Grant: Doctoral: Vanier Canada Graduate Scholarships

The behaviour of human cells is controlled by a vast signalling array composed of thousands of proteins and other molecules. The activity of these signalling components and the ways in which they interact with one another are what allow a cell to respond to stimuli, maintain a specific cellular state, and at the most basic level to survive. Protein kinases are a large family of signalling proteins that control all aspects of cell behaviour through the modification of other proteins, and aberrations in their activity levels or interaction states have been shown to affect or trigger several diseases, for example breast cancer, leukemia and Crohn's disease. Understanding how the members of this protein family act is absolutely critical to deciphering the complex behavior of cells and offers many avenues for drug design and disease therapy. One member of this family is the p38 mitogen-activated protein kinase (p38). p38 is a crucial regulator of cellular differentiation, the process by which an immature proliferating cell becomes a fully functioning mature cell. The role that p38 plays in muscle biology is the subject of much study as there are many diseases and injuries for which muscle recovery, growth and regrowth are requisite components of a return to full health. To understand the role of this kinase in muscle biology, it is necessary to know which proteins it modifies during cellular differentiation, something which has not been possible to date for this or any other kinase. However, our lab is developing a method that will allow us to determine which proteins p38 is modifying during the process of muscle differentiation, a method that will be easily adaptable to any kinase and cell type. If successful, this method will allow our laboratory and many others to rapidly produce large amounts of data on cellular signalling in a variety of healthy and diseased cell states, something that will be of benefit in designing therapeutic strategies for a number of diseases.