Transgenic modelling of beta-cell homeostasis

糖尿病的特点是胰腺中β细胞数量不足，导致血糖调节功能丧失，如果不及时治疗，将出现心脏病、失明和肾损伤等并发症，并带来毁灭性后果。目前，仅在英国就有超过200万人患有糖尿病，而且这个数字还在稳步增长。自1921年发现胰岛素以来，糖尿病的治疗取得了稳步进展，但没有一个能够解决β细胞的不足或阻止它们数量的下降。研究治疗靶点的复杂性和成本是开发新疗法或治愈方法的一个重大障碍。这也是试图开发计算模型的主要动机之一，该模型可用于预测和解释控制胰腺中功能β细胞数量调节的过程。这项工作的目的是把来自控制系统工程和生物科学的研究人员聚集在一起，在彼此的实验室里为开发这样的模型而工作。特别是，这项研究将应用适当的方法，从控制系统工程到从数据收集和错误分析到过程和网络建模的许多不同层次的生物问题的分析。研究人员的结合和他们共同使用的设施将使人们能够更深入地了解问题的要求和限制，可测量参数的性质以及潜在的信号和过程结构。这将使更有生物学意义的模型得以构建，进而可以用于以有针对性的方式推动实验过程。虽然这里的工作考虑了β细胞稳态问题，但我们完全期望这项研究的结果在系统生物学和其他领域具有更广泛的意义。

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.