Dr Tom Wishart

The Roslin Institute

Research Interests

Research Summary: 

Research in the Wishart laboratory is aimed at understanding the cellular and molecular processes which underpin the development and stability of the nervous system in health and disease, with a more specific focus on the biology of the neuron.

It is accepted that the neuron can be compartmentalized (grossly speaking) with respect to both form and function into three units: the cell body (or soma and associated dendrites), the axon and the synapse. It is also known that stability of the axon and synapse can be affected independently of one another. 

Synapses are of special interest to us as it is becoming increasingly accepted that they are a primary pathological target in a number of neurodegenerative conditions, including but by no means limited to; Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and motor neuron diseases. That is to say, synapses go first and the rest of the neuron follows. As age increases the susceptibility to many of these neurodegenerative conditions, the ever increasing life expectancy of current society means that the costs associated with neurodegenerative diseases are only going to escalate over the coming years. It is therefore critical that we develop a clearer understanding of the mechanisms which underpin healthy development and stability of synapses and the regulators of altered synaptic/neuronal vulnerability.

In order to address these points we combine anatomical knowledge with high resolution imaging and biochemical/molecular biological techniques in vivo and in vitro to identify the key players and tease apart the mechanisms involved in these processes.

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Selected Publications

  • Maria del carmen Llavero hurtado, Heidi R Fuller, Andrew Wong, Samantha Eaton, Thomas Gillingwater, Giuseppa Pennetta, Jonathan Cooper, Thomas Wishart. 2017. Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo.. Scientific Reports Pages: 7. More»
  • C. Kielar, T. M. Wishart, A. Palmer, S. Dihanich, A. M. Wong, S. L. Macauley, C. H. Chan, M. S. Sands, D. A. Pearce, J. D. Cooper, T. H. Gillingwater. 2009. Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Human Molecular Genetics Vol: 18 Pages: 4066-4080. More»
  • Jamie Mcqueen, Tomás J Ryan, Sean Mckay, Katie Marwick, Paul Baxter, Sarah M. Carpanini, Thomas Wishart, Thomas Gillingwater, Jean Manson, David Wyllie, Seth Grant, Barry McColl, Noboru Komiyama, Giles Hardingham. 2017. Pro-death NMDA receptor signaling is promoted by the GluN2B C-terminus independently of Dapk1. eLIFE. More»
  • T. M. Wishart, J. P. W. Huang, Lyndsay Murray, D. J. Lamont, C. A. Mutsaers, J. Ross, P. Geldsetzer, O. Ansorge, K. Talbot, S. H. Parson, T. H. Gillingwater. 2010. SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy. Human Molecular Genetics Vol: 19 Pages: 4216-4228. More»
  • Penelope J Boyd, Wen-Yo Tu, Hannah K Shorrock, Ewout J N Groen, Roderick N Carter, Rachael A Powis, Sophie R Thomson, Derek Thomson, Laura C Graham, Anna A L Motyl, Thomas M Wishart, J Robin Highley, Nicholas M Morton, Thomas Becker, Catherina G Becker, Paul R Heath, Thomas H Gillingwater. 2017. Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy. PLoS Genetics Vol: 13. More»
  • Samantha Eaton, Thomas Wishart. 2017. Bridging the Gap: large animal models in neurodegenerative research. Mammalian Genome Vol: 28 Pages: 324-337. More»
  • Sarah M Carpanini, Thomas M Wishart, Thomas H Gillingwater, Jean C Manson, Kim M Summers. 2017. Analysis of gene expression in the nervous system identifies key genes and novel candidates for health and disease. Neurogenetics Vol: 18 Pages: 81-95. More»
  • Ines Amorim, Laura Graham, Roderick Carter, Nicholas Morton, Fella Hammachi, Tilo Kunath, Giuseppa Pennetta, Sarah Carpanini, Jean Manson, Douglas J Lamont, Thomas Wishart, Thomas Gillingwater. 2017. Sideroflexin 3 is a α-synuclein-1 dependent mitochondrial protein 2 that regulates synaptic morphology. Journal of Cell Science Vol: 130 Pages: 325-331. More»
