TURKU CENTRE FOR BIOTECHNOLOGY REPORT 2010 TURUN BIOTEKNIIKAN KESKUS ÅBO BIOTEKNIKCENTRUM TURKU CENTRE FOR BIOTECHNOLOGY

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1 TURUN BIOTEKNIIKAN KESKUS ÅBO BIOTEKNIKCENTRUM TURKU CENTRE FOR BIOTECHNOLOGY Congratulations to our 14 new PhDs! TURKU CENTRE FOR BIOTECHNOLOGY REPORT 2010 TURUN BIOTEKNIIKAN KESKUS Tykistökatu 6 B P.O.BOX 123 FI Turku, Finland Tel: , Fax

2 Annual Report 2010 Turku Centre for Biotechnology Published by: Turku Centre for Biotechnology P.O. Box 123, FI Turku, Finland Tel. int , fax int Editorial Board Riitta Lahesmaa (Chair) Tero Aittokallio Eleanor Coffey Garry Corthals Michael Courtney Konstantin Denessiouk Attila Gyenesei John Eriksson Jyrki Heino Johanna Ivaska Panu Jaakkola Marko Kallio Olli Kallioniemi Päivi Koskinen Tassos Papageorgiou Lea Sistonen Jukka Westermarck Linnéa Linko Juha Strandén Mikael Wasberg Photographs: Roni Lehti, Photograph archives of the Centre for Biotechnology Front cover image: Patrik Jones Graphic Design: Anne Asplund, Finepress Oy Printed by: Finepress Oy, Turku ISSN

3 CONTENTS Board of Trustees... 2 Chairman s Foreword... 4 From the Director... 5 Year 2010 in a Nutshell... 7 PhD and MSc Theses Funding Personnel The Finnish Microarray and Sequencing Centre Cell Imaging Core (CIC) The Proteomics Facility Protein Crystallography Core Facility Bioinformatics Core Virus Vector Facility Coordination of European Biobanking Mechanisms and Biosensors of GTPases Protein Kinase Regulation of Brain Development and Disease Translational Proteomics Cytoskeletal and Survival Signaling Cell Adhesion and Cancer Hypoxia in Cell Survival Kinetochore and Cancer Research Group Canceromics Research Programme Signaling Pathways regulated by Oncogenic Pim Kinases Molecular Systems Immunology and Stem Cell Biology Protein Crystallography Cell Fate Targeting Strategies for Gene Therapy Regulation and Function of Heat Shock Transcription Factors Cancer Cell Signaling Structural Bioinformatics Group Data Mining and Modeling Group Organisation of Neuronal Signaling Pathways Bioenergy Group Computational Systems Biology Publications PhD Defences Life outside the Lab

4 ORGANIZATION Board of Trustees Chairman HEINO Jyrki, Professor, University of Turku, Department of Biochemistry and Food Chemistry, Scientific Director, BioCity Turku Vice-chairman ERIKSSON John, Professor, Åbo Akademi University, Department of Biology Secretary LAHESMAA Riitta, Professor, Director, Turku Centre for Biotechnology Assistant Secretary JAAKKOLA Minttu, Coordinator, Turku Centre for Biotechnology and BioCity Turku ( ) ALANKO Satu, Coordinator, Turku Centre for Biotechnology and BioCity Turku ( ) Members ARO Eva-Mari, Academy Professor, the Academy of Finland, University of Turku, Department of Biology JALKANEN Sirpa, Professor, University of Turku, MediCity Research Laboratory JOHNSON Mark, Professor, Åbo Akademi University, Department of Biochemistry and Pharmacy LAHTI Reijo, Professor, University of Turku, Department of Biochemistry and Food Chemistry LASSILA Olli, Professor, University of Turku, Department of Medical Microbiology PIISPANEN Tero, Project Manager, Turku Science Park Ltd PYRHÖNEN Seppo, Professor, University of Turku, Department of Oncology SAXÉN Henrik, Vice Rector ( ) SERE Kaisa, Vice Rector, Professor, Åbo Akademi University, Department of Information Technology ( ) TÖRNQUIST Kid, Professor, Åbo Akademi University, Department of Biology Vice-members ARO Hannu, Professor, University of Turku, Department of Surgery HUPA Leena, Lecturer, Åbo Akademi University, Åbo Akademi Process Chemistry SALAKOSKI Tapio, Professor, University of Turku, Department of Information Technology SISTONEN Lea, Academy Professor, the Academy of Finland SOUKKA Tero, Academy Research Fellow, Academy of Finland, University of Turku, Department of Biotechnology TOPPARI Jorma, Professor, University of Turku, Department of Physiology VUORELA Pia, Professor, Åbo Akademi University, Department of Pharmaceutical Chemistry Board of Trustees Chairman HEINO Jyrki, Professor, University of Turku, Department of Biochemistry and Food Chemistry, Scientific Director, BioCity Turku Vice-chairman ERIKSSON John, Professor, Åbo Akademi University, Department of Biology Secretary LAHESMAA Riitta, Professor, Director, Turku Centre for Biotechnology Assistant Secretary ALANKO Satu, Coordinator, Turku Centre for Biotechnology and BioCity Turku Members ARO Eva-Mari, Professor, University of Turku, Department of Biochemistry and Food Chemistry JALKANEN Sirpa, Professor, University of Turku, Department of Medical Microbiology and Immunology JOHNSON Mark, Professor, Åbo Akademi University, Department of Biosciences POUTANEN Matti, Professor, University of Turku, Institute of Biomedicine SAVILAHTI Harri, Professor, Univer sity of Turku, Department of Biology TERHO Perttu, Project Engineer, Turku Centre for Biotechnology TÖRNQUIST Kid, Professor, Åbo Akademi University, Department of Biosciences WILLFÖR Stefan, Professor, Åbo Akademi University, Department of Chemical Engineering Vice-members FARDIM Pedro, Professor, Åbo Akademi University, Department of Chemical Engineering HÄNNINEN Pekka, Professor, University of Turku, Institute of Biomedicine JAAKKOLA Ulla-Marjut, Group Leader, Project Director, Turku Centre for Biotechnology LASSILA Olli, Professor, University of Turku, Department of Medical Microbiology and Immunology PETTERSSON Kim, Professor, University of Turku, Department of Biochemistry and Food Chemistry PRIMMER Craig, Professor, University of Turku, Department of Biology SLOTTE J. Peter, Professor, Åbo Akademi University, Department of Biosciences VUORELA Pia, Professor, Åbo Akademi University, Department of Biosciences 2 3

5 CHAIRMAN S FOREWORD Seventeen years ago, 1994, the Scientific Advisory Board of BioCity decided to join all biotechnology and molecular biology employing research groups under one single umbrella: BioCity Turku. To reflect the success of BioCity concept professors Eero Vuorio and Pekka Mäntsälä edited a book introducing all 40 research groups that were actively working in this growing research field. The total number of researcher and graduate students was estimated to be c The forewords of the first BioCity Turku book ended: It (the book) should also serve as an invitation for more researchers and industries to join BioCity Turku since the most exciting research still lies, unexplored, ahead. The present, international, Scientific Advisory Board of BioCity Turku evaluated the applicant research programmes in October, The total number of research groups in the applications was 120 and the number of researchers and graduate students was c Thus, the BioCity concept does indeed have the keys to growth and success. The corner stone of BioCity Turku is close collaboration between two Universities, the University of Turku and the Åbo Akademi University, which share the common campus. The most important strategic decision has been the establishment of highlevel, common research infrastructure. From the very beginning, the core facilities in the Turku Centre for Biotechnology have been critical for the development of life science and molecular medicine research in the Turku campus area. They provide modern research services and allow the access to the latest technologies for all scientists working in Turku. The Turku Centre for Biotechnology has also played a crucial role in making the Turku campus attractive for new researchers and research groups. Happily many of the new group leaders have moved from abroad. For comparison to year 1994 only one out of forty group leaders was not originally from Finland. In Finland the new Biocenter Finland -process has expanded the role of many core facilities from a local to a national service provider. In Turku most core facilities have already for a long time served a wide scientific community in Finland and also abroad. Turku Centre for Biotechnology has therefore been in many ways a forerunner in the creation of the national infrastructure networks. Biocenter Finland has significantly helped in the modernization of research equipment and technologies. Its present funding will end on 2012 and after that the continuation of this critical process is still uncertain. An equally demanding future challenge is to link the Finnish infrastructure and the largest core facilities to the emerging European infrastructure networks. The present ESFRI (European Strategy Forum on Research Infrastructures) process is preparing ground for the forthcoming networks that in the future will strengthen the European Research Area. It is essential for the development of life sciences in Finland that also Finnish researchers participate in this process. Turku scientists have been especially active in the Euro-bioimaging project. Jyrki Heino, M.D., Ph.D., Professor of Biochemistry, Scientific Director of the BioCity Turku and Chairman of the Board of the Turku Centre for Biotechnology FROM THE DIRECTOR Turku Centre of Biotechnology (CBT) continued further developing its strengths in research and core competence in research infrastructure in molecular biosciences. The Centre provided state-of the-art core facilities, education and training for altogether 80 BioCity Turku research groups and six research programs featuring altogether seven Academy of Finland Centers of Excellence. Research was focused on cell signalling, regulation of gene and protein expression, and systems biology. In 2010 a total of 63 papers were published, including top ranked journals. Altogether 14 Ph.D. students presented their dissertations in 2010, which is a record of our Centre. Two new international group leaders started research groups at the Centre, of whom Daniel Abankwa was awarded the prestigious Marie Curie grant and Patrik Jones, who joined us in 2009, received the distinguished ERC young investigator s award. We have made significant investments in developing the stateof-the-art platforms in genomics and functional genomics, proteomics, cell imaging and bioinformatics. The animal core facility takes up a sizeable portion of basic resources in serving researchers and Turku Centre for disease modelling. A joint organization of the Finnish biocenters, Biocenter Finland, was estabished in 2006 to facilitate national collaboration and to coordinate development of research infrastructres in Finland. Special funding from the Ministry of Education for provides an excellent opportunity to significantly improve research infrastucture and improve interactions between the biocenters. Several of our group leaders are actively engaged in these Biocenter Finland infrastructure networks. Hence, in addition to serving local needs, CBT now further develops and provides national services in several areas within the Biocenter Finland infrastucture network. Bioimaging and systems biology infrastructures are at the core of the research strategy of both our universities and central infrastructures in the research strategy of Biocity Turku. As seen from this report significant progress has been made already during the first year of these Biocenter Finland networks. University of Turku and Åbo Akademi University along with all the universites in Finland started with new judicial status in the beginning of 2010 with increased independence and responsibility. This should provide a substantial opportunity to execute strategic decisions to improve our resources in research and education in selected areas. The change has come with lots of new administrative challenges as structures, processes and tools have been re-established with a unforeseen speed. The sooner these obstacles are met the better so that our reserachers and administrative personnel can concentrate on achieving our main goals in research, education and devoloping cutting-edge research infrastructure. 4 5

