Grant: Emerging Team Grant: From Genes to Proteins, Cells, Tissues and Patients

Protein palmitoylation is a dynamically regulated posttranslational modification critical for proper cellular trafficking. Our recent studies show that defects in palmitoylation of selected neuronal proteins are associated with Huntington Disease. We will effectively explore this process by using our novel proteomic technology to identify most of the neuronal proteins showing altered palmitoylation in HD, and define the relationship between defects in palmitoylation of these proteins and HD. The discovery of enzymes that remove palmitate will be important for the identification of small molecule inhibitors that target these enzymes and the development of therapeutic tools. This CIHR Team brings together investigators who have made landmark discoveries in the field, including the development of technologies to detect palmitoylation, description of the palmitoyl proteome, identification and characterization of the first palmitoyl transferases, and the first demonstration of altered palmitoylation in Huntington Disease. Thus, our overall goals are to determine the mechanism by which altered palmitoylation contributes to the pathogenesis in HD, and to develop therapeutic tools designed to increase palmitoylation, thereby improving the outcomes for patients with this devastating disease for which there is currently no effective therapy.