MéditerranéeInfection Foundation

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1 MéditerranéeInfection Foundation Scientific Seminar Gordes, France 11 th, 12 th, 13 th October 2012 Prof. Didier Raoult, Marseille, France Foundation Director

2 -What is it? -Our goals The building Excellence in Marseille Infectiopole Sud -Our production - Our priorities

3 MEDITERRANEE INFECTION: Environment and Collaborations HIA Laveran, Marseille IRT, Lyon Morphology IHU BUILDING P3A3 Lab cell culture arthopods Drug screening IBISA Immunophenomics Proteomic IBiSA MicroBioGenomic Structural Genomics IRD Montpellier SOUTH NETWORK CHU, Nice Immunomonitoring SENEGAL ALGERIA

4 Study of contagion management in the 21 century Observation, evaluation, traceability, prevention in personnel Flu paradigm, unforeseeable outbreaks, Measles, Cholera in Haiti Optimising care (diagnostic treatment) Detection of abnormal phenomena and quantification, syndrome based (seasonal variation, mortality/bacteriema) Observatory Africa (Senegal) The Comoros Euro-Mediterranean Maghreb project E-CDC travellers WHO centres Homeless population Soldiers Environment Water, ground, arthropods Humans samples /year for diagnostic 10 kits/pathologies Emerging organisms Problem sample isola on sequence tool for diagnosis evalua on publica on test dissemina on

5 UNIQUE CAPACITIES IN DIAGNOSIS INFECTIOUS AND TROPICAL DISEASES, 2011 Tested serum specimens: Cultured clinical specimens: Testedspecimens, PCR : High-throughput sequencing capacity: 10 gigab/year Real-time genomic capacity, 50 genomes year(on-going) Biotheque-collections French bloodbank: tissue collections CSUR WDCM874 : largest intracellular bacteria collection worldwide EVA (European Viral Archives): largest virus collection worldwide(2.000 strains)

6 Objective: 75 beds for clinical research, and research (as NIH)

7 Budget on 10 years - Including the Building - Including each year spending BILAN PREVISIONNEL TOTAL OPERATION ESTIME AMO HT * Y compris révisions et équipements supp. TOTAL OPERATION ESTIME AMO TTC Hors aléas en euros TTC Marché groupement* Prestataires études Autres études Frais divers Total

8 -What is it? -Our goals The building Excellence in Marseille Infectiopole Sud -Our production - Our priorities

9 Budget building COUT GLOBAL PREVISIONNEL BATIMENT / RECHERCHE & SOIN Estimation Egis TTC Nature des travaux Partie Recherche Partie Soin Prévisionnel Etudes, démolition, parking Prévisionnel Conception réalisation gros œuvre Prévisionnel Conception réalisation gros œuvre et finitions Sout total Coût global prévisionnel RECETTES PREVISIONNELLES Estimation Egis ANR 2012 (obtenu) ANR 2013 (obtenu) APHM (obtenu) Mairie CG MPM Coût global prévisionnel * Conseil Régional 4 millions en équipement

10 The Building Milestones 30/07/2010 Dépôt de l'appel à projet Avril 2011 Début des groupes de pilotage hebdomadaires 12/05/2011 Acceptation du projet par l'anr 17/06/2011 Annonce officielle de l'ihu 21/06/2011 Publicité pour la programmation 13/07/2011 Présélection des candidatures des programmistes. (sur 9 candidats 6 ont été retenus) 18/08/2011 Sélection finale du programmiste. PRIX A B C D E IOSIS CONSEIL Phase 1 HT 31K 43,32K 52,4 K 61,6K 19,2K 7,6K Phase 2 HT 18K 63,35K 51,8 K 28,8 K 17,7K 36,7K Total Phase 1&2 HT 49K 106,67K 104,2 90,4K 36,9K 44,3K Total TTC 58,6K 127,57K 124,6K 108K 44,1K 52,9K

11 The Building Milestones 07/09/2011 Entretien avec Egis Conseil Bâtiment (Iosis)[Y. Obadia, D. Francal, M. Filleul]. 13/09/2011 Envoi du contrat de programmation à Egis Conseil Bâtiment 19/09/2011 Début de la mission de l étude de programmation [2 mois] /09/11 Audition des groupes de travail IHU POLMIT. du 13/10/2011 au 15/12/ /10/2011 Restitution des surfaces et de la faisabilité du programme. Vote par le Conseil d Administration de l attribution de la maîtrise d ouvrageà la Fondation 2/12/2011 Parution au JO de la création de la Fondation Méditerranée Infection 21/12/2011 Restitution d un pré-programme pour le Conseil d administration du 21/12/12 23/01/2012 Signature de la convention ANR 26/01/2012 Phase 1 : programme fonctionnel (remise du rapport à la Fondation). 07/02/2012 Phase 2 : programme technique (remise du rapport à la Fondation). 14/02/2012 Publicité Assistance à Maîtrise d Ouvrage (AMO). 3/04/2012 Publicité Conception-Réalisation-Maintenance.

12 The Building Milestones 04/04/2012 Contrat notarié signé pour la mise à disposition du terrain. 05/04/2012 Jury de Sélection AMO : candidat choisi Egis Conseil Bâtiment (montant HT). PRIX EgisConseil bâtiment A B C Total TTC , , , ,80 30/04/2012 Réception des candidatures CRM. Sur 24 candidature, 4 ont répondu du 1er au 06/05/12 Analyse des candidatures CRM. 15/05/2012 Jury / Remise du DCE aux candidats sélectionnés. 01/06/2012 Remise des pièces aux candidats 27/06/2012 Remise des offres du 25/06 au 13/07/12 Analyse des offres 13/07/2012 Jury de sélection - Déclaration des offres inacceptables 27/07/2012 Remise du dossier de consultation en procédure négociée 20/08/2012 Réception des offres semaines 34 à 36 Négociations 10/09/2012 Réception des offres finales

13 The Building Milestones 14/09/2012 Deuxième jury de désignation du lauréat HT seront versés aux candidats non retenus Titre Enveloppe Maître d'ouvrage A Fondeville B conception , , ,72 réalisation , , ,89 honoraire ,68 travaux ,21 Maintenance , , ,39 Rabais ,00 TOTAL HT , , ,00 Montant des options ,00 Montant des variantes ,00 TOTAL HT , , , ,00 Prix à l'ouverture initiale (27/06): , , ,79 Moins Values , ,72 - Prix offre du 20/08/ , , ,79

14 The Building Milestones 4/10/2012 Fin octobre 2012 Signature du contrat de Conception-Réalisation- Maintenance Objectif : déposer la demande du P 1 er juillet 2013 Démarrage travaux 23 mois Délai travaux 1 er trimestre 2015 Livraison bâtiment 1 er Septembre 2015 Ouverture de l IHU

