Grant: CIHR Fellowship

Oligodendrocytes are specialized cells in the brain and the spinal cord. These cells make myelin - a protective cover for nerves. In individuals with multiple sclerosis, the body's immune system mistakenly attacks and damages this myelin. This myelin damage disrupts the signalling from the brain and spinal cord to the rest of the body. Drugs that stimulate oligodendrocytes to repair the damaged myelin could offer treatment. To produce such treatments, in-depth knowledge about the formation of oligodendrocytes in humans is required. At the moment, most knowledge comes from studying mice. The differences between mice and humans make it challenging to create treatments that work well in humans. In this project, we aim to create a detailed description of how oligodendrocytes and myelin are formed in the human brain. We will first identify the available data from other researchers who collected human brain samples during surgery or after death. We will focus on the measurements of gene activity in individual myelin-producing cells. Similar to audio volume control, there are proteins called transcription factors that control the activity of genes (on, off and how much). By controlling which genes are active and how much, transcription factors determine the characteristics of cells. We recently improved the available software to model how these transcription factors control gene activity, including how two or more transcription factors can work together (rather than in isolation). We will apply this improved software to compare data from people with and without multiple sclerosis to see if and how myelin formation differs. These insights may help the development of new treatments. We will take the first step towards drug development by identifying some chemical molecules that can change myelin formation in a way relevant to multiple sclerosis.