Dr Guy Bewick

Senior Lecturer

BSc, PhD

Dr Guy Bewick

Contact Details

Telephone: +44 (0)1224 437398
+44 (0)1224 437388
Fax: +44 (0)1224 437465
Email: g.s.bewick@abdn.ac.uk
Address: School of Medical Sciences
Institute of Medical Sciences
AB25 2ZD



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 synaptic connections are made and maintained, particularly using the neuromuscular junction as a model synapse. Currently, he has an ongoing interest in examining how transmitter release is adapted to in vivo synaptic activity patterns and how these differing functional roles relate to the synaptic structure. He is also examining the modulation of transmitter release from central endings by the endogenous cannabinoid system. Most recently, he has begun elucidating the role of the intriguing system of synaptic-like vesicles in mechanically sensitive sensory endings, he recently 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.

Current Research

My laboratory has 2 major lines of investigation:

1) 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.

2) 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 the system might be a targeted to treat one of the most prevalent and life-threatening conditions - high blood pressure (hypertension).

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.


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