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A German Initiative on Systems Biology of Human Hepatocytes

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

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A German Initiative on Systems Biology of Human Hepatocytes

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

  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. WS 1 WS 2 WS 3 WS 4 The „Design-Process“ Expert panel structuring thematic priority recommendations March 2001 May July September November December 2001 elicit thematic topic funding- strategies core expert panel (9) documentation informations external expert panel (>70) „Systems of Life - Systems Biology“ data-screening, conferences, interviews

  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. 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. 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. 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. Structure of the National Competence Network on Systems Biology Steering Committee collaborative project A collaborative project B coordinating committee project-management plattform cell biology plattform modeling

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

  10. Speakers for WTEC visit: Prof. Reuss Dr. Ursula Klingmueller Prof. Hengstler Prof. Gilles, Dr. Ursula Kummer 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

  11. Geographic Distribution of the Projects

  12. Facts on the Starting Phase • call for project proposals December 2001 • number of proposals 40 • start of the research work January 2004 • under this programme • first funding period 13 Mio. € /3 years • collaborative projects 2 • platform projects: • cell biology 3 • modeling 3 • number of partners 25

  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

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