15 The building The winner is Fondeville Cost including maintenance: 55M Cost of TVA m²

16 INSTITUT HOSPITALO-UNIVERSITAIRE DES MALADIES INFECTIEUSES ET TROPICALES DE MARSEILLE Conception Réalisation Maintenance Agence de Montpellier

17 GENESE DU PROJET

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19 RÉPARTITION FONCTIONNELLE VOLUMETRIE SOINS RECHERCHE Laboratoires Enseignement SOCLE FEDERATEUR

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22 Façade filtre LA PROTECTION DU SAVOIR Le socle fédérateur Un prisme de lumière

23 REPARTITION FONCTIONNELLE DIAGNOSTIC CONSULTATIONS BIOBANQUE VESTIAIRES HÔPITAL DE JOUR RDC haut ENSEIGNEMENT VETERINAIRE LOGISTIQUE RDC bas Hall haut Hôpital de jour Consultations Diagnostic Hall bas Enseignement Biobanque Vestiaires Logistique Consultation vétérinaire Stationnement du personnel S1 Stationnement du personnel

24 VALORISATION LT TRAITEMENT D AIR REPARTITION FONCTIONNELLE N4 TERTIAIRE DIRECTION LOCAUX TECHNIQUES TRAITEMENT D AIR Valorisation Tertiaire Direction Locaux techniques TERTIAIRE MEDICAL UH-PH N3 LABORATOIRES NSB3 HEBERGEMENT UNITE DE SOINS 1 NSB3 Hébergement unité de soins 1 NSB3 Tertiaire médical UH-PH Laboratoires NSB3 N2 LABORATOIRES NSB2 N1 TERTIAIRE SCIENCES HUMAINES TERTIAIRE ETUDIANTS TERTIAIRE CHERCHEURS HEBERGEMENTS UNITE DE SOINS 2 HEBERGEMENTS UNITE DE SOINS 3 LABORATOIRES MODULES DE RECHERCHE FONDAMENTALE Hébergement unité de soins 2 Tertiaire Sciences humaines et Chercheurs Laboratoires NSB2 Hébergement unité de soins 3 Tertiaire étudiants Laboratoires de recherche fondamentale

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26 L EXPRESSION DU PROJET L azur comme fil conducteur

27 -What is it? -Our goals The building Excellence in Marseille Infectiopole Sud -Our production - Our priorities

28 SCIENTIFIC STRATEGIES Emergence, technology, contradiction Emergence Collecting Isolating Identifiying Detecting Detecting resistance Genome sequencing Diagnostic tools Treatment Prevention Results Technology Sequencing Serology MALDI-TOF Culturomics

29 SURVEILLANCE IN MARSEILLE (2011) Samples (101) Microorganisms ( ; 376 species) Rare new bacteria (86 single cases) New phenotypes of resistance (new programme) New viruses

30 A EXPERIMENTAL CENTER TO FIGHT THE TRANSMISSION OF MICROBES From the admission to the discharge of patient Tracking Contagion in Medical care Specific trails for contagious people Failure to control outbreaks (Norovirus,Influenza) Failure to halt diffusion (resistant bacteria, Clostridium difficile) We need new data to understand Following patient movements Controlling catheters Controlling hygiene of medical care personnel Sequencing any bacterial species with atypical phenotype (including antibiotic susceptibility) Real Time Genomic

31 SYNDROME-BASED SURVEILLANCE Epidemiological monitoring by EPIMIC is organized by type of sample, meaning by infectious syndrome: Ocular samples Uveitis, keratitis, conjonctivitis Respiratory samples Pneumonia HBV, HCV, HAV, HEV, Delta agent Viral hepatitis Stools Diarrheae Bone samples Bone infections Cerebro-spinal fluid CNS infections Blood cultures Bacteriemia, endocarditis Urinary samples pyelonephritis + «Point of care» (P.-O.-C.), HIV, hospital environmental samples

32 A STANDARDIZATION OF DIAGNOSIS:

33 STANDARDIZATION OF DIAGNOSTIC AND TREATMENT PROCEDURES OF THE MOST COMMON INFECTIOUS DISEASES Key to 10 most common acute infection Pneumonia Other ARI ( bronchitis, AECOPD..) HIV ( acute super infection) Skin infection Meningitis Osteomyelitis Arthritis Genital infection male and female Septicemia Endocarditis Diagnostic Kit POC Diagnostic Radiographic strategy CT Scanner PET Scanner PET MRI Treatment strategy

34 STANDARDIZATION OF CHRONIC INFECTION HIV (2100 patients in follow up) Hepatitis B and C Bone and Joint Prosthetic infection (900 Patients in follow up) Endocarditis ( 100 patients a year) Q fever (180 patient in follow up, 60 new patient a year) Whipple s diseases ( 120 patients)

35 Sampling kits tested in Marseille Pneumonia Tropical diseases Bone and joint infections Meningitis Encephalitis Endocarditis Pericarditis Uveitis Dont think, sample! U R

36 DIAGNOSIS BY SYNDROME Corneal abscess (2009) Pneumonia (February 2007) Osteoarticular infection (December 2004) Travel-associated disease (February 2002) Encephalitis Uveitis (March 200) Homeless (2000) Pericarditis (May 1998) Endocarditis (March 1994)

37 COHORTS Cohort Endocarditis 600 NumberofPatients per year Raoult Doctors Pericarditis 200 Gouriet Q fever 220 Raoult/Mege Whipple diseases Pilgrim& infection 50 Raoult/Fenollar 600 Gautret Homeless 500 Raoult/Brouqui Rickettsia& human 200 Raoult/ Fournier/ Parola Uveitis 200 Drancourt

38 Objective 2000/year

39 WP 1 (Contagion management in the hospital: Construction of a building): P. Brouqui WP 2 (Monitoring the emergence of vectors and vector-borne diseases): P. Parola WP 3 (Microbiogenomics): P.E. Fournier WP 4 (Emerging pathogens detection and studies of microbiota): B. La Scola WP 5 (Point-of-Care): M. Drancourt WP 6 (Physiopathology): J.L. Mège WP 7 (Organization of the collections): X. de Lamballerie WP 8 (Valorization and transfer): J.M. Rolain WP 9 (Life in Mediterranee infection): D. Raoult

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41 GeoSentinel Surveillance Network HEALTH SURVEILLANCE & EMERGENCE European CDC reference Center for Traveland Tropical Medicine WHO Collaborative Center MicrobiologicalSurveillance Consultations Hospitalisations BLS 3 Unit Laboratory of Microbiology

42 Building entomologicallaboratory Since lice (artificial) -fleas -5 tick species - 2 mosquito species -bed bugs MALDI-TOF identifications (P Parola JM Beranger)

43 Repertoire of Microbes Clinical Specimens / Diagnosis kits Culturomics Gut microbiota 10 stools colonies MALDI-TOF 450 species 220 novelspeciesin gut Viral metagenomics Pericarditis Meningitis Uveitis Blood Nasal swab Amniotic fluid Bacterial metagenomics Gut microbiota Cystic fibrosis microbiota Brain abscess 50 new species 9 new genera: Microvirga massiliensis Senegal virus genome sequencing

