RA4: Modeling of protein interaction networks

To put the broader implications of our experimental findings into context, bioinformatics and modeling studies will be utilized to uncover essential protein networks for specific cellular processes:

A large-scale static network of PPIs will be built upon the identified proteins (e.g. by MS/MS), of particular interest for epithelial cells. Through data mining of literature (to identify proteins related to epithelial cells and/or a specific disease), combined with databases such as KEGG (www.genome.jp/kegg/), we aim to identify and reconstruct interaction pathways. This interaction network will be analysed in silico using network analysis techniques to highlight sub-networks underlying specific cellular processes.

PPIs involved in sub-networks will be investigated further for the time series data necessary for reverse-engineering of dynamic network models. These models, although smaller, give detailed pictures of specific processes and complement static network models.

The dynamic networks will be compared to the large-scale static network in order to identify other proteins that may not have been previously referenced or identified, providing areas for further research. The dynamic networks will be used to examine how a network of PPIs is likely to respond to perturbations such as disease, enabling us to build hypotheses that can be tested in tailor made experiments