6 I wish to congratulate our scientists for their first-rate accomplishments and express my deepest appreciation and gratitude to the our administrative and technical staff for their continuing commitment to making the Centre a great place to work! Riitta Riitta Lahesmaa, M.D., Ph.D., Professor Director Turku Centre for Biotechnology University of Turku and Åbo Akademi University YEAR 2010 IN A NUTSHELL RESEARCH AND EDUCATION scientific papers were published (p. 101) 14 new Ph.D. s graduated CBT was awarded a substantial 1,5 million funding through Biocenter Finland The Academy of Finland granted a a new postdoctoral fellowship to Dr. Sanna Edelman Two new international group leaders, Drs. Daniel Abankwa and David Hawkins were recruited For undergraduate training, CBT organized lecture courses and practical demonstrations including a laboratory course on Functional Genomics for Health Bioscience and Biology students (4 study points) and on Medical Biotechnology for Medical students (5 study points) 9 M.Sc. theses were completed DEVELOPMENT OF INFRASTRUCTURE, RESEARCH SERVICES AND CORE FACILITIES 2010 Finnish Microarray and Sequencing Centre 2010 The Centre got substantial competitive funding through Biocenter Finland to develop and provide national services in the area of gene expression, regulation of gene expression and epigenetics Dr. David Hawkins, Ph.D. was recruited as a group leader to establish epigenomics with the Centre s scientists Prof. Jorma Palvimo and Dr. Sami Väisänen joined as affiliated group leaders to facilitate and develop ChIP-seq platforms Prof. Harri Lähdesmäki and Dr. Matti Nykter joined as affiliated group leaders to strengthen development and implementation of NGS analysis methods The Centre changed its name from the Finnish DNA Microarray Centre to the Finnish Microarray and Sequencing Centre to reflect its activities in nextgeneration sequencing services/platform. Next-generation sequencing instrument: ABI SOLiD 3 Plus was upgraded to version 4 in April. FMSC s website was renovated to improve the visibility of the centre s services Several events were organized in collaboration with various instrument manufacturers throughout the year to spread information on available and emerging technologies and the related FMSC s services. FMSC personnel gave talks in many scientific events and organized training courses to educate researchers on various topics. Major efforts were carried out in further developing the centre s project consultation services to help customers design their experiments. Also the centre s bioinformatics team continued developing bioinformatics data analysis services. Several high impact papers were published with contribution from the FMSC 6 7

7 Proteomics and Mass spectrometry Laboratory 2010 New facility Website (including new Project, Pricing and Sample submission forms) Received large 3 year funding through Biocenter Finland. The LTQ OrbiTrap Velos /ETD and nanolc system was installed in September. Several new software purchases and developments to enable quantitative MS analysis. Approximately 3500 hours of MS service operation. New methods published in 2010 for quantitative proteomics and phosphorylation analysis. Several Nordic Quantitative Proteomics courses in MS-based phosphoprotein analysis and Design and Analysis of Quantitative Proteomics Experiments, held. Additional courses in Imaging Mass Spectrometry at Novartis (Basel) and our annual (4th) Summer School in Mass Spectrometry in Biotechnology and Medicine in Dubrovnik. Three international meetings were organised, of which one locally, and 10 local seminars were held in proteomics (2 Frontiers of Science). Dr. Petri Kouvonen defended in October his Ph.D. on Simplified sample handling in mass spectrometry based protein research - focus on protein phosphorylation. in the Facility. Dr. Susumu Imanishi, recruited in November to bolster PTM and MS analytical capacity. Several Masters students completed (Olli Kannaste, Veronika Suni, Ahmed Bulbul) and started (Firouz Saedi, Noora Jaakola). Two new Ph.D. students started (Olli Kannaste, Veronika Suni, Ahmed Bulbul). Cell Imaging Core 2010 June 15: Turku Bioimaging Open Day. The seminar was also published online as webinar, web participants from Helsinki and Kuopio. November 25: Installation of the new BD FACS Aria II cell sorter December 9: Received Academy of Finland Infrastructure Grant FIRI2010 over 1.5 M for a new cutting edge confocal microscope to study key molecular interactions in cancer Turku Bioimaging is one of the first test sites that define access criteria for nodes of Euro-BioImaging, an infrastructure umbrella organisation from the EU Other demos during the year: Volocity Image analysis software, EvosFL microscope, Guava Flow Cytometer, Lambert Instrument FLIM-microscope Viral Vector Facility 2010 Ketlin Adel was recruited to produce viral vectors as part of the Biocenter Finland funded service The Virus Vector Facility added Lenti vector production to its service repertoire New and competitive pricing was introduced adhering to Biocenter Finland guidelines Bioinformatics Unit 2010 High-throughput screening of natural molecules was established in conjunction with Prof. Pia Vuorela at Åbo Akademi University Increased collaboration between our unit and CSC in high power computing and cloud computing Participated in projects involving analysis of protein-protein and protein-ligand interactions, computer-aided prediction and intelligent molecular modeling and design; computerbased ligand docking and analysis; effects of molecular recognition and mutations on protein function Training of Ph.D. students in Bioinformatics and Computational Biology within the National Graduate School of Informational and Structural Biology. Contribution to courses organized by CBT and Åbo Akademi University Plans made to increase high-capacity storage infrastructure for archiving services to support Structural Bioinformatics, Structural Biology, Translational Area, Drug Discovery, Chemical Informatics and Bioimaging The High-throughput Bioinformatics Group (HTB) also organized a Chipster course in collaboration with CSC during May, The HTB group purchased and installed a computer cluster for next-generation sequencing (NGS) services. The group has been setting up bioinformatics pipelines for various NGS applications. Protein Crystallography Facility 2010 Continuation of participation in several courses (Medical Biochemistry, TERBIO, Protein Crystallography and Structural Genomics, How to solve a protein structure ) with lectures and demonstrations in the X-ray facility. New web site launched. New links were added to provide quick access to crystallographic theory, techniques, crystallization, software, news and events. New projects at various stages were initiated in collaboration with other groups in Finland and abroad. All major crystallographic programs were kept upgraded to latest versions. New computers and 3Dmonitors were purchased. Several docking calculations and ab initio structure predictions were carried out for the needs of various projects. Quality Assurance Unit 2010 Organized courses for the university on (1) quality assurance and metrology and (2) how to assure the reliability of your laboratory test results Individual training for graduate and post-graduate students Carried out GLP inspections for the Central Animal Laboratory 8 9

8 PhD and MSc Theses 2010 PhD Theses (p. 99) Name Supervisor Site besides CBT Ahlfors Helena Lahesmaa Riitta UTU/Department of Medical Biochemistry and Genetics Ahlskog Johanna Sistonen Lea ÅA/Department of Biosciences Blomster Henri Sistonen Lea ÅA/Department of Biosciences Filén Sanna Lahesmaa Riitta ÅA/Department of Biosciences Kouvonen Petri Corthals Garry UTU/Department of Medical Biochemistry and Genetics Kukkonen-Macchi Anu Kallio Marko UTU/Department of Medical Biochemistry and Genetics Pallari Hanna-Mari Eriksson John ÅA/Department of Biosciences Peuhu Emilia Eriksson John ÅA/Department of Biosciences Sandqvist Anton Sistonen Lea ÅA/Department of Biosciences Tahvanainen Johanna Lahesmaa Riitta UTU/Department of Medical Biochemistry and Genetics Tiikkainen Pekka Kallioniemi Olli UTU/Department of Pharmacology, Drug Development and Therapeutics Toivonen Raine Savontaus Mikko UTU/Department of Medical Biochemistry and Genetics Tuomi Saara Ivaska Johanna UTU/Department of Medical Biochemistry and Genetics Vuoriluoto Karoliina Ivaska Johanna UTU/Department of Medical Biochemistry and Genetics MSc Theses Name Supervisor Site besides CBT Deshpande Prasannakumar Coffey Eleanor University of Skovde, Sweden Eerola Sini Koskinen Päivi UTU/Department of Biology Högnäs Gunilla Ivaska Johanna ÅA/Department of Biosciences Kannaste Olli Corthals Garry UTU/Department of Biology Laiterä Tiina Westermarck Jukka UTU/Department of Biology Md Bulbul Ahmed Corthals Garry University of Skovde, Sweden Piilonen Katri Jaakkola Panu UTU/Health biosciences Suni Veronika Corthals Garry UTU/Department of Information Technology Virtakoivu Reetta Ivaska Johanna UTU/Department of Biochemistry From left to right, front row: Juha Strandén, Terhi Jokilehto, Marjo Hakkarainen, Elina Arojoki, Perttu Terho, Markku Saari, Virpi Korpiranta, Eva Hirvensalo, second row: Mårten Hedman, Sirkku Grönroos, Petri Kouvonen, Päivi Junni, Riitta Lahesmaa, Susanna Pyökäri, Aila Jasmavaara, Anne Rokka, third row: Mikael Wasberg, Satu Alanko, Pasi Viljakainen, Hannele Vuori, Sarita Heinonen. FUNDING Sources of funding received by Centre for Biotechnology in 2010 (9.8 Million ) Academy of Finland 14% Services 6% Biocenter Finland 15% EU 16% Others 8% Universities 41% 10 11