44 IDENTIFICATION OF POTENTIAL PATHOGENS IN THE ENVIRONMENT Objectives Means - Expertise of the CNR and WHO Collaborating Centers on rickettsioses - Detection of pathogens in: and other bacterial diseases transmitted by arthropods - Ticks, lice, fleas, bugs - Entomological expertise (IRBA Marseille) - Mosquitoes - Field collections - Phlebotoms - Microbiological platform for detection - Collaboration (IRD, EID, WHO,VeBorNet) Create a multidisciplinary research and investigation platform - Physicians, entomologists, microbiologists, parasitology, epidemiology and veterinary specialists in statistical and mathematical modeling - Remote sensing tools - Intervention team Monitoring of animal reservoirs - A group of veterinary epidemiology Action targeted with Southern partners - South field location : Senegal Etiology of fevers Detection of pathogen in arthropod - South field location: Algeria Study of rickettsialreservoirs Detection of pathogens in arthropods Eco-epidemiology of the plague - Collaborations (IRD, Mali) Identify pathogens associated with free - Characterization and experimental models of giant mamaviridae viruses water amoebae and soil - High-speed isolation and identification - Systems of co-culture of amoebae African human microbiotastudy and study of investigation of the role of probiotics pyrosequencing - Microarrays - Special culture

45 Arthrop ods Soft ticks Ixodid ticks Arthropod species Ornithodoros sonrai Hyalomma marginatum rufipes; H. truncatum; Rhipicephalus evertsi evertsi Rh. e. evertsi Bacteria Borrelia crocidurae(21%) Coxiella burnetii(8.3%) Bartonella spp. Rickettsia aeschlimannii (0.5-51%) R. c. conorii(0.4%) Rh. guilhoni R. massiliae (22.4%) H. truncatum R. sibirica mongolitimonae (13.5%) Rh. e. evertsi Rh. annulatus Amblyommaspp; Rhipicephalusspp. Hyalomma spp. R. africae(0.7-20%) Coxiella burnetii (0.8-37%) Fleas Synosternus pallidus Rickettsia sp. (91.4%) Repertoire of fever, Senegal POC Preliminary study Borrelia spp. Tropheryma whipplei Senegal, West Africa 2000 bloods of febrile patients without malaria Large population-based studies (1943 blood samples) Rickettsia felis 15.4% Borrelia spp. 7.5% Lice Pediculus humanus capitis Bartonella quintana Tsetse flies Animals Smal mammals Sang Other Dust samples Acinetobacter baumannii Glossina morsitans Rickettsia sp. (100%) Bacteria Borrelia crocidurae(12%) Anaplasma spp. Coxiella burnetii( %) Other human samples Selles Saliva Bartonella spp Coxiella burnetii Tropheryma whipplei( %) Rickettsia spp. (2%) Rickettsia felis(1.3%) Tropheryma whipplei(3.5%) Tropheryma whipplei 2.8% Bartonella spp. 0.9 Bartonella quintana 0.3% Coxiella burnetii 0.5% 25% identified

46 16S rrna gene sequence-based identification of clinical bacterial isolates Systematic 16S rrna gene sequencing of atypical clinical isolates identified 27 new bacterial species associated with humans. Drancourt M, Berger P, Raoult D. J Clin Microbiol May;42(5): Clinical microorganisms isolated during a 5-year study in our hospital that could not be identified by conventional criteria were studied by 16S rrna gene sequence analysis. Each isolate yielded a > or =1,400-bp sequence containing <5 ambiguities which was compared with the GenBank 16S rrna gene library; 1,404 such isolates were tested, and 120 were considered unique (27 isolates) or rare (< or =10 cases reported in the literature) human pathogens. Eleven new species, "Actinobaculum massiliae," "Candidatus Actinobaculum timonae," Paenibacillus sanguinis, "Candidatus Bacteroides massiliae," Chryseobacterium massiliae, "Candidatus Chryseobacterium timonae," Paenibacillus massiliensis, "Candidatus Peptostreptococcus massiliae," "Candidatus Prevotella massiliensis," Rhodobacter massiliensis, and "Candidatus Veillonella atypica" were identified. Sixteen species were obtained from humans for the first time. Our results show the important role that 16S rrna gene sequence-based bacterial identification currently plays in recognizing unusual and emerging bacterial diseases. 16S ribosomal DNA sequence analysis of a large collection of environmental and clinical unidentifiable bacterial isolates. DrancourtM, BolletC, CarliozA, MartelinR, GayralJP, Raoult D. J Clin Microbiol Oct;38(10): Some bacteria are difficult to identify with phenotypic identification schemes commonly used outside reference laboratories. 16S ribosomal DNA (rdna)-based identification of bacteria potentially offers a useful alternative when phenotypic characterization methods fail. However, as yet, the usefulness of 16S rdna sequence analysis in the identification of conventionally unidentifiable isolates has not been evaluated with a large collection of isolates. In this study, we evaluated the utility of 16S rdna sequencing as a means to identify a collection of 177 such isolates obtained from environmental, veterinary, and clinical sources. For 159 isolates (89.8%) there was at least one sequence in GenBank that yielded a similarity score of > or =97%, and for 139 isolates (78.5%) there was at least one sequence in GenBank that yielded a similarity score of > or =99%. These similarity score values were used to defined identification at the genus and species levels, respectively. For isolates identified to the species level, conventional identification failed to produce accurate results because of inappropriate biochemical profile determination in 76 isolates (58.7%), Gram staining in 16 isolates (11.6%), oxidase and catalase activity determination in 5 isolates (3.6%) and growth requirement determination in 2 isolates (1.5%). Eighteen isolates (10.2%) remained unidentifiable by 16S rdna sequence analysis but were probably prototype isolates of new species. These isolates originated mainly from environmental sources (P = 0.07). The 16S rdna approach failed to identify Enterobacter and Pantoea isolates to the species level (P = 0.04; odds ratio = 0.32 [95% confidence interval, 0.10 to 1.14]). Elsewhere, the usefulness of 16S rdna sequencing was compromised by the presence of 16S rdna sequences with >1% undetermined positions in the databases. Unlike phenotypic identification, which can be modified by the variability of expression of characters, 16S rdna sequencing provides unambiguous data even for rare isolates, which are reproducible in and between laboratories. The increase in accurate new 16S rdna sequences and the development of alternative genes for molecular identification of certain taxa should further improve the usefulness of molecular identification of bacteria. i.e. 47 new pathogens!

