Dr Guy Bewick
I graduated with a BSc in Zoology and Animal Physiology from the University of East Anglia in 1979. After 3 years working for the Ministry of Agriculture, Fisheries and Food inspecting export grain for insect infestation, I began my research career with a PhD position in the Department of Physiology, King’s College London with Dr David A Tonge. This initiated my research interest studying how appropriate nerve-muscle connections are made and then adapted to their diverse functions. I gained my PhD in 1986, investigating the regeneration of nerve-muscle connections. Subsequent postdoctoral work investigated other aspects of neuromuscular function. First, with Prof Glen Cottrell in St Andrews, investigating how simple (acetylcholine) and complex (neuropeptides) molecules, called 'neurotransmitters', are used simultaneously for neuromuscular signalling. Later, I worked in the Department of Physiology, University of Bristol with Dr Tony Ridge, studying the developmental pruning of nerve-muscle connections. This led to a major 2-year period at the University of Colorado Health Sciences Center, Denver, Colorado, USA. Here, with Dr Bill Betz, we developed technique for using FM1-43 and related dyes for fluorescent studies of the kinetics and distribution of the tiny neurotrnamsitter packets (vesicles) during activity in living nerve terminals. Between 1991 and 1994, I worked with Prof Clarke Slater in the Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital investigating the role of muscular dystrophy-related structural proteins in building nerve-muscle specialisations. I joined the University of Aberdeen in 1994.
PhD positions available - NOW! Deadline 16th December
We have two exciting PhD opportunities.
Mitochondria & motor control : nerves detecting muscle length are full of mitochondria. Is this why unco-ordination is so common in mitochondrial disease? This project explores mitochondria in terminal function and as potential therapeutic targets.
Ageing & motor weakness : motor nerve cells die as we age causing weakness, falls & hospitalisation. Surviving nerve cells then get stressed. How can this stress be ameliorated to slow this process?
Spindles are doin' it for themselves: Glutamatergic autoexcitation in muscle spindlesContributions to Journals
Mechanotransduction channels in proprioceptive sensory nerve terminals: still an open question?Current Opinion in Physiology, vol. 20, pp. 90-104Contributions to Journals: Articles
Physiology 2019, AberdeenContributions to Specialist Publications: Featured Articles
Physiology 2019Physiology News, pp. 28Contributions to Specialist Publications: Articles
New functions for the Proprioceptive System in Skeletal BiologyPhilosophical Transactions of the Royal Society B: Biological Sciences, vol. 373, no. 1759, 20170327Contributions to Journals: Articles
Dr Bewick’s research interests are centred on understanding how appropriate nerve-muscle signalling is established and maintained, both in motor and sensory systems. One focus is elucidating the role of the intriguing system of synaptic-like vesicles in mechanically sensitive sensory endings, he uncovered in collaboration with Dr Robert Banks of Durham University. This vesicle-based system seems to regulate the excitability of these sensory endings over a wide range, and is even capable of turning off the ending entirely. The other focus is on the neuromuscular junction, where he is examining how transmitter release from the motor terminal is maintained over a range of in vivo activity patterns. As well as understanding the basic neuroscience, he is exploring these control mechanisms as potential targets for strategies to ameliorate weakness in neuromuscular diseases.
My laboratory has 2 major lines of investigation:
1) Characterising a novel system for regulating sensory nerve ending sensitivity.
Mechanosensory endings tell us where our arms and legs are, whether we're touching anything, and monitor our blood pressure. Tiny vesicles, just like those that contain neurotransmitter, occur in all such endings throughout the animal kingdom. So, this suggests they are probably important. In fact, in muscle stretch receptors, they can greatly increase sensitivity or, alternatively, even turn the ending off completely! The major interest now is to understand why this system is there and what advantage it confers. Then, we can understand if there are disease processes affecting it that were previously unsuspected, or might benefit from targetting this system with new drugs. For example, we are now testing if this same system in stretch-sensitive endings around blood vessels might be a targeted to treat one of the most prevalent and life-threatening conditions - high blood pressure (hypertension).
2) Making appropriate nerve-muscle connections:
We are studying how nerve terminals, which are very varied in their functions, learn what they should do when they get to the right target. They become adapted to maintaining neurotransmitter output over their normal range of everyday activity patterns. We want to know how this is done. Also, we want to find ways to rectify or enhance nerve terminal output if diseases, such as myasthenias, make them defective. One recent interesting discovery is that a protein secreted by the muscle (transforming growth factor beta 2, TGF-beta2) is able to boost nerve-muscle signalling, and make it more efficient. This probably helps regulate signalling in normal, healthy muscles as they adapt to changing demands, such as growth, training and ageing. Importantly, however, we are now testing if it can be targeted to increase signalling in conditions where nerve-muscle signalling is weakened by disease, such as early stage motor neurone disease, and myasthenic conditions.
Page 4 of 6 Results 31 to 40 of 55
Attenuation of the stretch-activated discharge of rat muscle and spindle afferents by ENaC channel inhibitorsProceedings of the Physiological Society, vol. 10, no. PC41Contributions to Journals: Articles
Transforming growth factor-ß2 increases synaptic vesicle loading at rat neuromuscular junctionsProceedings of the Physiological Society, vol. 10, no. PC4Contributions to Journals: Abstracts
Autogenic modulation of mechanoreceptor excitability by glutamate release from synaptic-like vesicles: evidence from the rat muscle spindle primary sensory endingThe Journal of Physiology, vol. 562, no. 2, pp. 381-394Contributions to Journals: Articles
Postnatal emergence of mature release properties in terminals of rat fast- and slow-twitch musclesEuropean Journal of Neuroscience, vol. 19, no. 11, pp. 2967-2976Contributions to Journals: Articles
Glutamate-enhanced muscle spindle excitability - inhibition by PLD-coupled metabotropic glutamate receptor antagonistsThe Journal of Physiology, vol. 557P, C91Contributions to Journals: Abstracts
Activity-dependent plasticity of transmitter release from nerve terminals in rat fast and slow musclesJournal of Neuroscience, vol. 23, no. 28, pp. 9340-9348Contributions to Journals: Articles
Maintenance of transmitter release from neuromuscular junctions with different patterns of usage "in vivo"Journal of Neurocytology, vol. 32, no. 5-8, pp. 473-487Contributions to Journals: Articles
Evidence for activity-dependent modulation of sensory-terminal excitability in spindles by glutamate release from synaptic-like vesiclesAdvances in Experimental Medicine and Biology, vol. 508, pp. 13-18Contributions to Journals: Articles
Functional expression of cell surface cannabinoid CB(1) receptors on presynaptic inhibitory terminals in cultured rat hippocampal neuronsNeuroscience, vol. 98, no. 2, pp. 253-262Contributions to Journals: Articles
Functional expression of cell surface cannabinoid CB1 receptors on presynaptic inhibitory terminals in cultured rat hippocampal neuronsNeuroscience, vol. 98, pp. 253-262Contributions to Journals: Articles