Grant: Master's Award: Canada Graduate Research Scholarships - Master's program

The Central Nervous System (CNS) is the primary integration centre of the human body as it translates and consolidates electrical information received through nerve impulses conducted by nerve cell fibres termed axons. White matter regions of the brain are distinguished by their abundance of myelin - the fatty, insulating layer produced and maintained by oligodendrocytes that wrap axons for increased efficiency of the propagation of nerve impulses in the CNS. As we age, the deterioration of myelin precedes cognitive decline and other age-related brain issues. A protein called Sirtuin 2 is thought to fulfill an important function in maintaining myelin health and integrity. While it is found in high levels in both oligodendrocytes and myelin, its role and the consequence of changes in its activity in the ageing brain remain poorly understood and characterized. Research suggests that SIRT2 may help stabilize myelin by modifying certain myelin proteins and that the loss of its function might contribute to the loss of myelin. This study aims to understand the distribution of the protein isoforms of SIRT2 throughout the ageing brain, and how their differential expression affects myelin in ageing. The proteomic changes of the myelin sheath will be explored in the absence of SIRT2 by using mice lacking the SIRT2 gene. These changes will help identify specific myelin proteins that are potential substrates of SIRT2 and to understand how its loss accelerates myelin degeneration. This work could reveal novel targets for preventing or slowing the loss of myelin integrity, potentially laying the foundations for therapies that aim to protect brain health in the ageing population.