1. HepatoSys – Program and Mission Jens Timmer Speaker of the Project-Committee of HepatoSys

2. One large German-wide project ? Join an European initiative ? Local centres ? Several medium sized projects ? How to spend XX Mio. for Systems Biology ?

3. Decision of the German Federal Ministry for Education and Research: One large German-wide project: HepatoSys Join an European initiative: SysMO Local centres: Four Research Units for Systems Biology Several medium sized projects: MedSysBio How to spend XXX Mio. for Systems Biology ?

4. 2001-2003: Preparation 2004-2006: First funding period: Getting Started 2007-2009: Second funding period: Integration The History of HepatoSys

5. Advisory board Definition of Systems Biology Choice of cell system: Primary hepatocytes Structure of HepatoSys 2001-2003: Preparation

6. Two Networks - Regionally organised - Concentrating on specific topics - Comprise dry & wet labs Two Platforms - German-wide organised - One for Cell Biology, one for Modelling Preparation: Structure of HepatoSys

7. Two Networks : Network Regeneration: Freiburg, Heidelberg Signalling networks Network Detoxification/Dedifferentiation: Stuttgart Metabolic networks Two Platforms : Platform Cell Biology: All over Germany Standardised cell material, supply with human hepatocytes Platform Modelling: Berlin, Magdeburg, Heidelberg General methods, cooperations with Networks 2004-2006: First Funding Period

8. First Funding Phase: Getting Started

9. Standardisations A number of wet lab groups switching to hepatocytes A lot of meetings and communication Cooperations between people who never met before A change in culture HepatoSys is more than the sum of its parts Achievements of First Funding Period

10. Standardisation Klingmüller U., Bauer A., Bohl S., Nickel P., Breitkopf K., Dooley S., Zellmer S., Kern C., Merfort I, Sparna T., Donauer J., Walz G., Geyer M., Kreutz C., Hermes M., Götschel F., Hecht A., Walter D., Egger L., Neubert K., Borner C., Brulport M., Schormann W., Sauer C., Baumann F., Preiss R., MacNelly S., Godoy P., Wiercinska E., Ciuclan L., Edelmann J., Kleemann W.J., Zeilinger K., Heinrich M., Zanger U.M., Reuss M., Bader A., Gebhardt R., Maiwald T., Timmer J., von Weizsäcker F., Hengstler J.G. Primary mouse hepatocytes for systems biology approaches: a standardized in vitro system for modelling of signal transduction pathways. IEE Proc. Systems Biology 153, 2006, 433-447

11. Two new Networks Endocytosis: Dresden, Mannheim, Aachen, Hamburg Iron Regulation: Berlin, Heidelberg Motto: Integration Integration of parts of Platforms into Networks Integration of Modules into Processes 2007-2009: Second Funding Period

12. The Structure of HepatoSys

13. Cooperations of HepatoSys

14. Putting all the omics together So far: large scale, qualitative Understanding biomedical systems by data-based mathematical modelling of their dynamic behaviour So far: small scale, quantitative Two Definitions of Systems Biology

15. Convergence of the two approaches: Large scale, quantitative Integrated mathematical models of central functions of hepatocytes: Detoxification of xenobiotics Proliferation after liver damage Metabolic regulation of homeostasis Virtual hepatocyte Goals of HepatoSys

16. Clinical & pharmaceutical implications: Personalised medicine Efficient model-based drug targeting Improved strategies for liver regeneration Less animal experiments Improved iron-substitution therapies Mission of HepatoSys

17. August 27, 2008, Gothenburg Workshop Systems Biology of the Liver at ICSB 2008 http://sysbio.uni-freiburg.de/Workshop_Liver_ICSB08.html Towards HepatoSys-worldwide

18. Our Steering Committee: Hans Westerhoff (Chair) Siegfried Neumann (Vice-Chair) Roland Eils Jan Hoek Uwe Sauer Marius Üffing Thanks to

19. Federal Ministry for Education and Research Special thanks to Projektträger Jülich: Gisela Miczka Erich Stüttgen Thanks to