Grant: CIHR New Investigator

TOR is a key signaling protein that regulates cell growth in the body. Abnormal activation of TOR is associated with the uncontrolled cell growth and proliferation observed in many cancerous tumors. TOR is thus increasingly recognized as a compelling target for designing new cancer drugs. In the cell, TOR functions as part of two larger sized protein complexes. However, the molecular mechanisms through which the two TOR complexes coordinate cell growth are poorly defined. I have used a cutting-edge imaging technique called single-particle electron microscopy (EM) to characterize, for the first time, the intricate structural features and internal organization of one of the two TOR complexes. Building on this pioneering study, I propose to apply a multidisciplinary approach, integrating single-particle EM and other biochemical and molecular biology approaches, to determine the differences in overall structure and molecular organization between the two TOR complexes, and to further define their mechanisms of action and regulation. A comprehensive understanding of the molecular function of the two TOR complexes will provide critical insights into the fundamental basis of cell growth regulation and how cancer arises from problems in this process. This work will pave the way for the development of novel cancer treatment that target the TOR complexes, and thereby improve the health outcomes and survival rates of patients inflicted by cancer, a devastating disease that affects over 40% of the Canadian population.