Studies of local and global properties of interactome networks

Abstract

Classical genetic approaches have successfully assigned functional descriptors to thousands of genes across many species. However, daunting challenges remain ahead to associate genotype-phenotype relationships considering that rarely is a gene responsible for a single function. The central hypothesis of systems biology considers that complex and intricate networks of interacting genes and macromolecules, interactomes, underlie cellular functions. Here, we describe efforts to experimentally chart the first binary proteome-scale systematic protein-protein interactome network map for a plant. Through an empirical framework, we demonstrate that the resulting dataset is of similar quality to well-documented interactions from the literature. We then describe an experimental strategy based on reference sets to standardized experimental methods for quality control of binary interactome data sets. Finally, we explore three types of interactome network alterations that can help understand interactome function and help assign genotype-phenotype relationships: (1) engineered interaction-specific perturbation, (2) natural pathogen perturbation and, (3) perturbations of interaction through rewiring at the scale of evolution. We show that specific phenotypes can be associated to specific interaction loss.

Date of Award	31 May 2011
Original language	French
Awarding Institution	University of Namur
Supervisor	Jean VANDENHAUTE (Supervisor), Marc Vidal (Co-Supervisor), Thierry Arnould (President), PO Vidalain (Jury) & Jan TAVERNIER (Jury)