47 MALDI-TOF Tentative characterizationof new environmentalgiantvirusesby MALDI-TOF mass spectrometry. La Scola B, CampocassoA, N'Dong R, FournousG, BarrassiL, FlaudropsC, Raoult D. Intervirology. 2010;53(5): Global analysis of circulating immune cells by matrix-assisted laser desorption ionization time- of-flight mass spectrometry. OuedraogoR, FlaudropsC, Ben Amara A, Capo C, Raoult D, MegeJL. PLoS One Oct 27;5(10):e13691 Classification of ancientmammalindividualsusingdental pulpmaldi-tof MS peptide profiling. TranTN, AboudharamG, GardeisenA, DavoustB, Bocquet-Appel JP, FlaudropsC, BelghaziM, Raoult D, Drancourt M. PLoS One Feb 25;6(2):e17319.

48 WP 1 (Contagion management in the hospital: Construction of a building): P. Brouqui WP 2 (Monitoring the emergence of vectors and vector-borne diseases): P. Parola WP 3 (Microbiogenomics): P.E. Fournier WP 4 (Emergingpathogensdetectionand studiesof microbiota): B. La Scola WP 5 (Point-of-Care): M. Drancourt WP 6 (Physiopathology): J.L. Mège WP 7 (Organizationof the collections): X. de Lamballerie WP 8 (Valorizationand transfer): J.M. Rolain WP 9 (Life in Mediterraneeinfection): D. Raoult

49 This month s Genome Watch describes the impact of next- generation sequencing on the real-time analysis of pathogen genomes during outbreaks. Chin, C. S. et al. (2011). The origin of the Haitian cholera outbreak strain. N. Engl. J. Med. 364, (2011). Github. E. coli O104:H4 genome analysis crowdsourcing. Github [online] https://github.com/ ehec-outbreak-crowdsourced/bgi-data-analysis/wiki (accessed 24 Jul 2011).

50 Rapid comparative genomic analysis for clinical microbiology: the Francisella tularensis paradigm. La Scola B, ElkarkouriK, Li W, WahabT, FournousG, RolainJM, BiswasS, DrancourtM, Robert C, AudicS, LöfdahlS, Raoult D.Genome Res May;18(5): It is critical to avoid delays in detecting strain manipulations, such as the addition/deletion of a gene or modification of genes for increased virulence or antibiotic resistance, using genome analysis during an epidemic outbreak or a bioterrorist attack. Our objective was to evaluate the efficiency of genome analysis in such an emergency context by using contigs produced by pyrosequencing without time-consuming finishing processes and comparing them to available genomes for the same species. For this purpose, we analyzed a clinical isolate of Francisella tularensis subspecies holarctica (strain URFT1), a potential biological weapon, and compared the data obtained with available genomic sequences of other strains. The technique provided 1,800,530 bp of assembled sequences, resulting in 480 contigs. We found by comparative analysis with other strains that all the gaps but one in the genome sequence were caused byrepeats. No new genes were found, but a deletion was detected that included three putative genes and part of a fourth gene. The set of 35 candidate LVS virulence attenuation genes was identified, as well as a DNA gyrase mutation associated with quinolone resistance. Selection for variable sequences in URFT1 allowed the design of a strain-specific, highly effective typing system that was applied to 74 strains and six clinical specimens. The analysis presented herein may be completed within approximately 6 wk, a duration compatible with that required by an urgent context. In the bioterrorism context, it allows the rapid detection of strain manipulation, including intentionally added virulence genes and genes that support antibiotic resistance. High throughput sequencing and proteomics to identify immunogenic proteins of a new pathogen: the dirty genome approach. Greub G, Kebbi-Beghdadi C, Bertelli C, Collyn F, Riederer BM, Yersin C, Croxatto A, Raoult D. PLoS One Dec 23;4(12):e8423. BACKGROUND: With the availability of new generation sequencing technologies, bacterial genome projects have undergone a major boost. Still, chromosome completion needs a costly and time-consuming gap closure, especially when containing highly repetitive elements. However, incomplete genome data may be sufficiently informative to derive the pursued information. For emerging pathogens, i.e. newly identified pathogens, lack of release of genome data during gap closure stage is clearly medically counterproductive. METHODS/PRINCIPAL FINDINGS: We thus investigated the feasibility of a dirty genome approach, i.e. the release of unfinished genome sequences to develop serological diagnostic tools. We showed that almost the whole genome sequence of the emerging pathogen Parachlamydia acanthamoebae was retrieved even with relatively short reads from Genome Sequencer 20 and Solexa. The bacterial proteome was analyzed to select immunogenic proteins, which were then expressed and used to elaborate the first steps of an ELISA. CONCLUSIONS/SIGNIFICANCE: This work constitutes the proof of principle for a dirty genome approach, i.e. the use of unfinished genome sequences of pathogenic bacteria, coupled with proteomics to rapidly identify new immunogenic proteins useful to develop in the future specific diagnostic tests such as ELISA, immunohistochemistry and direct antigen detection. Although applied here to an emerging pathogen, this combined dirty genome sequencing/proteomic approach may be used for any pathogen for which better diagnostics are needed. These genome sequences may also be very useful to develop DNA based diagnostic tests. All these diagnostic tools will allow further evaluations of the pathogenic potential of this obligate intracellular bacterium. U R

51 EXPLOSION OF BACTERIAL GENOME SEQUENCING Total :3,381 genomes as of September 26, 2012 URMITE: 150 (4.4% overall, 2.5% in 2012) Unpublished genomes (%) Number of sequenced genomes

52 Microbio-Genomicsproject Taxono-genomics: 73 new species Neo-genomics: 45 species Pan-genomics: 6 species, 249 strains Metagenomics: 214 metagenomes Objective 2012 = 100 bacterial genomes Proposalto describenew speciesbasedon phenotype, incl. MALDI-TOF spectrumand electronmicroscopy, 16S rrnasimilarity, and genomecharacteristics, incl. nucleotide sequence similarity at the core level.

53 Reconcilingtaxonomyand genomics? Currently not accepted by all taxonomists (conflicts of interest ) «Clearly, it s not possible to characterize a species by a single genome sequence, but how many sequences are necessary?» C. Frazer Transcriptomic and proteomic data also needed? Need for standardized quality of genomic sequences Need to obtain genomic sequences from all type strains Congruence of genomics data and classical taxonomic techniques? Influence of LGT? A subcommittee within the ICSP should consider a paradigm shift in species definition to incorporate genomic data. TIMETOWORK!

