1. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 1 A German Initiative on Systems Biology of Human Hepatocytes Systems of Life - Systems Biology Presentation to the WTEC delegation by Gisela Miczka, Roland Eils, and Siegfried Neumann Heidelberg, July 7 th, 2004

2. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 2 2001: How to establish a BMBF funded national research network on Systems Biology Start of the „design-process“: Discussion forum with a multidisciplinary team of 9 leading scientists to develop a funding strategy. The key criteria are  medium to long term research programme  synergy with existing BMBF funded research programmes in Genomics and Proteomics  Considers the international status of the art  reckognizes international standards and contributes to them

3. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 3 Expert panelstructuring thematic priority recommendations core expert panel (9) documentation informations elicit thematic topic funding- strategies WS 1WS 2WS 3WS 4 data-screening, conferences, interviews external expert panel (>70) March 2001 December 2001 NovemberMayJulySeptember „Systems of Life - Systems Biology“ The „Design-Process“

4. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 4 Goal of the Systems Biology Initiative on Hepatocytes The long-term goal of this systems biology approach is to understand the dynamic processes in a human cell and to build up mechanism-based mathematical models of these processes in order to predict the behaviour of the system under defined conditions.

5. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 5 Why Hepatocytes? Attractivity central functions in metabolism (for lipids, carbohydrates, amino acids …) central role in the uptake and conversion of drugs (transport, metabolic conversions, detoxification...) ability of regeneration I. e. high impact on problems in pharmacology and pathophysiology

6. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 6 Challenges high complexity of mammalian cells human diffentiated cells are not easy to handle and not easy to cultivate while keeping properties simular to in vivo living cells the mathematical tools for modelling of cellular dynamics and systems analysis basically are not developed for complex systems Aim to overcome the obstacles in order to do systems biology on a medically relevant cell type. !

7. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 7 The Approach set up an interdisciplinary competence network linking bioscience with computer science, mathematics and engineering sciences Start with studies on defined biological functions establish standardized cells, methods, and tools

8. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 8 Structure of the National Competence Network on Systems Biology plattform cell biology plattform modeling coordinating committee Steering Committee collaborative project B project-management collaborative project A

9. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 9 Biology Systems Engineering Bioinformatics Mathematics Tools (HTS) Systemic Behaviour Algorithms Software Databases Systems Biology biological models generation of quantitative data, anlysis of functional relations; tool development modelling (study on regulation, structure, robustness, etc. of system) establishment of databases, development of in silico models and software

10. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 10 Main Objectives Project A: Detoxification and the dedifferentiation in hepatocytes Project B: Regeneration of hepatocytes Platform Cell biology: Development of new cells, of optimized culture conditions, of high throughput technology and supply of cells for the projects in the national network Platform Modelling: Development of bioinformatics and mathematical tools for data management, data handling etc. and service for the projects of the national network Speakers for WTEC visit: Prof. Reuss Dr. Ursula Klingmueller Prof. Hengstler Prof. Gilles, Dr. Ursula Kummer

11. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 11 Geographic Distribution of the Projects

12. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 12  call for project proposalsDecember 2001  number of proposals40  start of the research workJanuary 2004 under this programme  first funding period13 Mio. € /3 years collaborative projects 2 platform projects: cell biology3 modeling3 number of partners 25 Facts on the Starting Phase

13. Dr. Siegfried Neumann-hg: WTEC_Demo_050704.ppt 13 Members of the Steering Committe Prof. Dr. Dieter Oesterhelt, MPI for Biochemistry Munich (chairman) Dr. Roland Eils, DKFZ Heidelberg Prof. Dr. Joseph Heijnen, Technical University of Delft Prof. Dr. Karl Kuchler, Institute for Medical Biochemistry, University of Wien Prof. Dr. Siegfried Neumann, Merck KGaA Darmstadt, Office of Technology Prof. Dr. Hans V. Westerhoff, Molecular Cell Physiology & Mathematical Biochemistry, BioCentrum Amsterdam