9 PERSONNEL 2010 Administration LAHESMAA Riitta, Director, Professor, Group Leader ALANKO Satu, Coordinator GRÖNROOS Sirkku, Senior Administrative Assistant HIRVENSALO Eva, Clerical Official JASMAVAARA Aila, Clerical Official JOKILEHTO Terhi, Coordinator PLOSILA Riina, Coordinator BioCity Turku HEINO Jyrki, Biocity Turku Scientific Director, Professor HEINO Ilona, Student ALANKO Satu, Coordinator JAAKKOLA Minttu, Coordinator Technical Staff ANDERSEN Raija, Laboratory Technician HEDMAN Mårten, Systems Manager KORPIRANTA Virpi, Instrument Maintenance STRANDÉN Juha, Laboratory Engineer VAHAKOSKI Petri, Systems Manager VILJAKAINEN Pasi, Senior Technician VUORI Hannele, Instrument Maintenance WASBERG Mikael, Laboratory Manager Mechanisms and Biosensors of GTPases ABANKWA Daniel, Group Leader GUZMAN Camilo, Postdoctoral Fellow IFTIKHAR Zuhair, Scientific Programmer NAJUMUDEEN Arafath Kaja, Graduate Student SOLMAN Maja, Graduate Student Data Mining and Modeling AITTOKALLIO Tero, Group Leader, Adjunct Professor NEVALAINEN Olli, Group Leader, Professor ELO Laura, Postdoctoral Fellow ERONEN Ville-Pekka, Undergraduate Student GAO Bin, Graduate Student HEISKANEN Marja, Graduate Student HIISSA Jukka, Graduate Student JÄRVINEN Aki, Undergraduate Student KOSKINEN Ville, Graduate Student LAAJALA Essi, Undergraduate Student LAAJALA Teemu Daniel, Undergraduate Student LINDEN Rolf, Graduate Student NATRI Lari, Undergraduate Student OKSER Sebastian, Graduate Student PIIPPO Mirva, Undergraduate Student SALMELA Pekka, Undergraduate Student SALMI Jussi, Postdoctoral Fellow SUOMI Tomi, Graduate Student TUIKKALA Johannes, Graduate Student VÄHÄMAA Heidi, Graduate Student Protein Kinase Function in Brain Development and Disease COFFEY, Eleanor, Group Leader, Academy of Finland Research Fellow ADEL Ketlin, Laboratory Technician DESHPANDE Prasannakumar, Graduate Student HEIKELÄ, Hanna, Undergraduate Student KOMULAINEN, Emilia, Graduate Student MOHAMMAD Hasan, Graduate Student MYSORE, Raghavendra, Graduate Student PADZIK, Artur, Graduate Student PYÖKÄRI Susanna, Laboratory Technician SUN Lihua, Graduate Student TUITTILA Minna, Postdoctoral Researcher ZDROJEWSKA, Justyna, Graduate student Proteomics and Mass Spectrometry CORTHALS Garry, Group Leader, Head of Proteomics ANDERSÉN Raija, Laboratory Technician HAKANEN Emmi, Undergraduate Student HEINONEN Arttu, Project Engineer IHERMANN Anneliis, Undergraduate Student IMAMURA Motonori, Undergraduate Student JAAKKOLA Noora, Undergraduate Student KANNASTE Olli, Undergraduate Student KAUNISMAA Katri, Undergraduate Student KOUVONEN Petri, Researcher MD BULBUL Ahmed, Undergraduate Student NEES Susanne, Coordinator RALPH Eliza, Systems Administrator ROKKA Anne, Postdoctoral Fellow SAEIDI Firouz, Undergraduate Student SUNI Veronika, Graduate Student VEHMAS Anni, Undergraduate Student VIRTANEN Fanni, Student YADAV Avinash, Undergraduate Student Organisation of Neuronal Signaling Pathways COURTNEY Michael, Professor, Group Leader HO Franz, Postdoctoral Researcher LI Lili, Graduate Student LIU Xiaonan, Graduate Student LOPEZ RODRIGUES Maykel, Graduate Student MARTINSSON Peter, Postdoctoral Researcher PEVGONEN Veera, Technicain TUITTILA Minna, Postdoctoral Researcher VERGUN Olga, Postdoctroal Researcher WANG Xijun, Graduate Student YADAV Leena, Graduate Student Cytoskeletal and survival signaling ERIKSSON John, Group Leader, Professor ASAOKA Tomoko, Graduate Student FERRARIS Saima, Graduate Student HYDER Claire, Graduate Student IMANISHI Susumu, Postdoctoral Fellow KASTU Juha, Project Engineer KAUNISTO Aura, Postdoctoral Fellow KOCHIN Vitaly, Postdoctoral fellow LAZARO, Glorianne, Exchange Student LINDQVIST Julia, Graduate Student LUNDGREN, Jolanta, Undergraduate Student ISONIEMI Kimmo, Graduate Student PALLARI Hanna-Mari, Postdoctoral Fellow PAUL Preethy, Graduate Student PEUHU Emilia, Postdoctoral Fellow REMES Mika, Graduate Student ROBERTS Maxwell, Undergraduate Student SAARENTO Helena, Research Associate SÖDERSTRÖM Thomas, Postdoctoral fellow TORVALDSON Elin, Graduate student Cell Imaging Core Abankwa Daniel, Group Leader, Head of Cell Imaging Core COFFEY Eleanor, Academy of Finland Research Fellow, Coordinator of the Cell Imaging Unit ERIKSSON John, Group Leader, Professor KORHONEN Jari, Project Engineer SANDHOLM Jouko, Research Engineer SAARI Markku, Project Engineer TERHO Perttu, Project Engineer Cell Adhesion and Cancer IVASKA Johanna, Group Leader, Professor ALANKO Jonna, Graduate Student ARJONEN Antti, Graduate Student DE FRANCESCHI Nicola, Graduate student HÖGNÄS Gunilla, Graduate Student KAUKONEN Riina, Graduate Student LAHTINEN Laura, Graduate Student MAI Anja, Graduate student MATTILA Elina, Postdoctoral Fellow MUHARRAM Ghaffar, Postdoctoral Fellow POUWELS Jeroen, Postdoctoral Fellow SIIVONEN Jenni, Laboratory Technician TUOMI Saara, Postdoctoral Fellow VELTEL Stefan, Postdoctoral Fellow VIRTAKOIVU Reetta, Graduate Student Hypoxia Group JAAKKOLA Panu, Group Leader, Adjunct Professor BORBELY Gabor, Exchange Student HEIKKINEN Pekka, Graduate Student HÖGEL Heidi, Graduate Student JOKILEHTO Terhi, Graduate Student KALEVO-MATTILA Taina, Laboratory Technician NUUTILA Maiju, Undergraduate Student RANTANEN Krista, Graduate Student Kinetochore and Cancer Research Group KALLIO Marko, Group Leader, Chief Research Scientist, Adjunct Professor JAAKKOLA Kimmo, Postdoctoral Fellow KUKKONEN-MACCHI Anu, Graduate Student LAINE Leena, Postdoctoral Fellow MÄKI-JOUPPILA Jenni, Graduate Student NARVI Elli, Postdoctoral Fellow OETKEN-LINDHOLM Christina, Postdoctoral Fellow SALMELA Anna-Leena, Graduate Student TOIVONEN Pauliina, Laboratory Technician WINSEL Sebastian, Postdoctoral Fellow VUORILUOTO Mariaana, Graduate Student Canceromics Research Programme KALLIONIEMI Olli, Group Leader, Director PLOSILA Riina, Coordinator AAKULA Anna, Graduate Student BUCHER Elmar, Graduate Student BJÖRKMAN Mari Graduate Student GUPTA Santosh, Graduate Student KETOLA Kirsi, Graduate Student KOHONEN Pekka, Graduate Student POLLARI Sirkku, Graduate Student VAINIO Paula, Graduate Student Signaling Pathways Regulated by Oncogenic Pim Kinases KOSKINEN Päivi, Group Leader, Adjunct Professor EEROLA Sini, Undergraduate Student EKMAN Heidi, Undergraduate Student LAITERÄ Tiina, Undergraduate Student RAINIO Eeva-Marja, Postdoctoral Fellow SANDHOLM Jouko, Graduate Student SANTIO Niina, Undergraduate Student VAHAKOSKI Riitta, Graduate Student Molecular Immunology Group LAHESMAA Riitta, Director, Professor, Group Leader ALANEN Veera, Undergraduate Student EDELMAN Sanna, Postdoctoral Fellow ENGSTRÖM Emilia, Undergraduate Student FILEN Sanna, Graduate Student HAKKARAINEN Marjo, Laboratory Technician HAHNE Lauri, Undergraduate Student HEINONEN Mirkka, Graduate Student HEINONEN Sarita, Laboratory Technician KALLIONPÄÄ Henna, Graduate Student KYLÄNIEMI Minna, Graduate Student LAAJALA Essi, Undergraduate Student LUND Riikka, Senior Scientist LÖNNBERG Tapio, Graduate Student MOULDER Robert, Senior Scientist NÄRVÄ, Elisa, Graduate Student OIKARI Lotta, Undergraduate Student PIETILÄ Elina, Laboratory Technician PURSIHEIMO Juha-Pekka, Senior Scientist RAHKONEN Nelly, Graduate Student RAJAVUORI Anna, Student RASOOL Omid, Adjunct Professor, Senior Scientist SALO Verna, Undergraduate Student SARAPULOV Alexey, Graduate Student SOMANI Juhi, Undergraduate Student SPARVERO Louis, Senior Research Fellow TAHVANAINEN Johanna, Postdoctoral Fellow TRIPATHI Subhash, Graduate Student TUOMELA Soile, Graduate Student VALTONEN Joona, Undergraduate Student 12 13

