Grant: Operating Grant

Understanding how all the proteins encoded by the genome of a microbe work together to form a living cell requires a complete description of the 'wiring circuits' that underlie the various fundamental cellular processes. A key feature is the tendency of proteins to interact physically to form molecular complexes that serve as molecular machines. Proteins with similar or overlapping biological roles generally belong to the same complex. Here, we propose to explore the physical interaction architecture of complexes of membrane proteins found at the outer bacterial cell envelope in the classical model bacterium Escherichia coli (E. coli) using powerful technology developed by our group. Our experimental approach will enable us to generate circuit diagrams for all the membrane bound proteins involved in important biological processes essential for bacterial cell growth and infection, which represent important targets for antibiotics. Since many bacterial genes are conserved across microbial evolution, the identification of the pathway architecture of E. coli should also reveal the organization of membrane proteins in other bacterial species, including pathogens. The data generated in this project will therefore serve as a valuable resource for the entire biomedical research community, and should spur on the development of new antibiotics.`