Diaz- Bone & Robert Salais on Conventions and Institutions from a Historical Perspective (translation by Susan Taponier), 36, 4, Thevenot L., coll. Monso O., 2010, Les questionnements sur la société française pendant quarante ans d enquêtes, Formation et Qualification Professionnelle, Économie et Statistique,

285 LTCI (Laboratoire Traitement et Communication de l Information) (UMR Telecom Paristech, Département de Sciences Économiques et sociales / CNRS) Created in the 1994, the department of Economics and Social Sciences is part of the LTCI (UMR 5141). It includes 30 permanent researchers (5 belonging to the CNRS), 29 PhD students, 23 post- doctoral fellows and X affiliated professors and associate professors. It is highly multi- disciplinary - economics, management sciences, sociology, information and communication sciences, cognitive psychology and ergonomics and focusing on economic and social issues related with the development of ICT, at three levels: The link between innovation and regulation (macro level). The shifting boundaries between content producers and amateurs/consumers; Detailed empirical studies of mediated interactions at the micro level. The AERES committee noted how the department was «analyzing with highly complementary perspectives shared issues about innovation, regulation and use of IT, Telecom ParisTech being the most relevant place in the French scientific landscape to tackle this issue» (AERES report, p. 38), and gave it an A notation. Academic publications, : 27 books and edited collections (including 4 in English), 67 articles in international peer- reviewed journals, 115 articles in French peer- reviewed journals, 35 chapters in collective books (including 16 in English) The total is 234 publications in all, i.e. about 1.5 articles or books per year and per permanent researcher. Exploitation of results Annual contractual research budget of 2 M, and two research chairs Innovation et regulation, et Modelisation of Imaginaries, with the active participation of several leading industrial partners (Orange, Dassault Systèmes, Alcatel Lucent, Peugeot, Ubisoft). The department is also involved in two joint research laboratories, one with Alcatel Lucent, and the other with Renault under the Paistech frame. Higher education 1 st year courses (economy, human fundamentals) and master courses (finance, project management, strategy, IT management, design ). Several courses are also provided in the formation of the Mines Telecom Corps engineers Several Master 2 tracks (M2 Design, medias, technologies with Paris 1 and l ENSI), M2 IREN (Network Industries & Digital Economy) with Ecole Polytechnique, Supelec, Paris West - Nanterre La Défense, Paris- Sud 11, Pierre et Marie Curie) et specialized masteres ( Technological Project Management with ESSEC, New Technologies and Management with HEC). Contribution to the ISIS project The SES department at Telecom Paristech will bring to the LISI its ICT perspective. It will contribute to the ISIS research axes 2 and 4. The SES department will also bring its specific interdisciplinary 54

286 perspective and ability to move from general economic questions to ethnographic studies of actual innovative contexts of use. Table indicating the status and number of involved researchers CR CNRS Pr MCF Ingénieur de recherche Post- doctorant Doctorants Valérie Beaudouin, MCF, Sociology, axis 2 Jérome Denis, MCF, Sociology, axis 3 Valérie Fernandez, Prof., Management Sciences, axis 2 Thomas Houy, MCF, Management Sciences, axis 2 Christian Licoppe, Prof., Sociology, axis 4 Rémi Manyak, MCF, Management Sciences, axis 2 Maud Verdier, Post- doc, Anthropology, axis 4 55

287 PESOR (Pilotage Économique et Social des Organisations) EA3546 Université Paris- Sud Created in 1999, PESOR is the academic research center of University Paris- Sud 11. It brings together all the researchers of the University Paris- Sud 11 who work in management, located in different areas: Jean Monnet Faculty (Law, Economics and Management), IUT Sceaux, Sciences Faculty, Polytech Paris- Sud (engineers). 9 PR, 19 MCF, 1 associate researcher, 14 PhD students and 5 invited professors from several countries, work on management (organization, marketing, finance, human resources and accountability). The emergence of our research on the theme of innovation is relatively new and is related to recruitment these last years of colleagues working on innovation and the beginning of collaborative researches. Research is organized around four main axes: - Competitiveness clusters and Ecosystems - Intangible and knowledge assets - Open innovation and co- creation - Venture capital Academic publications, (innovation axis) 5 books (including in English), 3 collective books, 26 articles in peer- reviewed journals, 19 book chapters (including 9 in English), 1 HDR defence, 6 PhD defence The researchers of the team are frequently solicited as reviewers for international journals. They also serve as member of editorial board of the following journals: Finance Contrôle Stratégie, M@n@gement, Systèmes d Information et Management. They are also members of the executive committees of the following academic associations: Association Internationale de Management Stratégique (AIMS), Association Information et Management (AIM). Exploitation of results 1 Chair Intangible Assets Management. Every year, many communications in national and international conferences (AIMS, AIM, AGRH, EGOS, EURAM). Higher education The members of the PESOR are involved in teaching activities in the University Paris- Sud 11 at various levels: formation from BA (L1- L2- L3 generalist in management) to specialized Masters (M1- M2 in management) and PhD program. Our goal is to develop programs that combine research and teaching and we are responsible of two master programs : - Master 2 Pro/Research Strategies and Management (specialized on cluster management) - Master M2 Pro Marketing of Innovation (specialized on new product/service development) - Engineers (Polytech Paris- Sud) : course on Innovation and knowledge management The members of the PESOR are involved in local PhD program (different courses on methodology) and are engaged in national training program for doctoral candidates in management, Centre Doctoral Européen de Gestion (CDEG). 56

288 Contribution to the ISIS project PESOR will bring to the ISIS project its management perspective on innovation. It will contribute to the ISIS research axe 2. Table indicating the status and number of involved researchers Pr MCF Doctorants Julien Anfrun, Doctorant, axis 2 Andres Barreneche, Doctorant, axis 2 Ahmed Bounfour, PR, axis 2 Denis Chabault, MCF, axis 2 Sandra Charreire- Petit, PR, axis 2 Emmanuelle Dubocage, MCF, axis 2 Florence Durieux, PR, axis 2 Serge Edouard, MCF, axis 2 Géraldine Galindo, MCF, axis 2 Elodie Loubaresse, MCF, axis 2 Ahu Ozcan, Doctorante, axis 2 Publications Bounfour A., 2009, Organisational Capital, Modelling, Measuring, Contextualising, London- New York, Routledge. Bounfour A., Stahle P., 2008, Understanding Dynamics of Intellectual Capital of Nations, Journal of Intellectual Capital, 9, 2, Bounfour. A., 2007, Dynamic Capabilities and Finland s New Path, in Stahle P., (ed.), Five Steps for Finland s Future, Special Number Technology Review, 202, Chabault D., Hulin, 2011, Talents, innovation et pôles de compétitivité, la gestion des compétences, de nouveaux territoires, Paris, l Harmattan. Charreire- Petit S., Livieratos A., Papoulias B., 2011, An Open Innovation Growth Strategy for Knowledge- Intensive SMEs : The Case of and Advertising Agency, in de Pablos Heredero C., Lopez D., (eds.), Open Innovation at Firms and Public Administrations: Technologies fur Value Creation. Loubaresse E., 2008, Influence des caractéristiques des pilotes de réseaux locaux d organisations sur leurs rôles, Management International, 13, 1, Edouard S., 2011, Confiance institutionnelle et pérennité des écosystèmes d affaires, in Gratacap A., Le Flanchec A., (dir.), La confiance en gestion, Paris, De Boeck, Collection «Méthodes et Recherches»,

289 PRINTEMPS (Laboratoire Professions, Institutions, Temporalités ) UMR 8085, Université de Versailles Saint Quentin en Yvelines - CNRS The PRINTEMPS laboratory, since February 2011 directed by Jérôme Pélisse (maître de conferences en sociology, CNRS chair between 2010 and 2015), was evaluated by AERES in November 2008 and was subsequently awarded an overall A grade. PRINTEMPS specializes in sociology and demographic studies. It is jointly supervised by the University of Versailles- Saint- Quentin- en- Yvelines and by CNRS. Finally, members of Printemps are involved in 5 masters and notably one specialized on quantitative methods (Traitement des données quantitatives et démographie) and an other in research (sociology of profession and policy). Its main areas of research are the sociology of professions, the study of public involvements and policies, of careers, and of perceptions of time. Since its foundation in 1995, it has become one of France's most prestigious laboratories of sociology, both nationally and internationally. PRINTEMPS maintains a website and a blog ( Carnet de recherche du Printemps ) which describes the activities of its members and science in the making. It hosts three or four scientific events each year in order to promote recent publications. In June 2010, 80 researchers took part in a PRINTEMPS thematic conference entitled Sociology of Professional Groups: a Blossoming Scientific Field? The main purpose of this conference was to present three books, which had been published by members of the laboratory. In May 2011, the laboratory organized an international meeting on the work of Andrew Abbott (doctor honoris causa of the UVSQ): 120 researchers took part to this important meeting and methodological issues and professional perspectives developed by A. Abbott were notably analyzed. PRINTEMPS organized in 2012 a symposium on the ways in which social scientists grasp of globalization, and the lab will host a major conference in 2014 on Merton (including his sociology of science). The PRINTEMPS contribution to the social science s project appears in the very particular engagement of the laboratory in the fields of profession (and notably profession and career of scientific), science and technologies studies, quantification and measure, but also sociology of law. 1) sociology of scientific work, profession and career. Grounded in the historical topics developped for the creation of the laboratory (1995), the sociology of profession is the main and well- known area of research which contributes to the international rank of the PRINTEMPS. The renewal of the CNRS members of the laboratory since the end of 2000 s was assured notably with the recruitement of two young researchers specialized in Science and Technology Studies: M. Jouvenet (2007) and Arnaud Saint Martin (2011). They developped research about scientific carreer and profession of researcher in the domain of nanotechnology or spatial and aim at studying environnemental sciences or consciousness as a boundary object between natural sciences (and notably neurosciences) and social sciences. One postdoct (M. Hauchecorne) and a Phd student (R. Juston) are working today with them and a CNRS ingenieur coming from the LAL (Laboratoire d accélérateur linéaire) and starting a conversion disciplinary (microelectronics to the sociology of scientific professions) would probably join the PRINTEMPS to work on the activities, status and profession of CNRS ingenieur in the scientific laboratory of Saclay. Finally, with other researcher specialized in an other area (cultural or judicial professions) of the PRINTEMPS, the concept of carreer by project proposed by M. Jouvenet is one important track and analyze heuristic for scientific careers. 58

290 2) Methodology and notably quantitative methodology which take into account the modelisation of time, temporality and longitudinal logic is one other speciality of the PRINTEMPS. Demographs and some sociologists of the laboratory are specialized with this reasonning and technical methods. PRINTEMPS is also one main actor of a research project ending Spring 2013 on quantification of social and professional world through the classification of socio- economic categories in Europe (ANR Eurequa). The extension of this project is notably one important piece of the axe 1 of the project. 3) The last topic on which members of PRINTEMPS will contribute to the project will be the axis on law, justice, science and technology, and notably on the activity and identity of judicial forensic. J. Pélisse realized recently a research on these intermediate between science and justice and two phd (R. Juston and J. Minoc) are beginning on forensic and psychiatric/ psychologist forensic in the courts. Équipe CR CNRS Pr MCF Ingénieur de recherche Professeur associé Post- doctorant Doctorants Liste nominative des chercheurs de chaque laboratoire impliqués dans le projet : Philippe Cibois, Pr émérite UVSQ, sociologue, axe 1 Jérôme Deauvieau, MCF UVSQ, sociologue, axe 1 Eric Drais, Maître de conférence associé, sociologue, axe 3 Céline Dumoulin, Ingénieure de recherche UVSQ, sociologue, axe 1 Isabelle Fréchon, CR CNRS, démographe, axe 1 Morgan Jouvenet, CR CNRS, sociologue, axe 3 Jérôme Pélisse, MCF UVSQ (chaire CNRS), sociologue, axe 4 / axe 3 / axe 1 Nicolas Robette, MCF UVSQ, démographe, axe 1 Arnaud Saint Martin, CR CNRS, sociologue, axe 3 Olivia Samuel, MCF UVSQ, démographe, axe 1 Laurent Willemez, Pr UVSQ, sociologue, axe 4 Mathieu Hauchecorne, postdoctorant UVSQ (région IdF), sociologie, axe 3 Ruggero Iori, doctorant UVSQ (fléchage Labex 6S Printemps - Cesdip), sociologie, axe 1 Romain Juston, doctorant UVSQ (DIM IS²IT), sociologie, axe 4 Julien Kubiak, doctorant UVSQ, sociologie, axe 3 Julie Minoc, doctorante UVSQ (DIM Gestes), sociologie, axe 4 Publications significatives depuis

291 Deauvieau J., 2011, Est- il possible et souhaitable de traduire sous forme de probabilités un coefficient logit?, Bulletin de Méthodologie Sociologique, 112, Jouvenet M., 2013 (à paraître), Boundary Work between Research Communities. Culture and Power in a French Nanosciences and Nanotechnology Hub, Social Science Information, 52, 1. Jouvenet M., 2012, Nanosciences et nanotechnologies : une coopération modèle? Expériences et sens politique des scientifiques, Terrain, 58, Jouvenet M., 2011, Profession scientifique et instruments politiques. L impact du financement «sur projet» dans des laboratoires de nanosciences, Sociologie du Travail, 53, 2, Pélisse J., Bessy Ch., Delpeuch T., 2011, Droit et régulations des activités économiques, Paris, LGDJ, Collection «Recherche». Pélisse J., (dir.), Charrier E., Larchet K., Protais C., 2012, Des chiffres, des maux et des lettres. Une sociologie de l expertise judiciaire, Paris, Armand Colin, Collection «Recherche». Saint- Martin A., 2012, Autorité et grandeur savantes à travers les éloges funèbres de l Académie des sciences à la Belle Époque, Genèses. Sciences sociales et histoire, 87, Saint- Martin A., Lamy J., 2011, Pratiques et collectifs de la science en régimes, Revue d Histoire des Sciences, 64, 2,

292 STEF (ENS Cachan) The laboratory STEF main focus is the study the scientific and technological curriculum, taking into account both the evolution of science and technology, computerization issues and societal problems. STEF specificity is its ability to analyse issues in science and technology education, mutations of scientific and technical practices (research, development, specialized training and general education) in their relations with politics, economy and culture. STEF, with its roots in ENS Cachan and participation in the center d'alembert (Interdisciplinary Center for the Study of the Evolution of Ideas, Science and Technology - UPS) is sensitive to changes in over science and technology and can achieve good coverage of science and technology education and their current changes. Among these mutations, the laboratory places a major issue on computerization in its various dimensions: modifications in content, new forms of instrumentation, modifications frameworks for teachers and students... STEF also gives a prominent place to societal issues which the curricular changes must meet. Studies are focused on current or foreseeable curricular changes, whether these changes are in relation to changes in context, or likely to occur in a more or less distant horizon. It involves analyzing curriculum construction or design and to explore their conditions and consequences. It is not a simple upgrade or update content to teach, but a mapping between missions that can fulfill education and training in science and technology and changes in science and technology (education of citizens, users education, training specialists to their social responsibilities...). Table indicating the status and number of involved professors and researchers in ISIS Pr MCF ATER Doctorants Liste nominative des chercheurs : Virginie Albe, Didactique des sciences et des techniques, PU, axe 3 Volny Fages, Histoire des sciences et des techniques, ATER, axe 3 Pascale Hannoun, Didactique des sciences, MCF, axe 3 Bénédicte Hingant, Didactique des sciences, Doctorante, axe 3 Elie Rached, Didactique des sciences, Doctorant, axe 3 61

293 Summary partners, staff and financial contributions Nom du partenaire Affiliation Effectifs / Catégorie de personnel CESDIP CRG UVSQ CNRS Polytechnique CNRS - chercheurs et ens. chercheurs : 8 - ingénieurs : 2 - doctorants, post- doc : 5 - associate members : 2 - chercheurs et ens. chercheurs : 6 - ingénieur : 1 - doctorants, post- doc : 8 - associate member: 2 DANTE UVSQ chercheurs et ens. chercheurs : 6 - ingénieur : 1 - doctorants, post- doc : 1 EST (équipe GHDSO) IDHE / Equipe Cachan et Evry ISP Equipe ISP Cachan CREST Equipe LSQ LTCI Univ. Paris Sud ENS Cachan CNRS ENS Cachan CNRS ENSAE- ParisTech Télécom ParisTech CNRS - chercheurs et ens. chercheurs : 7 - Chercheurs et ens. chercheurs : 11 - doctorants, post- doc : 6 - chercheurs et ens. chercheurs : 2 - doctorants et post- doc : 1 - chercheurs et ens. chercheurs : 3 - doctorants et post- doc : 1 - associate member : 10 - chercheurs et ens. chercheurs : 6 - doctorants, post- doc :1 PESOR Univ. Paris Sud - chercheurs et ens. chercheurs : 8 - doctorants, post- doc : 3 PRINTEMPS GREGHEC Innovation and Entrepreneurship Society and Organisation STEF Nombre total de chercheurs impliqués : 154 chercheurs UVSQ CNRS HEC CNRS ENS Cachan IFE ISIS Saclay - chercheurs et ens. chercheurs : 9 - ingénieur : 1 - doctorants, post- doc : 5 - associate member : 1 - chercheurs et ens. chercheurs : 21 - doctorants, post- doc : 8 - associate member : 2 - chercheurs et ens. chercheurs : 2 - doctorants, post- doc : 3 chercheurs / ens.chercheurs/ing. : 95 postdoc / doc : 42 associés : 17 Apports financiers sur 3 ans : 128 ke (IE) + 50 ke (mi- tps AI 50%) + 9 ke (Summer School) + 51 ke (moitié doc fléchée UVSQ ) : 164 ke (ANR Travcher ) + 70ke (contrat ANSES ) + 24 ke (moitié IE stat ENS Cachan) + 15 ke (moitié Tech gestion ENS Cachan) (projet «Les barreaux face aux questions éthiques et à la communication électronique», GIP Mission de recherche Droit et justice, déposé janvier 2013) (contrat INSEE PCS en Europe, ) : 102 ke (1 doctorant) + 35ke (AAP UPsud)+ 30ke (Chaire) : 95 ke (ANR Eurequa ) ke (doc DIM IS²IT ) + 51 ke (moitié doc fleché UVSQ ) : moitié des chaires GDFSUEZ (40), Safran (60) et FT- Orange (60) + Fondation HEC (40). Total (minimum) des apports des partenaires au projet : euros 62

294 Interactions between Science, Innovation, and Society (ISIS) IDEX Paris- Saclay APPEL A PROJET RECHERCHE IDEX 2013 Project Name : Interactions between Science, Innovation, and Society (ISIS) Project Type : Social Sciences Project ISIS Coordinators : Christian BESSY (Chargé de recherche CNRS en économie, directeur adjoint de l IDHE- Cachan) christian.bessy@idhe.ens- cachan.fr Christian LICOPPE (Professeur de sociologie des technologies d information et de communication, directeur adjoint du LTCI) christian.licoppe@telecom- paristech.fr Jérôme PÉLISSE (Maître de conférences en sociologie, chaire d excellence CNRS , Directeur du PRINTEMPS) jerome.pelisse@uvsq.fr 0