54 Microorganisms isolated and/or characterized in the UMR7278 and the discovery diseases

55 Microorganisms isolated and/or characterized in the UMR7278 and the discovery diseases

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59 Rickettsia slovaca Rickettsia sibirica sibirica Anaerococcus senegalensis Rickettsia sibirica mongolitimonae Rickettsia helvetica Diplorickettsia massiliensis Rickettsia conorii indica Alistipes senegalensis Alistipes timonensis Anaeroccoccus vaginalis "grossensis" PH9 Clostridium senegalense Rickettsia honei Rickettsia conorii caspia Bacillus timonensis Rickettsia conorii israelensis Rickettsia australis Kingella kingae Paenibacillus senegalensis Peptoniphilus Timonensis Rickettsia japonica Reyranella massiliensis Legionella tunisiensis Bartonella birtlesii Methanomassiliicoccus luminyensis Borrelia crocidurae Brevibacterium massiliense Actinomyces massiliensis Tsukamurella sp. Microbacterium yanicii Acinetobacter baumannii colis Acinetobacter baumannii colir Actinomyces timonensis Coxiella burnetii 109 Bartonella rattimassiliensis Bartonella rattiaustralianii Microbio-genomics October 8th genomes published

60 Sanguibacter massiliensis/ Timonella senegalensis Peptoniphilus grossensis Herbaspirillum massiliense Senegalemassilia fastidiosa Brevibacterium senegalense Peptoniphilus obesiensis Aeromicrobium massiliense Cellumonas massiliensis Grosso massiliensis/alistipes obesiensis Peptoniphilus senegalensis Enterobacter massiliensis Enorma massiliensis Kurthia massiliensis Afipia birgiae Microbio-genomics October 8th genomes submitted

61 WP 1 (Contagion management in the hospital: Construction of a building): P. Brouqui WP 2 (Monitoring the emergence of vectors and vector-borne diseases): P. Parola WP 3 (Microbiogenomics): P.E. Fournier WP 4 (Emerging pathogens detection and studies of microbiota): B. La Scola WP 5 (Point-of-Care): M. Drancourt WP 6 (Physiopathology): J.L. Mège WP 7 (Organizationof the collections): X. de Lamballerie WP 8 (Valorizationand transfer): J.M. Rolain WP 9 (Life in Mediterraneeinfection): D. Raoult

62 REPERTOIRE OF INTENSIVE CARE UNIT PNEUMONIA MICROBIOTA. Bousbia S, Papazian L, Saux P, Forel JM, Auffray JP, Martin C, Raoult D, La Scola B. PLoS One. 2012;7(2):e32486 Abstract Despite the many studies reported to date, the causative agents of pneumonia are not completely identified. We comprehensively extended modern and traditional laboratory diagnostic techniques to identify microbiota in patients who where admitted to or developed pneumonia in intensive care units (ICUs). During a three-year period, we tested the bronchoalveolar lavage (BAL) of patients with ventilator-associated pneumonia, community-acquired pneumonia, non-ventilator ICU pneumonia and aspiration pneumonia, and compared to patients without pneumonia(controls). Samples were tested by amplification of 16S rdna, 18S rdna genes followed by cloning and sequencing and by PCR to target specific pathogens. We also included culture, amoeba co-culture, detection of antibodies to selected agents and urinary antigen tests. Based on molecular testing, we identified a wide repertoire of 160 bacterial species of which 73 were never previously reported in pneumonia. Moreover, we found 37 putative new bacterial phylotypes with a 16S rdna gene divergence 98% from known phylotypes. We also identified 24 fungal species of which 6 have not been previously reported in pneumonia and 7 viruses. Patients may present up to 15 different microorganisms in a single BAL (mean ± SD; 3.75 ± 2.83). Some pathogens considered to be typical for ICU pneumonia such as Pseudomonas aeruginosa and Streptococcus species may be detected as commonly in controls as in pneumonia patients which strikingly highlights the existence of a core pulmonary microbiota. Differences in the microbiota of different forms of pneumonia were documented.

63 Microbiota diversity between studies Lung microbiota may vary greatly between individuals, depending on underlying diseases, habits and geographic origin.

64 Microbiota diversity in molecular assays 24 Bacteria, 3 Viruses and 3 Fungi were commonly found in patients and in controls =====>> existence of a core lung-resident microorganisms???

65 3 WORLD RECORDS FROM GUT MICROBIOTE IN 1 YEAR 1 in discovering bacteria from humans since 10 years Largest virus (Senegalvirus) 1st cultivated giant virus of a human sample Size genome: 372 Kb Largestbacteria(Microvirgamassiliensis) larger genome of a bacterium isolated from a human sample. Size genome: 9,3 Mb Largest Archae(Methanomassilicoccus luminyensis) Size genome: 2,6 Mb LagierJC, ArmougomF, Million M, Hugon P, PagnierI, Robert C, et al. Microbialculturomics: paradigmshift in the humangutmicrobiomestudy. ClinicalMicrobiologyand Infection 2012; in press. GorlasA, Robert C,GimenezG, DrancourtM,Raoult D GenomeAnnouncementsComplete GenomeSequenceofMethanomassiliicoccusluminyensis, the Largest Genome of a Human-Associated Archaea Species J. Bacteriol. September 2012; 194:4745doi: /JB

66 The humanvirome What about viral diversity in healthy humans? Haynes and Rohwer, Chapter in «Metagenomics of the Human Body» 2011

67 Immunofluorescence usingmarseillevirusantibodieson viral particles purified from serum Cytoblock Geloseinclusion of purified viral particles Paraffin inclusion Thin slice section Giant virus in the blood Green : MarVpolyclonalAb Red: DAPI 100X

68 WP 1 (Contagion management in the hospital: Construction of a building): P. Brouqui WP 2 (Monitoring the emergence of vectors and vector-borne diseases): P. Parola WP 3 (Microbiogenomics): P.E. Fournier WP 4 (Emergingpathogensdetectionand studiesof microbiota): B. La Scola WP 5 (Point-of-Care): M. Drancourt WP 6 (Physiopathology): J.L. Mège WP 7 (Organizationof the collections): X. de Lamballerie WP 8 (Valorizationand transfer): J.M. Rolain WP 9 (Life in Mediterraneeinfection): D. Raoult

69 Types of tests realisedby the POC in 2011 TESTS Nb % Flu RSU Streptococcus A Legionella urine Pneumococcus urine PCR M.pneumoniae Rotavirus Adenovirus Streptotococcus B Clostridium.difficile PCR N.meningitidis PCR Enterovirus HIV rapid test PCR Coxiella burnetii Procaloitonine PCR Herpes virus Varicelle zona virus TESTS Nb % PCR S.pneumoniae Malaria CSF PCR Bordetella.pertussis Cell count cryptococcus EBV Dengue PCR Staphylococcus aureus Helicobacter pylori Norovirus PCR Atopobium.vaginae PCR Pneumocystis jiroveci Tetanos TOTAL ALL < 2 ½ h

