Objective The aim of our research is to enhance our understanding of the molecular mechanisms underlying the behavior of complex living systems. In particular, we investigate how large and complex regulatory networks control the response of a living cell to its ever-changing environment.The stress response to environmental events is induced by the interaction of several interwoven modules with complex dynamic behavior, acting on different time scales. To deal with this complexity we need mathematical modeling and computer-supported analysis. So far, the methods of systems biology are mostly applied to individual modules, such as particular metabolic pathways and genetic networks. But to understand the global behavior, we need an integrated description of the regulatory network. We must develop new, scalable methods for modeling and analysis of integrated networks.We will apply our methods to the stress response system of the enterobacterium Escherichia coli, one of the best-studied organisms and a model for several pathogenic bacteria. In the project, we will develop an integrated model of the stress response system of E. coli, including key metabolic, genetic and signaling modules. We also develop methods to reduce high-dimensional nonlinear systems of equations, and to approximate them by discrete automata. Parallel model checking algorithms will be developed for verifying specific properties at the model. So we can explore the models and predict the outcome of experiments.Finally, we will validate our model by experimentally testing predicted properties in our labs. Our cross-disciplinary European team of biologists, mathematicians and computer scientists will develop a coherent and generic methodology, generalizable to other complex (biological) systems. Our models will be accessible via the Silicon Cell and the International E. coli Alliance. They could improve many medical and biotechnological applications, e.g. strain improvement and rational drug design. Fields of science natural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesbasic medicinemedicinal chemistrynatural scienceschemical sciencesinorganic chemistrymetalloidsnatural sciencesmathematicsapplied mathematicsmathematical model Keywords bacterial stress response complex systems integration of regulatory networks model checking systems biology Programme(s) FP6-POLICIES - Policy support: Specific activities covering wider field of research under the Focusing and Integrating Community Research programme 2002-2006. Topic(s) NEST-2005-Path-COM - Tackling Complexity Call for proposal FP6-2005-NEST-PATH See other projects for this call Funding Scheme STREP - Specific Targeted Research Project Coordinator UNIVERSITEIT TWENTE Address Drienerlolaan 5 217 Enschede Netherlands See on map Links Website Opens in new window EU contribution € 0,00 Participants (6) Sort alphabetically Sort by EU Contribution Expand all Collapse all INSTITUT NATIONAL DE RECHERCHE EN INFORMATIQUE ET EN AUTOMATIQUE France EU contribution € 0,00 Address Domaine de voluceau - rocquencourt BP 105 Le chesnay See on map Links Website Opens in new window VRIJE UNIVERSITEIT AMSTERDAM Netherlands EU contribution € 0,00 Address De boelelaan 1105 Amsterdam See on map Links Website Opens in new window UNIVERSITY JOSEPH FOURIER - GRENOBLE 1 France EU contribution € 0,00 Address 621 avenue centrale - domaine universitaire Grenoble See on map Links Website Opens in new window MASARYKOVA UNIVERZITA Czechia EU contribution € 0,00 Address Zerotinovo nam. 9 Brno See on map Links Website Opens in new window THE UNIVERSITY OF EDINBURGH United Kingdom EU contribution € 0,00 Address Old college, south bridge Edinburgh See on map Links Website Opens in new window STICHTING CENTRUM VOOR WISKUNDE EN INFORMATICA Netherlands EU contribution € 0,00 Address Kruislaan 413 94079 Amsterdam See on map Links Website Opens in new window