Project 446709

Type 1 diabetes (T1D) is an autoimmune disease that occurs when the immune system mistakenly kills the cells in the pancreas that produce the hormone, insulin. A true cure for T1D requires the immune system to be re-set so it no longer attacks the pancreas, and the insulin-producing cells to be replaced or regenerated. We have assembled a unique team of experts in immune cell and insulin-producing cell biology and diabetes, to study why the immune system becomes over-activated and kills insulin-producing beta cells and causes T1D. We will focus on a growing area of research known as immunometabolism, which is the study of how metabolic pathways inside cells affect their ability to divide and function. We hypothesize that beta cells may create a metabolic environment that promotes autoimmunity. We will use samples from mice or people that are healthy or have T1D to study how cellular metabolic pathways might be altered in T1D. We will also investigate how factors made by the beta cells themselves might influence the metabolic activity of immune cells. This work will lead us to discover new ways that we could intervene to inhibit immune cell killing. We also plan to use new genetic engineering approaches to manipulate the ability of immune cells to respond to islet-derived factors and/or change the activity of specific metabolic pathways. The outcome of this work is that we will gain a better understanding of how altered metabolism influences autoimmunity and be able to design new ways to manipulate key metabolic processes to prevent or slow T1D progression.