295 Table of contents 1. Origins of the project Partners of the project Positionning Summary of the project ISIS s National and International Ambition Established Partnerships and Existing Links to National and International Actors ISIS s impact on teaching Governance: «Executive Comittee» and «Scientific Committee» Presentation of the scientific project... 4 INTRODUCTION... 4 WP 1: Quantification, modeling and metrology... 6 WP 2: Innovation, entrepreneurship and market development WP 3: Norms and Regulations of scientific work WP4: Law and Justice, Science and Technology ANNEXES Funding Justification References Partners CESDIP (Centre de Recherches Sociologiques sur le Droit et les Institutions Pénales) CRG (Centre de recherche en gestion) DANTE (Laboratoire de Droit des Affaires et Nouvelles Technologies) EST (équipe GHDSO) GREGHEC (Innovation & Entrepreneurship - Society and Organizations) IDHE- Cachan (Institutions et dynamiques historiques de l économie) ISP- CACHAN (Institut des Sciences Sociales du Politique) LSQ (laboratoire de sociologie quantitative) LTCI (Laboratoire Traitement et Communication de l Information) PESOR (Pilotage Économique et Social des Organisations) PRINTEMPS (Laboratoire Professions, Institutions, Temporalités ) STEF (ENS Cachan) Summary partners, staff and financial contributions

296 1. Origins of the project The ISIS (Interactions Science, Innovation, Society) is the result of a merger between two Labex projects in social sciences (6S and LISI). Even though these projects were well evaluated, they were not funded. Given the evolution of the IDEX partnerships, a new perimeter is suggested. Indeed, 4 new research centers joined the preexisting teams: GHDSO- EST and PESOR from Université Paris Sud, DANTE from UVSQ, and IDHE from Université d Évry (Histoire Economique Sociale et des Techniques). These teams will considerably enhance the interdisciplinary aspect of the project through their expertise in history, law and business administration. 2. Partners of the project CESDIP (UVSQ- CNRS- Ministère de la Justice) CRG (Polytechnique CNRS) DANTE (UVSQ) GHDSO (équipe de EST - Université Paris Sud) IDHE Cachan and Evry (ENS Cachan Université d Evry- CNRS) ISP Cachan (ENS Cachan- CNRS) LSQ (équipe du CREST- GENES) LTCI (Télécom ParisTech - CNRS) PESOR (Université Paris Sud) PRINTEMPS (UVSQ- CNRS) GREGHEC (HEC CNRS) STEF (ENS Cachan/IFE) 3. Positionning 3.1. Summary of the project Knowledge production is the complex result of a combination of scientific activities, social constraints and law that in turn orients the organization and government of activities, as well as the regulation of social life. By combining the approaches and competencies of researchers from different disciplines: sociology, economics, business administration, law, education and history, the consortium s goal is to examine the way measurements, organizational models, scientific results, norms and regulations circulate, are debated in public arenas, are interpreted and implemented in different areas, and also to shed light on their social and economic implications. In this attempt, objects such as the construction of socio- economic categories and indicators, clusters, open innovation, interactions between laboratory life, education and industry, as well as the use of science in the judicial sphere will be examined ISIS s National and International Ambition ISIS s ambition is to develop and structure social sciences research and education in Saclay by relying on researchers domains of excellence and on the exceptional scientific environment of the area. By integrating different disciplines in common research operations (sociology, history, law, education, business administration and economics), the project aims to structure a cluster of research and education in social sciences that will have both a national and an international attractiveness in the following domains: 2

297 - Use of quantification in social sciences but also in firms and public administrations. Here our research operations will be complementary to those of Labex ECODEC. - Processes of innovation and entrepreneurship relying on scientific developments. - Analysis of scientific work as well as its norms and regulations. - Interactions between «law and justice» and «sciences and technologies». The project will be developed in two phases until 2019: During the phase, the goal is to structure research in the social sciences. More precisely, Saclay partners will be gathered to work together on complementary objects with the aim of renewing the domains of science, innovation, technology and knowledge. As such, the research operations presented in this project rely on well recognized competencies (awarded ANR funding, European Coordination action or other types of institutional grants) that are extended and articulated in a way that gives coherence to the collective goal. Our interaction with national partners (such as IFRIS- Institut Francilien recherche, Innovation, Société located in Marne- la- Vallée) will ensure that our research orientations have by 2016 a real added value both for involved organizations and for national partners. During the phase, international reputation will be our main goal. We intend to transform Université de Saclay s social sciences into a world class program. Internal and external funding will be applied for in order to attract competitive international researchers in our domains but also to develop international research and educational programs and partnerships Established Partnerships and Existing Links to National and International Actors Our project will benefit from universities and schools facilities and grants as well as from the national initiatives to which some of the involved researchers participate. Île- de- France s Domaines d Intérêt Majeur (DIM) will be one of them. Indeed, the IS²IT (Innovation, sciences, techniques, société directed by P.B. Joly) and GESTES (Groupe d Étude sur le Travail et la Souffrance au Travail, co- directed by M. Gollac and J. Pélisse) are DIMs with consequent budgets (700 to 800k Euros per year) that offer access to PhD, Post- doctoral or Scientific event funding. Besides, they give access to a network of researchers on which our group can rely to have fruitful scientific discussions and enhance its attractiveness. A partnership is also being negotiated with the IFRIS. The goal is to develop an internationally renowned Ile- de- France based scientific group specialized in questions related to interactions between science, innovation and society. ISIS also intends to further develop partnerships with the private sector. Here, we can already rely on the existing network of some of the teams involved in this project (GREGHEC, SnO, PESOR ). Indeed, our exchanges include research contracts as well as training and educational funding partnerships. These will be further deepened in order to expand the existing network. Last but not least, researchers involved in this project have different research networks on the international academic scene. By merging seminars, and organizing international joint conferences, our goal is to strengthen and widen our networks ISIS s impact on teaching Our efforts to structure the research milieu will be coupled with the inception of two new Masters Programs - - the Master of Quantitative Methods in Social Sciences, and the Master of Science and Society Studies - - that involve a large number of partner research centers. Research will moreover 3

298 influence educational goals through different channels. First, a wide range of case studies will be developed in this project. These can become supports for teaching. Second, our continous efforts towards research complementarities will help define a coherent educational and training strategy. Furthermore, two summer schools will be organized. First, an annual summer school on Innovation and Entrepreneurship is planned in this project (WP2). Second, partners involved in this project will participate in an international summer school that will be hosted at Saclay in Finally, the numerous seminars, workshops and conferences that will be organized by the involved partners in this project will be open to Saclay s students, researchers, professors as well as private actors and public administrations. They will constitute an occasion to develop knowledge, discuss and debate various topics ranging from quantification to the use of science in the judicial sphere. Thus the knowledge developed in this project will also allow for providing training for firms (in management, for instance) or public administrations (policy- makers, police or judicial bodies, for instance) Governance: «Executive Comittee» and «Scientific Committee» The ISIS light governance will rely on a single, wide coverage (one member per contributing organization), decision committee, called the ISIS Scientific Committee (ISC) which will convene at least three times a year. The day- to- day operations, supervision, and ISIS outside representation, will be managed by a three- member ISIS Executive Committee, representing ENS Cachan, UVSQ and Télécom ParisTech (i.e. the actual coordinators of the project). The ISIS Executive Committee will prepare issues to be decided upon by the ISC, such as budget allocation, expenses, new project kick- offs, former projects closures, workshops, PhD & post- doc financing, etc. The ISC will also collect the inputs from ISIS members about potential projects to be launched, and will evaluate ongoing projects once a year. 4. Presentation of the scientific project INTRODUCTION Knowledge production is the complex result of a combination of scientific activities, social constraints and law that in turn orientates the organization and government of activities, as well as the regulation of social life. Scientists, experts, public organizations and others participate to this endeavor in a deliberative or in an involuntary way. They thereby introduce new indicators and categories thought as democratic, organizational forms deemed as efficient, regulation systems designed to bring cohesion in social activities, or scientific results that can be transformed into facts in decision making. Recently, a large set of artifacts has been introduced and this project aims to examine some of them. The selection of the following topics reflects the areas of research in which the consortium is recognized as or aims to become a leading actor on a longer term both on the national and international level. The consortium s goal is to examine the way measurements, organizational models, scientific results and regulations circulate, are debated in public arenas (Chateauraynaud 2011), interpreted and implemented in different areas, and to shed light on their social and performance implications. Quantifying and categorizing the social and economic activities or governing with numbers 4

299 (Desrosières 2008) and benchmarks have probably become the main concern of policy- makers. In parallel, organizational models such as clusters (Porter 1998) or open innovation (Chesbrough 2003) are believed to bring efficiency to the business world. In the scientific sphere, new funding schemes and law (Silbey, Husing, 2011), performance indicators, mergers and partnerships are introduced to regulate knowledge production. The knowledge hereby produced is itself mobilized by experts in the judicial sphere (Dumoulin, 2007; Pélisse, 2012). However, the construction, circulation and reception of these artifacts as well as their appropriateness to reach their goals, that is, a more democratic, efficient or integrated system is still to be examined. Each of the four axis of research presented in this project aims to contribute to the debate on the circulation, the social reception, the effectiveness, and the implications of a range of artifacts. In particular, the first axis will contribute to developing quantitative research while proposing a reflection about the way metrologies and categorizations are used in different disciplines, organizations and countries. The second axis examines organizational models that aim to enhance innovation in the business sphere. In extension, the third axis focuses on the way new forms of regulating and norming science affect knowledge production and circulation in academic, industrial and educational spheres. Last but not least, the fourth axis aims to shed light on the way experts use scientific results in the judicial system and the way justice but also the definition of human being can be reshaped by science. These axes will be examined by combining approaches and competencies of researchers from different disciplines: sociology, economics, business administration, law, education and history. A common concern is the focus on mechanisms of artifacts creation and circulation. These can include mediations (norms, cognitive artifacts, technical equipment) or intermediaries (go- between) enabling coordination among different logics of action and communities. 5

300 WP 1: QUANTIFICATION, MODELING AND METROLOGY This WP primarily brings together CESDIP, the IDHE at Cachan, the LSQ, PRINTEMPS and the SnO, but also involves researchers from LCTI and the CRG. Drawing on a tradition of research on quantification, both from the viewpoint of its construction, and from that of its social uses, ISIS will promote the use of databases, will open new fronts in quantitative research, seeking to spread a reflexive data culture in the social sciences (Desrosières, 2008), thus encouraging a confrontation between scientists who study the same social processes and realities using different methodologies. ISIS will benefit from cutting- edge equipment such as EQUIPEX CASD (a secured remote data center, permitting access to individual or sensitive data to which several partners participate and contribute funds), and DIM- SHS (social surveys center). ISIS will also rely on the on- going creation of a specialized Master on Quantification in social sciences at Paris Saclay. It will moreover also seek a rapprochement with other sciences that use quantification for the problematization and causal inference, such as the sciences and technologies analyzed below in WPs 2 and 3. Three research projects will be conducted during the period. The first two will be completed in 2016, whereas the third one is meant to be deployed over the entire period. The years constitute boot years to establish the conditions for the completion of these studies. The first project will be devoted to the Comparison of strategies of quantification in the social sciences. The second project deals with the categorizations of the occupational space in Europe. The third project focuses on metrology and governance, in cooperation with the three other streams or axis of the overall project. WP 1.1: Comparing measurement and quantification strategies in the social sciences A growing number of researchers routinely resort to increasingly sophisticated quantitative methods. This, as expected, has raised several criticisms (on compositional effects, on the use of causality concepts, on the influence of unobserved variables...). Refusing to view statistics as a mere tool for social sciences, Michael Sobel (2000) rightly described an interplay between statistics and social sciences, and pointed out that it was a fruitful phenomenon, simultaneously urging researchers in social sciences to take advantage of the latest research in statistics and econometrics. In Saclay, there is a confrontation between observational and statistical techniques versus simulation techniques. Indeed, while social scientists most often use census or survey data, experts in complex systems modeling favor simulation or agent- based modeling (on the usefulness of the combination of both methods, see Bruch and Mare, 2006). We therefore plan to investigate the construction of variables and nomenclatures, and the development of devices to collect information (e.g., surveys or experiments) that help to bridge the gap between learned conceptions and ordinary judgments. Some devices, especially large- scale ones, are formatted not only by the scientific debate, but also by political and societal issues (Monso and Thévenot, 2010). Variables are seldom comparable to concepts, and many methods have difficulty addressing this issue. This is the moment when the issue of interpretation and of the gap between what figures suggest and what we say about them really emerges. We wish therefore to create modeling experiments by using a combination of various methods to explore common objects or data, which will lead us to compare not only the results, but also their potential interpretations, as well as researchers activities. We will 6

301 particularly focus on the intrinsic capabilities of different types of modeling in order to describe regularities and structures, or to support causal analysis (Goldthorpe, 2001; Spirtes, Glymour and Scheines, 2000; Durand and Vaara, 2009). To make circulation and discussion possible between the different projects, teams and research centers mobilized on this axis, we will merge the three research seminars in quantitative studies (CREST s sociology seminar, the seminar on reflexive Quantitativism at ENS Cachan, and PRINTEMPS s seminar on quantitative sociology and the sociology of quantification). A specific attention will be devoted to the reception of regression analysis methods in French social sciences, through the constitution of a database collecting methods used in the articles published in the main academic social sciences journals since Our project will then consist in one international seminar on this question of quantification at the level of Saclay. SnO already received the first workshop organized with ASQ s editorial board (June 2010), and has been part of European initiatives such as OTREG seminars and European Theory Development Workshops in cooperation with the Academy of Management Review. Furthermore, a Summer school for PhD students will be organized in by CESDIP (F. Vesentini), together with PRINTEMPS, 2 Belgian research units (Louvain, Liège) and one Canadian center (Univ. of Montreal). A third year will take place in UVSQ (25 to 30 PhD Students for 5 days). Aim: Making Saclay a renowned national and international cluster for research and education on quantification in the social sciences. Operations: a common seminar ( ); an international Conference (2014); a Summer School. Involved researchers: J. Deauvieau (PRINTEMPS), C. Dumoulin (PRINTEMPS), I. Fréchon (PRINTEMPS), N. Robette (PRINTEMPS), O. Samuel (PRINTEMPS), C. Bessy (IDHE), H. Harari- Kermadec (IDHE), A. Perdoncin (IDHE), T. de Saint- Pol (IDHE), R. Durand (SnO), D. Goux (LSQ), M. Gollac (LSQ), L. Wolff (LSQ). Funding granted until now: Summer School ( ): (different partners, incl. 3 x CESDIP). Requested Funding: A 6 months post- doc position for the organization of the international conference ( ). - Travel expenses, invitations, accommodation ( ) - Summer School: for the year 2015 in UVSQ. Scientific results: learning actions (seminars + Summer School) + 1 edited book on soc. sc. jnls in France. WP1.2: Categorizations of the occupational space in Europe This project deals with the categorizations of the occupational space at the European level. It will continue several comparative researches on statistical institutions such as Eurostat, financed so far by an ANR ( ). 7

302 The first question deals with ordinary categorizations of social space (Boltanski and Thévenot, 1983). 30 years ago in France, and at the end of 2000 in Europe, studies on ordinary categorizations were conducted, relying on an imaginative empirical procedure: subjects were invited to comment on and sort cards depicting individuals according to their putative social similarity. A project aiming at generalizing this card game study has been submitted by the LSQ (Cécile Brousse) for the period, based on a sample of 1500 individuals an unprecedented sample size for this type of experimental surveys. In a second phase, the links between scientific and lay practices of categorization will be studied in different new domains (categorizations related to gender, delinquency, suspicion regarding past or present criminal activities ). The second question is concerned with the statistical categorizations of the occupational space. The goal here is to study the history and uses of occupational classifications in various countries: Belgium, Germany, France and Great- Britain. National classifications are based on different social experiences and on histories of labor. We want to understand the modes of description of the occupational world through the prism of statistical production in the countries mentioned. Is there a specific classification? What are the uses of these classifications? How have they evolved since statistical harmonization has been required at the European level? What are the links between the statistization of the occupational world and the institutional forms of work? The third question aims at a study using statistical data from European surveys (in particular the SILC- EUROSTAT survey). The point here is to use the statistical harmonization as a resource for the study of the European social space. Most social stratification theories are framed within national spaces (Wright, Goldthorpe, Esping- Andersen, Bourdieu). Our goal is to study how much the different regions of the European social space (defined by income- diploma proximity) are organized around socio- occupational groups. Our goal is thus to articulate a sociology of the quantification of the European occupational space (projects 1 and 2) with a quantitative sociology dealing with the same question (projet 3). Aim: To deal with the current discussions on common occupational classifications at the European level. This is a contribution to the proper way to describe social structures in Europe and to sketch the relationships between lay and professional categorizations. Involved Researchers: C. Brousse (LSQ), J. Deauvieau (PRINTEMPS), C. Dumoulin (PRINTEMPS), M. Gollac (LSQ), C. Ollivier (PRINTEMPS Girsef, Belgique), I. Petev (LSQ), T. Razafindranovona (LSQ), L. Thévenot (LSQ), L. de Verdalle (PRINTEMPS), F. Jobard (CESDIP), F. Vesentini (CESDIP). Funding granted until now: ANR ( ): Requested funding and grants ( ): 1/ DIME- SHS: access to DIME- SHS resources devoted to the 1500 units sample. 2/ IDEX Paris Saclay: : Travel expenses: Card games, tablet computers and documentation: Research engineer (12 months full job): Scientific results (until 2016): Submission to different French and non- French academic journals. 8

