MRC MRes/PhD Studentship in Diabetes - Understanding the role of cell connectivity in preserving the pancreatic beta-cell phenotype.

Islet transplantation is a life-changing therapy for people with poorly controlled Type 1 diabetes. However, to achieve improved glycaemic stability, patients often require 2-3 transplants due to the loss of functional islets during isolation, culture and the transplant itself. Optimising islet function before and during transplantation is essential to improve outcomes.
Contained within the islet, pancreatic beta-cells play a vital role in the regulation of glucose homeostasis by releasing insulin in response to glucose. Given this crucial role, beta-cells exhibit a characteristic phenotype to ensure appropriate glucose-stimulated insulin secretion. This phenotype includes expression of specific enzymes to ensure that glucose metabolism is tightly coupled to mitochondrial energy production allowing for maximal insulin release in response to glucose. Loss of these markers correlates with decreased beta-cell function in human diabetes. Maintaining the beta-cell phenotype during islet isolation / culture is essential to ensure optimal preparation of human islets for transplantation.

Based in the Institute of Cellular Medicine, this PhD project will explore whether the glucose-responsive phenotype of the pancreatic beta-cells can be preserved by improving cell connectivity between neighbouring cells. The successful applicant will receive training in the Diabetes Research Laboratories in a wide breadth of technologies including cell culture, basic molecular and cell biology (real-time RT-PCR, western blotting etc), metabolic flux analysis, fluorescence microscopy, statistical treatment of data and experimental planning / design. The work will be carried out in close association with the Newcastle University Islet Isolation and Innovation Hub, established for the provision of research grade human islets.