Grant: Doctoral Research Award: Canada Graduate Scholarships

Inside each of our cells, we have a number of specialized compartments called organelles that perform different tasks. Recently we have learned that these compartments are not simply floating around in our cells but are in fact held together at places called "membrane contact sites". These contact sites have an important role in transporting nutrients, fats and proteins from one compartment to another. When this transport is disrupted, disease can occur. My proposed research focuses on VPS13C and VPS13D, related proteins found at membrane contact sites that are believed to transport fats between cellular compartments. Mutations in these proteins cause two different neurodegenerative diseases: early-onset Parkinson's disease and childhood-onset spastic ataxia, respectively. Evidence suggests that these human VPS13 proteins localize to different membrane contact sites which may explain why mutations in the two proteins result in distinct neurological disorders. My research is focused on determining how VPS13C and VPS13D are sent to contact sites and how mutations in these proteins can change their cellular locations resulting in neurodegeneration. We have been using yeast as a model system to study VPS13C and VPS13D, because yeast carries a single, related Vps13 protein which goes to many different cellular compartments. We have found that the yeast Vps13 is sent to different contact sites with the help of adaptors. These adaptors bind Vps13 at a site we have named the Vps13 Adaptor Binding (VAB) domain, which is conserved in human VPS13C/D proteins. My work will identify the adaptors needed for VPS13C/D recruitment and will examine the role of a secondary site in helping to send these proteins to the right compartments. Understanding how VPS13C and VPS13D are localized within the cell will give us a better understanding of the disease mechanisms associated with each disorder and give us insights into potential therapeutic interventions.