70 Arthrop ods Soft ticks Ixodid ticks Arthropod species Ornithodoros sonrai Hyalomma marginatum rufipes; H. truncatum; Rhipicephalus evertsi evertsi Rh. e. evertsi Bacteria Borrelia crocidurae(21%) Coxiella burnetii(8.3%) Bartonella spp. Rickettsia aeschlimannii (0.5-51%) R. c. conorii(0.4%) Rh. guilhoni R. massiliae (22.4%) H. truncatum R. sibirica mongolitimonae (13.5%) Rh. e. evertsi Rh. annulatus Amblyommaspp; Rhipicephalusspp. Hyalomma spp. R. africae(0.7-20%) Coxiella burnetii (0.8-37%) Fleas Synosternus pallidus Rickettsia sp. (91.4%) Repertoire of fever, Senegal POC Preliminary study Borrelia spp. Tropheryma whipplei Senegal, West Africa 2000 bloods of febrile patients without malaria Large population-based studies (1943 blood samples) Rickettsia felis 15.4% Borrelia spp. 7.5% Lice Pediculus humanus capitis Bartonella quintana Tsetse flies Animals Smal mammals Sang Other Dust samples Acinetobacter baumannii Glossina morsitans Rickettsia sp. (100%) Bacteria Borrelia crocidurae(12%) Anaplasma spp. Coxiella burnetii( %) Other human samples Selles Saliva Bartonella spp Coxiella burnetii Tropheryma whipplei( %) Rickettsia spp. (2%) Rickettsia felis(1.3%) Tropheryma whipplei(3.5%) Tropheryma whipplei 2.8% Bartonella spp. 0.9 Bartonella quintana 0.3% Coxiella burnetii 0.5% 25% identified

71 POC SENEGAL Point of Care laboratory implemented in Dielmo village

72 WP 1 (Contagion management in the hospital: Construction of a building): P. Brouqui WP 2 (Monitoring the emergence of vectors and vector-borne diseases): P. Parola WP 3 (Microbiogenomics): P.E. Fournier WP 4 (Emergingpathogensdetectionand studiesof microbiota): B. La Scola WP 5 (Point-of-Care): M. Drancourt WP 6 (Physiopathology): J.L. Mège WP 7 (Organizationof the collections): X. de Lamballerie WP 8 (Valorizationand transfer): J.M. Rolain WP 9 (Life in Mediterraneeinfection): D. Raoult

73 WP PATHOPHYSIOLOGY 1- PROJECTS - MICROBIAL PERSISTENCE AND IMMUNOSUPPRESSION (Models of bacterial infectious diseases(q Fever) and HPV infection) -TISSUE TROPISM (Models of bacterial infectious diseases(q Fever Whipple s disease- Brucellosis) - INSTALLATION OF RELEVANT MODELS OF INFECTION (Transgenicmiceincludinghumanizationof somecompartmentof immune system) 2 PARTNERS Center of Immunology, Research Center for Oncology and URMITE 3 METHODOLOGICAL DEVELOPMENTS Developpment of patient cohorts Development of highthroughput methods for gene expression Development of live imaging T.Whipplei in cadiac valve Duodenum biopsy Q fever endocarditis

74 WP 1 (Contagion management in the hospital: Construction of a building): P. Brouqui WP 2 (Monitoring the emergence of vectors and vector-borne diseases): P. Parola WP 3 (Microbiogenomics): P.E. Fournier WP 4 (Emergingpathogensdetectionand studiesof microbiota): B. La Scola WP 5 (Point-of-Care): M. Drancourt WP 6 (Physiopathology): J.L. Mège WP 7 (Organisation of the collections): X. de Lamballerie WP 8 (Valorizationand transfer): J.M. Rolain WP 9 (Life in Mediterraneeinfection): D. Raoult

75 WP 1 (Contagion management in the hospital: Construction of a building): P. Brouqui WP 2 (Monitoring the emergence of vectors and vector-borne diseases): P. Parola WP 3 (Microbiogenomics): P.E. Fournier WP 4 (Emergingpathogensdetectionand studiesof microbiota): B. La Scola WP 5 (Point-of-Care): M. Drancourt WP 6 (Physiopathology): J.L. Mège WP 7 (Organizationof the collections): X. de Lamballerie WP 8 (Valorization and transfer): J.M. Rolain WP 9 (Life in Mediterraneeinfection): D. Raoult

76 WP8 VALORISATION - JM Rolain Milestones Years WP8 Tasks 1 Comment Year WP8.1 1 Find a temporary office to locate the valorization team X JMR Office 2 Recruitment of 1 project manager, 3 persons in charge and 1 assistant X 3 Setting up, follow monthly and report of KPI's to control & monitor activity X X X X X 4 Transfer of the valorization team to the new building X WP8.2 1 Identification of a person in charge of IHU access to partners X yes 2 Realization of a best practice benchmarking on the IHU access to partners X in progress 3 Preparation of commercial offers to external partners X in progress X 4 Setting up an effective policy of management of the conflicts of interest X Yes CEPCI L Camoin X X 5 Deployment of business intelligence X Yes X X X 6 Deployment of sales force, marketing brochures, web site X in progress X X X 7 Signing public private partnerships contracts X Yes in progress X X X WP8.3 1 Identification of an interlocutor for clinical research coordination X CIC? 2 Setting up methods & procedures for the realization of IHU clinical trial X Cohorts - In progress X 3 Integration of IHU to national & international network of clinical research X in progress X X X X 4 Deployment of information systems for inclusion study feasibility X X X 5 Mobilization of extra hospital cohorts of patients X in progress X X 6 Realization of clinical trials in relation with the socio-economic world X X X WP8.4 1 Identification of an interlocutor for translational research coordination X Yes JL Balzer (SATT) X 2 Signing collaborative conventions with translational research structures X yes X 3 Setting up methods & procedures to realize translational projects X X X 4 Subcontracting translational research platforms to industrial partners in progress X X X 5 Setting up "starting contracts" and "risks contracts" to explore new tracks X in progress X X X 6 Realization of translational research programs X yes X X X 7 creation of new start-up and spin-off X yes X X WP8. Total costs :

77 WP8.2 3 Preparation of commercial offers to external partners realization of a portfolio in progress 4 Setting up an effective policy of management of the conflicts of interest done L CamoinCEPCI Seminar L Camoin«Prévention des conflits d'intérêts» 07/09/ Deployment of business intelligence to improve performances objectives/year (publications, IF, patents, cohorts ) OK to monitor KPIs -OK 6 Deployment of sales force, marketing brochures, web site Name and logo of the foundation Image of the building Presentation of IHU to industrials : «Expert meeting on diagnosis and detection of antimicrobial resistance in developing countries» Les Pensières Conference Centre - Veyrier-du-Lac October 2011 Fondation Merieux «Maladies infectieuses, les nouveaux défis?» Pôle Arbois (Aix en Provence) 18/11/2012 Eurobiomed 1st Edition of «SepsisCollaborative Day» Lyon 16/03/2012 LyonBiopole Marketing presentation of IHU International article Provence Promotion May 2012

78 WP8.4 Contractsand ProjectsIHU Strategies Patents from1994 to patents (4/year) 2012 : 7 patents Strategy_1 : «Culturomics» to optimize culture of Mycobacterium tuberculosis with Biomerieux (Biomerieux IHU AMU : Contrat culture M. tuberculosis: 165 k ) Rapid detection of M. tuberculosis in culture media : solid medium (Petri dishes) liquid medium in Bactec media with BacTAlert apparatus Methods of Identification of Mycobacteria Potential patents and Royalties

79 Intellectual property Patents: culturomics Milieu de culture empirique acellulaire pour la croissance de Coxiella burnetii, l agent de la maladie de la fièvre Q. D. Raoult Identification des Archae par analyse de spectres protéiques par Spectrométrie de Masse MALDI-TOF. M. Drancourt, D. Raoult 05/07/11- FR «Culture et detection d une Archaea méthanogène» M. Drancourt, D. Raoult. 05/12/08 WO/2010/ «Mycobacteria culture medium and method including mycobacteria of mycobacterium tuberculosis complex» M. Drancourt, D. Raoult. 26/10/06 WO/2008/ «Method for molecular identification and genotyping of bacteria of the mycobacterium tuberculosis complex». M. Drancourt, Z. Djelouadji, D. Raoult. Creation of a start-up Culture?