10 Quality Assurance Unit LINKO Linnéa, Adjunct Professor Protein Crystallography PAPAGEORGIOU Tassos, Group Leader, Adjunct Professor DHAVALA Prathusha, Graduate Student HAIKARAINEN Teemu, Graduate Student KINARET Pia, Undergraduate Student MATTSSON Jesse, Graduate Student MOHAMMADI Omid, Graduate Student MULETA Abdi, Undergraduate Student SUBEDI Bishwa, Undergraduate Student WECKSTRÖM Kristian, Senior Scientist Bioinformatics Unit DENESSIOUK Konstantin, Group Leader (Structural Bioinformatics) GYENESEI Attila, Senior Scientist (High-throughput Bioinformatics) CHOUHAN Bhanupratap Singh, Graduate Student JUNTTILA Sini, Graduate Student LAIHO Asta, Project Engineer KYTÖMÄKI Leena, Undergraduate Student Cell fate SAHLGREN Cecilia, Group Leader, Academy of Finland Research Fellow ANTFOLK Daniel, Undergraduate Student ANTILA Christian, Undergraduate Student BATE-EYA Laurel Tabe, Graduate Student HIETAMÄKI Marika, Graduate Student GRANQVIST Cecilia, Undergraduate Student LANDOR Sebastian, Graduate Student MAMAEVA Veronika, Postdoctoral Fellow NIEMI Rasmus, Undergraduate Student SAARENTO, Helena, Laboratory Technician Targeting Strategies for Gene Therapy SAVONTAUS Mikko, Group Leader, Adjunct Professor EEROLA Kim, Graduate Student MATTILA Minttu, Undergraduate Student TOIVONEN Raine, Graduate Student Transcriptional Regulation of Heat Shock SISTONEN Lea, Group Leader, Professor AHLSKOG Johanna, Postdoctoral Fellow ANCKAR Julius, Postdoctoral Fellow BERGMAN Heidi, Undergraduate Student BJÖRK Johanna, Graduate Student BLOM Malin, Undergraduate Student BLOMSTER Henri, Postdoctoral Fellow BUDZYNSKI Marek, Graduate Student CHITIKOVA Zhanna, Graduate Student ELSING Alexandra, Graduate Student HENRIKSSON Eva, Postdoctoral Fellow HYRY Annukka, Undergraduate Student JOUTSEN Jenny, Graduate Student PUUSTINEN Mikael, Undergraduate Student RAUTOMA Karoliina, Undergraduate Student SAARENTO Helena, Research Associate SANDQVIST Anton, Postdoctoral Fellow VARTIAINEN Aki, Undergraduate Student VASARA Jenni, Undergraduate Student VIHERVAARA Anniina, Graduate Student ÅKERFELT Malin, Postdoctoral Fellow The Finnish Microarray and Sequencing Centre Full-time personnel: GYENESEI Attila, Senior Scientist HAWKINS David, Group Leader JUNNI Päivi, Laboratory Technician JUNTTILA Sini, Project Engineer KYTÖMÄKI Leena, Biotechnology Engineer LAIHO Asta, Project Engineer LUND Riikka, Senior Scientist NURMI Miina, Laboratory Technician PURSIHEIMO Juha-Pekka, Senior Scientist RISSANEN Oso, Laboratory Technician VENHO Reija, Laboratory Technician VIRTANEN Eveliina, Project Engineer Part-time personnel: ALA-KULJU Ritva, Undergraduate Student ISOJÄRVI Janne, Undergraduate Student SIPILÄ Anna, Undergraduate Student SUNDSTRÖM Robin, Undergraduate Student TAMMINEN Seppo, Undergraduate Student Cancer Cell Signaling WESTERMARCK Jukka, Group Leader, Professor CÕME Christophe, Postdoctoral Fellow CVRLJEVIC Anna, Postdoctoral Fellow HALONEN Tuuli, Graduate Student KALEVO-MATTILA Taina, Laboratory Technician KAUKO Otto, Graduate Student KAUR Amanpreet, Graduate Student LAINE Anni, Graduate Student MANNERMAA Leni, Scientist NIEMELÄ Minna, Graduate Student OKKERI Juha, Postdoctoral fellow POKHAREL Yuba, Postdoctoral fellow VENTELÄ Sami, Postdoctoral Fellow Coordination of European Biobanking VUORIO Eero, Professor, Director, Biocenter Finland SALMINEN-MANKONEN Heli, Adjunct professor, Project manager GRÖNROOS Sirkku, Project assistant THE FINNISH MICROARRAY AND SEQUENCING CENTRE Scientists in charge: Attila Gyenesei, Ph.D., Senior Scientist FMSC services and daily issues, bioinformatics Juha-Pekka Pursiheimo, Ph.D., Senior Scientist SOLID NGS Riikka Lund, Ph.D., Senior Scientist Epigenetics David Hawkins, Ph.D., Group Leader Epigenetics and emerging technologies Contact information: Turku Centre for Biotechnology, BioCity, Tykistökatu 6A, P.O. Box 123, FIN-2050 Turku, Finland. Tel , Fax Personnel: Ritva Ala-Kulju, Päivi Junni, Sini Junttila, Leena Kytömäki, Asta Laiho, Oso Rissanen, Reija Venho, Eveliina Virtanen, Seppo Tamminen Steering Committee: Prof. Olli Carpén, Chair (University of Turku), Prof. Eva-Mari Aro (University of Turku), Prof. Klaus Elenius (University of Turku), Prof. Riitta Lahesmaa (University of Turku), Prof. Tarja Laitinen (University of Turku), Prof. Harri Lähdesmäki (University of Turku, Aalto University), Prof. Craig Primmer (University of Turku), Prof. Harri Savilahti (University of Turku), Prof. Lea Sistonen (Åbo Akademi University), Prof. Stina Syrjänen (University of Turku) General description: The Finnish Microarray and Sequencing Centre (FMSC), an internationally recognised Functional Genomics Core Facility belongs to the Turku Centre for Biotechnology. As a national core facility, we provide state-of-the-art research technologies and services in the areas of genomics, epigenomics, transcriptomics and bioinformatics for the Finnish as well as the international scientific community. Our services include next-generation sequencing and microarray based services mainly facusing on gene expression and regulation as well as epigenetics, Real-Time PCR and traditional DNA sequencing. Our service covers all steps from experimental planning and design to sample processing and bioinformatics data analysis. The Centre also regularly organizes courses, symposia and training for its users. FMSC hosts a high-throughput next-generation sequencing (NGS) instrument SOLiD TM 4 from Life Technologies. The system supports a wide range of genetics applications covering genomics, transcriptomics and epigenomics and it is distinguished by its unmatched accuracy and capability of generating more than 100 gigabases of mappable sequence data per run. The combination of increased throughput, shorter run times, and improved data analysis make the SOLiD technology an ideal choice for research applications in any genetics project. The system enables for example distinguishing strand specific expression patterns, 14 15

