Research
Our work is concerned with mitochondrial function; how this is altered in metabolic diseases, during development and ageing, and with changes in diet, exercise and oxygen; and what effects these changes have on physiological performance. We aim to elucidate the causes of mitochondrial dysfunction and the impact this has on function at the level of the tissue, intact organ and whole body.
Mitochondrial function in health and disease
Our interest lies in the control of mitochondrial respiration and energy metabolism. We are interested in the metabolic response to dietary manipulation and alterations in oxygen supply, including the matching of oxygen demand and supply. We study this in cells, tissues, animal models and healthy humans at high altitude, and in relation to diseases such as heart failure, COPD, anaemia and pathologies of pregnancy such as preeclampsia. A major recent interest is the role of dietary nitrate in the regulation of metabolism.
Collaborators
Research team
Dr Katie O’Brien
Mrs Sarah Millington-Burgess (British Heart Foundation funded student)
Miss Alice Sowton (British Heart Foundation funded student)
Mr Lorenz Holzner (Wellcome Trust funded student)
Miss Paula Darwin (BBSRC CASE funded student)
Previous team members
Dr Tom Ashmore
Dr Helen Atherton
Dr Francesca Colleoni
Dr James Horscroft
Dr Aleksandra Kotwica
Dr Ross Lindsay
Dr David Menassa
Dr Andrea Morash
Dr Augustine Ocloo
Main research collaborators
Professor Graham Burton (PDN)
Professor Kieran Clarke (University of Oxford)
Professor Florin Despa (University of Kentucky, USA)
Professor Martin Feelisch (University of Southampton)
Professor Abby Fowden (PDN)
Professor Dino Giussani (PDN)
Professor Erich Gnaiger (University of Innsbruck, Austria)
Professor Julian Griffin (Dept. of Biochemistry, University of Cambridge)
Professor Mike Grocott (University of Southampton)
Professor Hugh Montgomery (UCL)
Dr Lee Roberts (University of Leeds)
Publications
Horscroft JA, Kotwica AO, Laner V, West JA, Hennis PJ, Levett DZH, Howard DJ, Fernandez BO, Burgess SL, Ament Z, Gilbert-Kawai ET, Vercueil A, Landis BD, Mitchell K, Mythen MG, Branco C, Johnson RS, Feelisch M, Montgomery HE, Griffin JL, Grocott MPW, Gnaiger E, Martin DS, Murray AJ, (2017). Metabolic basis to Sherpa altitude adaptation. Proc Natl Acad Sci USA. 24:6382-6387
Roberts LD, Ashmore T, McNally BD, Murfitt SA, Fernandez BO, Feelisch M, Lindsay R, Siervo M, Williams EA, Murray AJ, Griffin JL, (2017). Inorganic nitrate mimics exercise-stimulated muscular fiber-type switching and myokine and γ-aminobutyric acid release. Diabetes. 66:674-688
Murray AJ, Knight NS, Cole MA, Cochlin LE, Carter E, Tchabenenko K, Pichulik T, Gulston MK, Atherton HJ, Schroeder MA, Deacon RMJ, Kashiwaya Y, King MT, Pawlosky R, Rawlins JNP, Tyler DJ, Griffin JL, Robertson J, Veech RL, Clarke K, (2016). Novel ketone diet enhances physical and cognitive performance. FASEB J. 30:4021-4032
Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K, (2016). Nutritional ketosis alters fuel preference and thereby endurance performance in athletes. Cell Metab. 24:256-68
Cole MA, Abd Jamil AH, Heather LC, Murray AJ, Sutton ER, Slingo M, Sebag-Montefiore L, Tan SC, Aksentijević D, Gildea OS, Stuckey DJ, Yeoh KK, Carr CA, Evans RD, Aasum E, Schofield CJ, Ratcliffe PJ, Neubauer S, Robbins PA, Clarke K, (2016). On the pivotal role of PPARα in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury. FASEB J. 30:2684-97