80 WP8.4 Contractsand ProjectsIHU Strategies Strategy_2 :MALDI-TOF for identification: Patents Références dépôt prioritaire Titre Inventeur(s) (Co-)propriétaires 09/58603 Méthode d'identification des virus au moyen de RAOULT AP-HM (03/12/2009) MALDI TOF-SM LA SCOLA +/- Université 10/51379 (26/02/2010) 10/54581 (10/06/2010) 12/53057 (03/04/2012) Procédé d'identification de l'espèce animale mammifère d'origine des protéines contenues dans un échantillon à tester La spectrométrie de masse MALDI-TOF, un outil d'identification des cellules eucaryotes, en particulier des cellules de la réponse immune et de leur état d'activation Méthode de détermination de la nature tumorale ou non tumorale ou du type de tumeur d'un fragment d'organe solide humain ou animal RAOULT DRANCOURT RAOULT MEGE CAPO BEN AMARA OUEDRAOGO RAOULT ROLAIN D'JOURNO BREGEON FLAUDROPS -ValorizationwithAPHM : installation of a MALDI-TOF in surgicalblock for rapid detection and identification of cancer - MALDI-TOF in Dakar with Mérieux - ID of arthropods by MALDI-TOF AP-HM AP-HM AP-HM

81 WP8.4 Contractsand ProjectsIHU Strategies Strategy_3 : Fight against contagion: Medi-Handtrace P brouqui 1. Intelligent catheters with Medi-Handtrace: in progress 2. Circuits of contagion : Création d un kit d audit automatisé de traçabilité pour lutter contre les maladies nosocomiales en milieu hospitalier Monitoring de l hygiène des mains, de tâches et de flux, par technologie RFID Incidence sur les infections nosocomiales en milieu hospitalier Médi-Handtrace

82 . Entreprises Médinorme Micro BE Hygienic System Ephygie-Hand Développement d un outil d audit par technologie RFID à13,56 MHz Antennes au sol, badges par personnel, coupleurs. Détection/identification au passage portes, devant auges, distributeurs SHA, zones lits. Monitoring, comparaison (protocoles), alarmes (go/no go), statistiques, affichages. Expérimentation via CCLIN/UMR 6236 Observation/évaluation en service d infectiologie (1 chambre) Validation en infectiologie (15 chambres) Evaluation scientifique. Analyse de l impact sur les IAS Programme de 2 ans Deux labellisations Eurobiomed CNRFID Oseo Patents

83 WP8.4 Contractsand ProjectsIHU Strategies Strategy_4 : New antimicrobial drugs: Patent 1«Utilisation de composés aminostéroïdiens en application topique locale pour la décolonisation cutanéo-muqueuse de Staphylococcusaureus» décembre JM Brunel, JM Rolain, D Raoult Patent 2 «Utilisation de la squalaminecomme désinfectant de matériel de nébulisation infecté par diverses suspensions bactériennes ou fongiques» JM Brunel, JM Rolain, V Andrieu, D Raoult 2012 Patent 3 «Dérivés imidazolés à activités accrues vis à vis des archébactéries méthanogènes humaines» (JM Brunel, M Drancourt, D Raoult) Evaluation of Squalamine derivatives in veterinary diseases Collaborative contract + license with Virbac- 250 k 2. Evaluation of aminosterols derivatives as topic for nasal S. aureus decontamination In discussion with Sanofi

84 WP8.4 Contractsand ProjectsIHU Strategies Strategy_4 : New antimicrobial drugs: 3. Decontamination of neurotoxic agents Start-up Patent «Brevet WO/2008/ Phosphotriestérasechimérique thermostable. UHP(Nancy)/CNRS» Brevet - UHP/CNRS - E. Chabrière et M. Elias inventeurs Fondateurs - E. Chabrière - M. Uzan - J. Kadouche - M. Elias Licence exploitation Start-up Autres intervenants - D. Raoult - P. Masson - D. Tawfik

85 WP8.4 Contractsand ProjectsIHU Strategies Strategy_4 : New antimicrobial drugs: 5. Lactonases as quorum sensor inhibitors Patent. «Phosphotriestérase chimérique thermostable». E Chabriere 6. HPBP and protein DING : new antiviral agents and markers of infection (E Chabriere) Brevet WO/2005/ "Nouvelle protéine de fixation du phosphate, compositions pharmaceutiques la contenant et ses utilisations. UHP(Nancy)/CNRS Brevet WO/2010/ "Nouvel agent antiviral". AMU/ULP(Strasbourg)/CNRS

86 WP8.4 Contractsand ProjectsIHU Strategies Strategy_5 : New diagnostic strategies 1. Development of new mobile Point Of Care suitcase Imebio/Fondation Merieux/IRD and POC (WP5_MD) - POCRAME 2. Evaluation of POC on cruiseship Partnership between IHU/APHM and CMA CGM (WP5_MD) 3. Evaluation of MALDI-TOF mass spectrometry in Senegal Biomerieux IHU : ContractMALDI-TOF Dakar (WP5_MD) 4. Amikana Biologics(start-up P Gluschankoff) Drug resistance diagnostic for HIV and HCV (start-up)

87 WP8.4 Contractsand ProjectsIHU Strategies Strategy_6 : Development of vaccines Patent JP Gorvel«MODIFIED GRAM-NEGATIVE BACTERIA FOR USE AS VACCINES» AptentJP Gorvel«METHODS FOR OBTAINING A POPULATION OF REGULATORY T CELLS» 12/54623 (21/05/2012) Procédé d'atténuation d'une bactérie du complexe Mycobacteriumtuberculosis pour la fabrication d'un vaccin contre la tuberculose RAOULT DRANCOURT LAMRABET AP-HM Université Projects 1. Virbac and CβG. Clinical trials in dogs and brucellosis 2. LPS and CβGas vaccines adjuvants in humanmedicine: Roche et Sanofi 3. Attenatued M. tuberculosis and vaccine??

