Grant: Vanier Canada Graduate Scholarships - Doctoral

Skeletal and heart muscle are formed during a process called differentiation. One of the mechanisms that is important to muscle differentiation is splicing. Splicing results in changes to the activity of proteins that control differentiation. Two splicing factors are the RNA binding motif (RBM) proteins RBM5 and RBM10. These two proteins also play a role in the control of cell death in cancer cells by changing the splicing of cell death regulatory factors. RBM5 and RBM10 protein levels are high in both heart and skeletal muscle. My question is 'Does the splicing activity of RBM5 and RBM10 play an important role in muscle differentiation?' I am going to find this out using cardiac and skeletal muscle models for differentiation. I will be a) measuring when RBM5 and RBM10 are expressed during differentiation, b) changing these levels to see if that change will alter the way the cells differentiate, and c) identifying and measuring the levels of spliced muscle proteins to see if the changes relate to RBM5 and RBM10 expression. This is the first study concerning the role of RBM5 and RBM10 in muscle differentiation and also in a non-cancer cell. Determining their expression patterns and how these relate to splicing changes in muscle-specific factors will help us to further analyse their importance during development. The outcomes of my research will allow us to look at the connection between RBM proteins, splicing and differentiation. It will provide the essential background information for better understanding the complex involvement of RBM5 and RBM10 and allow us to study the link between cell death during muscle differentiation in the future. I anticipate that in the long run, it will open up avenues for studying muscle development versus muscle regeneration and in tissue remodelling as well.