Ashmore T, Roberts LD, Morash AJ, Kotwica AO, Finnerty J, West JA, Murfitt SA, Fernandez BO, Branco C, Cowburn AS, Clarke K, Johnson RS, Feelisch M, Griffin JL, Murray AJ, (2015). Nitrate enhances skeletal muscle fatty acid oxidation via a nitric oxide-cGMP-PPAR-mediated mechanism. BMC Biol. 13:110
Ashmore T, Fernandez BO, Evans CE, Huang Y, Branco-Price C, Griffin JL, RS Johnson, Feelisch M, Murray AJ, (2015), Suppression of erythropoiesis by dietary nitrate, FASEB J, 29:1102-1112
Roberts LD, Ashmore T, Kotwica AO, Murfitt SA, Fernandez BO, Feelisch M, Murray AJ, Griffin JL, (2015), Inorganic nitrate promotes the browning of white adipose tissue through the nitrate-nitrite-nitric oxide pathway, Diabetes, 64:471-484
Ashmore T, Fernandez BO, Branco-Price C, West JA, Cowburn AS, Heather LC, Griffin JL, Johnson RS, Feelisch M, Murray AJ, (2014), Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart, J Physiol, 592:4715-4731
Colleoni F, Padmanabhan N, Yung H-W, Watson ED, Cetin I, Tissot van Patot MC, Burton GJ, Murray AJ, (2013), Suppression of mitochondrial electron transport chain function in the hypoxic human placenta: a role for miRNA210 and protein synthesis inhibition, PLOS One, 8:e55194
Levett DZ, Radford EJ, Menassa DA, Graber EF, Morash AJ, Hoppeler H, Clarke K, Martin DS, Ferguson-Smith AC, Montgomery HE, Grocott MP, Murray AJ, (2012), Acclimatization of skeletal muscle mitochondria to high-altitude hypoxia during an ascent of Everest, FASEB J, 26:1431-1441
Roberts LD, Murray AJ, Menassa D, Ashmore T, Nicholls AW, Griffin JL, (2011), The contrasting roles of PPARδ and PPARγ in regulating the metabolic switch between oxidation and storage of fats in white adipose tissue, Genome Biol, 12:R75
Cole MA, Murray AJ, Cochlin LE, Heather LC, McAleese S, Knight NS, Abd Jamil A, Sutton E, Parassol N, Clarke K, (2011), A high fat diet increases mitochondrial fatty acid oxidation and uncoupling to decrease efficiency in rat heart, Basic Res Cardiol, 106:447-457
Murray AJ, Knight NS, Cochlin LE, McAleese S, Deacon RM, Rawlins JN and Clarke K, (2009), Deterioration of physical performance and cognitive function in rats with short-term high-fat feeding, FASEB J, 23:4353-4360
Murray AJ, Cole MA, Lygate CA, Carr CA, Stuckey DJ, Little SE, Neubauer S, Clarke K, (2008), Increased mitochondrial uncoupling proteins, respiratory uncoupling and decreased efficiency in the chronically infarcted rat heart, J Mol Cell Cardiol, 44:694-700
Murray AJ, Lygate CA, Cole MA, Neubauer S, Clarke K, (2006), Insulin resistance, abnormal energy metabolism and increased ischemic damage in the chronically infarcted rat heart, Cardiovascular Res, 71:149-157
Murray AJ, Panagia M, Hauton D, Gibbons GF, Clarke K, (2005), Plasma free fatty acids and peroxisome proliferator-activated receptor α in the control of myocardial uncoupling proteins, Diabetes, 54:3496-3502
Murray AJ, Anderson RE, Watson GC, Radda GK, Clarke K, (2004), Uncoupling proteins in human heart, Lancet, 364:1786-1788
Teaching and Supervisions
Course Organiser - 1B NST Physiology
Lecturer - 1A NST Physiology of Organisms, 1B NST Physiology, Part 2 PDN Systems and Clinical Physiology
