TAGC U928 case 928
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CALAMAR
Compositional modelling and Analysis of LArge MoleculAr Regulatory networks - application to the control of human cell proliferation.
CALAMAR (ANR-08-SYSC-003) supported by the ANR SYSCOMM program 2008 (Agence Nationale de la Recherche, Systèmes Complexes et Modélisation Mathématique).
TAGC Inserm U 928
Project-team Contraintes, INRIA
Institut Curie, Bioinformatics Group
Spectacular advances in molecular biology, genomics and functional genomics open the way to the understanding of regulatory mechanisms controlling essential biological processes. These regulatory mechanisms interplay and operate at diverse levels (transcription and translation of the genetic material, protein modifications, etc.). They define complex networks, which in turn constitute a crucial functional framework to assess their spatio-temporal properties. Appropriate tools for the dynamical modelling, analysis and simulation are thus required to delineate the functionning of these networks. In this context, different formalisms can be considered, from logical (qualitative) models to differential (quantitative) models. This project intends to develop novel methods to efficiently represent and analyse the behaviour of large regulatory networks. This challenge will be addressed through the conception of efficient computational methods for network reduction and (de)composition (yet keeping track of essential dynamical properties). Formal relationships between qualitative and quantitative models will be generated by the application of dedicated abstraction techniques. These generic methodological developments will be systematically confronted with a reference application, namely the analysis of a comprehensive map of the RB/E2F regulatory network, which plays a key role in the control of human cell proliferation. Functional genomic data and literature mining tools will be combined to complete this generic map and to instantiate it for normal or transformed epithelium, particularly the urothelium cell types and for T lymphocytes. Modularity, (de)composition and abstraction approaches will be applied to this complex network in order to access critical dynamical properties. Network and modules models will be progressively amended and refined by confronting their dynamical behaviours with reported characteristics in the wild-type situation, as well as for documented perturbations. Once stabilised, these models will be used to perform extensive in silico experiments, in order to select novel informative or counter-intuitive situations, which will induce the design of a limited number of validation in vitro or in vivo experiments.
CalamarLast Update 2009-03-24 19:13:41