  • Rachael Powis, Evangelia Karyka, Penelope Boyd, Julien Côme, Ross Jones, Yinan Zheng, Eva Szunyogova, Ewout Groen, Gillian Hunter, Derek Thomson, Thomas Wishart, Catherina Becker, Simon H. Parson, Cécile Martinat, Mimoun Azzouz, Thomas Gillingwater. 2016. Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy. JCI Insight Vol: 1. More»
  • Heidi R Fuller, Laura Graham, Maica Llavero Hurtado, Thomas Wishart. 2016. Understanding the molecular consequences of inherited muscular dystrophies: advancements through proteomic experimentation. Expert review of proteomics Vol: 13 Pages: 659-671. More»
  • Heidi R Fuller, Thomas Gillingwater, Thomas Wishart. 2016. Commonality amid diversity: multi-study proteomic identification of conserved disease mechanisms in spinal muscular atrophy. Neuromuscular Disorders Vol: 26 Pages: 560-569. More»
  • Kirsty A. Ireland, Thomas M. Wishart, Rona Barron. 2016. In vitro seeding of amyloid plaques. Prion Vol: 10 Pages: S45-S46. More»
  • Andrew R. Castle, Dominic Kurian, Thomas M. Wishart, Andrew C. Gill. 2016. Lack of stress protection by the cellular prion protein: An alternative role in regulating growth factor signaling. Prion Vol: 10 Pages: S39-S39. More»
  • Bruce McGorum, Sandra Scholes, Elspeth Milne, Samantha Eaton, Thomas Wishart, Ian Poxton, Sharon Moss, Ulli Wernery, Tracey Davey, John Harris, Scott Pirie. 2016. Equine grass sickness, but not botulism, causes autonomic and enteric neurodegeneration and increases SNARE protein expression within neuronal perikarya. Equine Veterinary Journal Vol: 48 Pages: 786-791. More»
  • Samantha Eaton, Elizabeth Cumyn, Declan King, Rachel A. Kline, Sarah Carpanini, Jorge Del-Pozo, Rona Barron, Thomas Wishart. 2016. Quantitative imaging of tissue sections using infrared scanning technology. Journal of Anatomy Vol: 228 Pages: 203-213. More»
  • Bruce McGorum, Robert Pirie, Samantha Eaton, John Keen, EM Cumyn, DA Arnott, W Chen, DJ Lamont, Laura Graham, M Llavero Hurtado, Alan Pemberton, Thomas Wishart. 2015. Proteomic profiling of cranial (superior) cervical ganglia reveals Beta-amyloid and ubiquitin proteasome system perturbations in an equine multiple system neuropathy.. Molecular and Cellular Proteomics Vol: 14 Pages: 3072-3086. More»
  • Inês S. Amorim , Nadia L. Mitchell, David N. Palmer, Stephen J. Sawiak, Roger Mason, Thomas Wishart, Thomas Gillingwater. 2015. Molecular neuropathology of the synapse in sheep with CLN5 Batten disease. Brain and Behavior Vol: 5. More»
  • Thomas M Wishart, Chantal A Mutsaers, Markus Riessland, Michell M Reimer, Gillian Hunter, Marie L Hannam, Samantha L Eaton, Heidi R Fuller, Sarah L Roche, Eilidh Somers, Robert Morse, Philip J Young, Douglas J Lamont, Matthias Hammerschmidt, Anagha Joshi, Peter Hohenstein, Glenn E Morris, Simon H Parson, Paul A Skehel, Thomas Becker, Iain M Robinson, Catherina G Becker, Brunhilde Wirth, Thomas H Gillingwater. 2014. Dysregulation of ubiquitin homeostasis and beta-catenin signaling promote spinal muscular atrophy. Journal of Clinical Investigation Vol: 124 Pages: 1821-1834. More»
  • Chantal A. Mutsaers, Douglas J. Lamont, Gillian Hunter, Thomas M. Wishart, Thomas H. Gillingwater. 2013. Label-free proteomics identifies Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers for spinal muscular atrophy. Genome Medicine Vol: 5. More»
  • Samantha L. Eaton, Sarah L. Roche, Maica Llavero Hurtado, Karla Suchacki, Colin Farquharson, Thomas H. Gillingwater, Thomas M. Wishart. 2013. Total Protein Analysis as a Reliable Loading Control for Quantitative Fluorescent Western Blotting. PLoS ONE Vol: 8. More»
  • Thomas M Wishart, Timothy M Rooney, Douglas J Lamont, Ann K Wright, A Jennifer Morton, Mandy Jackson, Marc R Freeman, Thomas H Gillingwater. 2012. Combining Comparative Proteomics and Molecular Genetics Uncovers Regulators of Synaptic and Axonal Stability and Degeneration In Vivo. PLoS Genetics Vol: 8. More»
  • J. W. Benedict, A. L. Getty, T. M. Wishart, T. H. Gillingwater, D. A. Pearce. 2009. Protein Product of CLN6 Gene Responsible for Variant Late-Onset Infantile Neuronal Ceroid Lipofuscinosis Interacts with CRMP-2. Journal of Neuroscience Research Vol: 87 Pages: 2157-2166. More»