11 discoverage of novel stranscripts and splice variation without the bias of microarrays, detecting SNPs at low coverage with a low false positive rate, global assessment of DNA-protein binding interactions and charaterization of structural rearrangements including balanced translocations. Our Centre also provides services on commercial microarray platforms for genome-wide RNA expression profiling, SNP genotyping and comparative genomic hybridization needs. These platforms include Affymetrix GeneChip, Illumina Sentrix Bead Array and Agilent DNA technology services for all of which we have been granted the Certified Service Provider status. All platforms have dedicated scanners and software for array data analysis. Diverse aspects of the microarray techniques are continuously developed and tested. The Microarray and Sequencing Centre also offers a number of other genomic analysis technologies for gene expression, SNP and genotyping studies including a sequencing facility and realtime PCR service. Services include BioRad Experion and Agilent Bioanalyzer runs for verifying the RNA quality. Bioinformatics data analysis and data mining are included in the data analysis service that is provided for microarray and nextgeneration sequencing customers. The data handling is done by our bioinformaticians, using both commercial and R/Bioconductor software tools. and its regulation. Publications and unpublished data by Helicos scientists and their collaborators indicated this to be a method of choice for single molecule sequencing applied to digital gene expression and ChIP sequencing. Biocity Turku decided to test this technology - as BF funding was not available, strategic funding was reserved by our university for purchase. The instrument was installed in March 2010 for evaluation. Methods and data analysis pipelines were set up and tested for Digital Gene Expression (DGE), RNA-Seq and ChIP-Seq analysis. These have provided invaluable data not possible to generate through the other platforms available. During the summer 2010 the company went through reorganization and changed their business strategy. Thus, Heliscope instrument was not purchased, however, the collaboration with the company continues. The advantages of the Helicos technique include low amount of starting material needed, short sample preparation time (3h-3d) and amplification free sample processing for DGE and ChIP-Seq applications. Funding: University of Turku Biocenter Finland Users: Finnish Microarray and Sequencing Centre has national and international customers from universities, biocenters and research institutes in the field of biosciences. Seminars and practical courses on microarrays, next-generation sequencing and related bioinformatics are held frequently to facilitate knowledge transfer within the field, often this is done in collaboration with graduate schools. Major achievements in 2010: According to the division of tasks within the Biocenter Finland Genome-wide Methods Network Turku node focuses on developing technologies in the areas of gene expression. Accordingly, we have focused on optimising methods to implement services for: Sequencing of immunoprecipitated DNA/RNA (ChIP-seq, CLIP-seq, ChIP-chip) RNA sequencing Gene expression microarrays Additionally, the Centre is focusing on developing advanced techniques and optimizing reagents for studies on epigenetics and chromatin structure exploiting both next generation and later nextnext generation platforms. To achieve the goals the following was accomplished in 2010: SOLiD 3 was successfully installed, upgraded to SOLiD 3.5 and then to SOLiD 4; during the first quarter of the 2011 the instrument will be further upgraded to the latest version, 5500xl SOLiD. 84 service projects were carried out in 2010 including both microarray and NGS projects. For the next-next generation sequencing, HeliScope Instrument from Helicos BioSciences was tested. Based on our thorough survey in 2009 Helicos Single Molecule Sequencing was identified as one of the most promising emerging technologies and particularly useful for studies in our focus area of expertise - gene expression From left to right: Sini Junttila, Reija Venho, Leni Mannermaa, Eveliina Virtanen, Päivi Junni, Attila Gyenesei, Asta Laiho, Sanna Vuorikoski and Juha-Pekka Pursiheimo

12 CELL IMAGING CORE (CIC) Coordinator and Group Leader Daniel Abankwa, Ph.D., PI, Turku Centre for Biotechnology, BioCity, 5 th floor, Tykistökatu 6B, FI-20521, Finland. Tel , Fax daniel.abankwa@btk.fi Technical Team/Technical Team leaders Perttu Terho, M.Sc., Technical Engineer Flow Cytometry, perttu.terho@btk.fi, Markku Saari, M.Sc., Researcher Microscopy, msaari@btk.fi, Jari Korhonen, M.Sc., Researcher Microscopy, jari.korhonen@abo.fi, Jouko Sandholm, M.Sc., Senior Researcher Microscopy, jouko.sandholm@btk.fi Most of the instruments are provided in two facility areas of the CBT, while others are housed nearby within Biocity. In mid 2011, we will expand our instrumentation to feature a new confocal microscope with fluorescence lifetime imaging and fluorescence correlation spectroscopy capabilities. In addition, image treatment workstations will become available, that run the locally developed BioImageXD advanced image treatment software. We organize local and national training programs, service existing equipment, sustain research on new imaging techniques, and implement the latest technological advances demanded by the research community. A number of international leaders in the field of microscopic imaging have visited Turku for scientific presentations and lectures, such as Jennifer Lippincott-Schwartz (NIH, USA) and Kota Miura (EMBL, Germany). Steering Committee: Prof. Olli Carpén, M.D., Ph.D., University of Turku, Prof. John Eriksson (chairman), Ph.D., Åbo Akademi University, Prof. Jyrki Heino, M.D., Ph.D., University of Turku, Prof. Pekka Hänninen, Ph.D., University of Turku, Prof. Sirpa Jalkanen, M.D., Ph.D., University of Turku, Prof. Riitta Lahesmaa, M.D., Ph.D., University of Turku, Prof. Olli Lassila, M.D., Ph.D., Prof. Matti Poutanen, Ph.D., University of Turku, Prof. Lea Sistonen, Ph.D., Åbo Akademi University, Kid Törnquist, Ph.D., Åbo Akademi University Core facility description: The mission of Cell Imaging Core (CIC) is to provide state-of-theart cell imaging and flow cytometry technologies and to make them available to scientists and students mainly coming from the University of Turku, Åbo Akademi University and VTT Technical Research Centre for Medical Biotechnology. Importantly, CIC is open to both academic and industrial researchers. One major goal of CIC is to enhance the research and teaching environment locally, nationally and internationally. Therefore, CIC: provides technical training to local and visiting researchers and to industries offers consultation on experimental design and image analysis evaluates new methods and fluorescence tools and communicates acquired knowledge to users implements advances in hardware and software relevant for biomedical sciences provides ongoing education in theory and practice by organizing training courses and international workshops Our staff include a coordinator and experienced application specialists, who maintain the instruments, learn new technologies and most importantly, provide personal training to users. Our areas of technical expertise are STED-superresolution microscopy, F-techniques (FRET, FRAP and FLIP-imaging), confocal microscopy (including timelapse and spectral detection), high-content imaging, widefield fast CCD imaging, laser microdissection, high throughput cell sorting, flow cytometry FRET and advanced flow cytometry software development. The STED-technique was developed by Stefan Hell in the group of Prof. Pekka Hänninen in the mid 1990s in Turku. Complementary to this superresolution technology, we have two Atomic Force Microscopy (AFM) setups, which are coupled to a Zeiss 510 and the Leica STED microscope From left to right: Daniel Abwanka, Perttu Terho, Markku Saari, Jari Korhonen

13 Current information on events, services and pricing can be found on the facility webpages. CIC has succeeded both as a service provider and as a point of integration of emerging imaging technologies. Added value is achieved by the first-class expertise in the fields of fluorescenceactivated cell sorting, fluorescence-based screening and robotic instrumentation, high-content screening, in vivo animal imaging, and viral gene transfer in the Turku scientific community. CIC is nationally and internationally networked (e.g. through the Nordic Network on Imaging in Medicine and Biology). Importantly, CIC is one of the major contributors to Turku Bioimaging, an umbrella organization, which aims at organizing and supporting bioimaging expertise in the Turku area. Through this activity, Turku Bioimaging sites have become one of the first three test sites for the Euro-BioImaging initiative. Euro-BioImaging aims at providing access, service and training to state-of-the-art imaging technologies in Europe. To this end a harmonized infrastructure deployment is planned in the next few years, which is meant to facilitate excellence in research. Funding: The Academy of Finland, University of Turku, Åbo Akademi University, BioCity Turku Research Groups, Biocenter Finland, Health and Welfare Ministry THE PROTEOMICS FACILITY Coordinator and Group Leader: Garry Corthals, Ph.D. (2005). Address: Turku Centre for Biotechnology, BioCity, Tykistökatu 6, P.O. Box 123, FI Turku, Finland. Tel , Fax garry.corthals@btk.fi Personnel: Senior scientists: Dr. Anne Rokka, Ph.D.; Petri Kouvonen, Ph.D.; Susumu Imanishi, Ph.D.; Laboratory Engineer: Arttu Heinonen; Technician: Raija Andersen; Bioinformatician: Eliza Ralph Steering Committee: Prof. Eva-Mari Aro (University of Turku), Dr. Eleanor Coffey (Åbo Akademi University), Prof. John Eriksson (Åbo Akademi University), Prof. Jyrki Heino (University of Turku), Prof. Riitta Lahesmaa (CBT), Prof. Matti Poutanen, Prof. Craig Primmer (University of Turku), Prof. Jukka Westermarck (CBT) and Prof. Johanna Ivaska (VTT & CBT) General description: The Turku Proteomics Facility is engaged in the development and application of proteomics and mass spectral methods in key areas of life science research. In doing so we have developed a wide basis of operation and expertise in Quantitative proteomics, Posttranslational modification analysis, Imaging mass spectrometry, Biological mass spectrometry, Protein separation and Bioinformatics. The Mission of the Facility is to advance MS methods and instrumentation to meet the needs in molecular biotechnology and medicine. Our goals are to identify new areas appropriate for MS in biological sciences and to develop new approaches involving MS, to apply cutting-edge MS to tackle critical questions in biological sciences, and train students, postdoctoral fellows and practicing scientists in the use of MS and encourage its wide and appropriate use. We are a nationally funded technology platform supported by Biocentre Finland, spearheading mass spectrometric strategies for quantitative analysis of proteins and proteomes, and structural analysis of PTMs. Analytical services The facility offers access to sophisticated instruments and performs structural analytical protein and proteome measurements. Most services involve mass spectral methods integrated with protein and peptide enrichment workflows for large-scale analysis of proteomes or detailed characterisation of single proteins. We aim to offer the best possible analytical proteomics services to bioscience researchers in academia and industry, both locally and nationally through Biocentre Finland coordinated activities. A broad range of mass spectral analyses are performed, and at the nationally level the facility spearheads developments in two of its services; MSbased quantitative proteomics and phosphorylation determination

