Dr Timothy West
Department: Comparative Biomedical Sciences
Research Centres: Structure & Motion Laboratory
Structure & Motion Lab manager. Lead researcher on studies of skinned muscle fibre mechanics and energetics
I began my research career in the field of animal energetics in the laboratories of Prof. E.T. Garside at Dalhousie University (MSc) and Prof. P.W. Hochachka at the University of British Columbia (PhD). My work as a research associate with Dr. R.G. Boutilier (Cambridge, Zoology) and as research fellow with Prof’s N.A. Curtin, R.C. Woledge and M.A. Ferenczi (Imperial College London, Molecular Medicine) focused on the regulation of muscle energy turnover at rest, during hypoxic hypo-metabolism, and during contraction in skeletal and cardiac muscle. I am currently Lab Manager in the Structure & Motion Laboratory, Royal Veterinary College, where my reseach focuses on comparative skeletal muscle mechanics.
Research skills acquired include:
• in vivo exercise and respirometry testing; chronic cannulation techniques; radiolabel measurement of in vivo substrate kinetics, muscle enzyme and metabolite profiles.
• isolation of intact and skinned fibres; direct and indirect muscle calorimetry; muscle micro-dialysis; isotopic transmembrane ion fluxes; protein purification and fluorophore labelling; fibre mechanics, heat + work, and time-resolved ATPase activity.
My research is on comparative mechanics and energetics of striated muscle. At the RVC my focus has been on measuring the mechanical properties of single demembranted (skinned) skeletal muscle fibres from animal locomotory muscles. The aims are to integrate single fibre force, velocity, power and myosin heavy chain (MHC) isoform with (i) intact muscle fibre mechanics and fibre-type distribution, and (ii) with whole-animal locomotory behaviour and economy in both lab settings and in the wild. Single fibre work is front-and-centre in this integrative scheme because with most species (eg. cheetah, lion, wild dog, antelope) we must work with small needle-biopsy material. Hence, an over-arching aim is to develop methods that give us confidence that single fibre mechanics are a robust surrogate of intact and in vivo muscle mechanics.
We use state-of-the-art Temperature-jump (T-jump) technology (Aurora Scientific) to measure single fibre mechanics. We are in constant contact with Aurora to innovate these methods. T-jump involves activating the fibre initially at 0°C and then rapidly exposing the fibre to the test temperature. Activation is not limited by calcium and/or ATP diffusion; hence, the total contraction time is reduced, thereby minimising sarcomere-level and fixed-end damage to the preparation. Moreover, we can begin to explore skinned fibre mechanics at physiologically relevant temperatures, which has implications both for evaluating fibre-specific power in vivo and for modelling molecular mechanisms of cross-bridge mechanoenergetics. As part of our assessment of fibre quality, we visualise sarcomere-shortening during contraction and compare sarcomere-level mechanical responses to those of the whole-fibre. Collaborators at the RVC use immuno-histochemistry to evaluate single fibre MHC, and they are keen to develop their methods for a range of species and muscle-types. T-jump methodology conducted in parallel with MHC analysis and, importantly, with whole-fibre mechanics and heat+work measurements provide novel means to advance our understanding of the physiological limits and environmental constraints on whole animal locomotion.
Selected Publications: Skeletal and Cardiac muscle mechano-energetics
Curtin, N.A., H.L.A. Bartlam-Brooks, T.Y. Hubel, J.C. Lowe, A.R. Gardner-Medwin, E. Bennitt, S.J. Amos, M. Lorenc, T.G. West & A.M. Wilson. 2018. Remarkable muscles, remarkable locomotion in desert-dwelling wildebeest. Nature https://doi.org/10.1038/s41586-018-0602-4.
Wilson, A.M., T.Y. Hubel, S.D. Wilshin, J.C. Lowe, M. Lorenc, O.P. Dewhirst, H.L.A. Bartlam-Brooks, R. Diack, E. Bennitt, K.A. Golbek, R.C. Woledge, N.A. Curtin & T.G. West. 2018. Biomechanics of predator-prey arms race in lion, zebra, cheetah and impala. Nature 544:183-88.
Toepfer, C., M.B. Sikkel, V. Carosi, A. Vydyanath, I. Torre, O. Copeland, A. Lyon, S. Marston, P.K. Luther, K.T. MacLeod, T.G. West & M.A. Ferenczi. 2016. A Post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation. Am J Physiol 311:H465-H475.
West, T.G. 2016. Aquatic and aerial animal athletes: adaptations for muscle power and speed in tuna and hummnigbirds. Physiological News 102:36-39.
C.N. Toepfer, T.G. West & M.A. Ferenczi. 2016. Revisiting Frank-Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (ktr) in a length-dependent fashion. J Physiol 594:5237-54.
