En”RAGE”ing the islet: Investigating the role of the Receptor for Advanced Glycation End-Products (RAGE) in islet edocrine cells and diabetes.
Type 1 diabetes is the most common chronic disease which manifests in early life. Although comprising only 10% of diabetes cases, type 1 diabetes makes up ~40% of the total cost of diabetes to Australia, due to its early life onset and complex clinical management. Type 1 diabetes is an autoimmune disease where the body "turns on itself" and actively destroys the cells which produce the sugar storage hormone insulin. Hence, there is no cure and individuals require life-long insulin administration for survival.
Our team is investigating novel therapies targeting RAGE, an immunoglobulin-like receptor present on many types of immune cells and on endocrine (beta and alpha) cells of the pancreas during the development of T1D. The gene for RAGE is also located in the major region responsible for inherited susceptibility to T1D development. We have previously shown that RAGE inhibition using therapy leads to improvement in beta cell function and health and increases in regulatory T cells (Tregs), decreases in pathogenic CD8+ T cells thereby delaying T1D onset in our preclinical models. We have also shown that having higher levels of certain forms of RAGE helps to protect young people from developing T1D. This PhD is part of a comprehensive program of research in partnership with hospitals, other research teams and industry, integrating both clinical and preclinical studies. During this PhD project, you will uncover the critical role that RAGE expression on the endocrine beta and alpha cells plays in glucose homeostasis, beta cell damage and susceptibility to diabetes.