303 WP 1.3: Metrology and governance Today rating agencies, professional reviewers and evaluators, or NGOs that establish rankings driven by environmental or social practices, strongly contribute to classify, evaluate, and allocate resources and power. Governance through norms (Thévenot, 2009) has emerged as a new method for managing state- related issues. Further, standardized indicators have become available in various fields such as cultural industries, service provision or security (Chiapello, 2009; Zauberman, 2009). Current governance modes are based on the worship of transparency and accountability (Guthrie and Durand, 2008; Espeland and Sauder, 2007). Capitalizing on Salais's work (2010), we will investigate indicator- based policies in such fields as social rights, psychosocial risks, and crime. We will also conduct further research on the roles played by quantification experts in corporate or public management, by studying the constraints associated with the professionalization of their trade, along with associated ethical aspects (link with axe 3 about the norms of scientific work). WP 1.3.1: The metrology of work via the studies of psychosocial risks In the field of labor research, two project members have, at the request of France's Ministry of Labor, set up and led a group of experts tasked with monitoring workplace psycho- social risks. This project is a unique opportunity to observe (1) how the issue of health at the workplace is construed by different actors, (2) how arguments justifying or criticizing quantification and indicators are being built and deployed (Clot, 2010; Dejours, 2010), (3) and various conflicting outlooks on the way they should be used and on the relations between quantification, management, and criticisms. One original research on this topic will be conducted by analyzing how the psychosocial risks are measured, and with what sort of tools, by consulting firms, by union s observatories, by the government or by other actors. It will analyze the interests and skills of the "encoders", and of users how the figures are used by companies or branches, how policies might be built on them, how they might help the judges to make their decisions? This research will be based on a large regional network (more than 200 scholars in Ile de France GESTES, Groupe d études sur le travail et la souffrance au travail, directed by two scholars involved in this project see which gives postdoctoral and PhD grants and other fundings on this topic. Moreover, parts of the questions submitted to the sampled population in the Ile- de- France penal metrology surveys (WP 1.3.2) are related to feelings of insecurity, and will give us a larger base to contextualise the data on perceived vulnerability (Robert and Pottier, 1997). Also, IDHE s research members (Mias et al., 2013) participate in a research on women s exposition to reprotoxic substances and prevention issues (ANSES research). Aim: Analyzing how the psychosocial risks are measured, and on what sort of tools these measures are based. Involved Researchers: L. Wolff (LSQ), M. Gollac (LSQ, co- director of GESTES), J. Pélisse (PRINTEMPS, co- director of GESTES), J. Kubiak (PRINTEMPS), A. Mias (IDHE). Funding granted until now: ANSES ( ): Requested funding in : 1/ Request submitted to GESTES: a postdoctoral ( ) or a PhD ( ) position 2/ Request submitted to IDEX Paris Saclay : Travel expenses: Documentation:

304 WP 1.3.2: Penal metrology In this field, a variety of quantification tools are now available: statistics of criminal justice agencies, other public statistics, specific population surveys (victimisation) or conducted in intersecting domains (public health ). For analysing such a complex field, our strategy is to organise within an Academic Observatory a confrontation between the major quantification tools and time series in use at LSQ or accessible through CASD (public transportation, household budgets, employment, national population census, national accounting). Through a dedicated project financed (ANR- CRIMINSEC- 07- BLANC- 0026) and the coordination of a European Coordination action from the FP6 (CRIMPREV ), the CESDIP has already conducted secondary analysis of all the insecurity and victimisation surveys (national, regional, local) available in France at the time. Our Observatory would be operated along two principles: i) long term observation of crime data ii) comparison of crime data from a variety of sources: institutional data and surveys, and sensitive nominative databases like the criminal records database and samples from the national census (échantillon démographique permanent - EDP). A long- term cooperation between CESDIP, LSQ and PRINTEMPS will serve this aim. In a first step, the Observatory structure would make its products available to a wider academic community, in particular by way of a web site. In a second step, at junction of projects 2 & 3, we will develop a CESDIP- LSQ s common project on the consequence of a criminal record for the employment outcomes of males in France. Two research designs could be implemented, each one based on what has been suggested so far in project 1 and project 2. We will either work on longitudinal survey data (samples from INSEE s national census (EDP) and samples from the criminal records database hold by the Ministry of Justice. This project would bring together researchers from CESDIP and LSQ. Criminal records are sensitive statistics, but apart from the fact that CESDIP is part of the Ministry of Justice, discussions are currently conducted in order to locate this database at CASD. We will choose an audit methodology or a testing methodology, in which the employment audit involves sending matched pairs of individuals ( testers ) to apply for real job openings in order to see whether employers respond differently to applicants on a basis of selected characteristics, including information on a criminal curriculum. This methodology builds a bridge to the next action (1.3.3). Aim: This operation, linked with the operations presented in axis 4, will contribute to make Saclay a large pole of sociology of law and justice, dedicated notably to quantitative research. Involved Researchers: J. Deauviau (LSQ), M. Gollac (LSQ), F. Jobard (CESDIP, and CASD scientific board s member), Ph. Robert (CESDIP), F. Vesentini (CESDIP), R. Zauberman (CESDIP). Funding granted until now: ANR : CESDIP : 1) The salary of one full- time engineer in statistics (F. Jouwahri) 128K / 3 years. 2) 50% of the salary of one half- time assistant- engineer in documentation and web (J.- Ch. Le Pellec) 9K /yr. Requested Funding ( ): : Two post- doctoral positions (2 x ); setting up and maintenance of an Internet observatory ( ); computer equipment (5 000 ) Expected Scientific Results: Creation of an academic observatory of quantification of crime ( ), a website 10

305 WP 1.3.3: The assessment of organizations and the use of performance indicators Research on the role of performance quantification within public or corporate organizations, and the ways in which actors produce it or use it will be conducted during the period ( ).This type of research has for instance been examined by SnO s researchers (Durand, Rao and Monin, 2007; Durand and Jourdan 2012) who investigated how market structures and macro- level institutions influence organizational efficiency, particularly on strategic decision- making using quantitative sociology (like the uses of panels at the micro- economic level). In the future, a cross- referenced database about the evaluations of international corporations carried out by rating agencies with various rationales (i.e. financial, humanitarian, or professional rationales) will be built. Research will also be conducted on the impact of the assessments made by rating agencies on the behavior of the actors, in particular in R&D activities or in the academic field (link with axe 3), through a collaboration between HEC, IDHE, DANTE, CESDIP and PRINTEMPS. Another object of study is the role of categorization in international contexts in mediated markets, i.e. markets in which intermediaries evaluate market players. For instance, when multiple guides or raters evaluate the same firms across territories, do these ratings converge? What is the impact of this convergence or divergence on their performance and their decisions? The first steps of a study on these questions have been undertaken at SnO, with a joint work by R. Durand and L. Paolella. The topic is corporate lawyers and how professional guides class and rank firms depending on their practices (i.e. categories of service). This project will be pursued by cross fertilization with the work of Christian Bessy on new organizational forms of corporate lawyers in France (Bessy, 2012). The research on raters and ratings will further be extend through reviving research designs in criminal justice, in which judges are asked to analyze fictitious criminal cases, and to give sentences on cases for which the variables of the defendant, the victim or the situation are changed. Marie- Emma Boursier (legal scholar, DANTE) and Anthony Amicelle (political scientist, CESDIP) would work on it in order to shed light on how crucial players in the criminal justice system (public players like judges and magistrates or private ones like compliance officers) have, or don t have, ratings on individuals, curricula, etc (Amicelle, Favarel- Garrigues, 2012). Carole Gayet- Viaud (CESDIP) will deploy this method in order to trace the difference between a misdemeanor and a crime, an anti- social behavior and a criminal action. This method is similar to one of the methodologies evoked in the penal metrology action (3.2) which also makes use of tests. Aim: Contribution to Saclay s pole of sociology of law and economic sociology, together with quantitative research. Involved Researchers: A. Amicelle (CESDIP), Marie- Emma Boursier (DANTE), Christian Bessy (IDHE), R. Durand (SnO), Carole Gayet- Viaud (CESDIP). Requested funding ( ): for the organization of interdisciplinary seminars on rating and indicators. 11

306 WP 2: INNOVATION, ENTREPRENEURSHIP AND MARKET DEVELOPMENT Innovation has always been a key driver to business development but the last decades have witnessed an abrupt break with the past: from what was basically a weapon for growth, limited to the most enterprising, innovation has become a condition of survival in saturated global markets, providing a strategic alternative to price wars. Contemporary forms of innovation are getting more and more complex, mixing up technological, economic, social, organisational aspects in an attempt to meet contemporary challenges (Benghozi et al. 2010; Midler et al. 2012). The objective of this axe is to support an interdisciplinary perspective focusing on the variety of collaborative practices involving a large number of potential actors (engineers, marketing departments, architects, artists, users, etc.), with different languages, tools and organizational forms. The challenge for these groups is to transform fuzzy concepts into objects and services adding value and values. This WP will take advantage of its location to develop research on and within the innovation processes in a close relationship with other involved actors. It takes advantage of existing research and educating collaborations in the past on the theme of innovation and entrepreneurship (PIMREP, 2010) (master program involving Ecole Polytechnique, HEC and TelecomParisTech, Chairs Ecole Polytechnique- HEC and Ecole Polytechnique- TelecomParis, etc). Specific efforts will be devoted to the promotion of cross- discipline research. Such initiative will help to foster the dialogue with all the Saclay s actors of innovation: innovators, firms, public authorities, civil society. The research program focuses on the relations between innovation management, entrepreneurship and market development, in both mature industries and high technology start- ups: it renews classical approaches by taking seriously the collective nature of innovation and the specificity of entrepreneurship in high technology contexts. The perspective mainly focuses on issues related to the traditional definition of innovation and entrepreneurship, i.e. economic and firms growth and market development thanks to the development of new products or service provisions. It approaches the question of innovation and entrepreneurship (I&E) within the firm, i.e. the micro- dynamics of activities (organisational design, management of creation processes and entrepreneurship, users practices) on the one hand, and the innovation in/as the firm s strategy (business models, structuring of markets and value chain), on the other. Besides, the project will also focus on others forms of entrepreneurial and organizational creativity that make society and markets evolve (megaprojects, financing, new forms of contracts, hierarchy, etc.). Innovation issues have generally been studied by distinct disciplines (strategic management, theory of organization, sociology and entrepreneurship). To understand the new forms of innovation requires a dialogue between them. More specifically, the program will focus on three main research operations and a pedagogical one. WP2.1: Innovation and coordination in high technology environments The first perspective is about R&D ecosystems in high technology environments (clustering, geographical externalities, open innovation, platforms structure) (Chesbrough, 2003; Iansiti et al. 2004; Gawer, 2009; Adner et al. 2010; Dougherty et al., 2011; Brousseau et al. 2011). This part of the program will study the deployment of I&E in a global business, confronted with market contexts 12

307 characterized by radically different usage and regulatory conditions. Actually, open innovation based strategies target specific organizational structure able to support a large number of contributors; to implement new forms of contracts and partnerships, to design new form of local proximity. Such dynamics have been, moreover, reinforced by the development of Information and communication technologies providing radically new means for innovation and market developments (Abecassis & Benghozi 2011). The following research actions will be undertaken to address these issues: (i) Characterization of industrial partnerships in open innovation ecosystems, (ii) Architecture of production and distribution platforms, (iii) New cooperative practices in the management of open innovation, (iv) The management of mega technological projects and the risks they present (v) Design and role of management tools in innovation project and (vi) The legal infrastructure of such cooperation, specifically as regards competition and intellectual property law requirements. These actions have already been launched through researches using different methodologies. One is the) characterization of the emerging digital ecosystems specificities through the identification of new forms of partnerships and of innovative processes overlapping on the infrastructures, the devices and the content (PJ Benghozi and E. Salvador). A second methodology consists in the exploitation of spatial data (Marie Le Pellec, CNES, CRG; Arnaud Saint Martin, Printemps). A third one is based on the measurement of innovation in territories by focusing on the characteristics of intangibles assets (Bounfour, Edvinsson, 2005). Five Phd students are examining these issues within different industries: three PhDs in electric mobility and new associated services (Felix von Pechmann, Renault, CRG ; VEDECOM, Telecom Paristech) and two PhDs on alternative mobility projects and European rail transport (Julia Heildermeier and Hervé Champin, IDHE Cachan) A seminar will be organized in addressing these issues across these fields and others. Indeed, each of these fields represents a very specific landscape. A PhD will be launched. Aim: exploring new forms of R&D organization using different empirical methodologies Involved researchers: This operation will involve the following members among others of the network: K. Dahlin, A. Masini and S. Jouini (HEC); P.J. Benghozi, F. Charue- Duboc, S. Lenfle, C. Midler and H. Dumez (Ecole Polytechnique); Tommaso Pardi, Isabel da Costa (IDHE), R. Maniak and V. Fernandez (LTCI); Ahmed Bounfour, Sandra Charreire- Petit and Florence Durieux (PESOR); M. Chagny, V.L. Benabou, M. Clément- Fontaine (DANTE); M. Le Pellec (CRG); A. Saint Martin (Printemps). Funding granted until now: several PhDs initiated Requested funding: a third of a post doc (each year) + 10K for the seminar + 10K for fieldwork missions Expected Scientific Results: publications, a workshop to debate on the researches engaged in the first perspective and a seminar innovation and society WP2.2: Entrepreneuship and start- ups In the innovation networks that emerge in high technology environment, entrepreneurship and start- ups play a crucial role and present specificities. For instance, academic spin- offs, acting as mediators between science and industry, engage in a wide range of partnerships with established firms and improve the innovative performance of their partners (Mindruta, 2008; Phelps et al. 2010; 2011). Therefore, a second line of research will investigate key issues relating to new ventures founding, development and growth, collaborations between incumbents and start- ups, specificities of entrepreneurship. The objective is to enhance our understanding of the factors that foster the 13

308 founding of new ventures (Astebro 2011; Yong et al. 2010), to study the development of a learning dynamics within innovative start- ups (Ben Mahmoud- Jouini et al. 2010), to investigate the factors that hamper growth dynamics in start- ups and innovative ventures, to examine how collaborations with high- tech start- ups impact the innovative performance of partner firms. The following research actions will be undertaken to address these issues: (i) Dynamic cartography of high technology start up and research spin off, (ii) Economic of start up: strategy, organization, life circle, growth, (iii) Venture capitalist and incumbent strategies vis à vis high tech start up, (iv) Specificities of social entrepreneurship, (v) Evaluation of business plans and management of performance through indicators and (vi) Repartition of value and ownership of intellectual innovation. These issues will be addressed through the database formed by startups hosted within the incubators of Saclay cluster: HEC Challenge plus 1, Ecole Polytechnique, Telecom- Paris and Incuballiance. Hence, raw data exists but needs further modelization in order to be exploitable. A quantitative and a qualitative methodology will be adopted to analyze trajectories of launch and growth of these start- ups as well as collaborations with incumbents through corporate venturing. Another field of research is the project that has been undertaken by the centre of entrepreneurship of HEC (Invivo start- up, up/start- up- In- Vitro) since 2011 matching innovators (researchers, etc) with HEC alumni that bring managerial and entrepreneurship competencies. This represents a rich field of experimentation and research. Some actions have already been launched through PhDs (Julie Fabbri, CRG; Isabelle Micaelli, HEC; Navid Bazzazian, HEC; Anisa Shyti, HEC) and other PhDs will be launched in the period Besides, IDHE launched a study on Optics Valley s entrepreneurs and start- ups. The study aims at understanding entrepreneurs trajectories and work as well as their relationship to the territory s actors (Andrey Indukaev, PhD), while trying to analyze indicators of their performance from different perspectives (Sabine Sépari and Hugo Harari- Kermadec, IDHE). Aim: a better understanding of the factors that foster the founding of new ventures and the dynamics of collective learning anchored in territories Involved researchers: F. Hoos, G. Di Stefano, D. Mindruta, K. Yong, S. Sommers, C. Phelps and E. Krieger (HEC), R. Maniak (LTCI), C. Midler, R. Beaume, F. Charue- Duboc (CRG), and Sabine Sépari, Andrey Indukaev, Hugo Harari- Kermadec (IDHE); V.L. Benabou, M. Clément- Fontaine (DANTE). Funding granted until now: several PhDs initiated, the study of Optics Valley and the experimentations launched at HEC entrepreneurship center Requested Funding: a third of a post doc (each year) + 10 K for fieldwork Expected Scientific results: publications, a database of the startups on the cluster, PhDs WP2.3: Industrial organizations from a historical perspective The third operation follows a historical perspective of industrial innovation. The Study of industrial and techno- scientists innovations during the 19th and 20th centuries needs to be revisited from a usage perspective. In fact, technical objects have been examined as inventions and innovations shedding light on periods that start with their adoption and end with their diffusion. The aim here is to examine their use starting from the prescription (conception and production) phase to their 1 HEC Challenge+ program (25 years old) is dedicated to innovative entrepreneurial projects with substantial growth potential. It welcomes 30 projects per year. It has trained over 380 projects with a success rate (company set up and crossing the 5- year markt) of over 70%. 4 companies are listed in the stock market and twenty have been sold. 14

309 appropriation by users in a workspace. The objective is to examine specifically, hydraulic and machinery technologies. Documents produced by study desks inside firms offer a promising historical material for the study of both design (projection, calculations, prescribed organization procedures) and implementation phases. This study will rely on archives identified by researchers in a set of firms. Restitution through the 3D modeling technology will be developed during the period of this project. Aim: Understanding organization and use of technical objects with 3D modeling methodology and historical work. Involved researchers: Jean- Louis Loubet, Nicolas Hatzfeld, Serge Benoît, Alain P. Michel, Florent Le Bot (IDHE Cachan and Evry). Required funding: 5K for documentations and archival missions Expected results: publications. A 3D video WP 2.4: Valorization The research program will be associated with the development of an educational operation. Its objective is to create a teaching platform on innovation and entrepreneurship, which will elaborate best practices for curricula on innovation through international comparisons, and to increase, therefore the scale of I&E activities on the Saclay Campus. The three following actions will be undertaken. A seminar in 2015 will gather instructors, incubators staff and start- ups and researchers in order to produce a kit for coaches and evaluators of innovative ventures targeting incubators and venture capitalists. It will rely on the network of Saclay Cluster incubators such as HEC, Ecole Polytechnique, Incuballiance, TelecomParisTech. An international summer school on entrepreneurship involving researchers and Phd Students will be organized in A previous edition was organized in 2011 by T. Astebro and C. Phelps (HEC). This edition will involve all Saclay Cluster and beyond. Involved Research fellows: Among other members of the network, the following researchers will be involved: P. Détrie, F. Iselin and S. Jouini (HEC); C. Midler and R. Beaume (Ecole Polytechnique). Obtained grants and funding: Funding of the PIMREP initiative by ParisTech Required funding: a third of post doc (each year) and 15K for the summer school organization Expected scientific results: a teaching program on entrepreneurship 15

