Principal Investigator (PI)
Dr. Schnappinger´s laboratory at Weill Cornell Medical College
The Foundation is providing £135,250 in support.
Dr. Shipra Grover
GSK provides in-kind contributions including access to BSL3 facilities, HTS and microbiology expertise as well as full access to antimycobacterial compounds sets.
Whole-cell screens (WCS) have recently been re-visited as an antibacterial drug discovery strategy. This change is due to the lack of success associated with biochemical target-based high throughput screens (HTS), where potent enzyme inhibitors poorly active as antibacterials were identified. However, the ability to select for whole-cell activity during the HTS phase comes at the price of knowing little (if anything) about the mechanism(s) by which a novel compound inhibits bacterial growth. The use of regulated expression sytems can help overcome this shortcoming and identify the molecular target(s) of growth-inhibiting small molecules
The mode of action elucidation of GSK antitubercular compound sets by means of the conditional mutants developed by Dirk Schnappinger´s group at Cornell will be the base of this new whole cell target-based project.