Interview with Professor Richard Ribchester, Ph.D DSc FPhysiol

In this column, I ask neuroscience professors from around the world the same five questions. Read on to learn more about their research, careers and goals for neuroscience in the future.

Interview with Professor Richard Ribchester, Ph.D DSc FPhysiol

Professor of Cellular Neuroscience, Euan MacDonald Centre for MND Research and Centre for Discovery Brain Sciences 

Biomedical Sciences, University of Edinburgh, Scotland

Professor Ribchester obtained a BSc with Joint Honours in Chemistry and Zoology from the University of Durham and a PhD in Experimental Neurology from the University of Newcastle-upon-Tyne. He did postdoctoral research at the University of Colorado Medical School in Denver, and at the Institute of Physiology, University of Oslo.

1. What inspired you to pursue neuroscience as a career? 
Thinking back as far as I can, my first inspiration probably came from my father, who was a career soldier in the Royal Signals, the telecommunications regiment of the British Army. When I was about 8 years old, we were on a family picnic and for no obvious reason that I can recall, he sat me on the bonnet (hood) of the family car, had me cross one leg over the other and then demonstrated the myotatic reflex by tapping my hanging leg just below the kneecap. I found the involuntary nature of this ‘knee-jerk’ reflex both fascinating and highly amusing. From then, I developed my childhood delight with knowledge generally, gradually drifting more towards science than arts and humanities.  I had difficulty deciding whether to pursue chemistry or biology as I had become particularly interested in both (I read for a joint Honours degree in both subjects at Durham University in the early 1970’s). In my zoology classes at Durham I found the physiology of neuromuscular junctions and neuromuscular transmission to be especially interesting (along with other topics, like mitochondrial biochemistry). Through a series of happenstances, after I graduated I was offered an MRC Research Studentship to study neuromuscular transmission in a mouse model of muscular dystrophy, at the Muscular Dystrophy Research Laboratories in Newcastle-upon-Tyne. I had an inspirational (and patient!) PhD supervisor, Professor John B Harris. I was also inspired by the energy and enthusiasm of Professor Clarke Slater. Thus, I became completely hooked on synaptic physiology. I wrote a successful 2-year fellowship application for my first postdoc, to work with Professor Bill Betz at the University of Colorado Medical School and I worked under his inspiring, rigorous and expert guidance on neuromuscular synapse elimination. It was during that period that I “discovered” neuroscience as a nascent discipline, independent from physiology. (I attended the fifth annual meeting of the Society for Neuroscience in St Louis in 1978; at the time it seemed like a huge conference, with over 5,000 delegates. Nowadays, SfN meetings have over 30,000 attendees). I then wrote a successful one-year fellowship application to work with Professor Jan Jansen in the Physiology Institute at Oslo University, where I worked from 1979-1980. We were studying the specificity and plasticity of monosynaptic and polysynaptic connections on motor neurones in the embryonic chick spinal cord (including those mediating the myotatic reflex) and from which we made the first intracellular microelectrode recordings in vivo. That was a very exciting year, as Jan was incredibly inspiring and what we were doing was so new. Every day ended with a detailed discussion of that day’s experiment and a decision on what experiment we therefore needed to do the following day. We progressed very rapidly and steadily with that approach, both technically and scientifically. During that year I applied for and was offered a Lectureship (assistant professorship) in Physiology at Edinburgh University. My evolution to calling myself a “neuroscientist” rather than “neurophysiologist” continued from then, although I do still have most fascination for the anatomy and physiology of neuromuscular junctions and other synapses. I have been on the academic staff of Edinburgh University since 1980 and I am now Professor of Cellular Neuroscience. I received a great deal of inspiration and support from senior colleagues, leading to that promotion, not least from Professor Richard Morris, who headed the Department of Neuroscience that I joined in the 1990’s (now integrated into the Deanery of Biomedical Sciences).  I still enjoy combining both research and teaching, and one of my greatest sources of satisfaction has been my part in training (and hopefully inspiring) my PhD students and postdocs, some of whom have developed successful careers as leaders in their fields.