Curtin, N.A., R.A. Diack, T.G. West, A.M. Wilson, R.C. Woledge. 2015. Skinned fibres produce the same power as intact fibre bundles from muscle of wild rabbits. J Exp Biol 218:2856-63.
T.G. West, C.Toepfer, R. Woldege, A Rowlerson, M. Kalakoutis, P. Hudson, A. Wilson & N. Curtin. 2013. Power output of skinned skeletal muscle fibres from the cheetah (Acinonyx jubatus). J Exp Biol 216:2974-82
Toepfer C, V Caorsi, T Kampourakis, MB Sikkel, TG West, MC Leung, SA Al-Saud, K Macleod, AR Lyon, SB Marston, J Sellers & MA Ferenczi. 2013. Myosin regulatory light chain (RLC) phosphor-rylation change as a modulator of cardiac muscle contraction in disease. J Biol Chem 288:13446-54.
Mansfield, C, TG West, NA Curtin & MA Ferenczi. 2012. Stretch of contracting cardiac muscle abruptly decreases the rate of phosphate release at high and low calcium. J Biol Chem 287:25696-709.
Park-Holohan, S.J., M. Linari, M. Reconditi, L. Fusi, E. Brunello, T. Narayanan, M. Irving, M. Dolfi, V. Lombardi, T.G. West, N.A. Curtin, R.C. Woledge & G. Piazzesi. 2012. Mechanics of myosin function in white muscle fibres of the dogfish Scyliorhinus canicula. J Physiol 590:1973-88
Bickham D.C, T.G. West, M.R. Webb, R.C. Woledge, N.A. Curtin & M.A. Ferenczi. 2011. Millisecond-scale biochemical response of muscle fibres to change in strain. Biophys J 101:2445-54
Ushakov, D.S., V. Caorsi, D. Ibanez-Garcia, H. B. Manning, A.D. Konitsiotis, T.G. West, C.W. Dunsby, P.M. French & M.A. Ferenczi. 2011. Response of rigor cross-bridges to stretch detected by fluorescence lifetime imaging microscopy of myosin essential light chain in skeletal muscle fibers. J Biol Chem 286:842-850
Caorsi, V., D.S. Ushakov, T.G. West, N. Setta-Kaffetzi & M.A. Ferenczi. 2011. FRET characterization for cross-bridge dynamics in single skinned rigor muscle fibres. Eur J Biophys 40:23-27
Garcia, D.I., J. Requejo-Isidro, M.R. Webb, T.G. West, P. French, & M.A. Ferenczi. 2010. Fluorescence lifetime imaging reveals that the environment of the ATP binding site in muscle senses force. Biophys J 99:2163-69
Park-Holohan, S-J, T.G. West, R.C. Woledge, M.A. Ferenczi, C.J. Barclay & N.A. Curtin. 2010. Effect of phosphate and temperature on force exerted by white muscle fibres from dogfish. J Muscle Res Cell Motil 31:35-44
West, T.G., G. Hild, V. Siththanandan, M.R. Webb, J.E.T. Corrie & M.A. Ferenczi. 2009. Time course and strain dependence of ADP release in contracting permeabilized muscle fibres. Biophys J 96:3281-94
Stubbings A., A.J. Moore, M. Dusmet, P. Goldstraw, T.G. West, M.I. Polkey & M.A. Ferenczi. 2008. Physiological properties of healthy human diaphragm muscle fibres and the effect of Chronic Obstructive Pulmonary Disease. J Physiol 586:2637-50
Garcia, D.I., P. Lanigan, M.R. Webb; T.G. West, J.R. Isidro, E. Ausorius, C. Dunsby, M. Neil, P. French & M.A. Ferenczi. 2007. Fluorescence lifetime imaging to detect actomyosin states in mammalian muscle sarcomeres. Biophys J 93: 2091-2101
West, T.G., M.A. Ferenczi, R.C. Woledge & N.A. Curtin. 2005. Influence of ionic strength on the time course of force development and Pi release by dogfish muscle fibres. J Physiol 567: 989-1000
West, T.G., N.A. Curtin, M.A. Ferenczi, H-Z. He, Y-B. Sun, M. Irving & R.C. Woledge. 2004. Actomyosin energy turnover declines while force remains constant during isometric muscle contraction. J Physiol 555:27-43
LOCATE: Locomotion, hunting and habitat utilisation among large African carnivores and their prey
LOCATE: Locomotion, hunting and habitat utilisation among large African carnivores and their prey. The carnivores of the southern African savannah have no domestic counterparts and are at the extremes of performance in terms of speed, agility and strength. They are amongst the most threatened species in the world and yet there is much we do not know about them. At the beginning of this project, we did not know how the predators or their prey achieve the speed and manoeuvring required for the chase, what makes the difference between success and failure in hunting or how far the animals travel in a day or night and many other factors that may influence success and survival.