310 WP 3: NORMS AND REGULATIONS OF SCIENTIFIC WORK The aim of this work package is to bring together different disciplines with diverse approaches in order to understand how norms and regulations emerge and how they influence scientific work, practices, contents and their circulation, by examining the interaction among different spheres (educational, research, industrial). More specifically, the aim here is to combine approaches coming from the disciplines of sociology, history, economics and education encompassing studies on objects such as policy, work, law, laboratories, curricula, journals, schools, careers or professional networks in a way that will allow us to understand the emergence, evolution, deviance from or contestation of the norms and regulations of scientific contents and practices, while acknowledging that different spheres of knowledge do interact. Our starting point is thus the shared belief that science and technology studies artificially split studied objects. First, a separation between levels of analysis can be observed. While some STS studies have dealt with the organizational and institutional mutations that have deeply altered the way in which science is regulated and linked to social and economic issues (Gibbons et al., 1994; Jasanoff, 2007; Etzkowitz and Leydesdorff, 1997 and 2000), others have focused on scientific practice per se, that is, on the experiments conducted by researchers who are grappling with objects and instruments whose characteristics govern the knowledge produced (Latour, 1989). Surprisingly enough, this micro- sociological point of view has only marginally contributed to the debate on changing regimes of knowledge production (Gibbons, 1994; Pestre, 2003). Second, micro- level studies did not take into account the results streaming from other approaches. In particular, they have been constructed without any sound dialogue with the sociology of law, work, labor and professional identities. As J. Wajcman (2006) and Doing (2004 and 2008) recently emphasized, this is the reason why, to a large extent, the joint work conducted by researchers interested in labor and researchers interested in science is a promising perspective, but has not yet come of age. Third, by separating public policy studies, academic laboratory studies, curricula studies and industrial research, scholars have underestimated the links among these spheres. Indeed, evidence from our previous studies shows that the transformation of academic researchers practices and work cannot be perceived independently from their educational activity or their interaction with industrial partners (Fages and Albe, 2007), and that transformations in laboratory life can t be seized without reference to public policies (Jouvenet, 2011), or that transformations in industrial researchers work cannot be understood without understanding transformations in academic researchers work and vice- versa (Younès 2013). Moreover, the recent intervention of labor unions in the area of R&D in large firms and public research policies is likely to change existing laboratory arrangements (Béthoux, da Costa, Didry, ongoing study). Taken altogether, these results show that studies on the emergence, transgression or evolution of norms should be revisited in a way that takes into account the interactions between the different spheres. We therefore intend to examine norms and regulations by shedding light on their characteristics, the deviance of local norms from those prescribed by policy- makers, their contestation, as well as their emergence and evolution, when interactions among education, industry, academic research, policy tools, law and labor relations are taken into account. 16

311 WP 3.1.: The evolution of norms and regulations of industrial research in perspective The goal of this operation is to understand the way in whichthe organization of knowledge production in firms has evolved during the recent years and to compare these changes with the transformations that occurred in other scientific spheres. We intend to confront our results with the studies of research teams that can increase our knowledge about the topic. While studies on industrial researchers work have mainly been examined at the IDHE and the CRG, academic researchers work has mostly been studied at the PRINTEMPS. The goal here is to combine these different competencies. WP : Understanding change in large firms Two sets of studies have recently contributed to the understanding of change in enterprises. First, the contribution of the project funded by an ANR and hosted at the IDHE- Cachan (TRAVCHER), The work of scientists, has helped to understand the current conditions of knowledge production in large firms by showing that the science- industry relations, as well as the increasing externalization of research towards suppliers, have considerably shifted the activities of some researchers towards network management. Also, a large range of functions inside the firm seem to influence researchers work (marketing, sales, production, development ) in a context of restructuring. Secondly, studies on managerial processes conducted on a longer time span show that these processes have evolved during the past decades. Marketing functions increasingly influence research orientations (Charue- Duboc and Midler, 2002) even if the balance between market and science concerns has shifted over time (Gastaldi and Midler, 2005). How have these changes affected research in industrial laboratories? In order to answer this question, we will organize a conference on the theme, and complete our knowledge by a future operation to be explored. WP : Capturing the transformation of scientific work in firms Indeed, given that both organizational and community belonging affect the professional oportunities of researchers (David and Foray, 2002; Bessy, 2009), we consider that the study of researchers careers can be a good indicator of the way the industrial and the academic organization of research has recently evolved. Empirically, we will use a combination of quantitative data (bibliometric and contracts) and biographic interviews. Starting with large French firms located in Saclay and belonging to research- intensive industries (such as telecommunications equipment, automobile and pharmaceutical industries), we aim to construct a database that will include researchers publications and patents. The analysis of this data will enable an identification of the way researchers expand their domains of expertise, change the position of authorship (from first to last author for instance), or stop publishing at one point of their careers. Biographic interviews help explain the factors and mechanisms of these changes. Are they due to commercial pressures, shifts in the interest of the scientific community of reference, financial pressures, or other factors? In order to construct a database and conduct interviews in at least one firm, a post- doctoral fellow will be recruited. WP : Capturing the transformation of scientific work in academic research centers In parallel, the PRINTEMPS team will conduct a comparable operation in academic laboratories. Based on its experience in laboratory studies, the goal here is to compare the work of industrial 17

312 researchers to that of the technical staff of academic laboratories. While researchers work has been studied during the last years by Morgan Jouvenet (cf. bibliography), the aim here is to include a new invisible category in laboratories: the technical staff that surrounds, supports and accompanies the research and the researchers (Doing, 2004). Bridges could be built to a further UVSQ research centre in management (LAREQUOI), specifically regarding works done by Pascal Corbel (Corbel 2011). WP : How law affects scientific work Interviews in both of these domains will also be the occasion to gather work contracts in order to construct a database similar to the one developed by Bessy (2009) and examine how law affects mobility of researchers and the distribution of property rights. In addition, a joint operation between the IDHE and CECOGI (a team that will join the École Normale Supérieure de Cachan) will focus on the emergence of property right conventions in different branches of the economy. On the longer run ( ), the aim is to conduct international comparisons in firms, curricula and academic laboratories in order to shed light on the way institutions in different countries affected scientific work in these organizations. Aims: The goal of this operation is to understand the way the organization of knowledge production in firms evolved through the last years and to compare these changes with transformations that occurred in other scientific spheres. Involved Researchers: IDHE (C. Didry, A. Mias, P. Boisard, A. Jobert, D. Younès, Z. Yi, Ch. Bessy and É. Béthoux), PRINTEMPS (J. Pélisse, M. Jouvenet, V. Tocut and A. Saint- Martin). Partnering team: CECOGI which particularly works on intellectual property issue in emergent sciences and technologies, P. Corbel (LAREQUOI, UVSQ). Funding granted untill now: ANR TRAVCHER ( ): One PhD (ENS- Cachan): One PhD (UVSQ): Requested funding (95,000 ): One post- doctoral position ( ) to assist the IDHE team in the study of careers, and the organization of a seminar (5 000 ) and an international conference ( ). The PRINTEMPS laboratory will ask for the mutation (détachement) of an Ingénieur de recherche (V. Tocut, a technical staff specialized in microelectronic, working currently in the Linear Accelerator Laboratory LAL and finalizing a process of conversion in the sociology of professions) in order to conduct the research on academic researchers (30,000 ). Expected scientific results: Case studies on scientific work. Organization of seminars and an international conference. Publications. WP 3.2.: Emergence and evolution of norms and regulations and the impact of clusterization on science Clusterization is here understood as the process of increasing proximities between research education and industry. It takes two forms: the decrease of geographical distances as well as the convergence of practices around instruments, projects, trainings and professionalization paths. When resulting from public policy initiatives, this process is coupled with a facilitation effort for technological transfers towards industry. If the plateau de Saclay is not yet the most cited case in this domain, the current endeavors are meant to bring the desired convergence. This part of the work package aims at analyzing the social conditions of this evolution and at comparing them with international cases using a reflexive quantitative as well as a qualitative method. It will thus both 18

313 contribute to the first axis on the construction of categories, and to the science- education- industry debate that will be captured in this work package. While the STEF laboratory has already gathered quantitative data on recent evolutions on the topic, partners now intend to focus on case studies in order to shed light on the process of clusterization in a way that will allow an analysis of the mechanisms of change, reorganization, transformation or reproduction of research and teaching practices induced by the geographical, institutional, economic, social and cognitive reorganization of academic and industrial territories. These case studies are all related: the first is the École Normale Supérieure de Cachan taken as a hub of education- research- industry relations, the second, is joint research structures that include laboratories from this school and the third is joint Masters programs in which the school participates. We argue that nanosciences and nanotechnologies, because of their particular national and transnational governance in the organization of this domain, as well as because of their weight in Saclay, constitute a particularly interesting case when the impact of clusterization on research and teaching practices is to be examined (Marcovich and Shinn, 2011; Sa, 2010; Thurs, 2007). The study will include a historical approach, and a change in progress approach. WP : Studying the evolution of norms and regulation at the ENS- Cachan First, an exploratory study conducted by an ENS- Cachan team (that includes members of IDHE and STEF) on the history (starting 1912) and protohistory of the school (going back to its origins in 1880) showed the relevance of this case in order to examine the evolution of the concept of applied science with its implications on the dynamics between education, research and science- industry relations. Deepening this study will then allow us to explicit the mechanisms of the emergence and evolution of the norms and regulations of scientific content and practices that led to the transformation of the ENS de Cacahn from a technical school to a Saclay partner on three domains: science- industry relations, academic research and education. In our forthcoming study, we intend to put a special emphasis on the evolution of nanosciences in comparison to other disciplines. Here, we will study the evolution of science- industry relations (through contracts and interviews), the evolution of practices and contents of research and curricula as well as the circulation of knowledge among the three spheres. In addition to researchers participation, this first part of the study will also rely on the participation of students from the Social Sciences Department at the ENS Cachan. This operation will be coordinated by Caroline Vincensini (IDHE), head of the social sciences department, Florent Le Bot (IDHE Evry), Elisabeth Chatel (IDHE Cachan) and Virginie Albe (STEF). WP : Ethnographic studies of joint Masters Programs and of joint technological platforms Taking into account the results of the first operation, and following the approach of Fages and Albe s study on the curricula strategies in the creation of specific Masters degrees in «nano», as well as Morgan Jouvenet s claim on the necessity to examine the impact of policy tools supporting new organizational forms of research that include multidisciplinary research, laboratory mergers or public- private partnerships (Matthieu, Jouvenet and Vinck, 2013), the STEF and the PRINTEMPS teams will conduct ethnographic studies in order to shed light on the mechanisms of knowledge circulation during the ongoing clusterization phase at Saclay. We will examine platforms of experimental teaching as well as technological platforms (such as NanoInnov and NanoMed) linking 19

314 researchers to local industrial actors. In particular, we will follow actors from different institutions intervening in the new Masters programs in order to describe the kind of interactions they have with each other, with their research colleagues, and with industrial actors, and in order to examine the way in which these interactions shape their teaching and research practices and contents. In addition, a PhD candidate has started a research on the professional integration of graduates from ENS- Cachan, CELSA, and an engineering school from the Saclay plateau. This PhD will allow a better understanding of the job market characteristics and the links between education and industry. Working sessions assembling researchers working on this topic in France and in other countries (for instance, A. Rip s team at the University of Twente), as well as a conference on scientific clusters will be organized. On the long- run ( ), we would like to compare this case with other initiatives implemented in France with similar organizational forms (in particular Grenoble) or introduced in other countries in nanosciences and nanotechnology. We also intend to conduct comparisons with other disciplines going through similar initiatives in the Saclay area. Aims: Capture the emergence and evolution of norms and regulations in changing environments. A particular attention to the process of clusterization will be given. Involved Researchers: from STEF laboratory (V. Albe and V. Fages), the IDHE Cachan and Évry (F. Le Bot, C. Vincensini, E. Chatel, Ch. Bessy), and PRINTEMPS (A. Saint- Martin, M. Jouvenet). Funding granted until now: The ENS- Cachan funded to conduct research, organize a conference and a publication on its history. It will also contribute through its students to the field work. Requested funding ( ): Two post- doctoral positions ( x 2) to work jointly with the PRINTEMPS team and the STEF team on ethnographies. They will also contribute to the coordination of joint seminars that gathers all the teams implied in this part of the work package (IDHE, STEF, PRINTEMPS), and to the organization of an international conference on the theme. Missions (documentations, travel ): Organization of seminars and a conference: Expected Scientific results: case studies on technology platforms and joint Masters program. Case study on ENS Cachan. Organization of seminars and an international conference. Publications. WP 3.3.: When norms and regulations are bypassed, controversed or contested The norms and regulations of scientific work can be bypassed, controversed or contested. This part of the project examines both contemporary and historical deviant cases, ongoing controversies around existing norms and regulations, and forms of organized contestation in this domain. WP : Transgressing norms in education Indeed, long term historical and sociohistorical studies have criticized the birth of science and scientific work s mode 2 regime that supposedly arose in the years 1950 (Shinn, 2002; Gingras, 2003; Pestre, 2003a). According to the tenants of the mode 2 regime, this scheme replaced a system in which a split between the academic world and society meant that no interactions between science and industry existed. Instead, scholars who examined the circulation and transmission of scientific knowledge in France showed that this classical histographical construction depended on objects, and sometimes, implicit methodological choices: a top- level history that examines policies and national prescriptions and that is limited to mostly Parisian academic and scientific elites and their institutions. By changing the perspective, these studies focused on mechanisms of circulation and transmission of scientific knowledge in the academic milieus as well as in a larger sphere that 20

315 encompasses the split in the history of sciences between, on the one side, a traditional academic sphere and, on the other, technical and professional spheres (for studies on scientific and technical education see Grossetti, 1994; Grelon and Grossetti, 1996; Rollet, 2007; d Enfert and Fonteneau, 2011; for the study of scientific and technical journals see Bret, Chatzis and Pérez, 2008; Nabonnand and Rollet, 2011; d Enfert, 2008). They could therefore show that deviant cases existed. In this part of the work package, we will first contribute to these history studies by examining deviant cases of local supply and local systems of scientific and technical education during the 19 th and 20 th centuries, examine the circulation of sciences by and through scientific journals during the same period, and analyze recent fraud cases both in the industry and academic worlds. The interest of studying local supply and local systems of scientific and technical education has been underlined by Michel Grossetti (1994) and Jean- Michel Chapoulie (2010) and has been reviewed by Laurent Rollet (2009). It will be reinvested in order to study the realities of local configurations when it comes to scientific and technical education in the 19 th and 20 th centuries. Starting from our study on national prescriptions on curricula and practices during the 19 th and 20 th centuries (Gispert, Hulin and Robic, 2007), we have shown that the norm was to separate educational filières by attributing to them differentiated scientific curricula. We now intend to select a number of local case studies in order to evaluate the effectiveness of these prescriptions and analyze transgressions. These cases will be further compared to the Ecole Normal Supérieure de Cachan case mentioned in WP 3.2. This operation will rely on archival work in regions, once the selected cases will have been defined. Since this operation is of common interest to researchers working on the history of ENS- Cachan and the GHDSO, the national seminar Local supply and local systems of scientific and technical education launched by the GHDSO in 2013 will be open to this consortium. WP : The circulation of sciences by and through scientific journals The second operation will focus on the circulation of sciences by and through scientific journals with the aim to show mechanisms of specialization and characterize norms and publics (19 th and 20 th centuries). An emerging field of research on scientific and technical periodicals beyond the most famous academic journals which have already be studied pays particular attention to long term journals specialization processes and their scientific and technical readership (Bret, Chatzis and Pérez, 2008; Gispert, 2011). Our goal is to analyze the norms of scientific production and activity that these publications promote, depending on their editorial project and targeted readership. In this attempt, we will construct corpuses of scholarly press, scientific and technical journals as well as industrial and commercial local press. The construction of different categories of actors and readerships will precede the realization of databases that will reveal the diversity of scientists productions and activities and the diversity of competing or coexisting norms, depending on the periodicals and their specialization. A special attention could be devoted here to the non- institutionalization process of criminology in France (a government order was taken in Feb and deleted six months later). WP : Discourses of Scientific Deviance 21

316 The third research perspective that allows for capturing deviance and for characterizing dominant scientific norms, focus on the issue of scientific deviance. Problems linked to scientific fraud are regularly debated and they may give rise to heated exchanges between scientists (Goodstein, 2010). Both in the industry and in the academic fields these issues have taken an increasingly important place. Recently, Diederik Stapel, a social psychologist at the University of Tillberg recognized falsifying the results of his experiments for 20 years, in order to fit the expectations of the system. By focusing on conflicts, deviances, transgressions, controversies and scandals, it becomes possible to elicit the norms of a social world and the role played by law and legal professionals (Bessy and Chateauraynaud, 1995). Our goal is to construct a database with the coverage of all these cases. While the media extensively covers industrial cases, we also intend to develop a partnership with the observatory of fraud located in HEC Switzerland 2. A textual analysis will be conducted in order to extract different registers structuring the discourses. The study will be carried out both by Jérôme Pélisse (PRINTEMPS) and Christian Bessy (IDHE). The École Normale Supérieure de Cachan will fund a PhD candidate to work on this topic. WP : Controversies on norms and regulations of scientific work Studies on changing regimes of scientific production have recently focused on either explaining the rationale behind the transformations or on their expected effects on scientific production. However, in the social sphere, these changes are not to be taken for granted. Rather, they are leading to public controversies on what the role of science should be and how it should be organized, funded and evaluated (Vinck et al., 2007). It is then particularly interesting to explore these controversies in order to shed light on the different logics at play. In this attempt, we will construct a database to gather media coverage, union press releases, research associations communications on the topic, etc A textual analysis will be conducted in order to extract competing argumentations. Depending on the results, further research operations could be conducted. These can include the constitution of social movements opposing changes, for instance. The research will be conducted by Morgan Jouvenet (PRINTEMPS) in collaboration with Matthieu Hubert (affiliated researcher to PACTE, Grenoble). While studies of controversies usually focus on argumentation, we intend to compare argumentative logics to changes that we observe in laboratories (in previous WPs). WP : Contestation of scientific norms and regulations Moreover, Elodie Béthoux, Isabel da Costa, Annette Jobert, Pierre Boisard and Claude Didry (IDHE) have been following the evolution of labor union debates and activities in the domain of industrial research, especially in multinational firms. Indeed, during the last years, trade unions have been concerned with R&D and investment decreasing budgets, particularly in times of restructuring. Finding ways to reverse this trend has therefore become one of their targets. Understanding how trade unions decided to intervene in this domain, what types of actions they are developing to reach their goals, and how these affect or not the firms decisions should therefore be examined. This will be done through the analysis of trade union documents, transnational negotiations, and interviews in order to understand the repertoires of trade union arguments and how they change. 2 Link to their webpage : 22

317 Aim of WP 3.3: to examine contemporary and historical cases that allow capturing the characteristics of norms and regulations, their justification, deviance, bypassing, and forms of contestation around them. Involved researchers: from the GHDSO- EST (R. d Enfert, V. Fonteneau, H. Gispert, L. Alfonsi, D. Berdah, A. Jacq, J. Robinet, N. Verdier), PRINTEMPS (J. Pélisse, M. Jouvenet), and IDHE (Ch. Bessy, É. Béthoux, I. da Costa, A. Jobert, P. Boisard and C. Didry). Partner: M. Hubert (affiliated researcher to PACTE, Grenoble). Funding granted till now: Two ongoing PhDs (ENS- Cachan and Université Paris- Sud): The ENS Cachan will fund a PhD on the theme of scientific deviance. Requested funding ( ): One post- doctoral position to work on contestation issues ( ). Missions (transport, hotels for regional archives ), documentation : 3 x ( ). Organization of a national seminar ( Local supply and local systems of scientific and technical education ): x 3. Total: Expected Scientific Results: case studies and Publications. Last but not least, this work project, will not only facilitate cooperation among researchers of this subgroup, it will also contribute to other WP through a wide number of results. As such, studies on industrial research and clusterization will contribute to WP2, research on norms and regulations that include metrics and categories can be discussed with scholars working in WP1, analysis of intellectual property rights, researchers contracts and inter- organizational contracts will contribute to the studies on law in WP4. 23

