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Dr Thomas H Gillingwater Senior Lecturer in Anatomy Hugh Robson Building George Square, Edinburgh EH8 9XD Tel: +44(0)131 650 3724 Email: t.gillingwater@ed.ac.uk

• Click here for further details on an easily printed single page (updated February 2009)

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Personal Profile

• BSc (Hons) in Human Biology, University of Leeds (1998)
• PhD in Neuroscience, University of Edinburgh (2001)
• MBA, University of Edinburgh (2006)
• Postdoctoral Research Fellow (2002-2004), Centre for Neuroscience, University of Edinburgh
• Lecturer in Anatomy (2004-2008), Biomedical Sciences, University of Edinburgh
• Senior Lecturer in Anatomy (2008- ), Biomedical Sciences, University of Edinburgh
• Receiving Editor: Journal of Anatomy (2008- )
• Teaching Responsibilities: Human Anatomy / Neuroanatomy (MBChB) and Course Director for Anatomy & Pathology 2 (BSc Medical Sciences)

Research

Recent advances in neurobiological research have demonstrated that axonal and synaptic compartments of neurons are capable of independently regulating their own development, stabilization and degeneration. These findings have significant implications for many neurodegenerative diseases – including motor neuron disease and Alzheimer’s disease – where axons and synapses are now regarded as primary pathological targets.

Our research aims to identify the incidence and importance of axon/synapse-specific regulation of neuronal form and function in the developing, normal and degenerating nervous system. We combine quantitative imaging (confocal and electron microscopy) and molecular biology techniques to study the structure and function of axons and synapses from the central and peripheral nervous systems, both in vivo and in vitro. We are currently attempting to identify novel therapeutic strategies for the treatment of neurodegenerative diseases in humans with axonal and/or synaptic involvement. In particular, we are investigating the mechanism of action, and therapeutic value, of a spontaneous genetic mutation known as Wallerian Degeneration-Slow (Wlds).

Electron micrograph of a control neuromuscular junction
(click on image for enlargement)

Funding

• BBSRC
• SHERT
• Anatomical Society of Great Britain and Ireland
• Batten Disease Support & Research Association (BDSRA)
• Tenovus Scotland
• BDF Newlife
• Wellcome Trust
• Sylvia Aitken Charitable Trust

Team Members

• Thomas Wishart
• Derek Thomson
• Lyndsay Murray
• Laura Comley
• Ann Wright
• Jack Pai-Wei Huang
• Chantal Mutsaers

Collaborations

• S Abrahams – University of Edinburgh
• A Aitken – University of Edinburgh
• J Cooper – Institute of Psychiatry, King’s College London
• M Dutia – University of Edinburgh
• M Freeman – University of Massachusetts
• G Hardingham – University of Edinburgh
• K Horsburgh – University of Edinburgh
• C Ingham – University of Edinburgh
• P Kind – University of Edinburgh
• C McCabe – University of Birmingham
• S Parson – University of Edinburgh
• R Ribchester – University of Edinburgh
• K Robertson – Scottish Centre for Genomic Technology and Informatics
• P Skehel – University of Edinburgh
• K Talbot – University of Oxford
• J Tyynelä – University of Helsinki
• M Walkinshaw – University of Edinburgh

Recent Publications

2010

Murray, L.M., Talbot, K. & Gillingwater, T.H. (2010) Neuromuscular synaptic vulnerability in motor neuron disease: amyotrophic lateral sclerosis and spinal muscular atrophy. Neuropathology & Applied Neurobiology In Press.

Murray, L.M., Lee, S., Baumer, D., Parson, S.H., Talbot, K. & Gillingwater, T.H. (2010) Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy. Human Molecular Genetics 19: 420-433.

Mutka, A-L., Haapanen, A., Käkelä, R., Lindfors, M., Wright, A.K., Inkinen, T., Hermansson, M., Rokka, A., Corthals, G., Jauhiainen, M., Gillingwater, T.H., Ikonen, E. & Tyynelä, J. (2010) Murine cathepsin D deficiency is associated with dysmyelination/myelin disruption and accumulation of cholesteryl esters in the brain. Journal of Neurochemistry 112: 193-203.

