Type 1 diabetes (T1D) results from an immune cell mediated destruction of insulin-producing pancreatic β cells. Currently there is no cure for T1D. The exact cause for T1D is unknown and evidence points to the contribution of genetic and environmental factors, leading to a breakdown in tolerance normally maintained by Regulatory T (Treg) cells. Environmental contributions associated with T1D are not well characterised but emerging studies suggest that they may alter the immune system via epigenetic modification. Recent data strongly link the breakdown in tolerance in multiple autoimmune diseases to alterations in the transcriptional program in CD4+ T cells, however, the molecular mechanisms are not well understood. We propose that in T1D causal SNPs alter the gene expression patterns in CD4+ T cells by either disrupting or creating new TF (transcription factor) binding sites in enhancers located in genetic susceptibility regions and epigenetic change alters chromatin accessibility. My project is using ATAC-seq and RNA-seq to compare the DNA accessibility and transcriptomes in CD4+ Treg (Regulatory T) and Th (Helper T) cells isolated from individuals with established T1D and age- and sex- matched healthy controls. This will identify changes in chromatin structure in T1D samples relative to healthy controls, enabling the identification of changes driven by both genetic and epigenetic variation that correlate with an altered transcriptional program in T1D. T1D associated SNPs at these regions can then be correlated with alterations in TF binding and putative epigenetically modified T1D regions will be validated in functional assays to demonstrate causality.