318 WP4: LAW AND JUSTICE, SCIENCE AND TECHNOLOGY Science and law are two dominant forms of truth discourse in contemporaneous societies. Ssocial sciences have put the stress on these two objects with a strong interest for their crossings. In particular, Science & Technology Studies have launched and developed a research program at the crossroads of sociology of science and sociology of law. The chapter wrote by Sheila Jasanoff in The Handbook of Science and Technology Studies clearly shows the perspectives opened by the idea of coproduction between science and society when it is applied to the analysis of science and law (also Jasanoff, 2004 and 2011). Expertise in courts has been one of the favorite domains of research. The question of the role of sciences and technology, and more specifically of varied kinds of expertise in judicial practices and sentencing has generated many different types of groundbreaking research. Some researchers focus on a single case (Jasanoff, 1998), others deal with matters such as forensic activities (Timmermans, 2007) or laboratories in genetics (Renard, 2008; Dufresne and Robert, 2012). The history of the uses of DNA in criminal justice has been written by sociologists of science (Lynch, Cole, McNally and Jordan, 2008), but we do not know so much about the uses of neurosciences in law and justice though some studies exist (Rafter, 2008; Freeman and Goodenough, 2010; Larrieu, 2011). The reception of science in/by courts puts into play more general issues concerning the reliance on mundane understandings of science (Lynch and McNally, 2005). Researches on judicial expertise are an important part of STS research, but socio- historical studies (Dumoulin, 2007) and the sociology of professions (Dumoulin, 2007; Pélisse, 2012) have brought many kinds of technical experts to the fore, like architects, economists, psychiatrists, interpreters or translators. Apart from this, law and justice are also relying on the extensive use of various technologies (and particularly information and communication technologies or ICT), to get the (judicial) job done at different levels of the civil and criminal processes (police work, making of the judicial file, legal reasoning, administration of proof, sentencing s. Dumoulin and Licoppe, 2011; Kaminski et al., in press 2013). Our partners cooperate to the program «Cyberjustice», an international research that has been launched by the University of Montreal ( Home/Home), and on virtual hearings and video- recording of police interrogations to the Digital Society Institute project. Moreover, a network has been created by some researchers who are involved in these hybrid objects (Law, Sciences & Techniques Network, which the DANTE is member of. Four main actions are proposed over the period They are chosen for their likelihood to cross- fertilize different research experiences and to allow the development of bilateral collaborations. While the program for focuses on what science and technology do to law and justice, the perspectives for should be more oriented toward what law and justice do to science and technology an aspect which would have been partly addressed in the third project (for example with the action on scientific fraud or the other one on patents). 24

319 WP 4.1: Research on CCTV as a new method of production of proofs The state of the art (Dumoulin, Germain and Douillet, 2010) has shown that some unexpected uses of CCTV have not been sufficiently investigated. If studies successfully describe the practical activities of the CCTV operators in concrete settings (Le Goff and Malochet, 2011) or CCTV s broader influence on police work (Neyland, 2011), the use of CCTV as a source for admissible evidence is still a blind spot in the literature (Jobard and Schulze Icking, 2004). This form of CCTV is able to provide an empirical basis to assess and discuss surveillance studies core assumptions. A specific research will focus on the way CCTV pictures may be relied on, or contested, as evidence in criminal process and courtrooms. Our first goal is to produce data documenting the actual uses of CCTV: how are pictures available? Under what conditions are they deemed good enough to be used as evidence? Are they really used or not? To charge and convict a defendant or to discharge him? As a sole element of proof, or as a complement to more receivable forms of proof. These questions have seldom been raised in the literature although they could reshape the direction of the research on CCTV, and more empirical and well- documented inquiries are clearly required. One aim of this action is to contribute to the theoretical and empirical displacement of surveillance studies debates from the administration of surveillance to the discussion of the ways in which CCTV s images are used as evidence in judicial settings context of making evidence is at stake. To study these new uses of CCTV and its consequences on criminal process, we request the funding for a postdoctoral position for 18 months ( ). The postdoctoral student would be hosted by ISP with a monitoring committee including researchers from CESDIP and LCTI. Aims: analyzing the use of images as proofs and evaluating the impact of this technology on penal processes. Involved researchers: L. Dumoulin (ISP), T. Le Goff (CESDIP), C. Licoppe (LCTI) Funding granted till now: a grant by the INHES ( ) ; a regional grant (Région Rhône- Alpes) for a seminar on the state- of- art of CCTV issues. Requested funding : Expected scientific results (2019): publications and case studies. WP 4.2: Exploratory research on electronic monitoring: a micro- sociological approach Electronic monitoring or tracking is linked to the transfer of the penalty from the prison to everyday social spaces. It involves non- professional agents and institutions in the surveillance at a distance. In this perspective, ethnographic approaches are particularly relevant to understand how penalty is transformed, who are the new actors involved, how space and sociality in everyday spaces are reshaped by electronic monitoring, and become contested sites. Space, place and proximity are experienced and used for action in a different way, which become empirically available to fine grained ethnographic approaches, while offenders representations of this kind of sanction are researchable with interviews and focus groups (Troshynski, Lee and Dourish, 2011). Researchers from ISP and CESDIP have produced research on electronic monitoring, specifically the reshaping of some judicial decisions with respect to the availability of this type of control (as a control measure mesure de sûreté - for parole offenders for example s. Pitoun and Lévy, 2004 at CESDIP, Dumoulin, 2011, and more broadly Devresse, 2011; Nellis, Beyens and Kaminski, 2012) This work could be articulated to the existing competences existing in LTCI regarding micro- sociological approaches (involving distributed cognition, activity theory and ethnomethodology). 25

320 Two actions will be undertaken within this frame. We plan first to realize a one year long ethnographic research concerning the implementation of electronic monitoring/tracking. A group of electronic monitored offenders would be followed by a researcher from the installation of the bracelet to the ending of the monitoring. The research design also includes ethnographic observations in the relevant sites (parole officers, prison warders, offenders) but above all in the coordination centers where the operators monitor offenders location and may act upon that basis. We also aim to describe the interactions and mutual accountability of participants at this nexus of devices and software, watchers and offenders, place and sociality. For this operation, we need a funding for a post- doc position for one year. In parallel, we propose to launch a multi- disciplinary workshop (or colloquium) on electronic monitoring, which will give the opportunity to valorize our project as an important site of excellence for the SHS research on technology and penal justice. Aims: Analyzing the electronic bracelet using a new approach. Involved researchers: A. Kensey (CESDIP), R. Lévy (CESDIP), L. Dumoulin (ISP), Ch. Licoppe (LCTI). Granted funding until now: a grant from GIP Mission de recherche Droit et justice ; a grant for the Rhône- Alpes Région to facilitate franco- brasilian academic events on supervision and new technologies. Requested funding : : one year post- doc ( ) and the organization of an international conference ( ) Expected scientific results (2019): articles and a multidisciplinary conference. WP 4.3: Research on neurosciences and law To fuel the debate on the ethical questions relating to the societal impact of the discoveries made by neurosciences and of their technical spin- offs, we propose to pay special attention to the growing reception of neuroscience in criminal law and criminal justice. Neurosciences impinge questions of law in two main domains: the ability of neurosciences to predict criminal behaviour (and then, to regulate it); the ability of neurosciences to give an accurate picture of the moral or ethical abilities of the persons, and from there to re- structure or re- define core notions such as individual responsibility. The contribution is relevant to what is now coming to be called neurojustice or neurolaw. Neurosciences in law is a thorny theme in France today (CAS, 2009; RFS, 2010). CESDIP's involvement in societal debates on the possible introduction of criminology in France (Mucchielli, 2009), as well as its researches on the history of forensic sciences, like phrenology (a proto- neuroscience), or of criminology (Piazza, 2011), provide a strong base to explore the contested links between neurosciences and law. Our project combines here in a distinctive way the sociology of law and the sociology of science and technology. CESDIP has an easy access to the bureau and agencies that participate in producing prospective for the ministry of Justice. Moreover, the existence and the proximity of the Saclay's NeuroSpin platform (5 laboratories) offer an easy access to the scientists in the field. We plan to launch later a qualitative research about their positioning in this field and the relationship between them and end users such as the ministry of Interior, the ministry of Justice, the customs services, the prison services, etc. The research would also explore more deeply the new tensions which occur in this field with respect to the «science/society», and try to understand the conditions of emergence of a networked assemblage between neurosciences researchers and judicial administrations and scientists, as well as to identify all the translations and intéressement processes involved, within a STS perspective. It will be based on the detachment of Pierre Piazza (a political 26

321 scientist who devote his works to the history of forensics and criminology) to the CNRS ( Accueil en délégation ) for two years and will require a budget only for research expenses (5 000 per year). Aims: Creating the first scientific location for the study of a possible introduction of neurojustice/neurolaw in France Involved researchers: Fabien Jobard (CESDIP), Morgan Jouvenet (PRINTEMPS), Pierre Piazza (CESDIP). Requested funding : (travel expenses on the field, international workshop) WP 4.4: Around expertise in courts The last domain of research deals more generally with the issue of the use of expert knowledge in courts, an activity which is by definition at the juncture between scientific knowledge and judicial process. Expertise is part of many controversies: concerning psychiatrists; economists; scientists specialized in the climate, the agro- alimentary, health and safety or the nuclear issues. But it takes a specific dimension when it is referred to in the courtroom, and is a key site with respect to the interactions between sciences, societies and law. Our purpose here is to capitalize on the multiple competences of our laboratories to build a network of excellence associating the researchers who have already done significant researches on this topic. This aim could be achieved by launching a seminar drawn to define where are the main gaps in the existing research, on which researchers in Saclay could develop a larger scale collaborative project (for instance for funding by the ANR). This exploratory seminar would bring together doctoral students who are actually working on expertise (R. Juston on forensic expertise, PRINTEMPS; J. Boirot on psychiatric expertise in Europe, CESDIP; A. Leroy on psychiatric expertise, ISP); researchers who have already developed extensive studies of expertise in judicial settings (L. Dumoulin, A. Gozhia, J. Pélisse); foreign colleagues with a recognized expertise (notably B. Renard, researcher in Louvain - Belgium). This seminar (requested budget ) could give birth to both to intermediate collaborative operations (collective academic book, seminar of research) and to the construction of a large scale collaborative project on expertise in the courtroom before Based on a 6 months postdoc ( euros), a special focus will be made on the question of the «cost» of the expertise as a potential threat on the independance of the expert and, moreover as a potential criterion to choose private litigation proceedings (mediation, arbitration) versus public service of justice. Aims: develop knowledge on judicial expertise as a heuristic activity where science and law meet. Involved researchers: J. Boirot (CESDIP), L. Dumoulin (ISP), F. Jobard (CESDIP), R. Juston (PRINTEMPS), A. Leroy (ISP), C. Licoppe (LCTI), J. Pélisse (PRINTEMPS), A. Gozhia (DANTE), N. Reboul- Maupin (DANTE), M. Court de Fontmichel (DANTE). Granted funding untill now: PhD grants (R. Juston, DIM IS²IT A. Leroy, allocation ENAP ) Requested funding : (6 months postdoc + missions and organizations of the seminar). In summary, this fourth axis which emerged from the fusion of the Labex 6S and LISI is particularly rich in perspectives. It promises the realization of excellent research and the development and reinforcement of cooperation between researchers belonging to constituent laboratories (CESDIP, DANTE, ISP, LTCI and PRINTEMPS) from different institutions within the Saclay perimeter. This is the reason why the presented operations aim to capitalize several well- established traditions of research 27

322 but also to go forward and to create synergies in order to build new collaborative projects. This is an ongoing process, open to the adjunction of colleagues from these other laboratories or other disciplines, especially legal scholars from Paris Sud in a near future. A transverse action which exemplifies its collective force and its potential impact on public policies and professionals will be the launching of a test formation seminar for magistrates and police officers on the social implications of science in police and judicial process (budget: ). ANNEXES 28

323 Funding Justification By Working Project, the funding Justification could be presenting in the following table : Postdoc/ingenieur Missions, documentation Sum and equipment WP 1 Quantification, modeling and metrology WP2 Innovation, Entrepreneurship and Market Development WP3 Norms and regulations of scientific work WP4 Law and Justice, Science and Technology To fund all its activities, ISIS needs approximatively per year. During 3 years : ISIS will provide funding to initiate four research programs, including postdoc, missions and equipment. Additional funding could be secured from ANR, ERC, PCRD programs, DIM IS²IT, DIM GESTES, etc. ISIS supports two Master s degree programs and organizes two international Summer school (WP 1.1 and WP 2.4 both in 2015). Postdoc Research ingenieur (1.1.) (1.3.2) (1.3.2) (2.1) (2.2) (2.4) (3.1) (3.2) (3.2) (3.3) (4.1) (4.1) (4.2) (4.4) (1.2) (1.3.2) (3.1) (1.3.2) (3.1) (1.3.2) Missions (seminar, field research, documentation, invitation of foreign scholars...) Equipment (CASD access, database) 5000 (1.1) 8000 (1.2) (1.3.1) 5000 (1.3.3) 7000 (2.1) (3.2) (3.3) 3000 (4.4) 5000 (1.2) 5000 (1.3.2) 5000 (1.1) 5000 (1.3.3) 7000 (2.1) 5000 (2.3) 5000 (3.1) 4000 (3.2) (3.3) 5000 (4.3) 2000 (4.4) (1.1) 6000 (2.1) (2.4) (3.1) (3.2) (3.3) (4.2) 5000 (4.3) Summer school (1.1) (2.4) Valorisation Governance / administration Total 252 ke 410,5 ke 312,5 ke 29

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329 Pélisse J., (dir.), coll. Charrier E., Larchet K., Protais C., 2009, Des chiffres, des maux et des lettres. Une sociologie des experts judiciaires, Paris, La Découverte, Collection «Recherche», Série «Territoires du Politique». Pélisse J., (dir.), Protais C., Larchet K., Charrier E., 2012, Des Chiffres, des maux et des lettres : une sociologie de l expertise judiciaire en économie, psychiatrie et traduction, Paris, Colin. Pestre D., 1992, Physique et physiciens en France, , Paris, Éditions des Archives Contemporaines- EAC. Pestre D., 2003a, Science, argent et politique, Paris, Editions Quae. Pestre D., 2003b, Regimes of Knowledge Production in Society: Towards a More Political and Social Reading, Minerva, 41, 3, Pestre D., 2006, Introduction aux science studies, Paris, La Découverte. Phelps C., Basu S., Kotha S., 2011, Towards Understanding who Makes Corporate Venture Capital Investments and Why, Journal of Business Venturing (forthcoming). Phelps C., Yang H., Steensma K., 2010, Learning from What Others have Learned from You: the Effects of Knowledge Spillovers on Originating Firms, Academy of Management Journal, 53, 2, PIMREP, 2010, Former à l innovation à ParisTech, effervescences et perspectives, livre- blanc- pimrep- pdf- d Porter M., 1998, Competitive Advantage of Nations, Free Press. Rafter N., 2008, The Criminal Brain: Understanding Biological Theories of Crime, New York, New York University Press. Ramirez C., 2009, Constructing the Governable Small Practitioner: the Changing Nature of Professional Bodies and the Management of Professional Accountants Identities in the UK, Accounting Organizations and Society, 34, Raynaud D., 2003, Sociologie des controverses scientifiques, Paris, Presses Universitaires de France. Renard B., 2008, Ce que l'adn fait faire à la justice : sociologie des traductions dans l'identification par analyse génétique en justice pénale, thèse de doctorat en criminologie soutenue à l Université Catholique de Louvain. Rosental C., 2007, Les capitalistes de la science. Enquête sur les démonstrateurs de la Silicon Valley et de la NASA, Paris, CNRS Éditions. Rothaermel F.T., Deeds D.L., 2004, Exploration and Exploitation Alliances in Biotechnology: a System of New Product Development, Strategic Management Journal, 25, 3, Salais R., 2010, Usages et mésusages de l argument statistique: le pilotage des politiques publiques par la performance, Revue Française des Affaires Sociales, 1-2, Saxenian A., 1994, Regional Advantage. Culture and Competition in Silicon Valley and Route 128, Cambridge- London, Harvard University Press. Shinn T., Ragouet P., 2005, Controverses sur la science. Pour une sociologie transversaliste de l activité scientifique, Paris, Raisons d Agir. Silbey S.S., Huising R., 2011, Governing the Gap: Forging Safe Science through Relational Regulation, Regulation & Governance, Sobel M., 2000, Causal Inference in the Social Sciences, Journal of the American statistical Association, 95, 450, Spirtes P., Glymour C., Scheines R., 2000, Prediction, Causation and Search, Cambridge, The MIT Press. Teece D., 2000, Managing Intellectual Capital: Organizational, Strategic, and Policy Dimensions, Oxford, Oxford University Press. 35

330 Teece D., 2008, The Transfer and Licensing of Know- How and Intellectual Property: Understanding the Multinational Enterprise in the Modern World, World Scientific Publishing. Thévenot L., 2009, Governing Life by Standards. A View from Engagements, Social Studies of Science, 39, 5, Timmermans S., 2007, Postmortem. How Medical Examiners Explain Suspicious Deaths, Chicago, University of Chicago Press. Tushman M.L., O'Reilly C.A.I., 1996, Ambidextrous Organizations: Managing Evolutionary and Revolutionary Change, California Management Review, 38, 4, Vinck D., 1999, Les objets intermédiaires dans les réseaux de coopération scientifique. Contribution à la prise en compte des objets dans les dynamiques sociales, Revue Française de Sociologie, XL, 2, Vinck D., 2007, Sciences et société, Paris, Armand Colin. Vinck D., 2009, De l objet intermédiaire à l objet- frontière, Revue d Anthropologie des Connaissances, 1, Vinck D., 2009, Les Nanotechnologies, Paris, Le Cavalier Bleu, Collection «Idées Reçues». Vinck D., Gallice P., Jouvenet M., Zarama G., 2007, Dynamique technologique controversée et débat démocratique. Le cas des micro et nanotechnologies, in Goujon P., Lavelle S., (dir.), Technique, communication et société : à la recherche d un modèle de gouvernance, Namur, Presses Universitaires de Namur, Vinck D., Hubert M., Jouvenet M., Zarama G., 2006, Culture de la différence et pratiques de l'articulation entre chercheurs en micro- et nanotechnologies, in Leresche J.P., Benninghoff M., Crettaz von Roten F., Merz M., (dir.), La fabrique des sciences. Des institutions aux pratiques, Lausanne, Presses Polytechniques et Universitaires Romandes, Wajcman J., 2006, New Connections: Social Studies of Science and Technology and Studies of Work, Work, Employment and Society, 20, 4, Wu L., 2000, Some Comments on «Sequences Analysis and Optimal Matching Methods in Sociology: Review and Prospects», Sociological Methods and Research, 29, 1, Yong K., Pettit N.C., Spataro E., 2010, Holding your Place: Reactions to the Prospect of Status Gains and Losses, Journal of Experimental Social Psychology, 46, 2, Younès D., 2013, Entre concurrence et cooperation. La place des équipes de recherche académique dans l économie locale, in Aust J., Crespy C., (dir.), Les mutations des politiques de recherche : entre Etat, marché et professions, Paris, Editions des Archives Contemporaines. Zauberman R., 2009, Les enquêtes de délinquance et de déviance autoreportées en Europe. État des savoirs et bilan des usages, Paris, l Harmattan, Collection «Logiques Sociales». 36