2009

Bäumer, D., Lee, S., Nicholson, G., Davies, J.L., Parkinson, N.J., Murray, L.M., Gillingwater, T.H., Ansorge, O., Davies, K.E. & Talbot, K. (2009) Alternative splicing events are a late feature of pathology in a mouse model of spinal muscular atrophy. PLoS Genetics 5: e1000773.

Wishart, T.M., Brownstein, D.G, Thomson, D., Tabakova, A.M., Boothe, K.M., Tsao, J.W. & Gillingwater, T.H. (2009) Expression of the neuroprotective slow Wallerian degeneration (WldS) gene in non-neuronal tissues. BMC Neuroscience 10: 148.

Kielar, C., Wishart, T.M., Palmer, A., Dihanich, S., Wong, A.M., Macauley, S.L., Chun, C-H., Sands, M.S., Pearce, D., Cooper, J.D. & Gillingwater, T.H. (2009) Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Human Molecular Genetics18: 4066-4080.

Mackenzie, F., 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, R. & Blanco, G. (2009) Upregulation of PKD1L2 provokes a complex neuromuscular disease in the mouse. Human Molecular Genetics 18: 3553-3566.

Benedict JW, Getty AL, Wishart TM, Gillingwater TH, Pearce DA (2009) The protein product of the CLN6 gene responsible for late-onset infantile neuronal ceroid lipofuscinosis interacts with CRMP-2. Journal of Neuroscience Research 87: 2157-2166

Gillingwater D, Gillingwater TH (2009) A neuroanatomical approach to exploring organizational performance. International Journal of Business Science and Applied Management 4: 34-52

Soriano FX, Baxter P, Murray LM, Sporn MB, Gillingwater TH, Hardingham GE (2009) Transcriptional regulation of the AP-1 and Nrf2 target gene sulfiredoxin. Molecules & Cells 27: 279-282

2008

Baxter B, Gillingwater TH, Parson SH (2008) Rapid loss of motor nerve terminals following hypoxia-reperfusion injury occurs via mechanisms distinct from classic Wallerian degeneration. Journal of Anatomy 212: 827-835

Court FA, Gillingwater TH, Melrose S, Sherman DL, Greenshields K, Harris JB, Morton AJ, Willison HJ, Ribchester RR (2008) Identity, developmental restriction and reactivity of extralaminar cells capping mouse neuromuscular junctions. Journal of Cell Science 121: 3901-3911

Gillingwater TH (2008) The importance of exposure to human material in anatomical education: A philosophical perspective. Anatomical Sciences Education 1: 264-266

Gkogkas C, Middleton S, Kremer AM, Wardrope C, Hannah M, Gillingwater TH, Skehel PA (2008) VAPB interacts with and modulates the activity of ATF6. Human Molecular Genetics 17: 1517-1526

Lawrence NJ, Sacco JJ, Brownstein DG, Gillingwater TH, Melton DW (2008) A neurological phenotype in mice with DNA repair gene Ercc1 deficiency. DNA Repair 7: 281-291

Murray LM, Comley LH, Thomson D, Parkinson N, Talbot K, Gillingwater TH (2008) Selective vulnerability of motor neurons and dissociation of pre- and post-synaptic pathology at the neuromuscular junction in mouse models of spinal muscular atrophy. Human Molecular Genetics 17: 949-962

Murray LM, Thomson D, Conklin A, Wishart TM, Gillingwater TH (2008) Loss of translation elongation factor (eEF1A2) expression in vivo differentiates between Wallerian degeneration and dying-back neuronal pathology. Journal of Anatomy 213: 633-645

