Modelling Receptor uptake in Glucose Homeostasis

This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address important applied biomedical research questions in priority areas aligned with industry. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice.

Project overview:
The goal of this project is to develop an increased understanding of the interplay between a number of receptors involved in glucose homeostasis that are under investigation by the collaborating pharmaceutical company Sosei Heptares. These receptors play key roles in a host of diseases including diabetes.

This will be done by developing mechanistic mathematical models to characterise these processes supported by an extensive preclinical drug kinetic and drug response data set created by Sosei Heptares using compounds with different pharmacology against these receptors. It is anticipated that the development of these models will generate knowledge on the interaction of novel drugs with their specific target(s) and offer the potential to predict their subsequent action on the pathways regulating glucose homeostasis. This will impact on and benefit patients (in particular diabetic sufferers) by enhancing our understanding of these pathways and the mechanisms of disease as well as providing a valuable tool that may be used to interrogate how the various pathways interact together, though the selection of applicable patient populations/disease indications for the target of interest, support the design of clinical trials and enable the development of further novel drug against targets of interest.

The PhD student will also gain industrial experience during the project in a dynamic, collaborative research environment at Sosei Heptares' UK base and will have access to emerging preclinical and clinical data for the leading drugs to be considered against a range of targets involved in the pathways of glucose homeostasis. They will have the opportunity to obtain hands-on insight into both preclinical and clinical drug discovery processes to enable the development of effective mathematical models to ensure robust translation of efficacy to the clinic as well as potential insight into the design and implementation of early clinical trials.