331 Partners CESDIP (Centre de Recherches Sociologiques sur le Droit et les Institutions Pénales) UMR 8183 Min. Justice, CNRS and University of Versailles- Saint- Quentin- en- Yvelines CESDIP was created by government order n under the triple supervision of CNRS, the Ministry of Justice and the University of Versailles- Saint- Quentin- en- Yvelines (UVSQ). Its main research area is the sociology of institution and penal law, of police and gendarmerie, of deviance and crime, and crime prevention. Thanks to its international structure GERN (European research Group on Normativities), which federates around 40 research centers in 12 countries of the EU, and implemented the CrimPrev (FP6) program between 2006 and 2009, CESDIP is at the forefront of European academic research in these domains. In the past years, CESDIP s members have received prestigious prizes for excellence in their publications : the Howard Society Prize was granted to F. Jobard in 2010, the Hermann Diederiks prize to E. Blanchard in 2008, J the second young author prize of Sociologie du Travail to J. Gauthier. Ph. Robert, an emeritus researcher with CNRS, received two honoris causa doctorates (Universities of Liège and Macerata). Further, since 2000, 8 researchers recruited by the CNRS have chosen CESDIP as their laboratory, which is a strong indicator of CESDIP s excellence in the French academic milieu. Over the period, CESDIP published 67 articles in peer- reviewed scientific journals, 26 books, collective books or thematic issues. Numerous CESDIP articles were published in France s most prestigious journals of social sciences (Genèses, Histoire & Mesure, RFS, RFSP, Politix, Vingtième Siècle ) and in major international journals (British Journal of Criminology, British Journal of Sociology, Criminologie - Montreal, Déviance & Société Bern, Howard Journal, International Journal on Violence Schools, International Review of Victimology, Journal of Ethnic and Migration Studies, Journal European Public Policy, Revista de Estudos de Conflito e Control Social, Social Research, Studi Sulla Questione Criminale, Terrorism & Political Violence ). CESDIP s team consists in 10 CNRS research fellows (incl. 1 emer.), 12 university members (incl. 2 emer.), 16 research fellows of other administrations and authorities (Min. Justice, Région Île- de- France, Gendarmerie nationale, post- docs ), 21 PhD students, 6 administrative staff members (4 CNRS + 2 Min. Justice) = 65 fellows. Higher Education: CESDIP is the laboratory of the Master 2 of Political Science Department UVSQ. CESDIP is partner of 2 Summer Schools: - one lead by Frédéric Vesentini on quantitative studies (s. Axis 1) (Quantitative Studies, UVSQ, Leuwen, Montreal), - one lead by Jacques de Maillard (GERN Summer School, with Universities of Ghent, Porto, Leeds and Sheffield). CESDIP contribution to our project consists in: - 17 involved research fellows: o Axe 1: Fabien Jobard (CNRS), Renée Zauberman (CNRS), Philippe Robert (CNRS), Frédéric Vesentini (CNRS), Bruno Aubusson de Cavarlay (CNRS), Fadoua Jouwahri 37

332 - - - o (IE CDD), Kathia Barbier (doctorante UVSQ), Matthieu de Castelbajac (doctorant UVSQ), Bénédicte Féry (doctorante UVSQ), Fadoua Jouwahri (CNRS), Jean- Christophe Le Pellec (CESDIP) gayet, amicel Axe 4: Fabien Jobard (CNRS), René Lévy (CNRS), Pierre Piazza (U. Cergy), Tanguy Le Goff (IAU- IdF), Annie Kensey (Min. Justice), Jennifer Boirot (doctorante UVSQ) The salary of one full- time engineer in statistics (F. Jouwahri) 128K / 3 years. The salary of one half- time assistant- engineer in documentation and web (J.- Ch. Le Pellec) 17K / yr. Summer School F. Vesentini : / 3 yrs. Table on status and involved researchers (n=17) CNRS CR CNRS DR Univ. Prof Univ. MdC Ingénieurs Post- doc Doctorants Autres Bibliographie Aubusson de Cavarlay B., 2009, Comparisons between Victimisation or Self- Reported Crime Surveys and Official Statistics in France, in Robert Ph., (ed.), Comparing Crime Data in Europe. Official Crime Statistics and Survey Based Data, Brussels, VUB Press, Jobard F., Lévy R., Lamberth J., Névanen S., 2012, Measuring appareance- based discrimination. An analysis of identity checks in Paris, Population- E, 67, 3, Lévy R., Mayer M., Haverkamp R., 2003, Will Electronic Monitoring have a Future in Europe?, Freiburg- im- Breisgau, Edition Iuscrim, Piazza P., Laniel L., 2008, The INES Biometric Card and the Politics of National Identity Assignment in France, in Benett C., Lyon D., (eds.), Playing the Identity Card. Surveillance, Security and Identification in Global Perspective, London- New- York, Routledge. Robert Ph., Zauberman R., et al., 2010, The Victim s Decision to Report Offenses to the Police in France : Stating Losses or Expressing Attitudes, International Review of Victimology, 17,

333 CRG (Centre de recherche en gestion) École Polytechnique- CNRS Discipline: management, economics, psychology & sociology. Date of Creation: 1972, 1981 first research unit to be CNRS affiliated in management discipline. Since 2004, CRG is the management component of UMR 7176 PREG (Pole de Recherche en Economie et Gestion). Staff: 10 Permanent researchers, 14 associated researchers, 25 PhD students, and 1 post doctorate student, 3 research engineers and 5 administrative staff. Research themes: for 40 years, the CRG as played a leading role in the development of French management academic community as the recognition of management research in professional environment. Its research identity can be define by (i) a large and deep scope of theoretic investigations in social and human disciplines (from organization theory, economics, clinical psychology to sociology of work or situated action theory), and (ii) a problem oriented and collaborative research approach deeply rooted in the contemporary strategic questions of private as public organizations. This identity is highly recognized in the international academic community of Management Sciences, as an emblematic case of relevant research strategy. Ongoing CRG research is structured through 5 programs: (i) Innovation- based Competition & Design Systems Dynamics; (ii) Business strategies, market structure and regulation policies; (iii) Economic effects and organizational impact of the development of information and communication technologies and Internet. (iv) The Territorial Dynamics and New Organizational Configuration; (v) Multicultural management approaches Academic publications and academic developments: CRG researchers published on the period 125 articles in peer- reviewed journals (78 in English), 28 Books, Edited books or special issues of journals, 107 chapters into collective books, 21 doctoral thesis or HDR, 297 communications in academic conferences. Awards: 2012, best research book (FNEGE Fondation nationale pour l enseignement de la gestion et European Foundation for Management Development); 2011: Syntec prize; 2010: the AREA thesis prize was awarded to CRG doctorate; 2008 best research paper, HEC foundation; 2007 Stephan Shrader Best Paper Award Finalist, division technology and innovation management Academy Of Management, and Academy of Management Best Paper Proceedings, Editorial activities: Researchers serve as reviewers or editors in top international journals and are members of executive committees in many academic associations. PJ Benghozi, H. Dumez and C. Midler are members of AERES evaluation committees. PJ Benghozi is former president of the French Management Society (SFM), former president of the Economics and Management Section (37) of the National Committee for Scientific Research, former member of the Scientific Council, Paris Dauphine University. Interaction with firms: Interaction with professional environments, applying problem- based approaches, has always been one of the research methodologies favored by the CRG. This explains the density of exchanges with professional milieu (both private and public) in a variety of forms: research partnerships; Cifre grants; teaching and research chairs (3 chairs at present with Orange, Renault, Valéo, Safran, Seb, Air Liquide). C. Midler is a Cercle de l Entreprise member, the think tank of the French Institut de l Entreprise. The École de Paris du Management, founded in 1993 by Michel Berry, former CRG director, and supported by the CRG since then, is a forum for discussion 39

334 between management researchers and practitioners within the framework of permanent seminars and conferences. Education: The CRG is responsible for management doctorate training at École Polytechnique. CRG researchers are highly involved in national training programs for the best doctoral candidates in the discipline: CEFAG & CDEG. The CRG has a longstanding involvement in 5 Masters programs, in partnership with universities and major engineering as business schools : Projet Innovation Conception, Industrie des Réseaux et Économie Numérique, Gestion et Dynamique des Organisations, Management des organisations et politiques publiques, Ingénierie de l'innovation Technologique. CRG contribution to the project 3S: The CRG research programs will be heavily involved in axe 2, but will also contribute to other axes. CRG will bring its expertise on the different themes as its deep and diversified empirical connections in professional environment. On the methodological side, CRG will bring its deeply rooted expertise in cooperative research within innovation projects and more specifically in emblematic innovative projects as electric mobility or the Innovation Lab that will be developed in the Saclay environment. Researchers involved in the project DR CNRS Pr MCF Ingénieur de recherche Doctorants Permanent researchers : Romain Beaume (Fellow Ecole polytechnique) Pierre- Jean Benghozi (Directeur de Recherche CNRS) Florence Charue- Duboc (Directeur de Recherche CNRS) Hervé Dumez (Directeur de Recherche CNRS) Alain Jeunemaître (Directeur de Recherche CNRS) Christophe Midler (Directeur de Recherche CNRS) 2 Research Associates Sylvain Lenfle (maître de Conférence - Université de Cergy- Pontoise) Rémi Maniak (maître de Conférence - Télécom ParisTech) 8 PhD students Bo Chen Julie Fabbri Julie Hardouin Nathalie Herberth Marie Le Pellec Felix von Pechmann Romaric Servajean Thorsten Sobe 40

335 DANTE (Laboratoire de Droit des Affaires et Nouvelles Technologies) EA 4498 (Université de Versailles- Saint- Quentin- en- Yvelines) The Research Unit of Business Law and New Technologies (DANTE) created in 1997 is formed by all the faculty members of private law as well as legal historians. Besides these tenured graduated academics, it includes many researchers. Doctors, PhD students and practitioners with a rich and recognized research and publishing background and who have chosen to join the laboratory because of its influence in France and internationally. With more than a hundred members, the laboratory DANTE leads many projects, either through events and transversal publications or inside the teams that form this structure, in conjunction with an attractive Masters courses offering. The Unit researches as well as the Masters degrees are mainly directed toward the business and the law applicable to it, in France, Europe and internationally. Alongside the traditional strengths such the new technologies (Team Law and Technology - Intellectual property laws and New technologies of the information and the communication) and the law of contracts and competition (Team Contracts and market), there are two other teams specialized in Law arbitration and Attractiveness of business law. Very active in the collective research programs, the DANTE has obtained several research contracts (in particular contracts ANR Lise and Prosody and contract with the GIP- Justice) in partnership with other french or foreign universities and institutions. Most of them have a multidisciplinary approach, involving, amongst others, computer, sociologists, economists... CR CNRS Pr Maître de conférences Ingénieur de recherche Post- Doctorant Doctorants Liste nominative des chercheurs de chaque laboratoire impliqués dans le projet, en indiquant leur discipline, leur statut, l'axe (ou les axes éventuellement) dans lequel ils vont mettre en œuvre le projet : V.L. Benabou, Professeur, (Intellectual property laws and New technologies of the information and the communication - droit de la propriété intellectuelle et des nouvelles technologies de l'information et de la communication) - Axis 2 M. Chagny, Professeur (droit de la concurrence - Competition law) - Axis 2 M.E. Boursier, Maître de conférences (droit pénal - Criminal law) Axis 1 M. Clément- Fontaine, Maître de conférences- HDR (Intellectual property laws and New technologies of the information and the communication - droit de la propriété intellectuelle et des nouvelles technologies de l'information et de la communication)- Axis 2 et 3 M. de Fontmichel, Maître de conférences (Business law - droit des affaires) - Axis 4 N. Reboul Maubin, Maître de conférences- HDR (Private law - droit privé) - Axis 4 B. Rutherford Iglesias, Ingénieur de recherche - Axis 4 Bibliographie - Projet ANR LISE (ANR- 07- SESU ) «Dommage et technique» , piloté par l INRIA, avec Supelec, LORIA, Université de Caen, DANTE. 41

336 - Projet CCP- Prosodie (ANR- AA- PPPP- 00) «Les communautés de pratique en ligne» , piloté par l'institut Télécom Bretagne, avec Institut Mines Télécom, Univ. Nice- Sophia Antipolis, UVSQ, Université technologique de Compiègne, INRIA (LORIA), DANTE. - Ouvrage: Manuel de Droit pénal des affaires internationales, contrat d édition en cours, Lextenso Editions Benabou V.L., 2011, The Chase (P2P), in Stamatoudi I., (dir.), Copyright Enforcement in the Cyberspace, Brussels, Kluwer. Clément- Fontaine M., 2013, Les communautés épistémiques en ligne, Revue Internationale de Droit d'auteur (RIDA) (à paraître). 42

337 EST (équipe GHDSO) Université Paris Sud EST «Études sur les sciences et les techniques» is a research unit of the University Paris Sud (EA 1610). The researches carried out in the unit are devoted to the transmission and circulation of scientific knowledge from an historical point of view, either didactical or ethical. Within EST, the GHDSO group conducts researches on social and cultural history of sciences and technology. More precisely, the group focuses on Scientific and technical knowledge, Actors, Places and Publics in nineteenth and twentieth century France through three main entries : history of scientific and technical teaching, history of scientific periodicals and their publics, sciences in society since World War Two. CR CNRS Pr MCF Ingénieur de recherche Post- doctorant Doctorants Liste nominative des 7 chercheurs pour l axe 3 : Liliane Alfonsi, MCF, histoire des sciences et des techniques Delphine Berdah, MCF, histoire des sciences et des techniques Renaud d Enfert, MCF, histoire des sciences et des techniques Virginie Fonteneau, MCF, histoire des sciences et des techniques, Hélène Gispert, PR, histoire des sciences et des techniques Annick Jacq, CR CNRS, biologie, histoire de la biologie Jacques Robinet, doctorant contractuel, histoire des sciences Norbert Verdier, MCF, histoire des sciences et des techniques Publications GHDSO d'enfert R., Fonteneau V., (dir.), 2011, Espaces de l'enseignement scientifique et technique Acteurs, savoirs, institutions, XVII e - XX e siècles, Paris, Hermann. d Enfert R., 2008, Une revue «scientifique et industrielle» militante : L enseignement professionnel, , in Bret, Chatzis, Perez, Gispert H., (dir.), 2011, Quels publics, pour quelles mathématiques?, Rencontre du CIRM mrs.fr/liste_rencontre/programmes/resumesgispert.pdf. Gispert H., Hulin N., Robic M.C., (dir.), 2007, Science et enseignement. L exemple de la grande réforme des programmes du lycée au début du XX e siècle, Paris, Vuibert/INRP. Verdier N., 2013 (accepté à paraître), Éditer puis vendre des mathématiques avec la maison Bachelier ( ), Revue d Histoire des Mathématiques. Verdier N., 2012, Panthéons, journaux et salons à Berlin, Londres ou Paris : fabriquer des réseaux de sociabilité savante, in Thoizet É., Wanlin N., Weber A.G., Panthéons littéraires et savants XIX e - XX e siècles, Amiens, Artois Presses Université,

338 GREGHEC (Innovation & Entrepreneurship - Society and Organizations) HEC- CNRS GREGHEC, awarded top grades from AERES in March 2009 (the unit's overall rating was A+), was founded in 2004 and was granted UMR (2959) status in As HEC's academic research center, it is composed of select faculty members (those who are directly involved in research activities) and of PhD students. GREGHEC takes part to the ISIS project through two research teams: Society and Organization (SnO) and Innovation and Entrepreneurship (I&E) Innovation & Entrepreneurship team presentation The I&E team is a multidisciplinary research group (management disciplines, economics, law, psychology) created in It counts 25 members (assistant, associate and full professor) and 10 doctoral students (25% of GREGHEC resources). Research themes: (i) management of innovation and entrepreneurship (12 researchers), (ii) growth strategies (5), (iii) corporate ecological and social responsibility (4), (iv) economics and innovation (4), (v) organizational structure, learning and performance (5). More precisely, the subjects addressed are: (i) how particular situations lead to choosing alliances over other modes of growth, complementarity of partners knowledge specifically between firms and university scientist researchers, (ii) creativity and idea generation management, (iii) creative Industries management such as Design, (iv) management of highly uncertain projects, (v) innovation through business models especially in emerging economies, (vi) the conditions under which firms form relationships with and learn from external sources of knowledge and how they translate this learning into technical innovations, (vii) exploration management, (viii) technological innovation, (ix) entrepreneurs motivation and the economic effects of entrepreneurship, (x) the strategic logic and the value creation mechanism of Private Equity investments and venture Capital (the provision in a dynamic agency model, the comparison of the VC success in USA and Europe). Academic publications : Researchers have since 2006 published: (i) 100 articles in peer reviewed journal of which 43 in journals such as Academy of Management Journal, Journal of Marketing, Management Sciences, Organization Sciences, Strategic Management Journal, Journal of Management Studies, Journal of Product Innovation Management, Organization Studies, Research Policy ), (ii) 9 books and (iii) 56 books chapters. Editorial activity : Researchers serve as reviewers or editors in top international journals and are members of executive committees in many academic associations (see vitae). Their work was acknowledged many times through awards (Best conference papers, Best doctoral dissertation, Syntec Management Consulting best article. T. Astebro is listed in top 3.0 th percentile of downloaded working papers at Social Science Research Network ( International Orientation: 60% of GREGHEC members are strongly embedded in international context (education, previous professional experience, citizenship ). 48 PHD degree from HEC work outside of France. GREGHEC members production is embedded in an international context: 70 articles (on 110) published in peer reviewed journals are with international co- authors. 96 articles are published in international journals. 40 chapters are in international books. Exploitation of results: 7 chairs and centres associated with innovation are sponsored by companies : (i) Innovation & Globalization (Orange), (ii) Innovation Management in Aeronautics, Aerospace, Defense and Security (SAFRAN), (iii) New Business Models in Energy Chair (EDF), (iv) Innovation & Entrepreneuriat (Paris Chamber of Commerce), (v) Digital Innovation for 44

