NEW INVESTIGATOR AWARD 2023 WINNER

Dr. Shaun Sanders, PhD

Assistant Professor, Department of Molecular & Cellular Biology University of Guelph

Grant Project: The role of palmitoylation of voltage-gated sodium channels in epilepsy

I am an Assistant Professor at the University of Guelph where I started June 2020. I have a PhD in Neuroscience from the University of British Columbia. My lab is generally interested in how proteins, the work horses of the cell, get to the right place in brain cells, which are big and complex, and how that goes wrong in neurological disorders. When I was young, a friend of mine was diagnosed with epilepsy and I understood the impact the diagnosis had on her and uncertainty she felt living with epilepsy. So, while I am new to working on epilepsy, I am inspired by these early experiences and wanting to help patients in the future.

Project Summary: Seizures occur when there is too much electrical activity in brain cells called neurons. Neurons are the basic working unit of the brain that send information in the form of electrical impulses from other neurons or sensory organs to downstream neurons or muscles. Ion channels are proteins that open and close to form small holes in the outer layer of the neuron. A particular kind of ion channel that let sodium into the neuron are called Nav channels. Nav channels are responsible for the electrical impulses that travel along axons and must be in the right place, in the right amount to ensure normal brain function. In fact, mutations in the genes for Nav channels are a common cause of epilepsy. Nav channels are modified with a sticky tag in a process called palmitoylation. The sticky tag can act like a postal code that directs other proteins to their correct location. The goal of our research is to determine if the sticky tag directs Nav channels and retains them at the sites where electrical impulses are generated and if the amount of the sticky tag on the Nav channel can be manipulated to decrease electrical activity and prevent seizures. Untreatable epilepsy occurs in 30% of affected patients so new treatment approaches are needed. Nav channel regulation is of considerable interest as epilepsy is often caused by Nav channel mutations. These studies will allow me to determine if reducing palmitoylation of Nav channels could prevent seizures. Future work following the completion of this proposal will include determining if manipulating how much of the sticky tag is added in neurons derived from skin cells of human epilepsy patients prevents seizures and the importance of the sticky tag to Nav channel function in mouse models of epilepsy.

 Grant: $75,000