Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder where patients usually die in their early twenties. Much is now known about the disease pathogenesis and we are using this information to develop novel approaches to treatment. We have collaborated with Summit plc in defining a first in class molecule for increasing the levels of a protein which can compensate for the protein which is missing in patients. This is being taken forward to Phase 2 trials by Summit plc. We have developed an improved assay to identify compounds which could follow on from this into the clinic. We are also developing ways in which to improve the effificiency of exon skipping in DMD which has shown great promise in clinical trials carrried out by other groups. Another aspect of the programme is to study genes expressed in the brain which, when mutated, cause movement and behavoural disorders. By finding out what these genes are, we will be able to identify important genes involved in brain development and function in man which may be relevant to human disease such Parkinsons disease and Amyotrophic lateral sclerosis. One of the mouse mutants is a model for schizophrenia.

Recent advances in genetics have provided valuable new insights into mechanisms involved in the development of Type 2 diabetes. One of the more interesting observations is that several of the genes which influence individual risk of diabetes also play a role in the development of certain cancers. The research which I will perform, if awarded this fellowship, aims to understand some of the mechanisms involved in this cancer-diabetes overlap: I will focus on two genes where the evidence for shared effects is greatest. In one set of studies, I will look at families who harbour rare mutations in these genes which place them at particularly high risk of cancer, and establish whether these same individuals display metabolic changes which indicate they are also at altered risk of diabetes. In complementary laboratory-based studies, I will use human tissue samples (pancreas, muscle and fat) to explore the molecular events which account for these effects. This work will help us understand some of the fundamental processes involved in both diabetes and cancer. It may also contribute to development of improved clinical care, not least by aiding appreciation of the potential side-effects of manipulating some of these disease processes.

I am interested in using synthetic biology techniques to develop promising sources of bioenergy, and for engineering nitrogen fixation in plants.