Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory
Type-1 diabetes is caused by multiple genetic and environmental factors which interact and result in the immune system destruction of the insulin-producing beta cells of the pancreas. As a consequence people with the disease have a lifelong dependency on injected insulin.
The understanding of the genetic nature of type-1 diabetes leapt forward in 1987 when Professor John Todd, now Director of the Diabetes and Inflammation Laboratory, showed that genes encoding the HLA class II protein of the major histocompatability complex (MHC) are key determinants of type-1 diabetes. In 1990, Professor Todd was made a Wellcome Trust Senior Fellowship in Basic Biomedical Research. Since then he has been directly involved with the discovery of over 40 other regions of the human genome involved with susceptibility to type-1 diabetes.
The Diabetes and Inflammation Laboratory was initially funded for 5 years with a combined grant of around £18 million from the Wellcome Trust and the Juvenile Diabetes Research Foundation, which included the awarding of Wellcome Trust Principal Research Fellowships to Professors Linda Wicker and David Clayton. A further £12 million joint award was made in 2005 to support the centre until 2010.
Fundamental to the research at the Diabetes and Inflammation Laboratory was the creation of the Juvenile Diabetes Research Foundation/Wellcome Trust case sample, which contains 8000 samples and cell lines from people with type-1 diabetes. This resource was used in the Diabetes and Inflammation Laboratory's 2009 genome-wide association meta-analysis, which located 42 genetic loci involved with susceptibility to type-1 diabetes, 18 of which were previously undiscovered.
Other work in 2009 used high-throughput sequencing to uncover genetic variants that reduce the risk of type-1 diabetes. Four variants of the IF1H1 gene were identified; these produce proteins involved in the detection of enterovirus RNA and inducing an immune response. This is consistent with the known link between type-1 diabetes and enteroviral infection.
Professor Todd and colleagues at the Diabetes and Inflammation Laboratory are currently investigating correlations between potential susceptibility genes and their molecular characteristics or phenotypes, looking at RNA, proteins and cellular structure to identify the events that cause type-1 diabetes. Some of these phenotypes could serve as markers for the earliest precursors of the disease and serve as potential targets for early diagnosis.
The study of type-1 diabetes is also shedding new light on other autoimmune diseases, such as coeliac disease, multiple sclerosis and rheumatoid arthritis. Recent research has shown that the IL2RA gene region has one allele common to both type-1 diabetes and multiple sclerosis; each disease also has its own specific allele of IL2RA.
In October 2010 the Juvenile Diabetes Research Foundation and Wellcome Trust made additional awards of $4 million and £8.3 million, respectively, to the Diabetes and Inflammation Laboratory. This funding for the next five years will enable the laboratory to continue its world-class research on the causes of type-1 diabetes.