Diabetes and Inflammation Laboratory. (360G-Wellcome-107212_Z_15_Z)

Our goal is to identify clinical interventions in patients recently diagnosed with, or children at high risk of developing, type 1 diabetes (T1D), thereby maximising the health benefits of genetics and genomics in this common immune disorder. Our studies in T1D serve as a model for the investigation of other diseases and their treatment. We will take specific steps towards achieving this goal during the next five year programme: (1) Genetics. Define the genetic basis of T1D by fine-mapping di sease-associated causal variants and haplotypes, identify their target genes, and investigate the regulation of these genes before and after cell activation/differentiation. (2) Phenotypes and mechanisms. Identify aberrant cellular interactions and pathways caused by susceptibility genes that mediate a loss of immune tolerance to insulin-producing beta cells culminating in their destruction. These will provide potential targets for therapeutic intervention, as demonstrated by our work in the I L-2 pathway. (3) Experimental medicine. Complete our mechanistic investigations of the effects of IL-2 administration in patients, as a prelude to testing the efficacy of ultra-low dose IL-2 in the preservation of C-peptide and beta-cell function. Investigate, using the same mechanistic approach and depending on our emerging knowledge, another potential therapeutic.