Dr Guy Bewick

Dr Guy Bewick
BSc, PhD

Senior Lecturer

Dr Guy Bewick
Dr Guy Bewick

Contact Details

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The University of Aberdeen Rm 6:18
Institute of Medical Sciences
School of Medicine, Medical Sciences & Nutrition
Aberdeen AB25 2ZD
United Kingdom


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 was appointed to a Lectureship in Biomedical Sciences, University of Aberdeen, in 1994 and promoted to Senior Lecturer in 2001.


Research Interests

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.

Current Research

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.

Further Info

Mechanosensory endings take up synaptic vesicle markers


FM1-43 is spontaneously taken up into stretch-sensitive nerve endings in muscles. By sensing the length of the muscles, these endings tell us where our arms and legs are. Dye uptake is increased by mechanical activity (muscle stretch) and can then be released again in the same way. This means the dye is taken into vesicles that recycle locally. We have now shown that these vesicles contain a neurotransmitter (glutamate) that is released during recycling, regulating the sensitivity of the ending. 

In vivo activity entrains synaptic fatiguability


Muscles used routinely in posture and supporting the body weight, such as the soleus, are active for long periods during our waking day. We have known for several decades that these muscles become more fatigue resistant due to this regular use and training, whereas infrequently used muscles (e.g. the toe extensor, extensor digitorum longus - EDL) fatigue rapidly. More recently, we have shown that the motor nerve terminals that make these muscles contract also adapt to being able to trigger contraction for longer. We also showed this is due to changes in activity pattern. This figure shows transmitter chemical release from motor terminals (which triggers contraction) is better maintained during repeated stimulation in soleus than EDL. Conversley, if the terminal activities are switched over by stimulation electrodes, the abilities are entirely switched within a few weeks. Paralysis has no effect on release ability - showing a change in actiivty is very different from no activity. More recent work in our laboratory is now showing that the muscles release signalling molecules in response to activity to control the strength and fatiguability of the nerve-muscle signalling. We are also investigating if these pathways can be targetted to help boost nerve-muscle signalling in neuromuscular diseases.