Professor Richard Ribchester’s Journey into Science and Motor Neuron Disease Research

To celebrate both National Science and Engineering Week and Brain Awareness Week, we have invited our new trustee, Professor Richard Ribchester, to tell us more about what fuelled his passion for science and how he became interested in motor neuron disease research.

When did you first become interested in science?

I’ve been interested in science for almost as long as I can remember. I was first aware of being curious about the world and what life comprises when I was about five years old. The most compelling incident was on a family picnic, when I was about seven years old, when my father, a telecommunications engineer in the Royal Signals, sat me on the bonnet of our car and showed me my own “knee jerk” stretch reflex. I was fascinated by the involuntary nature of the response to a simple tap. That interest in movement and how it is controlled then lay dormant for several years, while I became more interested in chemistry and general biology, but was resurrected during my undergraduate years, studying Chemistry and Zoology for a joint honours’ degree at Durham University in the early 1970s.

What impact did your experience in school have on your interest in science?

I had excellent biology and chemistry teachers, who recognised my interest and ability and encouraged me in every way. I went through several schools as I travelled with my parents through overseas military postings, but won school prizes in chemistry, physics and biology. Those rewards helped sustain and develop my interest and enthusiasm for embarking on a scientific career.

What inspired you to get involved in MND research?

My initial ambition was to become a school science teacher, but I caught the “research bug” during my six-week undergraduate Zoology project, which involved measuring an aspect of the cell biology of insect flight muscles. I then accepted the offer of an MRC-funded PhD studentship in the Muscular Dystrophy Lab at Newcastle University, to investigate the structure and function of neuromuscular (nerve-to-muscle) junctions in a mouse model of Duchenne Muscular Dystrophy. That project struck a tremendous chord and I continued to study the “NMJ” for most of my subsequent research and university teaching career.

What did you research?

After my PhD studies, I continued my research training via two postdoctoral fellowships. During the first, in the Physiology Department at the University of Colorado School of Medicine in America, I studied the development and maturation of neuromuscular junctions and their compensatory “plasticity” after nerve damage. My second postdoctoral fellowship was at the University of Oslo, where I spent most of my time studying the physiology of motor neurons in the developing spinal cord and partly researching the importance of activity – use or disuse – in the regeneration of NMJs in adult animals. I continued these lines of research through the rest of my career, after I was appointed to a Lectureship in Physiology at the University of Edinburgh, in 1980.

During the 1990’s I became interested in a genetic abnormality (Wlds), discovered in mice by researchers at Oxford University, which protects nerve fibres (“axons”) from degeneration that occurs after axons are damaged. The relevance of this to MND research slowly dawned on me and I began to think about how research at the University of Edinburgh might become better focused on advancing understanding, and improving treatment, of this brutal disease.

In 2004, at a think-tank retreat, I tentatively proposed the formation of a group of about ten researchers in Edinburgh who had an interest in motor neurons and/or MND, as a nucleus for future research in this area. Two years later, this idea developed and became realised in the formation of the Edinburgh Motor Neuron Disease (EdMoND) Research Group.

At around this time I was introduced to Donald and Euan MacDonald, who had independently expressed interest in supporting research into MND at the University. Together we were able to create, in 2007, the Euan MacDonald Centre for MND Research, which is based at the University of Edinburgh but embraces scientific and medical researchers throughout Scotland. In 2009, we recruited Professor Siddharthan Chandran as centre director. Until my retirement in 2020, I continued to work on understanding how axonal degeneration can be prevented but also branched out to explore why agricultural insecticides used in southern Asia were leading to high levels of muscle paralysis and death.

What impact did funding from MND Scotland have on your work?

I received grants from MND Scotland, the Motor Neuron Disease Association (MNDA) and the Medical Research Council (MRC) to support our laboratory research, both on the mechanisms of neuroprotection of axons by the mutant WldS gene, and the development of a confocal microendoscopy technique for imaging NMJs in their natural location. These grants were invaluable for progressing the research.

In collaboration with my colleague at Cambridge University, Professor Michael Coleman, we made discoveries relating to how the WldS gene works, which showed that after this, specific type of motor neuron damage, it is possible to completely prevent axon and NMJ degeneration. Further MND Scotland-funded research indicated that either excessive disuse (inactivity) or excessive use (activity) of NMJs can facilitate their degeneration, but moderate levels of activity appear to be protective.

However, although these represent important steps forward, we still don’t yet understand, nor know how to prevent, degeneration of synapses, axons and motor neurons in MND. Many laboratories around the world are working hard to meet this challenge.

Richard Ribchester is a trustee of MND Scotland. As Emeritus Professor of Cellular Neuroscience at the University of Edinburgh, Richard’s career focuses on motor neurons, particularly in Motor Neuron Disease. He founded the Edinburgh Motor Neuron Disease (EdMoND) research group in 2006, which later led to the establishment of the Euan MacDonald Centre. Richard received the Delsys Prize in 2015 and became an Honorary Fellow of the Physiological Society in 2020.