The Target Of Rapamycin (TOR) kinases reside in two distinct multi-protein complexes: TOR Complex 1 (TORC1), and TORC2. These two complexes are conserved among eukaryotes and function in signalling pathways that regulate different aspects of cell growth. By exploiting the facile genetics of the model eukaryote Saccharomyces cerevisiae, my lab aims to flesh out details of the TOR signalling network with the ultimate goal of understanding how cell, organ and organism growth is regulated. Specifically, the molecular mechanisms that regulate their activity, and the effectors by which TORC1 and TORC2 influence their distal readouts, remain largely unknown. Using both hypothesis-driven approaches and unbiased genetic screens we want to learn how TORC1 activity is regulated by environmental cues and to identify the physiological regulators of TORC2. In addition we will use biochemical approaches to elucidate the signalling mechanisms that couple TORC1 and TORC2 to their downstream effectors/readouts. Lastly, given the conservation of the TOR complexes and their clinical importance, especially in oncology, we will employ both directed chemistry and ‘target-inferred’ high throughput chemical library screens to identify drug-like compounds that inhibit yeast and mammalian TORC1 and TORC2.
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