Centre for Integrative Physiology Centre for Integrative Physiology

Prof Richard Ribchester

Richard Ribchester
  • Prof Richard Ribchester
  • Professor of Cellular Neuroscience
  • Centre for Integrative Physiology
  • Hugh Robson Building
  • 15 George Square
  • Edinburgh
  • EH8 9XD
  • Work: +44 (0)131 650 3256/3257
Email:

My research is concerned with the development, plasticity, degeneration, and regeneration of neuromuscular connections.

Personal profile

I obtained a BSc with Joint Honours in Chemistry and Zoology from the University of Durham in 1974 and a PhD in Experimental Neurology from the University of Newcastle-upon-Tyne in 1977.

I did postdoctoral research between 1977 and 1979 at the University of Colorado Medical School in Denver, and between 1979 and 1980 at the Institute of Physiology, University of Oslo.

I was appointed Lecturer in Physiology at the University of Edinburgh in 1980, then Senior Lecturer, then Reader in Neuroscience, and in 2005 to a Personal Chair in Cellular Neuroscience.

I was awarded a DSc by the University of Edinburgh in 2005 for my contributions to research on the Development and Plasticity of Neuromuscular Innervation.

I developed and directed the postgraduate course leading to MSc in Neuroscience from 1994-2004, and I was Head of Postgraduate Training in the Centre for Neuroscience Research from 2000-2005.

I was an Editor of the Journal of Physiology from 1986-93 (Distributing Editor between 1988-90), a member of the national Committee of the Physiological Society from 1994-98, and I served on the national Committee of the British Neuroscience Association from 2002-2005.

I was a founder member of the Euan MacDonald Centre for Motor Neurone Disease Research and its Acting Director from 2006-2008.

With the support of a Royal Society of Edinburgh Research Leave Fellowship, I spent 2007-2008 on sabbatical leave, conducting collaborative research and learning new techniques with colleagues at:

I am presently Programme Manager for the final Honours BSc/BMedSci Programme in Neuroscience, which accepts up to 60 students per year.

Research

Focus

Our research is relevant to understanding the causes and finding new treatments for neurodegenerative diseases such as Motor Neurone Disease, in which axons and neuromuscular synapses become dysfunctional and degenerate at an early stage in the disease process.

We mainly apply electrophysiological techniques together with immunocytochemistry and confocal microscopy to studies of mutant and transgenic lines that model neurodegenerative disease or protection from disease, including the role of environment and neuromuscular activity on disease progression in a mouse model of ALS.

The use of transgenic mouse lines that selectively express fluorescent protein (CFP or YFP) in neurons greatly facilitates these studies. Recent collaborative studies have included joint research with Prof Peter Brophy’s group, in Edinburgh, from which we recently identified and established the co-existence of a neglected type of fibroblast-like cell (‘kranocyte’) at mammalian neuromuscular junctions. These cells may play an important role in responses to nerve injury, paralysis and muscle atrophy.

Ongoing collaboration with Dr Michael Coleman's group (Babraham Institute) established the gene mutation responsible for protecting axons and synapses from degeneration in Wld(S) mutant mice and we are now collaborating in the identification and characterization of potent modifiers of the gene that enhance protection of neuromuscular synapses.

Collaboration with Dr Gonzalo Blanco’s group at the MRC Mammalian Genetics Unit, Harwell, led to development of fibre-optic confocal microendoscopy (CME) as a tool for screening and identifying novel neuromuscular phenotypes produced by mutagenesis. We have used this to discover novel mouse lines that show selective protection of neuromuscular synapses from degeneration and to monitor progressive degeneration and repair of neuromuscular junctions.

Direction

Our research targets the causes, diagnosis and potential treatments of Motor Neurone Disease.

Our studies of mutant and transgenic WldS mice suggest that neurodegenerative mechanisms are compartmentalised, and that motor neurone cell bodies, axons and motor nerve terminals represent separate neurodegenerative compartments.

We are using mice that express fluorescent proteins in motor neurones to examine the mechanisms of axonal and synaptic protection, and as a tool to seek other genes and mechanisms that may offer improved protection of synapses in established animal models of neurodegenerative disease.

We are currently attempting to extend applications of CME imaging technology to diagnosis and assessment of neuromuscular pathology, with the long-term aim of utilising it for monitoring effectives of treatments intended to mitigate progression of neuromuscular disease.

Team members

Funding

Publications

Oyebode OR, Hartley R, Singhota J, Thomson D, Ribchester RR. Differential protection of neuromuscular sensory and motor axons and their endings in Wld(S) mutant mice. Neuroscience. 2012 Jan 3;200:142-58. PubMed PMID: 22062136

Babetto E, Beirowski B, Janeckova L, Brown R, Gilley J, Thomson D, Ribchester RR, Coleman MP. Targeting NMNAT1 to axons and synapses transforms its neuroprotective potency in vivo. J Neurosci. 2010 Oct 6;30(40):13291-304. PubMed PMID: 20926655.

Wong F, Fan L, Wells S, Hartley R, Mackenzie FE, Oyebode O, Brown R, Thomson D, Coleman MP, Blanco G, Ribchester RR. Axonal and neuromuscular synaptic phenotypes in Wld(S), SOD1(G93A) and ostes mutant mice identified by fiber-optic confocal microendoscopy.(2009) Mol Cell Neurosci. 42:296-307.

Ribchester RR.(2009) Mammalian neuromuscular junctions: modern tools to monitor synaptic form and function. Curr Opin Pharmacol. 9:297-305.

Beirowski B, Babetto E, Gilley J, Mazzola F, Conforti L, Janeckova L, Magni G, Ribchester RR, Coleman MP. Non-nuclear Wld(S) determines its neuroprotective efficacy for axons and synapses in vivo.(2009) J Neurosci. 29:653-68.

Court FA, Gillingwater TH, Melrose S, Sherman DL, Greenshields KN, Morton AJ, Harris JB, Willison HJ, Ribchester RR. (2008) Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions. J Cell Sci. 121:3901-11.


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