CORDIS - Resultados de investigaciones de la UE

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

Final Report Summary - COMBIO (An integrative approach to cellular signalling and control processes: Bringing computational biology to the bench)

It is increasingly being recognised that progress of modern-day biology will require the understanding and harnessing the network of interactions between genes and proteins and the functional systems that they generate. Given the complexity of even the most primitive living organism, and our still very limited knowledge, it is unreasonable to expect that we might, in the near or even medium term, reach such understanding the level of an entire cell. However, significant progress towards a system-level understanding should be achievable by applying an integrated approach to the analysis of a set of well-defined and biologically important cellular process.

The major goal of COMBIO was to bring computer models and simulations to the experimental community. The focus was on two key processes, which were selected because they exemplify important and different biological systems. The first process was the p53-Mdm2 regulatory network, which can be approximated as a network of free components. The second system was the spindle formation, the self-organisation event whereby chromatin controls microtubule nucleation and organisation and where localisation, self-organisation and gradient play fundamental roles. The added benefit of using these two systems was that they were already well characterised in the published literature.

The transcription factor p53 was among the most studied proteins at the time, considering that inactivation of the p53 pathway is a common, if not universal, feature in human cancers. The main objective of work package (WP) 1 was to study the complex p53 network in a quantitative way, in various cellular contexts (i.e. mammalian or yeast cells) and under different conditions (i.e. normal conditions or stress-related conditions like drugs or irradiation). The groups developed novel sophisticated experimental strategies combined with profound computational analysis as well as system modelling.

The project created a common database to store the available information on all the genes and proteins taking part in the two networks under study (p53 and spindle), including the knowledge acquired as well as information from external sources. The database was made available to the partners through the COMBIO website and was planned to be released to the scientific community.