14 A full representation of our services are as follows: Quantitative proteomics Targeted analysis of proteomes following isobaric or isotopic labelling with itraq and SILAC reagents. Additionally we have established a framework for label-free quantitative analysis, particularly useful for large-scale clinical studies. Qualitative proteomics -omic-scale analysis of cells, tissues and fluids is available in all areas of life science. We have developed several integrated fractionation techniques to provide deep proteome coverage from minimal sample amounts. Post-translational modifications a long standing history with phosphorylation analysis exists on campus, and we are actively expanding our PTM tool set through newly developed methods by various closely affiliated groups, such as sumoylation. Imaging mass spectrometry imaging of tissues is offered as a collaborative service with the proteomics research group. IMS is expanding its activities in Turku in the new Master s Degree Programme in Turku Bioimaging. Biological mass spectrometry various analytical measurements for protein, peptide and small molecule structure determination, mass determination and peptide and protein purity are offered. Protein separation numerous separation technologies including liquid chromatography and a variety of gel based methods such as 1-DE, 2-DE, peptide-ipg and blue native gel electrophoresis. Bioinformatics in all areas of proteomics bioinformatics services are offered including identification, quantitation and validation studies, reporting and software development. Funding: Biocenter Finland, The Academy of Finland, TEKES, City of Turku, Ministry of Education/Proteomics and the Centre of Expertise of Southwest Finland, Turku University and Åbo Akademi University, Bruker Daltonics, the Systems Biology Research Program. Users: Biocentre Finland universities, The University of Turku, Åbo Akademi University, Turku Polytechnic, VTT - Molecular Biotechnology. CoE s in: Translational Genome-Scale Biology; Evolutionary Genetics and Physiology; Integrative Photosynthesis and Bioactive Compound Research at Systems Biology Level; and Åbo Akademi CoE in Cell Stress. The Systems Biology Research Program, national research groups, Turku Hospitals, the Finnish Red Cross and the National Animal Research Centre. PROTEIN CRYSTALLOGRAPHY CORE FACILITY Head: Anastassios C. Papageorgiou, Ph.D., Adjunct Professor in Biochemistry and Structural Biology Turku Centre for Biotechnology, BioCity, Tykistökatu 6A, FI Turku, Finland. Tel , Fax tassos.papageorgiou@btk.fi Technical Team: Technical support: Juha Strandén, Pasi Viljakainen. Computational support: Petri Vahakoski, Mårten Hedman Steering committee: Jyrki Heino, Professor, Department of Biochemistry and Food Chemistry, University of Turku Reijo Lahti, Professor, Department of Biochemistry and Food Chemistry, University of Turku Tiina Salminen, Senior lecturer, Department of Biochemistry, Åbo Akademi Description of the Facility X-ray crystallography is a proven technique for detailed structurefunction studies of biological macromolecules. The Protein Crystallography Core Facility at CBT uses state-of-the-art equipment to determine the crystal structures of various proteins and their complexes. The Facility consists of an X-ray generator (soon to be replaced by a new one), Mar345 imaging plate detector, Osmic confocal mirrors, a Cryostream Cooler (Oxford Cryosystems) and several computers running under Linux operating systems for heavy duty calculations. The Facility has several workstations to run a variety of molecular graphics software (O, XtalView, Grasp, COOT, CCP4mg, PyMol, Chimera), modeling and docking programs (MODELLER, Hex, Discovery Studio, ROSETTA), and various crystallographic packages (HKL, XDS, CNS, CCP4, SHELX, SOLVE, SHARP, PHENIX) for data processing, analysis, phasing and refinement. The Facility has long expertise in all steps of a crystal structure determination: protein purification, crystallization, data collection (both in-house and in synchrotron radiation sources), data processing, phase determination, refinement and detailed analysis of the final structure. Incubators at different temperatures (4 C, 16 C and 23 C) for crystallization set-ups and a number of commercial screens for establishing initial crystallization conditions are available. In addition, we can provide homology modeling services and design of mutants for functional studies as well as ab initio predictions of protein structures. Since protein crystallography requires highly pure protein preparations, we can offer full support and consultation on protein purification strategies apart from the services in structure determination and modeling. The Facility is able to undertake research projects for academic groups and companies, either in the form of collaborative efforts or as services. Protein Crystallography requires a multi-disciplinary approach and we are especially interested in bringing together expertise from various groups in order to better understand the structure-function relationship of biological macromolecules in key biological processes. Funding: Systems Biology research program, Biocenter Finland, University of Turku 22 23

15 BIOINFORMATICS CORE Coordination: Konstantin Denessiouk, Ph.D., Docent in Biochemistry. Bioinformatics Group leader. Centre for Biotechnology, Tykistökatu 6, BioCity 5th floor, Turku, Turku. Attila Gyenesei, Ph.D., Senior Scientist, Turku Centre for Biotechnology, BioCity, Tykistökatu 6A, P.O. Box 123, FIN-2050 Turku, Finland. Tel , Fax Personnel: Bhanupratap Singh Chouhan, Sini Junttila, Asta Laiho, Leena Kytömäki, Seppo Tamminen Description of the Facility: The bioinformatics core at the Turku Centre for Biotechnology is divided into Structural Bioinformatics and High-throughput Bioinformatics facilities. The main goal of the Structural Bioinformatics Core is to apply methods and techniques of bioinformatics to study biological macromolecules, their interactions and function. We work in close collaboration with experimental groups and are able to provide structure-related analysis and prediction in different biological systems. The core works closely with the CSC Finnish IT Center for Science, the Finnish national supercomputing centre and the Structural Bioinformatics Laboratory at the Åbo Akademi University. High-throughput bioinformatics complements experimental genomics and transcriptomics by storing, analysing and integrating data and generating hypotheses to guide the design of new experiments to further elucidate gene function. The core provides services in the analysis of microarray and deep sequencing data. In addition to providing data analysis and data integration services we have robust methods for the design of experiments and novel microarrays for both diagnostics and biological marker selection. Our analysts are supported by robust super-computing facilities and state-of-the-art software. Team members are engaged in the ongoing development of advanced analysis tools and research on generating novel approaches for the analysis of high-throughput data sets. The main services of our core are: Experimental design consultation Data analysis of various microarray and deep sequencing data types Data analysis education and training Computer-based analysis of protein-protein and protein-ligand interactions Computer-aided prediction and intelligent molecular modeling and design Computer-based ligand docking Analysis and prediction of effects of molecular recognition and mutations on protein function Selected Publications: Kankare M, Salminen T, Laiho A, Vesala L, Hoikkala A. Changes in gene expression linked with adult reproductive diapause in a northern malt fly species: a candidate gene microarray study. BMC Ecol Feb 1;10:3.PMID: Sirén A, Polvi A, Chahine L, Labuda M, Bourgoin S, Anttonen AK, Kousi M, Hirvonen K, Simola KO, Andermann E, Laiho A, Soini J, Koivikko M, Laaksonen R, Pandolfo M, Lehesjoki AE. Suggestive evidence for a new locus for epilepsy with heterogeneous phenotypes on chromosome 17q. Epilepsy Res Jan;88(1):6575. Epub 2009 Nov 14.PMID: Huvila J, Brandt A, Rojas CR, Pasanen S, Talve L, Hirsimäki P, Fey V, Kytömäki L, Saukko P, Carpén O, Soini JT, Grénman S, Auranen A. Gene Expression profiling og endometrial adenocarcinomas reveals increased apolipoprotein E expression in poorly differentiated tumors. Int J Gynecol Cancer Oct;19(7): Oksala N, Levula M, Airla N, Pelto-Huikko M, Ortiz RM, Järvinen O, Salenius JP, Ozsait B, Komurcu-Bayrak E, Erginel-Unaltuna N, Huovila AP, Kytömäki L, Soini JT, Kähönen M, Karhunen PJ, Laaksonen R, Lehtimäki T. ADAM-9, ADAM-15, and ADAM-17 are upregulated in macrophages in advanced human atherosclerotic plaques in aorta and carotid and femoral arteries--tampere vascular study. Ann Med. 2009;41(4): Levula M, Airla N, Oksala N, Hernesniemi JA, Pelto-Huikko M, Salenius JP, Zeitlin R, Järvinen O, Huovila AP, Nikkari ST, Jaakkola O, Ilveskoski E, Mikkelsson J, Perola M, Laaksonen R, Kytömäki L, Soini JT, Kahonen M, Parkkinen J, Karhunen PJ, Lehtimäki T. ADAM8 and its single nucleotide polymorphism 2662 T/G are associated with advanced atherosclerosis and fatal myocardial infarction: Tampere vascular study. Ann Med Jul 2:1-11. Fan YM, Karhunen PJ, Levula M, Ilveskoski E, Mikkelsson J, Kajander OA, Järvinen O, Oksala N, Thusberg J, Vihinen M, Salenius JP, Kytömäki L, Soini JT, Laaksonen R, Lehtimäki T. Expression of sterol regulatory element-binding transcription factor (SREBF) 2 and SREBF cleavage-activating protein (SCAP) in human atheroma and the association of their allelic variants with sudden cardiac death. Thromb J Dec 30;6:17. Funding: Grants from the Sigrid Jusélius Foundation, and the Borg Foundation (Åbo Akademi University); Grant from the National Graduate School in Informational and Structural Biology (ISB). Biocenter Finland Infrastructure fund. Users: The Bioinformatics core has users from Finnish universities, biocenters and research institutes in the field of biosciences. From left to right: Sini Junttila, Asta Laiho, Leena Kytömäki, Attila Gyenesei

