Grant: Operating Grant

Type 1 Diabetes is an autoimmune disease caused by a patients own immune cells killing the insulin producing cells in the body. This life-long disease typically occurs in children and is a major health concern in Canada. The transplantation of donor islets can cure patients with Type 1 diabetes; however, the recipient needs to take immunosuppressive drugs that have serious side effects, and the transplanted islets typically fail within a few years. A great deal remains unknown about how and why immune cells kill the insulin-secreting cells in patients with Type 1 Diabetes, and a better understanding of these processes is essential for developing a cure for this disease. When immune cells start to kill insulin-secreting cells the genes expressed within the insulin-secreting cells change dramatically. For example, we have identified a gene, called Myt3, whose expression is dramatically lowered in insulin-secreting cells when immune cells attack. Interestingly, Myt3 is almost exclusively expressed in the body's insulin-secreting cells, and is a member of a family of genes called transcription factors that are master regulators of gene expression. We have shown that reducing Myt3 expression causes insulin-secreting cells to stop producing insulin efficiently, and to start to die. Based on our research thus far, we believe that Myt3 regulates genes that control insulin production and secretion, while at the same time preventing the expression of genes that induce insulin-secreting cells to die. We propose that by preventing immune cells from reducing Myt3 expression we can improve the number of healthy functional insulin-secreting cells in patients with Type 1 Diabetes. The work in this grant is aimed at testing these hypotheses. We believe that this will bring us one step closer to a cure for Type 1 Diabetes.