Blood glucose concentrations are tightly controlled in the body. This is via the action of two hormones secretion from the pancreas; insulin (which lowers blood glucose) and glucagon (which increases blood glucose). Type-2 diabetes (which costs the NHS a whopping £1million/hour!) is typically characterised by a loss of control of blood glucose. Everybody knows the role that insulin plays in this disease; insulin therapy has been around as a treatment for over 90 years. Yet the disease remains poorly treated! This is because diabetes is a bi-hormonal disease; part of the increase in blood glucose in diabetes is actually due to an excess glucagon.
It is therefore very surprising how little we know about the pancreatic cells that secrete glucagon (the alpha-cells). We don’t know whether glucagon secretion is regulated by the cells themselves or by their neighbouring cells. We don’t know some very basic facts about these cells, like whether glucose increases or decreases their activity (unlike their much studied cousins – the pancreatic beta-cells.) The mechanisms regulating glucagon secretion from pancreatic alpha-cells are therefore insufficiently investigated, poorly understood and hotly debated.
His research aims involve understanding which mechanism(s) are important for regulating glucagon secretion from pancreatic alpha-cells. Due to the complexity of this system, he is taking both, experimental (patch-clamp electrophysiology and imaging techniques) and computational (conductance-based modelling) approaches to identify important mechanisms for regulating glucagon secretion. By taking this integrated approach, he aims at understanding how glucagon secretion becomes impaired in diabetes.
Linford graduated with an MSc in Mathematics at the University of Bristol in 2009. His masters project involved investigating simple groups (Galois Theory). He spent a year working at the Centre for Public Health (LJMU, Liverpool) working with Dr Penelope Philips-Howard on The Big Drink Debate. He then began a PhD in Engineering Mathematics/Physiology and Pharmacology (with Prof Alan Champneys/Dr Tony Pickering - University of Bristol). His PhD was using predominantly computational techniques to understand sympathetic over-activity in hypertension.
In November 2015 he began a postdoctoral position with Prof Patrik Rorsman and Prof Blanca Rodriguez investigating alpha-cell dysfunction in diabetes. He was award his Henry Wellcome fellowship shortly after. During his fellowship he will use both computational and experimental techniques to understand which electrophysiological properties of alpha-cells are important for driving glucagon secretion, and how these may contribute to the impaired glucagon secretion seen in diabetes.