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

In order to achieve the COMBIO objectives, a series of inter-linked work packages have been devised with defined deliverables and milestones, as outlined in the following diagram.

Work Package 1: p53-Mdm2

This WP is linked to WP 3, 4 and 5. Primary focus will be the quantitative and global understanding of the p53/Mdm2 network. Different, complementary strategies will be adopted, including knock-outs and knock-ins, GFP labelling and fluorescent recording, soft mutations that partly inactivate proteins, and simulation of the network.

Work Package 2: Dynamics of Spindle Assembly

This WP is linked to WP 3, 4 and 5. We propose to study spindle assembly using a combination of experiments performed in vivo and in vitro and theoretical modelling and simulations. This combined approach for studying cellular organization is in fact complementary to the study of genetic regulatory networks that will be performed in WP1.

Work Package 3: Database

A major effort in this project will be devoted to in silico annotations of the molecular functions and interactions made by all the genes and proteins that take part in the selected set of central biological processes. These in silico annotations refer to information obtained from the analysis of related genes, or groups of genes involved in similar functional or genomic contexts, across different organisms. Particular care will be taken to incorporate this data in a way suitable for computer simulations and more important informative enough for non-specialists in the field.

Work Package 4: Visualisation

The main goal is to make available a modular database environment for loading, storing, querying, analysing and visualising information on complex cellular networks.

Work Package 5: Different Simulation Strategies

Different simulation strategies, some developed by the consortium, some developed by other groups will be used on the same experimental systems. The objective will be to evaluate and offer the community a set of rules and suggestions of which simulation tool is more appropriate for a particular problem depending also on the experimental information available.