Investigating the role of Viperin in beta cell survival and the development of type 1 diabetes.

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Diabetes currently affects 463 million people worldwide, of which approximately 10% suffer from type 1 diabetes (T1D), the most common form of diabetes in children. During T1D the cells in the pancreas that produce insulin (beta cells) are attacked by the immune system, for reasons we don't yet fully understand, leading to a loss of insulin and increased blood sugar levels and a number of complications. Identifying new ways to prevent the loss of beta cells is vital to develop new treatments for this disease. Likewise, new ways to improve the function and survival of islet transplants (which some T1D patients receive) are urgently needed to improve control of blood sugar. We have identified that a protein called Viperin, that forms part of the body's immune system, plays a role in controlling beta cell survival following exposure to substances released during immune attack, in vitro (in a dish in the lab). In the present application, we will extend these findings by genetically altering Viperin levels in mouse models of T1D and in mouse islet transplants, to determine if Viperin plays a role in beta cell survival, inflammation and function. We will also explore the mechanisms by which Viperin controls cell survival, and extend our work to human tissue. Future directions include exploring the role of Viperin in the response of beta cells to systemic viral infection, screening for activators of Viperin (as drug candidates) and investigating Viperin action in other cell types relevant to T1D. If this project validates a protective role for Viperin in beta cells, this will potentially lead to the development of new therapeutic approaches for the treatment of T1D in people, and improvement of clinical islet transplantation.