Grant: Doctoral Research Award: Canada Graduate Scholarships

Type 1 diabetes (T1D) is a disease in which the beta cells of the pancreas, which produce and secrete insulin, are destroyed. Treatment of T1D patients relies on daily insulin injections to control their blood glucose. Although this treatment is lifesaving, it is not a cure. An exciting new therapeutic option is the transplantation of donor beta cells to restore functional insulin production. However, T1D is a prevalent disease, and there are nowhere near enough donor beta cells. Synthesizing insulin-secreting beta cells in the lab is a promising alternative, but we don't know enough about how to make these cells fully functional, aka "mature". My research focuses on a protein complex called Mediator, which regulates the process by which genes instruct cells on how and when to make the proteins they need. In particular, I study Mediator sub-unit 15 (Med15). Our lab has shown that, in mice, Med15 is required for proper beta cell development and maturation before birth and weaning. However, beta cells would need to maintain their maturity and functionality after transplant to make this treatment viable long-term. Therefore, I am studying how Med15 can maintain function of beta cells in adults after maturation is complete. I have developed a model wherein adult mice cannot make Med15 in their beta cells, and I have found that these mice do not secrete sufficient insulin in the presence of high glucose and are unable to regulate blood sugar levels. I have extracted beta cells from these mice with no Med15 and found they have less of the proteins they need to secrete enough insulin. Overall, this study will reveal how Med15 can be used to improve the maturity of in vitro beta cells, and maintain their function for a long term transplant. T1D patients receiving transplants would no longer need to constantly monitor blood sugar levels and inject insulin or worry about the long-term complications of their chronic disease.