Abstract

Our aim is to further characterise the molecular basis for the autoimmune inflammatory disease type 1 diabetes. We have used integrated combination of genetics, in large collections of type 1 diabetic families and case/control, statistics, genome informatics and data mining, and gene expression and immunological studies. Our major effort now is to correlate susceptibility genotypes with biomarkers and phenotypes e.g. we have associated flow cytometric phenotypes of T lymphocytes with disease-predisposing genotypes of the IL-2RA (CD25) gene (Dendrou, C. et al. Nat. Genet. 41, 1011-1015, 2009). This is a first step towards identifying disease precursors that could be used in future therapeutic studies to stratify patients. To achieve this we have helped build a local biobank of volunteers and type 1 diabetes patients in whom we can study the effects of disease-associated genotypes and environmental factors (Cambridge BioResource: www.cambridgebioresource.org.uk/).

These immunology studies have underpinned the next major phase of our research: undertaking clinical studies with novel clinical trial design in patients with type 1 diabetes. Our initial clinical trials will be to assess the effects and mechanisms of ultra-low dose IL-2 on the immune system, with a focus on T regulatory cell activities. Our research efforts are part of the JDRF /Wellcome Trust Diabetes and Inflammation Laboratory (DIL), which has three other group leaders, John Todd (Director) Linda Wicker (Co-director, DIL ), and Chris Wallace (Head of Statistics group).