Partanen S, Haapanen A, Kielar C, Pontikis C, Alexander N, Inkinen T, Saftig P, Gillingwater TH, Cooper JD Tyynelä J (2008) Synaptic Changes in the Thalamocortical System of Cathepsin D Deficient Mice: a Model of Human Congenital Neuronal Ceroid-Lipofuscinosis. Journal of Neuropathology & Experimental Neurology 67:16-29

Wilbrey A, Haley J, Wishart T, Conforti L, Morreale G, Beirowski B, Babetto E, Adalbert R, Gillingwater TH, Smith T, Wyllie DJA, Ribchester RR, Coleman MP (2008) VCP binding influences intracellular distribution of the slow Wallerian degeneration protein, WldS. Molecular & Cellular Neuroscience 38: 325-340

Wishart TM, Pemberton HN, James SR, McCabe CJ, Gillingwater TH (2008) Modified cell cycle status in a mouse model of altered neuronal vulnerability (Wallerian Degeneration Slow; WldS). Genome Biology 9:R101

Wijetunge LS, Till SM, Gillingwater TH, Ingham CA, Kind PC (2008) mGluR5 regulates glutamate-dependent development of the mouse somatosensory cortex. Journal of Neuroscience 1: 264-266

2007

Wishart TM, MacDonald SHF, Chen PE, Shipston MJ, Coleman MP, Gillingwater TH, Ribchester RR (2007) Design of a novel quantitative PCR (QPCR)-based protocol for genotyping mice carrying the neuroprotective Wallerian degeneration slow (Wlds) gene. Molecular Neurodegeneration 2: 21

Wishart TM, Paterson JM, Short DM, Meredith S, Robertson KA, Sutherland C, Cousin MA, Dutia MB, Gillingwater TH (2007) Differential Proteomics Analysis of Synaptic Proteins Identifies Potential Cellular Targets and Protein Mediators of Synaptic Neuroprotection Conferred by the Slow Wallerian Degeneration (Wlds) Gene. Molecular and Cellular Proteomics 6: 1318-1330 (doi10.1074/mcp.M600457-MCP200)

2006

Barnett MW, Watson RF, Vitalis T, Porter K, Komiyama NH, Stoney PN, Gillingwater TH, Grant SGN, Kind PC (2006) SynGAP Regulates Pattern Formation in the Trigeminal System of Mice. Journal of Neuroscience 26: 1355-1365

Gillingwater TH, Ingham CA, Parry KE, Wright AK, Haley JE, Wishart TM, Arbuthnott GW, Ribchester RR (2006) Delayed Synaptic Degeneration in the CNS of Wlds Mice After Cortical Lesion. Brain 129: 1546-1556

Gillingwater TH, Wishart TM, Chen PE, Haley JE, Robertson K, MacDonald SH-F, Middleton S, Wawrowsky K, Shipston MJ, Melmed S, Wyllie DJA, Skehel PA, Coleman MP, Ribchester RR (2006) The Neuroprotective Wlds Gene Regulates Expression of PTTG1 and Erythroid Differention Regulator 1-Like Gene in Mice and Human Cells. Human Molecular Genetics 15: 625-635

Watson RF, Abdel-Majid RM, Barnett MW, Willis BS, Katsnelson A, Gillingwater TH, McKnight GS, Kind PC, Neumann PE (2006) Involvement of Protein Kinase A in Patterning of the Mouse Somatosensory Cortex. Journal of Neuroscience 26: 5393-5401

Wishart TM, Parson SH, Gillingwater TH (2006) Synaptic Vulnerability in Neurodegenerative Disease. Journal of Neuropathology & Experimental Neurology 65: 733-739 (Invited Review)

2005

Adalbert R, Gillingwater TH, Haley JE, Bridge K, Beirowski B, Berek L, Wagner D, Grumme SG, Thomson D, Addicks K, Ribchester RR, Coleman MP (2005) A Rat Model of Slow Wallerian Degeneration (Wlds) with Improved Preservation of Neuromuscular Synapses. European Journal of Neuroscience 21: 271-277