88 WP8.4 Contractsand ProjectsIHU Strategies Strategy_7 : Development of new bioinformatic tools for automatic genomic annotation Contract with Xegen for automatic pipeline annotation of genomes and resistome (WP_3_PEF_JMR) * Startup, spin off IHU

89 WP 1 (Contagion management in the hospital: Construction of a building): P. Brouqui WP 2 (Monitoring the emergence of vectors and vector-borne diseases): P. Parola WP 3 (Microbiogenomics): P.E. Fournier WP 4 (Emergingpathogensdetectionand studiesof microbiota): B. La Scola WP 5 (Point-of-Care): M. Drancourt WP 6 (Physiopathology): J.L. Mège WP 7 (Organizationof the collections): X. de Lamballerie WP 8 (Valorization and transfer): J.M. Rolain WP 9 (Life in Mediterranee infection): D. Raoult

90 Gouvernance Administration Board President Dr Yolande Obadia // Director Prof Didier Raoult Direction core-?? Scientific Director Prof Jean-Louis Mège Membres Fondateurs Initiaux 2membres représentants des Enseignantschercheurs, Enseignants et Chercheurs Dix Personnalités Qualifiées 1siège par Membre Fondateur 2sièges 10 sièges 1. AP-HM : Jean-Paul SEGADE 2. CNRS :Alain FUCHS 3. EFS : Gérard TOBELEM 4. INSERM : André SYROTA 5. MERIEUX : Alain MERIEUX 6. IRD : Michel LAURENT 7. Aix Marseille Université : Yvon BERLAND 1. Didier RAOULT 2. Bruno VENTELOU 1. Rodolphe HALAMA 2. Guy MOULIN 3. Yolande OBADIA 4. Jacques BERGER 5. Pierre DELLAMONICA 6. Jean-Olivier ARNAUD 7. Bernard DELORD 8. Jacques REYNES 9. Claudine RIGAL

91 Following commitee every Thursday 12h30-13h30 List of members Dr Yolande OBADIA, Présidente Pr Didier RAOULT, Directeur Pr Jean-Louis MEGE (Responsable Scientifique) Pr Michel DRANCOURT Pr Philippe BROUQUI Pr Jean-Marc ROLAIN Pr Laurence CAMOIN Pr Xavier de LAMBALLERIE ou Pr Remi CHARREL Mme Flore OBERHAUSER (Chargée de projet «Investissements d'avenir» Université de la Méditerranée, Pharo) Mr Pierre PINZELLI (Directeur du Groupe Hospitalier de la Timone) Mr Sébastien VIAL (Directeur des Travaux & des Services Techniques AP- HM) Mr Claude MARTIN (représentant CME) Mr Jean-Claude SAMUELIAN (Service de psychiatrie, Conception) Mr Bernard BELAIGUES (Direction de la Recherche AP-HM) Mr François-Jérôme AUBERT (Direction de la Recherche AP-HM) Mme Marie-Laure GUIDI (comptable)

92 Équipements FEDER -AP-HM: total 2,3 M Microscope électronique FEI et cryomicroscopie(1 M ) Séquenceur haut-débit SOLID ( ) Spectromètres de masse (3 unités) Équipements pour protéomique Ensemenceur automatique de géloses Automates de sérologie CPER: total actuel 3,8 M Séquenceurs haut-débit "junior" (2 unités) Spectromètres de masse (3 unités) Colony-picker Instrument Surface résonnance plasmonique(biacore, 3 unités) Serveur informatique Cytomètres de flux (2 unités) Microscopie confocale Microscopie optique (complément d'équipement) Lyophilisation

93 INCENTIVE POLICY BASED ON INTERNATIONAL SCIENTIFIC COMMITTEE 1 Financial support for the installation of new teams (50,000 per year) 2 Financial support for the installation of scientistsable to becomegroup leader 3 Financial support for oldies(30,000 per year) 3 Scientific awards -Awardsfor scientistpublishingin journal withif higherthan10 as first author -Awardsfor PhDstudentspublishing in journal withsignificantimpact in infectious diseases as first author BASED ON LOCAL COMMITTEE Awards for ingeneer or technician involved in research, diagnosis and care

94 -What is it? -Our goals The building Excellence in Marseille Infectiopole Sud. PhD Post-doc. Meetings. Awards -Our production - Our priorities

95 2012 Infectiopôle Sud PhD -7 Positions between2 cities - 3 Positions between 2 research units Post-Doc -6 Positions between2 cities - 2 Positions between 2 research units Excellence in Marseille PhD - 2 Position between 2 disciplines - 3 Positions crossing Humanities& Social Sciences & Medical Sciences -2 Positions boostingworkpackages Co-directed with African countries (supported by the PACA Region) PhD -6 Positions betweenmarseille and one Africancountry

96 BOURSIERSINFECTIOPÔLESUD Thèse Total thèses : 55 Post-Doc Total Post-Doc : 43 Master 2 Total Master 2 : 45 Internes Professeurs Internes : 14 Professeurs : 5 Total Boursiers : 162

97 RÉPARTITION DES FINANCEMENTS PAR VILLE BOURSES DE THÈSES 43 CONTRATS POST-DOCTORAUX Marseille 16 Marseille 12 Montpellier Nice Montpellier Nice Nîmes Nîmes

98 ORIGINE DES BOURSIERS INFECTIOPÔLE SUD Russie Légende 1 chercheur Mexique États-Unis Colombie Italie Espagne Turquie Maroc Chypre Liban Sénégal Tunisie Égypte Algérie Soudan Guinée Cameroun Burkina Faso Gabon Congo Comores Inde Chine Vietnam Thaïlande 5 chercheurs Argentine Sud-Afrique 10 chercheurs

99 ORIGINES DES CANDIDATURES FINANCEMENT2010 À2012 Légende Canada Etats Unis Mexique Guatemala Pérou 1 personne Cuba Guyane F Brésil Uruguay Argentine Russie Royaume-Uni Estonie Irlande Allemagne Belgique Pologne Autriche Ukraine France Slovénie Moldavie Roumanie Espagne Italie Bosnie Portugal Turquie Arménie Chine Tunisie Liban Iran Pakistan Corée du Sud Maroc Jordanie Nepal Koweït Algérie Bangladesh Egypte Bahreïn Inde Sénégal Mali Tchad Thaïlande Burkina Faso Bénin Soudan Vietnam Guinée Nigéria Djibouti Cameroun Ethiopie Philippines Cote d Ivoire Ghana Togo Sri Lanka Malaisie Kenya Congo RDC Indonésie Malawi Comores Namibie Afrique du Sud Madagascar Zimbabwe Australie 41 personnes Kenya 59 personnes Burkina Faso 83 personnes France 430 personnes Inde 441 personnes

100 TOTAL PUBLICATIONS IHU SUR2 VILLES Étudiants Infectiopole Sud travaillant sur 2 laboratoires de 2 villes différentes Nice 21 7 Montpellier Marseille 43 1 TOTAL 51 Montpellier / Marseille 29 Nice / Marseille 14 Nice / Montpellier 7 Nîmes / Marseille 1 Marseille 43 Montpellier 36 Nîmes 1 Nice 21 Nîmes 1

101 Published in Lancet, Science, NEJM, CMI ANNONCES

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