Grant: Doctoral: Vanier Canada Graduate Scholarships

RNA interference (RNAi) encompasses a series of gene-regulatory pathways that control the expression of more than half of all human genes. Not surprisingly, RNAi-dependent regulation of many cellular pathways is critical for normal growth and differentiation of cells and aberrant expression of RNAi pathway proteins is associated with multiple types of cancer. Because of its central role in governing gene expression, we believe that components of RNAi pathways are themselves tightly regulated. To this end, we are interested in understanding how molecular motor proteins modulate RNAi pathways. Specifically, we will focus on how motor proteins function to regulate stress granules, which are subcellular structures that function in RNAi. In addition to controlling gene expression, stress granules may play a critical role in how cancer cells evade normal death signals. To this end, we have preliminary evidence suggesting that a promising new class of anticancer drugs that inhibit molecular motor proteins, also affect stress granule formation. RNAi is arguably the most important biomedical discovery of the last 20 years. It has the potential to revolutionize the treatment of many human diseases including cancer. Most of the research into RNAi focuses on its potential use as a means to turn off genes that contribute to disease. Our recent studies suggest that molecular motor proteins play a role in formation of RNAi-associated structures which are called stress granules. Stress granules are abundant in tumor cells when oxygen levels are low and it is thought that these structures may confer resistance to drugs that normally kill cancer cells. We are interested in learning how a novel class of anti-cancer drugs regulates the formation and function of stress granules. Results from these studies may form the based for improved anti-cancer therapies that target stress granule formation and function.