339 Business (Free - Meetic - Pixmania Group - PriceMinister - vente- privee.com), (vi) Google@hec, (vii) Private Equity Observatory- Buyout Center. Researchers working on entrepreneurship can rely on the centre of entrepreneurship and on HEC startup in which two affiliate professors are involved and that represent a rich field for experimentation and research. Higher education: Several education programs address innovation & entrepreneurship and are taught by team members: electives in master program and MBA, master degree (Project, Innovation and design in collaboration with École Polytechnique and TelecomParistech), specialized master degree (Entrepreneurship, Project management, New Technologies with TelecomParisTech), major in Exec.MBA, lessons at the incubator and tutoring for company creation, certificates (100 hours specialization) in Innovation Management in Aeronautics and in digital business. HEC offers several programs for entrepreneurs. A program for entrepreneurs on management skills and entrepreneurship (Challenge+) for 36 entrepreneurs on average per year (400 alumni, 250 launched a high tech venture). They created jobs (10 staff on average). The average turnover is 2K. HEC incubator has been hosting 60 ventures since its creation in 2007 (Master degree, MBA and alumni). On top of the permanent faculty, 6 affiliate professors are highly involved in the teaching of entrepreneurship and innovation in various programs. Since 2006, 60 doctoral dissertations were defended. 150 HEC PhDs are currently active in education and research. Contribution to ISIS: I&E team will bring its skills in strategic management, new product development, entrepreneurship and economics, its strong relationships with firms and its high involvement in the international research community. ISIS will build on the strong relationship with the CRG already consisting of a common seminar in innovation management and a common master degree in innovation. Most importantly, it will bring an innovative field of experimentation through Challenge plus and the Entrepreneurship Center and its involvement in several incubators. I&E team will contribute to axe 2 and to a less extent to axe 3. Table indicating the status and number of involved professors and researchers in ISIS CR CNRS Full Professor Associate Assitant professors Affiliate professors Doctorants Paris, Thomas Phelps, Corey Détrie, Jean- Pierre Astebro, Thomas Jouini, Sihem Pacheco Almeida, Gonzalo Sommer, Svenja Dahlin, Kristina Di Stefano, Giada de Hoos, Florian Mindruta, Denisa Yong, Kevyn Iselin, Frédéric Bazzazian, Navid Krieger, Etienne Shyti, Anisa Micaelli, Isabelle Society and Organizations presentation The Centre for research on Society and Organizations (SnO) has been built around various competences, with a view to tackling the challenges posed by society to organizations, and those posed by organizations to society. SnO is an inter- disciplinary research center within the HEC Paris School of Management which aims to examine society- related issues that organizations face, 45

340 organizational issues within society, and the recursive relationship between the two. These issues are brought to light within the context of the increasing legitimacy of management as a discipline and the critique that current socio- economic models are inadequate to address these contemporary issues. By focusing on the societal role of management as a discipline, SnO aims to contribute towards a furtherance of our understanding of the socio- economic context in which we are embedded, as well as the organizations that are shaped by and are shaping this context. Society can be understood as the broad interactional space in which ties between individuals and groups of individuals are formed, developed and disintegrated. This social space is a locus of interactions, exchanges and conflicts within a community of people characterized by shared rules, norms and values. An Organization, on the other hand, can be defined as a structured group of actors, whose action is coordinated, interdependent and based on formal and informal rules. The primary purpose of an organization can be oriented towards economic (profit), institutional, moral and political motives, or towards a combination of these. Thus, organizations encompass public and private companies, professional associations, non- governmental organizations, regulatory agencies and even virtual communities, to name some. Given that organizational boundaries appear more and more blurred and fuzzy, the investigation of such provides us with a key research challenge. The objective of SnO is to develop research projects, to present rigorous empirical results and to promote analytical models designed to further our understanding of various contemporary issues. Our approach combines a broad range of methods (both quantitative and qualitative) tailored to the phenomena under study and uses theoretical lenses coming from various disciplines including: economics, sociology, psychology, philosophy and history in combination with our management focus. SnO is sponsored by the HEC Foundation. Table indicating the status and number of involved professors and researchers in ISIS Pr MCF Doctorants Name Status Discipline Fields of Interest DURAND Rodolphe QUELIN Bertrand RAMIREZ Carlos ARJALIES Diane- Laure KREMP Pierre- Antoine Professor Strategy and Business Policy Competitive advantage/conformity Professor Strategy and Business Policy Economics of Organization, PPP Associate professor Accounting and Management Control Assistant professor Accounting and Management Control Norms and soft laws Non- Financial Performance Measurement Systems. Assistant professor Strategy and Business Policy Sociology of Organizations MANI Dalhia Assistant professor Strategy and Business Policy Economic Sociology. MEHRPOUYA Afshin Assistant professor Accounting and Management Control Socially responsible investments. 46

341 CLEMENTE Marco JACQUEMINET Anne KIVLENIECE Ilze PAOLELLA Lionel TOUBOUL SAMUEL PhD student Strategic Management Institutional Theory PhD student Strategic Management Corporate Social Responsibility PhD student Strategic Management Public- private interorganizational arrangements PhD student Strategic Management Categories PhD student Strategic Management Corporate Social Responsibility Two foreign affiliate assistant professor, from Bocconi (Italy) and Ivey (Canada), are too involved in the project : - - Julien Jourdan (general management, specialized on management and technology institutional theory) Jean- Philippe Vergne (general management, specialized on organizational and industry evolution). Publications Astebro T., Thompson P., 2011, Entrepreneurs: Jacks of All Trades or Hobos?, Research Policy, 40, 5, Midler C., Ben Mahmoud- Jouini S., Maniak R., 2012, Le management des innovations de rupture : nouveaux enjeux, nouvelles pratiques, Paris, Éditions de l École Polytechnique. Mindruta D., 2008, Value Creation in University- Firm Research Collaborations: A Matching Approach, London, Academy of Management Best Papers Proceedings. Paris T., Veltz P., 2010, L'économie de la connaissance et ses territoires, Paris, Hermann. Phelps C., Yang H., Steensma K., 2010, Learning from what Others have Learned from You: The Effects of Knowledge Spillovers on Originating Firms, Academy of Management Journal, 53, 2, Sommer S., Loch C.H., Dong J., 2009, Managing Complexity and Unforeseeable Uncertainty in Startup Companies: an Empirical Study, Organization Science, 20, 1,

342 IDHE- Cachan (Institutions et dynamiques historiques de l économie) UMR 8533, École Normale Supérieure de Cachan Université d Evry CNRS) The IDHE- Cachan is a mixed unit of the CNRS and the ENS- Cachan. It is directed by Claude Didry (Directeur de recherche, CNRS) and was rated A+ by the AERES in November It gathers researchers from different disciplines: Till 2008, the main themes researched in this laboratory were «work and labor dynamics», «firms, products and territories», «financial institutions and markets» and «knowledge and law of public interventions». For the forthcoming period, the IDHE will introduce a new theme which it already started developing since its last evaluation: «knowledge, capabilities and innovation». IDHE (Institutions and Historical Dynamics of Economics) was set up in It is a joint research center involving CNRS, ENS Cachan, Université d Évry and Universities of Paris 1, 8 and 10. It brings together academics and CNRS researchers from different disciplines: economics, sociology, law, history and business administration. It is composed of 64 members and 160 doctoral students. Its scope is interdisciplinary research in Human and Social Sciences. It operates from five sites in Paris and its région: Université d Évry, Université Paris 1 Panthéon- Sorbonne, Université Paris 8- Vincennes Saint- Denis, Université Paris Ouest- Nanterre- La Défense and ENS Cachan. In this project, only IDHE's ENS Cachan (located on ENS Cachan's campus, please consult cachan.fr) and Université d Évry will be involved as partners. The first research team is composed of 13 researchers and professors, 3 post- doctoral researchers, 7 associate researchers, 3 research assistants and engineers, and 10 doctoral students. IDHE's scientific project mobilizes different disciplines around five trans- disciplinary research areas: 1) Work, wage systems, and employment dynamics ; 2) Businesses, products and territories ; 3) Institutions and financial markets ; 4) Knowledge, law, and public policies; and 5) knowledge, capabilities and innovation. IDHE's ENS Cachan arm focuses on three of the five areas sanctioned by the five- year research program currently under way within IDHE. The Cachan team more particularly specializes in six areas: 1) Sociology of labor relations; 2) Economic sociology; 3) Sociology of the entrepreneur; 4) Economics of conventions; 5) work and innovation; and 6) Economic history. IDHE, awarded excellent ratings by AERES in 2009 (Overall rating was A+), is a partner of EQUIPEX CASD (Center for Secure Acess to Data) which is coordinated by ENSAE in partnership with HEC and the École Polytechnique, and the DIM IS2IT, Innovation, sciences, techniques, société. Two researchers belonging to IDHE Cachan's arm were awarded the CNRS bronze medal: Claude Didry in 1997 and Pierre- Paul Zalio in Besides, Pierre- Paul Zalio was named a member of the Institut Universitaire de France (IUF) in Concerning Higher Education, the members of IDHE are involved in teaching activities in the ENS- Cachan in two departments (Social- Sciences, Economics and Business administration) which are implicated in different Masters. Several members participate to the conception of a new master on quantification in social- sciences at the level of Paris Saclay University. IDHE Cachan leads an integrated European program that is part of the 6th FP (Framework Program for Research and Technological Development), entitled CAPRIGHT «Resources, rights and capabilities: in search of social foundations for Europe» ( ) and also co- ordinates two research projects funded by France's Agence Nationale pour la Recherche (ANR, National Agency for Research), entitled «Social support for entrepreneurship» and «Production of knowledge: portrait of the researcher as a salaried worker». 48

343 IDHE- Cachan s contribution to the ISIS project is mainly centered on WP 3 but also on WP 1 and 2. IDHE- Evry s contribution is centered on WP2, but researchers will also contribute to WP3. Surname First Position Domain Partner Organization Contribution name or in the company project BESSY Christian CR Economics IDHE ENS Cachan Coordinator, WP1, 3 DIDRY Claude DR Sociology IDHE ENS Cachan WP3 BOISARD Pierre CR Sociology IDHE ENS Cachan WP3 MIAS Arnaud MCF Sociology IDHE ENS Cachan WP1, 3 BETHOUX Elodie MCF Sociologie IDHE ENS Cachan WP3 Da COSTA Isabel CR Economics IDHE ENS Cachan WP2, 3 HARARI Hugo MCF Busin. admin. IDHE ENS Cachan WP1, 2 JOBERT Annette DR Sociology IDHE ENS Cachan WP3 PARDI Tommaso CR Sociology IDHE ENS Cachan WP2, 3 SÉPARI Sabine MCF Busin. admin. IDHE ENS Cachan WP2 VINCENSINI Caroline MCF Economics IDHE ENS Cachan WP3 YOUNES Dima Post- doc Sociology IDHE ENS Cachan WP3 CHAMPIN Hervé PhD Sociology IDHE ENS Cachan WP2 HILDERMEIER Julia PhD Sociology IDHE ENS Cachan WP2 PERDONCIN Anton PhD Sociology IDHE ENS Cachan WP1 INDUKAEV Andrey PhD Sociology IDHE ENS Cachan WP2 VIEGAS Stéphanie PhD Sociology IDHE ENS- Cachan WP3 LOUBET J.- Louis PU Histoire IDHE Univ. d Évry WP2 LE BOT Florent PRAG Histoire IDHE Univ. d Évry WP2, 3 HATZFELD Nicolas PU Histoire IDHE Univ. d Évry WP 2 BENOÎT Serge MCF Histoire IDHE Univ. d Évry WP 2 MICHEL Alain P. MCF Histoire IDHE Univ. d Évry WP2 Publications Bessy C., Brousseau E., 1998, Licensing of Technology: Various Contracts for Diverse Transactions, International Review of Law and Economics, 18, Didry C., Jobert A., 2010, L entreprise en restructuration, Rennes, Presses Universitaires de Rennes, Collection «Économie et Société». Pardi T., Jullien B., 2012, In the Name of Consumer: The Social Construction of Innovation in the European Automobile Industry and its Political Consequences, European Review of Industrial Economics and Policy. Béthoux E., Didry C., Mias A., 2007, What Codes of Conduct Tell Us: Corporate Social Responsibility and the Nature of the Multinational Corporation, Corporate Governance: an International Review, 15, 1, Younès D., 2012, Why is Intersectoral Cooperation Difficult to Maintain? Insights from French Cluster Policy, Environment and Planning C, 30, 5, Co- Publications Bessy C., Delpeuch T., Pélisse J., (dir.), 2011, Droit et régulations des activités économiques : perspectives sociologiques et institutionnalistes, Paris, LGDJ- Lextenso Éditions. Number of involved researchers: DR, CR et MCF: 11 (École Normale Supérieure de Cachan) and 5 (Université d Évry) Post- doc: 1 PhD students: 5 49

344 ISP- CACHAN (Institut des Sciences Sociales du Politique) UMR 7220 Ens Cachan - CNRS ISP, which was evaluated by AERES in 2008 and obtained an A+ grade, was created in 2006 through the merging of LASP (Paris 10) and of GAPP (ENS Cachan). Its main research areas are democracy, public policy and sociology of law. Its staff includes political scientists, sociologists and historians, operating from two sites University Paris 10 Nanterre, and ENS Cachan. ISP focuses on four main priorities two of which are included in our research project, and mainly involve ENS Cachan researchers. ENS Cachan s ISP team is widely acknowledged, both at a national and international level, as a leading research team in the sociology of law and justice, as exemplified by the quality of its publications (in the best journals of social sciences in their field : British Journal of Criminology, Déviance et Société, Droit et Cultures, Droit et Société, L Année Sociologique ), by its role as a founding member of several networks (including Droit et Société Network), by the intellectual debates it has contributed to launching, as well as by its training programs focusing on the methodology of research. The laboratory includes several leading researchers in the field of the sociology of law and justice such as Benoit Bastard, Jacques Commaille, Laurence Dumoulin, Patrice Duran or Claire de Galembert. Their research activities are articulated around two priorities: 1) Norms and political regulation; and 2) Public action and political power. It contributed to training many researchers who have also become key players in the sociology of law and justice, and with whom it maintains fruitful collaborations (at University Paris 13, EHESS, and ENS- Ulm, for example). The scientific quality and energy of the ENS Cachan team can be appraised by such indicators as (1) the originality and the diversity of obtained results (over the period : 30 articles in national and international peer- reviewed scientific journals, 13 books, collective books or thematic issues), and (2) the fact that, both nationally and internationally, specialists of law as well as specialists of political science and of sociology have shown great interest in these results. These results can be summarized in three subsets: 1) Production and implementation of legal devices; 2) Transformations of the public policies of justice and 3) Expertise and new technologies (Concerning topics that will constitute the core of this project, the ENS Cachan team can boast results dealing with the place of experts in the processes of elaboration of public decisions, as well as with new technologies (Information and Communication Technologies, and monitoring technologies). Besides, together with the IDHE, the ISP has been involved in the setting up of a specialized technical infrastructure: the Emile Durkheim research library of social sciences, on the site of Cachan. The laboratory supports the quantitative processing of data collected through investigations; it houses in its premises the journal Droit et Société which is acknowledged as one of the top- ranked journals in social sciences. Members of ISP are involved in several masters: Master of Sociology (ENS Cachan) but also Masters of Political Science (IEP Grenoble) and Masters of Law (Paris 2, Grenoble ). They are involved in the training of judges (Ecole Nationale de la Magistrature), lawyers and social workers. ENS Cachan's ISP research group involved in the project DR CNRS CR CNRS PhD Students ISP contribution to this project consists in 3 research fellows in axe 4: Benoit Bastard (CNRS), Laurence Dumoulin (CNRS), Aude Leroy (doctorante ENAP- ISP, ENS Cachan). 50

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346 LSQ (laboratoire de sociologie quantitative) CREST- LSQ, GRECSTA, UMR ENSAE- PARISTECH Research topics at the LSQ- CREST include social structures and individual behavior; integration and discrimination; sociology of quantification and methodological issues of quantification. Most research efforts at LSQ make use of quantitative methods, generally combined with qualitative methods. LSQ researchers belong to diverse theoretical schools, such as methodological individualism, constructivistic structuralism and pragmatic sociology of action. They are used to confronting their points of view, their methods and their results, either during the seminars organized by the laboratory, or whilst jointly conducting empirical research. All LSQ researchers value methodological rigour, which makes it possible to share and discuss ideas in a fruitful fashion. LSQ researchers have published numerous books, along with numerous research articles in leading French and international journals such as Actes de la Recherche en Sciences Sociales, American Sociological Review, Économie et Statistique, European Sociological Review, Revue Française de Sociologie, Social Studies of Science, Sociologie, Sociologie du Travail. LSQ is in charge of CREST's sociology seminar. LSQ is a partner of the EQUIPEX DIME- SHS ( Données, Infrastructures, Méthodes d'enquêtes en Sciences humaines et sociales co- ordinated by Sciences- Po) and the GENES is a partner of EQUIPEX CASD, an infrastructure project that is aimed at developing a center for secure remote access to confidential data (CASD), which will be made available for French researchers in social sciences and economics. CASD will provide secure access to highly detailed individual data, making it possible to process highly detailed data. Members of the LSQ who are involved in the project Status Status at LSQ Number DR CNRS Associate member 1 CR CNRS Associate member 3 CR Sciences Po Associate member 1 MCF Associate member 1 Admin. INSEE Full time member 3 Admin. INSEE Associate member 4 Post doc Associate member 1 Name Christian name Status Status at LSQ Action BODIER Marceline Admin. INSEE Associate member 1.3 BUGEJA Fanny MCF Associate member 1.2 BROUSSE Cécile Admin. INSEE Associate member 1.2 COULANGEON Philippe DR CNRS Associate member 1.1 DUVAL Julien CR CNRS Associate member 1.1 GODECHOT Olivier CR CNRS Associate member 1.1 GOLLAC Michel Admin. INSEE Full time member 1.3 GOUX Dominique Admin. INSEE Full time member 1.1 LESNARD Laurent CR CNRS Associate member 1.1 MERON Monique Admin. INSEE Associate member 1.2 PETEV Ivaylo Post doc Associate member 1.1, 1.2 SAFI Mirna CR Sc-Po Associate member 1.1 STEHLÉ Juliette Admin. INSEE Associate member 1.1 THÉVENOT Laurent Admin. INSEE Full time member