16 VIRUS VECTOR FACILITY Coordination Eleanor Coffey, Ph.D., Adjunct Professor in Cellular and Molecular Biology, Turku Center for Biotechnology, BioCity, 5 th floor, Tykistokatu 6, FI-20521, Finland. Jukka Westermarck, M.D., Ph.D., Professor of the Cancer Society of Finland, Turku Center for Biotechnology, BioCity, 5th floor, Tykistokatu 6, FI-20521, Finland. Research, Development and Training Anna Cvrljevic, postdoctoral researcher (Westermarck lab), Turku Centre for Biotechnology, BioCity 5th floor, Tykistökatu 6, FI-20521, Finland. anna.curljev@btk.fi Technical Team Ketlin Adel, Laboratory Technician, kadel@btk.fi The Virus Vector Facility produces viral vectors for local and national research groups. During 2010, the Virus Vector Facility joined the national infrastructure network on Viral Gene Transfer, funded by Biocenter Finland. Our primary function is to facilitate the use of viral vectors by national researchers. To meet these goals the virus vector facility Produces on demand adenoviruses and lentiviruses expressing genes of interest, as a research service provides a fully equipped bio-safety level-2 lab for researchers wishing to produce their own vectors (replication deficient viruses only) supplies working protocols for production of adeno and lenti vectors and trains researchers in the safe preparation and handling of viral vectors organises seminars and courses emphasizing practical issues related to gene transfer technology coordinates a network of local experts from whom consultation on design of viral vectors can be sought The virus vector facility has a national user base with regular customers from the universities of Turku, Oulu and Helsinki as well as customers from biotech companies. In addition to customer service, our infrastructure is used by 16 local research groups producing adenoviruses, adeno-associated virus, retro- and lentivirus for their own research purposes. These viruses are typically used to obtain high efficiency gene transfer in difficult to transfect cells such as primary cultures of T lymphocytes and neurons and for in vivo cancer studies. Another typical application is the use of viral vectors for delivery of shrna. Protocol optimization has been completed for high efficiency gene silencing in primary cultured neurons and T lymphocytes and more recently investigators are using virally delivered mirnas for gene knockdown studies. To build on local expertise in gene transfer technologies, the Virus Vector Facility networks with experts in viral vector design. Thus a number of local experts on retroviruses and alpha-viruses are available for consultation on vector design, production and concentration. From left to right: Ketlin Adel, Susanna Pyökäri, Jukka Westermarck, Eleanor Coffey 26 27

17 COORDINATION OF EUROPEAN BIOBANKING Head: Eero Vuorio, Professor, Director, Biocenter Finland, P.O. Box 56, University of Helsinki, FI Helsinki, Finland Mobile phone , Project Manager: Heli Salminen-Mankonen, Ph.D., Docent, University of Turku, Centre for Biotechnology, Tykistökatu 6, FI Turku, Finland, Tel: , is the generation of an IT infrastructure capable of linking the existing biobank-derived genetic and molecular phenotyping data with data from clinical phenotyping and health-related registries. The new European legal entity (ERIC) developed by the European Commission to support the needs and operation of research infrastructures, foresees the establishment of operational sites (National Nodes) in different Member States under one legislation. The BBMRI Management Office in Turku has also played an active part in establishing the Finnish National Node, BBMRI.fi, and in organizing the collaboration of Nordic biobanks where many of the operational concepts and principles of BBMRI have been tested. Funding: The preparatory phase ( ) of BBMRI has been financially supported by the European Commission (grant agreement ). Description of project: Human biological samples, such as blood, tissues or DNA, plus associated clinical and research data, as well as biomolecular research tools are key resources in unravelling genetic and environmental factors underlying diseases and influencing their outcome. Biological samples are used in high-throughput techniques which allow examination of changes in the genome, transcriptome, proteome, or metabolome. Insights derived from these are expected to assist with the development of new diagnostic, prognostic, and therapeutic tools. Consequently, biological resources are considered as the essential raw material for the advancement of biotechnology, human health and research and development in life sciences. This is the landscape where the pan-european Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) is expected and prepared to integrate the existing quality controlled biobanks, biomolecular resources and enabling technologies into a novel pan-european biomedical research infrastructure, and to guide the way towards establishment of high quality de novo European biobanks adhering to the guidelines drafted by BBMRI. The European Commission has granted 5 Mio funding ( ) to the Preparatory Phase of BBMRI to conceptualise and secure funding for the construction of the European research infrastructure for biobanking and biomolecular resources. Management of BBMRI during the Preparatory Phase is divided between Universities of Turku and Graz. Eero Vuorio has served as a part-time Executive Manager and Heli Salminen as the Scientific Manager of BBMRI. This has been a sizeable task as BBMRI comprises 53 partners and nearly 250 associated organizations from 33 countries. The objectives addressed by the BBMRI consortium during the Preparatory Phase were to develop a plan to integrate existing quality controlled biobanks, biomolecular resources and enabling technologies into a novel pan-european biomedical research infrastructure (BBMRI-ERIC). BBMRI will not only provide a comprehensive source of information about existing biological sample collections and biomolecular resources, but will also provide an operational concept for a sustainable infrastructure, deliver standard operational procedures for future biobanking and codes of conduct for European biobanks. A particular challenge 28 29

18 MECHANISMS AND BIOSENSORS OF GTPASES Principle investigator: Daniel Abankwa, Ph.D., Turku Centre for Biotechnology, BioCity, 5 th floor, Tykistökatu 6B, FI-20521, Finland. Tel , Fax daniel.abankwa@btk.fi Biography: Daniel Abankwa (b. 1972) graduated in Chemistry (Dipl. Chem.) from the Georg-August University in Göttingen in 1997 and received his Ph.D. in Molecular Neurobiology from the Heinrich- Heine University Düsseldorf (2001). In 2002, he joined Prof. Horst Vogel at the EPFL in Lausanne as a Postdoc to become proficient in quantitative fluorescence techniques. In 2006, he went to the Institute for Molecular Biosciences in Brisbane, Australia with a Fellowship from the Swiss National Science Foundation. With Prof. John Hancock he worked as a senior postdoctoral fellow on Ras nanocluster and discovered a novel switch III in Ras that is associated with a previously undescribed nucleotide dependent orientation of Ras on the membrane. In 2008 he joined Prof. Kirill Alexandrov as a senior scientist at the same institute, to work on Rab nanoclustering and a chemical screening project to identify lipid transferase inhibitors. In July 2010, Daniel joined the Turku Centre for Biotechnology. Personnel: Graduate student: Arafath Kaja Najumudeen, MSc Graduate student: Ms Maja Solman, MSc Postdoc: Camilo Guzman, PhD Scientific Programmer: Mr. Zuhair Iftikhar, MSc Description of the project: Despite 30 years of intensive research, it is still not possible to block small GTPases, in particular Ras, specifically to treat cancer and other diseases. The major problem is to find a structural pocket or mechanism that is characteristic for one out of the over 150 structurally highly related small GTPases. Crystal structures provided detailed insight into the soluble G domain, revealing that two parts of the molecule change their conformation upon GTP-mediated activation. These structural elements, switch I and II, are conserved in all GTPases and therefore not suitable for specific drug-targeting. However, in the last few years novel structural insight emerged that takes the organisation of Ras in the membrane into account. For almost two decades, the lipid modified C-terminal HyperVariable Region (HVR) of small GTPases was recognized as the primary structural determinant for isoform specificity. However, a mechanistic explanation as to how the HVR realizes this was missing. For Ras, we now have mechanistic insight how the HVR is actually involved in this. Distinct HVRs of H-, N- and K-ras4B guide the lateral segregation into distinct nanoscopic proteo-lipid domains (nanoclusters) in the plasma membrane. From these distinct nanoclusters, isoform specific signalling emerges. In the last three years, we have described an additional mechanism, which provides the missing structure-function link for small GTPase specificity. Using a combination of computational biology and ex vivo biophysical measurements, we have recently described a novel switch III. This is formed by the b2-b3 loop and helix a5, and is associated with the orientation of the G domain on the membrane. Thus the Ras orientation is stabilized by the HVR and helix a4 (Figure). We also showed that this orientation-switch is specific for different Ras isoforms, regulates GTPase signalling and combines with lateral segregation of Ras. Research Questions: We are interested in understanding the molecular and structural determinants of GTPase isoform specificity. Building on our novel mechanistic insight, we are constructing specific biosensors to detect GTPase activity in cells. Finally, we are applying our insight into the design of novel screening assays, which will allow to identify novel isoform specific drugs. The balance-model for isoform specificity the missing structure-function link for small GTPases. (A) The two computationally simulated conformers of membrane anchored H-Ras are primarily stabilized either by helix α4 (left) or the HVR (right). (B) Schematic representation of the equilibrium, where the orientation of the G domain is represented by a balance -bar. Our balance-model explains that the conformational equilibrium depends on the relative membrane affinities of the HVR and helix α4, which differ among the Ras isoforms. The specific equilibrium then profoundly influences downstream interactions and signalling. We propose that this mechanism also operates in other members of the Ras-superfamily. Funding: The Academy of Finland, University of Turku, Åbo Akademi University, EU 7th framework (Marie-Curie grant), Cancer Society Finland, Biocenter Finland, Sigrid-Juselius Foundation. Collaborators: Prof. Alemayehu Gorfe and Prof. John Hancock (UT Medical School, Houston, USA), Prof. Kirill Alexandrov (Institute for Molecular Bioscience, Brisbane, Australia), Dr. Christian Eggeling (Max-Planck Institute Göttingen, Germany), Prof. Johanna Ivaska (VTT, Turku Centre for Biotechnology), Dr. Harri Härmä (University of Turku), Prof. Dimitrios Stamou (University of Copenhagen, Denmark), Prof. Jukka Westermarck (Turku Centre for Biotechnology), Prof. Parton (Institute for Molecular Bioscience, Brisbane, Australia), Dr. Krishnaraj Rajalingam (University of Frankfurt, Germany), Prof. Mike Waters (Institute for Molecular Bioscience, Brisbane, Australia) Selected Publications: Sinha, B., Koster, D., Ruez, R., Gonnord, P., Bastiani, M., Abankwa, D., Stan, R. V., Butler-Browne, G., Vedie, B., Johannes, L., Morone, N., Parton, R. G., Raposo, G., Sens, P., Lamaze, C., and Nassoy, P. (2011) Cells respond to mechanical stress by rapid disassembly of caveolae Cell 144,

