The overall theme of research within the group is type 2 diabetes. In particular, we focus on two major components of type 2 diabetes, namely obesity and insulin resistance, and how these two phenomena interlink to predispose to metabolic disease. Our general aim is to provide a better molecular understanding of these disease processes so that improved therapy can be designed. We approach these issues in three general ways.
Human studies. We have access to unique populations of subjects with extreme phenotypes of obesity and insulin resistance in addition to large populations relevant to the more common phenotypes of type 2 diabetes and obesity. Mutations which are detected in candidate gene studies are explored further for their role in human disease by linkage studies in pedigrees, functional studies of the properties of the mutant variant and detailed in vivo studies in humans.
Studies in cellular models. We have extensive activities in functional genomics with a major focus of the laboratory on exploring the cellular consequences of mutations found in candidate genes in humans with diabetes related phenotypes. In addition, we undertake basic studies into the biology of insulin and IGF-1 signalling and adipogenesis, processes which inform our more applied work in humans.
In vivo models. Recently we have begun to use murine models to explore certain aspects of the molecular pathogenesis of human diseases. This is a growing part of the programme.