Grant: Doctoral: Vanier Canada Graduate Scholarships

Supervisor: Dr. Swayne, University of Victoria. The beating of heart cells and firing of nerve cells result from electrical activity generated in their membranes. This electrical activity relies on worker molecules, proteins, that form doorways for ions called channels in the cell membrane. Severe health problems can arise if these channels are not in the right place or are dysfunctional. Ankyrin-B (ANKB) is a protein that anchors these channels in place by linking them to the internal structural scaffolding. Our group discovered an altered version, or variant, of ANKB. The presence of this variant is associated with several adverse health effects, including a host of electrical problems such as heart rhythm problems (linked to sudden death risk) and seizure. Notably, some individuals with the ANKB variant exhibited not only electrical problems, but also structural heart problems such as heart defects at birth and weakened heart muscle in later years. Given that ANKB interacts with channels and structural components in cells, ANKB likely regulates not only cellular function, but also cellular structure with implications for heart and brain health. It is critical to understand how ANKB influences these cell and tissue problems to best help those with the ANKB variant. To this end, I will investigate my prediction that ANKB regulates heart and brain cell development by regulating the amount and location of the channels and scaffolding. I will examine the role of ANKB within immature cells as they undergo the process of becoming cells with distinct function (called cell differentiation) within the heart and the brain. I will measure levels of ANKB, ANKB interactors, and proteins known to change during differentiation. I will use microscopy to observe how changes in ANKB impact the cell structure across differentiation. Improved understanding of ANKB's role in heart and brain cell development will provide critical insight into the impact of ANKB in disease.