Transgenic modelling of beta-cell homeostasis

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Diabetes, characterised by an insufficient number of beta-cells in the pancreas, leads to the loss of blood glucose regulation and, if left untreated, complications such as heart disease, blindness and kidney damage will occur with devestating consequences. Diabetes currently affects over 2,000,000 people in the UK alone and this number is steadily increasing. Since the discovery of insulin in 1921 there has be a steady progress in treatment of the disease but none that have been able to address the shortfall in beta-cells or arrest their decline in number. The complexity and cost of investigating therapeutic targets is a significant hurdle to the development of new treatments or a cure. It is also one of the main motivations for attempting to develop computational models that can be used to predict and explain the processes governing the regulation of the number of functioning beta-cells in the pancreas. The aim of this work is to bring together researchers from control systems engineering and biological science to work in each others' laboratories towards developing such models. In particular, this research will apply appropriate methodologies from control systems engineering to the analysis of the biological problem at a number of different levels from data collection and error analysis to process and network modelling. The combination of researchers and their shared use of facilities will enable a deeper understanding of the requirements and constraints of the problems, the nature of measurable parameters and potential signalling and process structures. This should enable more biologically meaningful models to be constructed that in turn can be used to drive the experimental process in a targeted manner. While the work here considers the problem of beta-cell homeostasis, we fully expect the results of this research to have wider significance in systems biology and elsewhere.