Grant: Operating Grant

Protein-protein interactions are involved in almost all cellular processes, and in particular, eukaryotic signaling pathways are controlled by complex protein networks. These networks are essential for normal development and cell function, and furthermore, many diseases are caused by imbalances in particular signaling networks. Thus, a major goal of modern biology is to define the interacting partners in cellular networks and to elucidate the molecular basis for key protein-protein interactions. Many of these interactions are mediated by modular peptide recognition domains, which are usually imbedded in large scaffolding proteins and function by recognizing distinct linear motifs within binding partners. Our laboratory has pioneered the use of combinatorial peptide libraries for identifying high affinity ligands for peptide recognition domains. We propose a large-scale project that will define the binding specificities of all human SH3 and WW domains, polyproline recognition modules that are involved in many important signaling pathways. This analysis will contribute to the understanding of cell signaling in normal and diseased cells, and the peptide ligands will be useful as inhibitors that can be used to study protein function inside cells. Immediate benefits of the research include new advances in Canadian biomedical science, more efficient use of Canadian research resources, and an increased pool of highly qualified personnel in the nationally underrepresented field of combinatorial biology. Longer term benefits for Canada from obtaining a better understanding of cell signaling networks include potential therapies for many diseases, including cancer and infectious diseases.