2. What do you think is the most important goal of neuroscience research? 
A glib answer to this is “to understand the brain”. Defining what that means exactly is more  problematical. I am constantly mindful of an interview I saw on TV in the early 1990’s with a contemporary Oxford philosopher (whose name I have alas forgotten), during which he pointed out that even if we understood everything there is to know about the anatomy and physiology of the brain, sufficient to enable us to build an exact replica, then that machine would most likely be conscious: but we would still not understand why! More prosaically, Bernard Katz, late doyen of our field,  remarked in his Fenn Lecture delivered in 1994 that neuromuscular junctions are  “experimentally favourable objects, whose study could throw considerable light on synaptic mechanisms elsewhere”. This became the most powerful principle guiding my research. Many years earlier, my former postdoc mentor Bill Betz, who received training himself as a postdoc in Katz’s laboratory in the late 1960’s, once mentioned in the lab another remark Katz had made: “we do what we can with what we have”. I consider that also to be an excellent guiding principle for contemporary neuroscience. Centuries earlier, Galileo urged that we should “measure what can be measured, and make measurable what cannot be measured”, which is similar goal, for all science. 

3. What are the main topics and goals of your research? 
I retain a complete fascination with every aspect of the biology of neuromuscular junctions and I am at my happiest when I am doing experiments on them in the lab myself (when I have time). Right now, I have three ongoing projects: the first an MRC-funded major project on the pharmacology and toxicology of organic solvents at neuromuscular junctions, which is relevant to a particular health issue in southern Asia. The second project, funded by MNDA, involves developing tools for visualisation of neuromuscular junctions in situ, ultimately with a view to enabling microendoscopic imaging to be used in research and diagnosis of neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS; called Motor Neurone Disease in the UK). My third parallel project is on fundamental mechanisms of neuromuscular function and excitability, utilising the considerable opportunities for combining powerful techniques of genetics and physiology in studying neuromuscular junctions in larval fruit flies (Drosophila). I am firmly of the view that insights into mechanisms and treatment of presently-incurable neurodegenerative diseases, especially ALS, will only come from achieving deep understanding of fundamental mechanisms in motor neurone and synaptic biology.

4. What accomplishment do you think is the most important out of your own research? 
This is a difficult one to answer, since good scientists are always behoven to be modest: all of our findings and explanations will ultimately be replaced with something better or more accurate. I have been fortunate to stumble on a few things, serendipitously. One was during my first postdoc when I noticed the dual innervation of rodent fourth deep lumbrical muscles by separate motor axons running in the sural and tibial nerves. This opened up possibilities for several crucial experiments that I subsequently carried out, with a succession of excellent students and postdocs, demonstrating the influences of neuromuscular activity on synapse elimination during development or regeneration of neuromuscular connections. Another has been my long association and collaboration (since 2000) with Professor Michael Coleman, now head of the John van Geest Centre for Brain Repair in Cambridge, on the mechanisms of slow axonal and synaptic degeneration following axotomy in the spontaneous mouse mutant that is now known as Wallerian-degeneration-Slow (WldS), which was discovered serendipitously in Oxford in the late 1980’s, by Hugh Perry and Michael Brown. I and my then-student Tom Gillingwater (now Professor of Anatomy in Edinburgh University) developed a conceptual model of neurodegeneration  (“compartmental neurodegeneration”) which has helped guide our thinking about neurodegenerative mechanisms and which I hope has influenced others. More recently, it has been satisfying to discover how cyclohexanol acts on neuromuscular transmission, and how derivatives of tetanus toxin can be used to vitally-stain NMJs and image them with a confocal microendoscope. I am intrigued at present by my observations on excitability of muscle fibres in larval Drosophila. Time (and more experiments) will tell what the fundamental significance of these may be. I also feel very gratified by the accomplishments of the PhD students I had the privilege to nurture during their formative scientific years. But I feel most satisfied by the work I did with the University of Edinburgh and a local philanthropic family, enabling us to establish in 2008  the Euan MacDonald Centre for Motor Neurone Disease Research, now directed by Professor Siddharthan Chandran. This research centre has brought together a substantial group of researchers in Edinburgh and elsewhere in Scotland, and we all work together on both the clinical and scientific challenges that accompany the devastating spectrum of illnesses that is ALS.

5. What do you hope to accomplish in the next 10 years in the field of neuroscience?  I will probably be retired by then (I am presently 65 years old), although I hope my mind will still be in sufficient shape to contemplate NMJs and to enjoy the accomplishments of others, including my former trainees and colleagues, who study synaptic structure and function. In the shorter term, I’d like to productively scratch my itch to understand excitability in larval Drosophila NMJs. I also have a burning desire to plug a hole I’ve identified in our understanding of non-linear summation of synaptic potentials at NMJs, in relation to muscle fibre size and synaptic strength. I’ve been putting off the voltage-clamp experiments I need to do on these for far too long….!