The goal of the TB Structural Genomics Consortium (TBSGC) is to structurally and functionally characterize proteins that are critical for the growth and survival of mycobacteria. The Chemical and Genefic Core is dedicated to supporting the TBSGC projects by identifying vital proteins and helping to define their functions. The Core will offer several services, aimed at determining whether a protein may be useful as a drug target, and combining high-throughput chemical screening with novel genetic methods to functionally characterize mycobacterial proteins and protein complexes. The Core will generate mycobacterial mutants that conditionally express essential proteins or mutant alleles, in order to validate potential drug targets and assist in functional characterization. The Core will identify interactions of targeted proteins using generic synergy, to identify proteins that act in concert with a target of interest, which may include protein complexes that would in turn be the focus of subsequent structural determination. The Core will determine protein localization in live cells and provide tools to biochemically define protein complexes in vivo. Finally, the Core will identify small molecule inhibitors of targeted proteins by high-throughput screening, which will serve as aids in structure-based functional studies and could be leads for new antibiotic discovery.
The Core will provide critical infrastructure and support to the other projects in this consortium. The TBSGC is unique in prioritizing targets for structure determination based on their relevance to drug discovery. We will take a variety of approaches to identify antibiotic targets and establish their roles in Mycobacterium tuberculosis.
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