Mi W, Beirowski B, Gillingwater TH, Adalbert R, Wagner D, Grumme D, Osaka H, Conforti L, Arnhold S, Hangoc V, Celik A, Addicks K, Wada K, Ribchester RR, Coleman MP (2005) The slow Wallerian degeneration gene, WldS, inhibits axonal spheroid pathology in gracile axonal dystrophy mice. Brain 128: 405-416

Newbery HJ, Gillingwater TH, Dharmasaroja P, Peters J, Wharton SB, Thomson D, Ribchester RR, Abbott CM (2005) Progressive Loss of Motor Neuron Function in Wasted Mice: Effects of a Spontaneous Null Mutation in the Gene for the eEF1A2 Translation Factor. Journal of Neuropathology & Experimental Neurology 64: 295-303

2004

Gillingwater TH, Haley JE, Ribchester RR, Horsburgh K (2004) Neuroprotection Following Transient Global Cerebral Ischaemia in Wlds Mutant Mice. Journal of Cerebral Blood Flow and Metabolism 24: 62-66

Gillingwater TH, Thomson D, Ribchester RR (2004) Myo-GDNF Increases Non-Functional Polyinnervation of Reinnervated Mouse Muscle. Neuroreport 15: 21-25

Nishimura AL, Mitne-Neto M, Silva HCA, Richieri-Costa A, Middleton S, Cascio D, Kok F, Oliveira JRM, Gillingwater T, Webb J, Skehel P, Zatz M (2004) A Mutation in the Vesicle Trafficking Protein VAP-B Causes Late Onset Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis. American Journal of Human Genetics 75: 822-831

Parson, S.H., Ribchester, R.R., Davie, N., Gandhi, N.P., Malik, R.Q., Gillingwater, T.H. & Thompson, D. (2004) Axotomy-dependent and -independent synapse elimination in organ cultures of WldS mutant mouse skeletal muscle. Journal of Neuroscience Research 76: 64-75

Ribchester RR, Thomson D, Wood NI, Hinks T, Gillingwater TH, Wishart TM, Court F, Morton AJ (2004) Progressive Abnormalities in Skeletal Muscle and Neuromuscular Junctions of Transgenic Mice Expressing the Huntington’s Disease Mutation. European Journal of Neuroscience 20: 3092-3114

2003

Gillingwater TH, Ingham CA, Coleman MP, Ribchester RR (2003) Ultrastructural Correlates of Synapse Withdrawal at Axotomised Neuromuscular Junctions in Mutant and Transgenic Mice Expressing the Wld Gene. Journal of Anatomy 203: 265-276

Gillingwater TH, Ribchester RR (2003) The Relationship of Neuromuscular Synapse Elimination to Synaptic Degeneration and Pathology: Insights from Wlds and Other Mutant Mice. Journal of Neurocytology 32: 863-881 (Invited Review)

Haley JE, Gillingwater TH, Ribchester RR (2003) SOS: Save Our Synapses! British Neuroscience Association Bulletin Autumn/Winter 2003 Edition: 10-11 (Invited Review)

2002

Gillingwater TH, Thomson D, Mack TGA, Soffin EM, Mattison RJ, Coleman MP, Ribchester RR (2002) Age-Dependent Synapse Withdrawal at Axotomised Neuromuscular Junctions in Wlds Mutant and Ube4b/Nmnat Transgenic Mice. Journal of Physiology 543: 739-755

2001

Gillingwater TH, Ribchester RR (2001) Compartmental Neurodegeneration and Synaptic Plasticity in the Wlds Mutant Mouse. Journal of Physiology 534: 627-639 (Invited Review)

Mack TGA, Reiner M, Beirowski B, Mi W, Emanuelli M, Wagner D, Thomson D, Gillingwater T, Court F, Conforti L, Shama Fernando F, Tarlton A, Andressen C, Addicks K, Magni G, Ribchester RR, Perry VH, Coleman MP (2001) Wallerian Degeneration of Injured Axons and Synapses is Delayed by a Ube4b/Nmnat Chimeric Gene. Nature Neuroscience 4: 1199-1206