Grant: Project Grant

Skeletal muscle health affects locomotion, breathing and general whole-body metabolism. Maintenance of skeletal muscle function is therefore essential to a healthy lifestyle. In response to injury the muscle has a remarkable capacity to repair itself. This requires a special population of muscle stem cells that are responsible for building new healthy muscle fibers. However, during aging or disease the ability of these muscle stem cells to repair muscle can be dramatically reduced. Our laboratory is examining the signals in muscle stem cells that govern their ability to repair muscle. In particular, we are interested in how muscle stem cell health is affected by changes in PARylation, which is when a protein is modified in a specific way to change its function in a cell. Drugs that stop PARylation can help kill cancer cells and are used to treat patients but are also in clinical trials for treating other diseases like stroke and heart disease. Importantly, these drugs are associated with muscle pain and related side effects. Despite this, very little is known about the importance of PARylation in muscle health. Our new data shows that imbalances in the PARylation of proteins in muscle stem cells dramatically alters their function and ability to repair muscle following injury, or with disease or aging. This proposal will therefore investigate how PARylation affects muscle stem cell health. Findings from this project will help us understand how muscle stem cells are affected by PARylation, while also providing information to help create new therapies for muscle.