After my first degree in Chemistry at Royal Holloway College I was encouraged by my Final Year Research Project supervisor, Les Suttcliffe, to do research using NMR. After a two year Research Assistant post using NMR to study cardiac carbohydrate metabolism in vivo, I decided to do a PhD in Biochemistry at The London Hospital Medical College (now Queen Mary's School of Medicine). I continued to do Post-Doctoral research in liver biochemistry at Queen Marys, being appointed as a Lecturer in the new Medical School in 2000. My work there revealed a novel mechanism by which the liver could regulate blood glucose, and much of my subsequent work is related to investigation of the precise biochemical mechanisms underlying glucose homoestasis. I moved to the Department of Chemical and Biological Sciences at Huddersfield in the Summer of 2004, taking on significant new teaching duties as a senior Lecturer; I run modules in Biochemistry, Molecular Evolution and the principle Year 2 research module, Case Study.
I have been the Year 2 Tutor in Biological Sciences since moving to Huddersfield, and I have been very fortunate to be part of the growing successes of our students in industry and academia. The Department of Chemical and Biological Sciences is an excellent environment for novel research, with a great mix of unique skills and facilities. I am an active member of the Biochemical Society (the Local Ambassador at Huddersfield and a Member of Council from 2011) and I enjoy being involved in promoting the molecular biosciences in local Schools. Outside of the University, I enjoy walking and gardening, and I am a keen Porsche 911 enthusiast (models up to 1994).
My research background is biochemistry and regulation of metabolism. I have used NMR and MRS extensively both in vivo and in vitro to investigate cellular and molecular mechanisms of metabolic control. I am interested in the mechanisms which underlie the relationship between poor fetal development and growth and onset of adult diseases some 50 years later (e.g. Type 2 diabetes). Little is known about how poor maternal nutrition or stress can have long-term 'programming' on the tissues and there are strong links between this area of research and stem cell research: this is because the developmental plan must be 'programmed' in to both stem cells and new born babies, yet still flexible enough to undergo environmental influences especially during stem cell lineage generation in utero. Epigenetic mechanisms are very likely to be involved but only limited evidence has been found supporting this hypothesis in the last 15 years as the first group to propose an epigenetic mechanism underlying fetal programming and particularly DNA methylation we have accumulated significant negative evidence for this proposed mechanism in specific circumstances strongly suggesting additional alternative programming mechanisms. I have proposed that the formation of graded structures in organs during fetal development could permanently re-set homeostatic switches by altering the cell populations of organs and tissues. This might also account for how stem cells are 'instructed' to divide and produce new types of cell lineages outside the control of the (epi)genetic information in the DNA.
Glucokinase (GK) is the key enzyme in liver responsible for hepatic glucose uptake. Low activity of this enzyme results in glucose remaining in the blood following a meal, contributing to the characteristic hyperglycemia in Type 2 diabetes (T2D). The enzyme is a central candidate for novel 'activator' compounds in man with several candidate drugs under development. Key discoveries in the last decade revealed exquisite and novel cellular and molecular mechanisms of regulation of this enzyme, and exploitation of these mechanisms is being undertaken to increase cellular activity of GK and treat subjects with Type II diabetes. However, the potential effects of these regulatory mechanisms directly influencing measured GK activity has not been fully considered. Research in this laboratory has shown that existing in vitro measurements of GK activity can be misleading and (normal) cellular activity is in fact much higher than often measured. Accurate assessment of GK activity has important implications for understanding both the etiology of T2D and its treatment, both with existing drugs and novel agents.
We have recently discovered an entirely new class of enzymes in liver which have important implications for how hepatic glucose metabolism. We are in the process of purifying these enzymes for sequencing to establish their significance in mammals. Distribution of organ, tissue and cellular expression as well as ontology and evolution will be important future areas of study for this enzyme.