Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Spinal muscular atrophy (SMA) is a genetic disorder highlighted by the loss of nervous system cells in the spinal cord and muscle shrinkage, which ultimately leads to death in children. The incidence rate of SMA is 1 in 10,000. SMA is caused by mutations in the Survival Motor Neuron (SMN) gene, a gene expressed in every cell of the body. SMA patients and physicians focus on disease management, as there is no effective medical treatment available. Although SMA is primarily a motor neuron disease, accumulating evidence is pointing towards skeletal muscle and muscle stem cells as primary players in the disease. Data from Dr. Kothary's laboratory and other laboratories demonstrated deregulation of muscle growth and muscle stem cell function. It is likely that these perturbations contribute to the intrinsic muscle weakness present in muscles of SMA mouse models. I hypothesize that SMN has a function in muscle stem cell biology and muscle cell growth. In this project, I will first assess SMA muscle stem cell biology and their efficacy to form muscle fibers. Then, I will investigate the ability of SMA stem cells to self-renew and to contribute to muscle healing. In the second part of the project, I will use muscle cell lines to characterize aberrations in gene expression that occur in the context of reduced SMN to identify the underlying mechanism of the muscle growth defects in SMA. I will also assess whether it can be reversed therapeutically. Taken together, this study will allow for a better understanding of whether muscle stem cell function is perturbed and inform us how muscle growth mechanisms are affected in SMA. Ultimately, the results of this project will shed light on muscle defects in mouse models of SMA and could open up new therapeutic avenues for SMA.