Structural and Functional Studies of Metabolic Enzymes and their Complexes

Keywords: multiprotein complexes, disease mutations, protein-protein interactions
Multiprotein complexes are key players in essentially all important cellular processes, including metabolism and organelle biogenesis. However, biochemical and structural analysis of such macromolecular assemblies remain technically challenging, which has precluded a molecular understanding of their architecture, mode of interactions, and relevance to function. This has also impeded the translation to drug discovery for those macromolecular complexes associated with monogenic and common diseases. The project aims to develop the tools, principles and technical know-how to express, purify and characterize native multi-protein complexes, as a starting point for novel target discovery. Focus will be on those protein complexes with genetic disease association, as they serve as good model systems for the study of protein-protein interactions (PPIs), due to their well-defined genetic and biochemical phenotypes. The student will combine high-throughput, multi-disciplinary techniques in structural biology, biochemistry and biophysics to Isolate and reconstitute the multiprotein complexes, dissect the complex assembly and delineate interaction patterns and probe the effect of disease mutations on protein-protein interactions.