Innovative strategies to predict progression rate to Stage 3 type 1 diabetes in adults and children

The aim of this PhD scholarship is to provide a broad training in laboratory-based basic and clinical science focused on a current critical gap in type 1 diabetes research - our inability to predict progression rate in those with pre-symptomatic autoimmune diabetes. The separate aims are focused on separate research questions. In Aim 1, the project will build on previous published work showing that immune cells from individuals progressing slowly to type 1 diabetes have different B and regulatory T cell expression patterns. In Aim 2, the role of anti-interferon alpha autoantibodies in slowing progression rates will be examined. If detected more often in those progressing slowly, the function of the autoantibodies will be tested in in vitro beta cell assays. In Aim 3, the role of the role of the exocrine pancreas as a measure of progression rate will be explored in three ways, first by genotyping a known genetic determinant of type 1 diabetes in CTRB1/2 and examining effects on Chymotrypsinogen and Trypsinogen levels; secondly by developing novel exocrine targets to examine whether cell-free DNA may offer additional insight to progression rate. Finally in collaboration with experts at the University of Exeter, pancreas histology will be examined.