An integrative approach to cellular signalling and control processes: Bringing computational biology to the bench.

The major objective of COMBIO is to benchmark the ability of current modelling and simulation methods to generate useful hypothesis for experimentalists and to provide new insights into biological processes of realistic complexity. The expected result will be a set of guidelines, specifying which and how simulation methods should be used, given the problem at hand. These guidelines will also indicate how best simulations and experimental procedures might be combined to answer key questions about biological function. This approach should make a fundamental contribution to the area of functional genomics, and provide ways for elucidating the mechanisms of pharmacological compounds. COMBIO will combine experimental, bioinformatics and simulation approaches in order to gain detailed understanding of two key processes: the p53-Mdm2 regulatory network and the self organisation process whereby chromatin controls microtubule nucleation and organization. These processes have been selected because they exemplify two important and different Biological Systems: the first which could be approximated as a network of free components, and the second in which localization, self-organization and gradients play an important role.
To achieve these aims we will pursue together the following specific scientific and technical objectives:

  1. Global quantitative understanding of the p53/Mdm2 network
  2. Global quantitative understanding of the dynamics of spindle formation
  3. Construction of a database for simulation and visualization tools
  4. Production of a standard guide for experimentalists showing which simulation tools should be used, depending on the problems been addressed and on the information available.