Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Each cell in the body coordinates thousands of different tasks every second. For this, the cell has a complex transportation system that moves materials, like nutrients, fats and proteins, to where they are needed. Cells use small spherical structures called "vesicles" to shuttle molecules from one compartment to another. These vesicles are especially important in the brain, where they transport the neurotransmitters that allow brain cells to communicate. Genetic mutations that disrupt the proper formation or movement of vesicles often cause mental disability or neurodegenerative disease. Learning more about the process of vesicle formation can therefore help us understand the cause of these diseases. My proposed research focuses on Fez1 and Fez2, two closely-related human proteins that act as cargo adaptors, attaching vesicles to the molecular motors that will move them to a specific destination. Fez1 and Fez2 are hub proteins that participate in many different pathways and their dysfunction has been linked to schizophrenia, muscular dystrophy and susceptibility to HIV. Using genome-wide screens in yeast, we have recently uncovered a previously-unsuspected link between the Fez proteins and Adaptor Protein (AP) complexes, important transport machinery that makes sure that each kind of vesicle contains the right molecules. I am interested in understanding the molecular factors that direct the Fez proteins to work in the AP complex trafficking pathway and the subsequent outcome of this association for the cell. Insight into new pathways that involve the Fez proteins may help to explain the multitude of different effects that Fez1/2 mutations can have on human health, and could suggest new avenues for treatment of diseases such as schizophrenia.