Grant: Doctoral Research Award: Canada Graduate Scholarships

Multiple sclerosis (MS) is a neurological disease that affects >90,000 Canadians, with no therapy that can stop its insidious progression. MS is caused by damage to myelin, a substance within the central nervous system (CNS), but how this damage begins, and the mechansims that cause it to progress in aging are unclear. The past few decades have uncovered that blood-derived immune cells aberrantly respond to myelin in MS to contribute to damage, but targeting them therapeutically does not halt progression, suggesting other mechanisms involved. Current models are thus limited as they primarily focus on these blood-derived immune cells. My project is exploring the role of microglia, CNS resident cells, in initiation and progression of myelin damage in the brain. Microglia are known to lose their regular functions in MS, and areas of initial microglia dysregulation without any myelin damage are known to progress to areas of active pathology in patients. My project will use a mouse model where microglia are absent to model this loss of microglia function that happens in early MS. We have observed that these mice have spontaneous myelin damage without their microglia, by similar mechanisms to what is already known about MS disease. We will further understand the mechanisms underpinning this process, and also investigate how this changes with age. All inferences on specific disease mechanisms that we make will also be validated with brain tissue from MS patients. Altogether, this will uncover new mechanisms that drive disease in MS, and may identify pathways that could serve as future drug targets to improve the quality of life of millions of people worldwide living with MS.