dr. siegfried neumann-hg: wtec_demo_050704.ppt 1 a german initiative on systems biology of human...

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 delegationby Gisela Miczka, Roland Eils, and Siegfried Neumann

Heidelberg, July 7th, 2004


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


Expert panel structuring thematic priority recommendations

coreexpertpanel (9)

documentation

informations

elicit thematic

topic

funding-strategies

WS 1 WS 2 WS 3 WS 4

data-screening, conferences, interviews

external expert panel (>70)

March 2001March 2001 December 2001December 2001NovemberNovemberMayMay JulyJuly SeptemberSeptember

„„Systems of Life - Systems of Life - Systems Biology“Systems Biology“

The „Design-Process“


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.


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


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 systemsbiology on a medically relevant cell type.

!


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


Structure of the National Competence Network on Systems Biology

plattform cell biology

plattform modeling

coordinating committee

Steering Committee

collaborative project B

project-management

collaborativeproject A


BiologyBiology

Systems Systems EngineeringEngineering

Bioinformatics Bioinformatics MathematicsMathematics

Tools (HTS)Tools (HTS)

Systemic Systemic BehaviourBehaviour

Algorithms Algorithms Software Software DatabasesDatabases

Systems BiologySystems Biology

biological models biological models generation of quantitative generation of quantitative data, anlysis of functional data, anlysis of functional relations; tool developmentrelations; tool development

modelling (study on modelling (study on regulation, structure, regulation, structure, robustness, etc. of system) robustness, etc. of system)

establishment of databases, establishment of databases, development of development of in silicoin silico models and software models and software


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


Hamburg

Mainz

Jena

Heidelberg

BirlinghovenDresden

Geographic Distribution of the Projects

Freiburg

Stuttgart

Aachen

Berlin

Magdeburg

Collaborative Projects

Platform Cell Biology

Platform Modeling

LeipzigDüsseldorfBochum

Geographic Distribution of the Projects


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 3modeling 3

number of partners 25

Facts on the Starting Phase


Members of the Steering CommitteProf. 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

dr. siegfried neumann-hg: wtec_demo_050704.ppt 1 a german initiative on systems biology of human...

Documents

platform projects

siegfried neumannhg

yearscollaborative projects

medical biochemistry

biochemistry munich

university of wien

technical university

karl kuchler