19 Nguyen, U. T., Goodall, A., Alexandrov, K., and Abankwa, D. (2011) Isoprenoid Modifications. in Post-Translational Modifications in Health and Disease (Vidal, C. J. ed.), 1st Ed., Springer. pp 486 Crouthamel, M., Abankwa, D., Zhang, L., Dilizio, C., Manning, D. R., Hancock, J. F., and Wedegaertner, P. B. (2010) An N-terminal polybasic motif of G{alpha}q is required for signaling and influences membrane nanodomain distribution Mol Pharmacol Abankwa, D., Gorfe, A. A., Inder, K., and Hancock, J. F. (2010) Ras membrane orientation and nanodomain localization generate isoform diversity Proc Natl Acad Sci U S A 107, Bastiani, M., Liu, L., Hill, M. M., Jedrychowski, M. P., Nixon, S. J., Lo, H. P., Abankwa, D., Luetterforst, R., Fernandez-Rojo, M., Breen, M. R., Gygi, S. P., Vinten, J., Walser, P. J., North, K. N., Hancock, J. F., Pilch, P. F., and Parton, R. G. (2009) MURC/Cavin-4 and cavin family members form tissue-specific caveolar complexes J Cell Biol 185, Hill, M. M., Bastiani, M., Luetterforst, R., Kirkham, M., Kirkham, A., Nixon, S. J., Walser, P., Abankwa, D., Oorschot, V. M., Martin, S., Hancock, J. F., and Parton, R. G. (2008) PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function Cell 132, Abankwa, D., Hanzal-Bayer, M., Ariotti, N., Plowman, S. J., Gorfe, A. A., Parton, R. G., McCammon, J. A., and Hancock, J. F. (2008) A novel switch region regulates H-ras membrane orientation and signal output Embo J 27, Abankwa, D., Gorfe, A. A., and Hancock, J. F. (2008) Mechanisms of Ras membrane organization and signalling: Ras on a rocker Cell Cycle 7, Gorfe, A. A., Bayer, M.-H., Abankwa, D., Hancock, J. F., and McCammon, J. A. (2007) Structure and dynamics of the fulllength lipid-modified H-Ras protein in a 1,2-dimyristoylglycero-3- phosphocholine bilayer J Med Chem 50, Abankwa, D., and Vogel, H. (2007) A FRET map of membrane anchors suggests distinct microdomains of heterotrimeric G proteins J Cell Sci 120, Abankwa, D., Gorfe, A. A., and Hancock, J. F. (2007) Ras nanoclusters: molecular structure and assembly Seminars in cell & developmental biology 18, Perez, J. B., Segura, J. M., Abankwa, D., Piguet, J., Martinez, K. L., and Vogel, H. (2006) Monitoring the Diffusion of Single Heterotrimeric G Proteins in Supported Cell-membrane Sheets Reveals their Partitioning into Microdomains J Mol Biol 363, From left to right: Daniel Abwanka, Arafath Kaja Najumudeen

20 PROTEIN KINASE REGULATION OF BRAIN DEVELOPMENT AND DISEASE Principal investigator: Eleanor Coffey, Ph.D., Academy Research Fellow, Turku Centre for Biotechnology, Åbo Akademi and Turku University, BioCity, Tykistökatu 6B, FI Turku, Finland. Tel , Fax Biography: Eleanor Coffey (b. 1967) graduated from Trinity College Dublin in 1990 and received her Ph.D. from the University of Dundee in She received a Wellcome Trust fellowship to carry out postdoctoral research in Prof. Karl Åkerman s laboratory from In 1997 she founded the Neuronal Signalling group at Åbo Akademi and in 2000 joined Turku Centre for Biotechnology as a group leader in molecular and cellular biology. In addition to running a research group, she directs the Cell Imaging Core at Turku Centre for Biotechnology and coordinates the nordic network on Imaging in Biology and Medicine. She was appointed to an Academy of Finland Research Fellow post from 2008 to Personnel: Graduate students: Artur Padzik, M.Sc., Justyna Zdrojewska, M.Sc., Emilia Komulainen, M.Sc., Raghu Mysore, M.Sc., Lihua Sun, M.Sc., Hasan Mohammed, M.Sc., Prasanna Deshpande, M.Sc. Undergraduate students: Hanna Heikelä Description of the project : Neurodegenerative disorders such as Alzheimer s and Parkinson s disease as well as stroke are characterised by the irreversible loss of nerve cell function. These diseases for which no cure is known are among the most costly to society. The protein kinase JNK is recognised as a critical player in stroke and neurodegeneration. However exactly how this family of kinases mediates cell death in the brain remains largely unknown. Although targeting of JNK for drug-based therapy is already underway, our understanding of the physiological function of JNK in the brain is in its infancy. A major challenge for signal transduction therapy is to selectively target the pathological function of signalling molecules without interfering with important physiological roles. To achieve this, our lab established a proteomics-based screen to identify protein kinase substrates and thereby broaden our understanding of kinase function. While we have used this methodology to successfully identify both novel and known substrates for JNK, p38 and PIM kinases (collaboration with Päivi Koskinen), among others (collaboration Erwin Wagner), the main focus of our research is to elucidate the molecular mechanism of JNK and JNK targets in the brain. Identification of novel JNK targets such as SCG10 and MAP2, as well as others under study, has highlighted a critical role for JNK in maintaining microtubule homeostasis and subsequently regulating axodendritic architecture and nerve cell movement. Identification of the JNK phosphorylation site on kinesin-1 helped characterize a role for JNK in regulation of fast axonal transport in neurons. We combine biochemical, proteomic, cell biology and imaging methods with neuronal and organotypic cultures as well as transgenic mice to validate kinase targets and elucidate their function. In collaboration with Laurent Nyguen, we have established methods to track radial migration of neurons in the developing telencephalon using 4D imaging. In addition, we are examining dendrite and spine morphology in JNK1-/- brains using lucifer yellow iontophoretic loading followed by quantitative 3D image analysis. An important finding from our lab is the compartmentalization of JNK function in neurons into physiological and pathological pools residing in the cytoplasm and nucleus respectively. By using compartment-targeted peptide inhibitors of JNK, we have shown that nuclear JNK activity is critical for neuronal death in response to trophic deprivation (neuronal death that occurs during brain development) and excitotoxic stimuli (neuronal death that occurs during epilepsy, stroke and is contributory in neurodegenerative disorders). To explore the therapeutic potential of compartmental targeted JNK inhibitors, we are collaborating with Peter Clarke (University of Lausanne). This study investigates the value of nuclear-targeted peptide inhibitors of JNK as protectants from brain damage that occurs following stroke. Interestingly, although JNK is highly localised to the cytoplasm in neurons, we find that cytosolic JNK does not to these particular death mechanisms in neurons of the central nervous system. Instead, JNK plays a critical role in corticogenesis, being required to control the duration of two critical steps during formation of the cortex, i.e. multipolar stage transition and radial migration. This function of JNK is mediated by SCG10 and is independent of nuclear JNK activity. An important new study in our lab is a proteomic screen for LRRK2 substrates. LRRK2 is a kinase that is the most frequently mutated protein in Parkinson s disease, both familial and sporadic. Mutations in LRRK2 lead to a gain of function in kinase activity which is believed to underlie Parkinson s pathology. Yet, substrates for LRRK2 have remained elusive and therefore the disease mechanism is unknown. In collaboration with European partners, we are searching for LRRK2 targets in brain using a shot-gun approach. We then examine the function of these targets in neurotoxicity and assess their potential as biomarkers for earlier detection of Parkinson s. We hope that in the long run this will contribute helpful information for therapeutic treatment of Parkinson s and in the shorter term, contribute tools that can be used for earlier clinical diagnosis. Funding: The Academy of Finland, the Sigrid Juselius Foundation, Finnish Graduate School in Neurosciences, Turku University Biomedical Sciences Graduate School, Sitra. Collaborators: Michael Courtney (University of Kuopio), Tuula Kallunki (Danish Cancer Society), Thomas Herdegen (University of Kiel), Peter Clarke (University of Lausanne), Erwin Wagner (Research Institute of Molecular Pathology), Scott Brady (Univeristy of Illinois at Chicago), Laurent Nguyen (University of Liege), Päivi Koskinen (University of Turku), Aideen Long (Trinity College, Dublin). Selected Publications: Westerlund N, Zdrojewska J, Padzik A, Komulainen E, Björkblom B, Rannikko E, Tararuk T, Garcia-Frigola C, Sandholm J, Nguyen L, Kallunki T, Courtney MJ, Coffey ET. Phosphorylation of SCG10/ stathmin-2 determines multipolar stage exit and neuronal migration rate. Nat Neurosci Feb