Professor Richard Ribchester
Richard Ribchester, DSc,
Professor of Cellular Neuroscience,
Euan MacDonald Centre for MND Research
School of Biomedical Sciences,
The University of Edinburgh,
1 George Square,
Edinburgh,
EH8 9XD,
Scotland, UK
Tel 44(0)131 650 3256
Fax 44(0)131 650 3255
Email Richard.Ribchester@ed.ac.uk
Click here for a printable 1-page CV
Biographical Profile
Professor Ribchester obtained a BSc with Joint Honours in Chemistry and Zoology from the University of Durham in 1974; PhD in Experimental Neurology from the University of Newcastle-upon-Tyne in 1977; and was awarded the degree of DSc by the University of Edinburgh in 2005 for his contributions to research on the Development and Plasticity of Neuromuscular Innervation.He carried out 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. He 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. He 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 served on the national Committee of the British Neuroscience Association from 2002-2005. Prof Ribchester was course organiser/manager of the CNR postgraduate course leading to MSc in Neuroscience from 1994-2004, and Head of Postgraduate Training in CNR from 2000-2005. He is currently convener of the Physiological Society’s Development and Plasticity Special Interest Group. He was a founder member and Convener of the Edinburgh Motor Neurone Disease (EdMoND) Research Group, then first Acting Director of the Euan MacDonald Centre for Motor Neurone Disease Research, from 2006-2008.
Research Overview
My research is concerned with the development, degeneration, and regeneration of neuromuscular connections. These studies are 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 use electrophysiological techniques together with immunocytochemistry and confocal microscopy to study 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. In collaboration with Prof Peter Brophy’s group, in Edinburgh, we recently 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. Collaboration with Dr Michael Coleman's group (Babraham) established the gene mutation responsible for protecting axons and synapses from degeneration in WldS mutant mice and we are currently collaborating on studies to identify potent modifiers of the gene that protect neuromuscular synapses more strongly. Collaboration with Dr Gonzalo Blanco’s group at the MRC Mammalian Genetics Unit, Harwell, involves high-throughput screening of randomly mutagenised mice expressing Yellow Fluorescent Protein in neurones, to seek novel mutations that selectively protect neuromuscular synapses from degeneration. We have developed a novel imaging methodology for this screen, based on fluorescence confocal microendoscopy (f-CoME) in vivo.Research Briefing: Plasticity of neuromuscular junctions in health and disease
Research Direction
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 axon protection, and as a tool to seek other genes and mechanisms that offer improved protection of synapses. These studies are relevant to research into the causes and treatment of neurodegenerative diseases such as Motor Neurone Disease, in which axons and synapses become dysfunctional at an early stage in the disease process.
Collaborators
Dr. Michael Coleman The Babraham Institute
Dr. Gonzalo Blanco Mammalian Genetics Unit, MRC Harwell
Professor Peter Brophy University of Edinburgh
Current Grants
- Motor Neurone Disease Association
- MND Scotland
Select Recent Publications
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. Mol Cell Neurosci. 2009 Aug 14. [Epub ahead of print] PubMed PMID: 19683573.
Mackenzie FE, Romero R, Williams D, Gillingwater T, Hilton H, Dick J, Riddoch-Contreras J, Wong F, Ireson L, Powles-Glover N, Riley G, Underhill P, Hough T, Arkell R, Greensmith L, Ribchester RR, Blanco G. Upregulation of PKD1L2 provokes a complex neuromuscular disease in the mouse. Hum Mol Genet. 2009 Oct 1;18(19):3553-66. Epub 2009 Jul 4. PubMed PMID: 19578180
Ribchester RR. Mammalian neuromuscular junctions: modern tools to monitorsynaptic form and function. Curr Opin Pharmacol. 2009 Jun;9(3):297-305. Epub 2009 Apr 23. Review. PubMed PMID: 19394273.
Conforti L, Wilbrey A, Morreale G, Janeckova L, Beirowski B, Adalbert R, Mazzola F, Di Stefano M, Hartley R, Babetto E, Smith T, Gilley J, Billington RA, Genazzani AA, Ribchester RR, Magni G, Coleman M. Wld S protein requires Nmnat activity and a short N-terminal sequence to protect axons in mice. J Cell Biol. 2009 Feb 23;184(4):491-500. PubMed PMID: 19237596
Beirowski B, Babetto E, Gilley J, Mazzola F, Conforti L, Janeckova L, Magni G, Ribchester RR, Coleman MP. (2009). Non-Nuclear WldS Determines Its Neuroprotective Efficacy for Axons and Synapses In Vivo. J Neurosci. 29(3):653-668. PMID: 19158292
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(23):3901-11. PMID: 19001504
Gillingwater TH, Wishart TM, Chen PE, Haley JE, Robertson K, Macdonald SH, Middleton S, Wawrowski K, Shipston MJ, Melmed S, Wyllie DJ, Skehel PA, Coleman MP and Ribchester RR (2006) The neuroprotective WldS gene regulates expression of PTTG1 and erythroid differentiation regulator 1-like gene in mice and human cells. Hum Mol Genet 15: 625-635
Gillingwater TH, CA Ingham, KW Parry, AK Wright, JE Haley, TM Wishart, GW Arbuthnott and RR Ribchester (2006). Delayed synaptic degeneration in the CNS of WldS mice after cortical lesion. Brain 129: 1546-1556. PMID: 16738060
Adalbert R, Gillingwater TH, Haley JE, Bridge K, Beirowski B, Berek L, Wagner D, Grumme D, Thomson D, Celik A, Addicks K, Ribchester RR and Coleman MP (2005) A rat model of slow Wallerian degeneration (WldS) with improved preservation of neuromuscular synapses. Eur J Neurosci 21:271-277
Gillingwater TH, D Thomson, TG Mack, EM Soffin, RJ Mattison, MP Coleman and RR Ribchester (2002) Age-dependent synapse withdrawal at axotomised neuromuscular junctions in Wld(s) mutant and Ube4b/Nmnat transgenic mice. J Physiol Sep 15; 543(Pt 3):739-755. PMID: 12231635
Key Earlier Publications
Mack TG, M Reiner, B Beirowski, W Mi, M Emanuelli, D Wagner, D Thomson,nT Gillingwater, F Court, L Conforti, FS Fernando, A Tarlton, CnAndressen, K Addicks, G Magni, RR Ribchester, VH Perry and MP Colemann(2001) Wallerian degeneration of injured axons and synapses is delayednby a Ube4b/Nmnat chimeric gene. Nat Neurosci Dec 4(12):1199-206. PMID: 11770485Gillingwater TH and Ribchester RR (2001) Compartmental neurodegeneration and synaptic plasticity in the Wld(s) mutant mouse. J Physiol 534:627-639
Costanzo EM, JA Barry and RR Ribchester (2000). Competition at silent synapses in reinnervated muscle. Nature Neuroscience. 3,694-700.
