Grant: Canada Postdoctoral Research Award (CPRA) program

For people living with diabetes, their pancreas cannot properly regulate blood sugar due to issues with two key hormones: insulin and glucagon. These hormones are made by islets, which are groupings of different specialized cells in the pancreas. Understanding how islets function, and why they stop working correctly in diabetes, is essential for developing better treatments. Cells contain a nucleus which houses our DNA. Regions of DNA, called genes, contain instructions to make proteins that carry out most of our cell's functions. These instructions are first copied into messenger RNAs (mRNAs) inside the cell nucleus. Before these mRNAs can be used to make proteins, they must travel out of the nucleus to the cytoplasm, where protein production happens. This transport step, called mRNA export, acts as a crucial gatekeeper. If certain mRNAs are not properly exported, their corresponding proteins will not be made. In my previous studies, I found changes in levels of a set of adaptor proteins that help select which mRNAs get exported. These changes could alter which proteins are made, contributing to the malfunction of insulin and glucagon secretion seen in diabetes. My research will investigate this new mechanism in two ways. First, I will reduce the levels of these specific adaptor proteins in human islet cells and study how this affects the cell's health, metabolism, and hormone secretion capabilities. Second, I will identify exactly which mRNAs depend on each adaptor for export. By comparing these results, I will connect changes in mRNA export selectivity to the resulting functional problems in islet cells. This project will create the first catalogue of adaptor-specific mRNAs and show how disrupted export contributes to diabetes. By revealing a completely new layer of gene regulation, these findings will improve our understanding of islets, open new opportunities for treatment development, and provide insights relevant to many other diseases beyond diabetes.