347 Publications Godechot O., 2011, La formation des relations académiques au sein de l'ehess, Histoire & Mesure, 26, 2, Godechot O., 2011, How did the Neoclassical Paradigm Conquer a Multi- disciplinary Research Institution?, Revue de la Régulation, 10. Godechot O., Louvet A., 2010, Academic Inbreeding: An Evaluation, La Vie des Idées, 24 pages. Gollac M., (dir.), 2012, Mesurer les facteurs psychosociaux de risque au travail pour les maîtriser, rapport pour le ministre du Travail, de l Emploi et de la Santé. Thevenot L., 2011, Conventions for Measuring and Questioning Policies. The Case of 50 Years of Policies Evaluations through a Statistical Survey, Historical Social Research, Special issue edited by Rainer Diaz- Bone & Robert Salais on Conventions and Institutions from a Historical Perspective (translation by Susan Taponier), 36, 4, Thevenot L., coll. Monso O., 2010, Les questionnements sur la société française pendant quarante ans d enquêtes, Formation et Qualification Professionnelle, Économie et Statistique,

348 LTCI (Laboratoire Traitement et Communication de l Information) (UMR Telecom Paristech, Département de Sciences Économiques et sociales / CNRS) Created in the 1994, the department of Economics and Social Sciences is part of the LTCI (UMR 5141). It includes 30 permanent researchers (5 belonging to the CNRS), 29 PhD students, 23 post- doctoral fellows and X affiliated professors and associate professors. It is highly multi- disciplinary - economics, management sciences, sociology, information and communication sciences, cognitive psychology and ergonomics and focusing on economic and social issues related with the development of ICT, at three levels: The link between innovation and regulation (macro level). The shifting boundaries between content producers and amateurs/consumers; Detailed empirical studies of mediated interactions at the micro level. The AERES committee noted how the department was «analyzing with highly complementary perspectives shared issues about innovation, regulation and use of IT, Telecom ParisTech being the most relevant place in the French scientific landscape to tackle this issue» (AERES report, p. 38), and gave it an A notation. Academic publications, : 27 books and edited collections (including 4 in English), 67 articles in international peer- reviewed journals, 115 articles in French peer- reviewed journals, 35 chapters in collective books (including 16 in English) The total is 234 publications in all, i.e. about 1.5 articles or books per year and per permanent researcher. Exploitation of results Annual contractual research budget of 2 M, and two research chairs Innovation et regulation, et Modelisation of Imaginaries, with the active participation of several leading industrial partners (Orange, Dassault Systèmes, Alcatel Lucent, Peugeot, Ubisoft). The department is also involved in two joint research laboratories, one with Alcatel Lucent, and the other with Renault under the Paistech frame. Higher education 1 st year courses (economy, human fundamentals) and master courses (finance, project management, strategy, IT management, design ). Several courses are also provided in the formation of the Mines Telecom Corps engineers Several Master 2 tracks (M2 Design, medias, technologies with Paris 1 and l ENSI), M2 IREN (Network Industries & Digital Economy) with Ecole Polytechnique, Supelec, Paris West - Nanterre La Défense, Paris- Sud 11, Pierre et Marie Curie) et specialized masteres ( Technological Project Management with ESSEC, New Technologies and Management with HEC). Contribution to the ISIS project The SES department at Telecom Paristech will bring to the LISI its ICT perspective. It will contribute to the ISIS research axes 2 and 4. The SES department will also bring its specific interdisciplinary 54

349 perspective and ability to move from general economic questions to ethnographic studies of actual innovative contexts of use. Table indicating the status and number of involved researchers CR CNRS Pr MCF Ingénieur de recherche Post- doctorant Doctorants Valérie Beaudouin, MCF, Sociology, axis 2 Jérome Denis, MCF, Sociology, axis 3 Valérie Fernandez, Prof., Management Sciences, axis 2 Thomas Houy, MCF, Management Sciences, axis 2 Christian Licoppe, Prof., Sociology, axis 4 Rémi Manyak, MCF, Management Sciences, axis 2 Maud Verdier, Post- doc, Anthropology, axis 4 55

350 PESOR (Pilotage Économique et Social des Organisations) EA3546 Université Paris- Sud Created in 1999, PESOR is the academic research center of University Paris- Sud 11. It brings together all the researchers of the University Paris- Sud 11 who work in management, located in different areas: Jean Monnet Faculty (Law, Economics and Management), IUT Sceaux, Sciences Faculty, Polytech Paris- Sud (engineers). 9 PR, 19 MCF, 1 associate researcher, 14 PhD students and 5 invited professors from several countries, work on management (organization, marketing, finance, human resources and accountability). The emergence of our research on the theme of innovation is relatively new and is related to recruitment these last years of colleagues working on innovation and the beginning of collaborative researches. Research is organized around four main axes: - Competitiveness clusters and Ecosystems - Intangible and knowledge assets - Open innovation and co- creation - Venture capital Academic publications, (innovation axis) 5 books (including in English), 3 collective books, 26 articles in peer- reviewed journals, 19 book chapters (including 9 in English), 1 HDR defence, 6 PhD defence The researchers of the team are frequently solicited as reviewers for international journals. They also serve as member of editorial board of the following journals: Finance Contrôle Stratégie, M@n@gement, Systèmes d Information et Management. They are also members of the executive committees of the following academic associations: Association Internationale de Management Stratégique (AIMS), Association Information et Management (AIM). Exploitation of results 1 Chair Intangible Assets Management. Every year, many communications in national and international conferences (AIMS, AIM, AGRH, EGOS, EURAM). Higher education The members of the PESOR are involved in teaching activities in the University Paris- Sud 11 at various levels: formation from BA (L1- L2- L3 generalist in management) to specialized Masters (M1- M2 in management) and PhD program. Our goal is to develop programs that combine research and teaching and we are responsible of two master programs : - Master 2 Pro/Research Strategies and Management (specialized on cluster management) - Master M2 Pro Marketing of Innovation (specialized on new product/service development) - Engineers (Polytech Paris- Sud) : course on Innovation and knowledge management The members of the PESOR are involved in local PhD program (different courses on methodology) and are engaged in national training program for doctoral candidates in management, Centre Doctoral Européen de Gestion (CDEG). 56

351 Contribution to the ISIS project PESOR will bring to the ISIS project its management perspective on innovation. It will contribute to the ISIS research axe 2. Table indicating the status and number of involved researchers Pr MCF Doctorants Julien Anfrun, Doctorant, axis 2 Andres Barreneche, Doctorant, axis 2 Ahmed Bounfour, PR, axis 2 Denis Chabault, MCF, axis 2 Sandra Charreire- Petit, PR, axis 2 Emmanuelle Dubocage, MCF, axis 2 Florence Durieux, PR, axis 2 Serge Edouard, MCF, axis 2 Géraldine Galindo, MCF, axis 2 Elodie Loubaresse, MCF, axis 2 Ahu Ozcan, Doctorante, axis 2 Publications Bounfour A., 2009, Organisational Capital, Modelling, Measuring, Contextualising, London- New York, Routledge. Bounfour A., Stahle P., 2008, Understanding Dynamics of Intellectual Capital of Nations, Journal of Intellectual Capital, 9, 2, Bounfour. A., 2007, Dynamic Capabilities and Finland s New Path, in Stahle P., (ed.), Five Steps for Finland s Future, Special Number Technology Review, 202, Chabault D., Hulin, 2011, Talents, innovation et pôles de compétitivité, la gestion des compétences, de nouveaux territoires, Paris, l Harmattan. Charreire- Petit S., Livieratos A., Papoulias B., 2011, An Open Innovation Growth Strategy for Knowledge- Intensive SMEs : The Case of and Advertising Agency, in de Pablos Heredero C., Lopez D., (eds.), Open Innovation at Firms and Public Administrations: Technologies fur Value Creation. Loubaresse E., 2008, Influence des caractéristiques des pilotes de réseaux locaux d organisations sur leurs rôles, Management International, 13, 1, Edouard S., 2011, Confiance institutionnelle et pérennité des écosystèmes d affaires, in Gratacap A., Le Flanchec A., (dir.), La confiance en gestion, Paris, De Boeck, Collection «Méthodes et Recherches»,

352 PRINTEMPS (Laboratoire Professions, Institutions, Temporalités ) UMR 8085, Université de Versailles Saint Quentin en Yvelines - CNRS The PRINTEMPS laboratory, since February 2011 directed by Jérôme Pélisse (maître de conferences en sociology, CNRS chair between 2010 and 2015), was evaluated by AERES in November 2008 and was subsequently awarded an overall A grade. PRINTEMPS specializes in sociology and demographic studies. It is jointly supervised by the University of Versailles- Saint- Quentin- en- Yvelines and by CNRS. Finally, members of Printemps are involved in 5 masters and notably one specialized on quantitative methods (Traitement des données quantitatives et démographie) and an other in research (sociology of profession and policy). Its main areas of research are the sociology of professions, the study of public involvements and policies, of careers, and of perceptions of time. Since its foundation in 1995, it has become one of France's most prestigious laboratories of sociology, both nationally and internationally. PRINTEMPS maintains a website and a blog ( Carnet de recherche du Printemps ) which describes the activities of its members and science in the making. It hosts three or four scientific events each year in order to promote recent publications. In June 2010, 80 researchers took part in a PRINTEMPS thematic conference entitled Sociology of Professional Groups: a Blossoming Scientific Field? The main purpose of this conference was to present three books, which had been published by members of the laboratory. In May 2011, the laboratory organized an international meeting on the work of Andrew Abbott (doctor honoris causa of the UVSQ): 120 researchers took part to this important meeting and methodological issues and professional perspectives developed by A. Abbott were notably analyzed. PRINTEMPS organized in 2012 a symposium on the ways in which social scientists grasp of globalization, and the lab will host a major conference in 2014 on Merton (including his sociology of science). The PRINTEMPS contribution to the social science s project appears in the very particular engagement of the laboratory in the fields of profession (and notably profession and career of scientific), science and technologies studies, quantification and measure, but also sociology of law. 1) sociology of scientific work, profession and career. Grounded in the historical topics developped for the creation of the laboratory (1995), the sociology of profession is the main and well- known area of research which contributes to the international rank of the PRINTEMPS. The renewal of the CNRS members of the laboratory since the end of 2000 s was assured notably with the recruitement of two young researchers specialized in Science and Technology Studies: M. Jouvenet (2007) and Arnaud Saint Martin (2011). They developped research about scientific carreer and profession of researcher in the domain of nanotechnology or spatial and aim at studying environnemental sciences or consciousness as a boundary object between natural sciences (and notably neurosciences) and social sciences. One postdoct (M. Hauchecorne) and a Phd student (R. Juston) are working today with them and a CNRS ingenieur coming from the LAL (Laboratoire d accélérateur linéaire) and starting a conversion disciplinary (microelectronics to the sociology of scientific professions) would probably join the PRINTEMPS to work on the activities, status and profession of CNRS ingenieur in the scientific laboratory of Saclay. Finally, with other researcher specialized in an other area (cultural or judicial professions) of the PRINTEMPS, the concept of carreer by project proposed by M. Jouvenet is one important track and analyze heuristic for scientific careers. 58

353 2) Methodology and notably quantitative methodology which take into account the modelisation of time, temporality and longitudinal logic is one other speciality of the PRINTEMPS. Demographs and some sociologists of the laboratory are specialized with this reasonning and technical methods. PRINTEMPS is also one main actor of a research project ending Spring 2013 on quantification of social and professional world through the classification of socio- economic categories in Europe (ANR Eurequa). The extension of this project is notably one important piece of the axe 1 of the project. 3) The last topic on which members of PRINTEMPS will contribute to the project will be the axis on law, justice, science and technology, and notably on the activity and identity of judicial forensic. J. Pélisse realized recently a research on these intermediate between science and justice and two phd (R. Juston and J. Minoc) are beginning on forensic and psychiatric/ psychologist forensic in the courts. Équipe CR CNRS Pr MCF Ingénieur de recherche Professeur associé Post- doctorant Doctorants Liste nominative des chercheurs de chaque laboratoire impliqués dans le projet : Philippe Cibois, Pr émérite UVSQ, sociologue, axe 1 Jérôme Deauvieau, MCF UVSQ, sociologue, axe 1 Eric Drais, Maître de conférence associé, sociologue, axe 3 Céline Dumoulin, Ingénieure de recherche UVSQ, sociologue, axe 1 Isabelle Fréchon, CR CNRS, démographe, axe 1 Morgan Jouvenet, CR CNRS, sociologue, axe 3 Jérôme Pélisse, MCF UVSQ (chaire CNRS), sociologue, axe 4 / axe 3 / axe 1 Nicolas Robette, MCF UVSQ, démographe, axe 1 Arnaud Saint Martin, CR CNRS, sociologue, axe 3 Olivia Samuel, MCF UVSQ, démographe, axe 1 Laurent Willemez, Pr UVSQ, sociologue, axe 4 Mathieu Hauchecorne, postdoctorant UVSQ (région IdF), sociologie, axe 3 Ruggero Iori, doctorant UVSQ (fléchage Labex 6S Printemps - Cesdip), sociologie, axe 1 Romain Juston, doctorant UVSQ (DIM IS²IT), sociologie, axe 4 Julien Kubiak, doctorant UVSQ, sociologie, axe 3 Julie Minoc, doctorante UVSQ (DIM Gestes), sociologie, axe 4 Publications significatives depuis

354 Deauvieau J., 2011, Est- il possible et souhaitable de traduire sous forme de probabilités un coefficient logit?, Bulletin de Méthodologie Sociologique, 112, Jouvenet M., 2013 (à paraître), Boundary Work between Research Communities. Culture and Power in a French Nanosciences and Nanotechnology Hub, Social Science Information, 52, 1. Jouvenet M., 2012, Nanosciences et nanotechnologies : une coopération modèle? Expériences et sens politique des scientifiques, Terrain, 58, Jouvenet M., 2011, Profession scientifique et instruments politiques. L impact du financement «sur projet» dans des laboratoires de nanosciences, Sociologie du Travail, 53, 2, Pélisse J., Bessy Ch., Delpeuch T., 2011, Droit et régulations des activités économiques, Paris, LGDJ, Collection «Recherche». Pélisse J., (dir.), Charrier E., Larchet K., Protais C., 2012, Des chiffres, des maux et des lettres. Une sociologie de l expertise judiciaire, Paris, Armand Colin, Collection «Recherche». Saint- Martin A., 2012, Autorité et grandeur savantes à travers les éloges funèbres de l Académie des sciences à la Belle Époque, Genèses. Sciences sociales et histoire, 87, Saint- Martin A., Lamy J., 2011, Pratiques et collectifs de la science en régimes, Revue d Histoire des Sciences, 64, 2,

355 STEF (ENS Cachan) The laboratory STEF main focus is the study the scientific and technological curriculum, taking into account both the evolution of science and technology, computerization issues and societal problems. STEF specificity is its ability to analyse issues in science and technology education, mutations of scientific and technical practices (research, development, specialized training and general education) in their relations with politics, economy and culture. STEF, with its roots in ENS Cachan and participation in the center d'alembert (Interdisciplinary Center for the Study of the Evolution of Ideas, Science and Technology - UPS) is sensitive to changes in over science and technology and can achieve good coverage of science and technology education and their current changes. Among these mutations, the laboratory places a major issue on computerization in its various dimensions: modifications in content, new forms of instrumentation, modifications frameworks for teachers and students... STEF also gives a prominent place to societal issues which the curricular changes must meet. Studies are focused on current or foreseeable curricular changes, whether these changes are in relation to changes in context, or likely to occur in a more or less distant horizon. It involves analyzing curriculum construction or design and to explore their conditions and consequences. It is not a simple upgrade or update content to teach, but a mapping between missions that can fulfill education and training in science and technology and changes in science and technology (education of citizens, users education, training specialists to their social responsibilities...). Table indicating the status and number of involved professors and researchers in ISIS Pr MCF ATER Doctorants Liste nominative des chercheurs : Virginie Albe, Didactique des sciences et des techniques, PU, axe 3 Volny Fages, Histoire des sciences et des techniques, ATER, axe 3 Pascale Hannoun, Didactique des sciences, MCF, axe 3 Bénédicte Hingant, Didactique des sciences, Doctorante, axe 3 Elie Rached, Didactique des sciences, Doctorant, axe 3 61

356 Summary partners, staff and financial contributions Nom du partenaire Affiliation Effectifs / Catégorie de personnel CESDIP CRG UVSQ CNRS Polytechnique CNRS - chercheurs et ens. chercheurs : 8 - ingénieurs : 2 - doctorants, post- doc : 5 - associate members : 2 - chercheurs et ens. chercheurs : 6 - ingénieur : 1 - doctorants, post- doc : 8 - associate member: 2 DANTE UVSQ chercheurs et ens. chercheurs : 6 - ingénieur : 1 - doctorants, post- doc : 1 EST (équipe GHDSO) IDHE / Equipe Cachan et Evry ISP Equipe ISP Cachan CREST Equipe LSQ LTCI Univ. Paris Sud ENS Cachan CNRS ENS Cachan CNRS ENSAE- ParisTech Télécom ParisTech CNRS - chercheurs et ens. chercheurs : 7 - Chercheurs et ens. chercheurs : 11 - doctorants, post- doc : 6 - chercheurs et ens. chercheurs : 2 - doctorants et post- doc : 1 - chercheurs et ens. chercheurs : 3 - doctorants et post- doc : 1 - associate member : 10 - chercheurs et ens. chercheurs : 6 - doctorants, post- doc :1 PESOR Univ. Paris Sud - chercheurs et ens. chercheurs : 8 - doctorants, post- doc : 3 PRINTEMPS GREGHEC Innovation and Entrepreneurship Society and Organisation STEF Nombre total de chercheurs impliqués : 154 chercheurs UVSQ CNRS HEC CNRS ENS Cachan IFE ISIS Saclay - chercheurs et ens. chercheurs : 9 - ingénieur : 1 - doctorants, post- doc : 5 - associate member : 1 - chercheurs et ens. chercheurs : 21 - doctorants, post- doc : 8 - associate member : 2 - chercheurs et ens. chercheurs : 2 - doctorants, post- doc : 3 chercheurs / ens.chercheurs/ing. : 95 postdoc / doc : 42 associés : 17 Apports financiers sur 3 ans : 128 ke (IE) + 50 ke (mi- tps AI 50%) + 9 ke (Summer School) + 51 ke (moitié doc fléchée UVSQ ) : 164 ke (ANR Travcher ) + 70ke (contrat ANSES ) + 24 ke (moitié IE stat ENS Cachan) + 15 ke (moitié Tech gestion ENS Cachan) (projet «Les barreaux face aux questions éthiques et à la communication électronique», GIP Mission de recherche Droit et justice, déposé janvier 2013) (contrat INSEE PCS en Europe, ) : 102 ke (1 doctorant) + 35ke (AAP UPsud)+ 30ke (Chaire) : 95 ke (ANR Eurequa ) ke (doc DIM IS²IT ) + 51 ke (moitié doc fleché UVSQ ) : moitié des chaires GDFSUEZ (40), Safran (60) et FT- Orange (60) + Fondation HEC (40). Total (minimum) des apports des partenaires au projet : euros 62

357 Réunion Comité Sciences du vivant Jouy, 14 mai 2013