Research in the Gillingwater lab focuses on understanding cellular and molecular mechanisms that regulate the form and function of the nervous system in health and disease. At present we are undertaking projects investigating:
i) mechanisms underlying pathogenesis of the childhood motor neurone disease Spinal Muscular Atrophy (SMA) ii) common mechanisms regulating degeneration of synaptic connections across a range of different neurodegenerative conditions (from Alzheimer's disease and Huntington's disease through to lysosomal storage disorders and motor neurone diseases) iii) novel neuroprotective treatment strategies that can delay or prevent neurodegenerative disease iv) novel in vitro screening platforms for modeling neurodegenerative diseases using human stem cells (iPSCs) v) the influence of axon-glial interactions for stability of the peripheral nervous system
We routinely combine quantitative imaging (e.g. confocal and electron microscopy) and molecular biology techniques (e.g. proteomics and microarray screens) to study the structure and function of the central and peripheral nervous systems, both in vivo and in vitro.
Further information on Professor Gillingwater's spin out company, NeuroORG Business Consulting Ltd, is available on the website;
Kay K, Smith C, Wright AK, Serrano-Pozo A, Pooler A, Koffie R, Bastin ME, Bak TH, Abrahams S, Kopeikina KJ, Frosch M, Gillingwater TH, Hyman BT & Spires-Jones TL (2013) Studying synapses in human brain with array tomography and electron microscopy. Nature Protocols In Press.
Bastin, M. E., L. D. Pettit, T. H. Bak, T. H. Gillingwater, C. Smith and S. Abrahams (2013). Quantitative Tractography and Tract Shape Modeling in Amyotrophic Lateral Sclerosis. Journal of Magnetic Resonance Imaging 38(5): 1140-1145.
Hamilton G & Gillingwater TH (2013) Spinal muscular atrophy: going beyond the motor neuron. Trends in Molecular Medicine 19:40-50.
Pettit, L. D., M. E. Bastin, C. Smith, T. H. Bak, T. H. Gillingwater and S. Abrahams (2013). "Executive deficits, not processing speed relates to abnormalities in distinct prefrontal tracts in amyotrophic lateral sclerosis." Brain 136: 3290-3304.
Simpson AH, Gillingwater TH, Anderson H, Cottrell D, Sherman DL, Ribchester RR & Brophy PJ (2013) Effect of limb lengthening on internodal length and conduction velocity of peripheral nerve. Journal of Neuroscience 33:4536-4539.
Wishart TM, Rooney T, Lamont DJ, Wright AK, Morton AJ, Jackson M, Freeman MR & Gillingwater TH (2012) Combining Comparative Proteomics and Molecular Genetics Uncovers Regulators of Synaptic and Axonal Stability and Degeneration In Vivo. PLoS Genetics 8:e1002936.
Avery M, Rooney TM, Pandya JD, Wishart TM, Gillingwater TH, Geddes JW, Sullivan P & Freeman MR (2012) WldS prevents axon degeneration through increased mitochondrial flux and enhanced mitochondrial Ca2+ buffering. Current Biology 22:596-600.
Mutsaers CA, Wishart TM, Lamont DJ, Riessland M, Schreml J, Comley LH, Murray LM, Parson SH, Lochmüller H, Wirth B, Talbot K, Gillingwater TH (2011) Reversible molecular pathology of skeletal muscle in spinal muscular atrophy. Human Molecular Genetics 20:4334-4344.
Patani R, Hollins AJ, Wishart TM, Puddifoot CA, Alvarez S, de Lera AR, Wyllie DJ, Compston DA, Pedersen RA, Gillingwater TH, Hardingham GE, Allen ND, Chandran S (2011) Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state. Nature Communications 2:214.
Comley LH, Fuller HR, Wishart TM, Mutsaers CA, Thomson D, Wright AK, Morris GE, Parson SH, Horsburgh K, Gillingwater TH (2011) ApoE isoform-specific regulation of regeneration in the peripheral nervous system. Human Molecular Genetics 20:2406-2421.
Wishart TM, Huang J P-W, Murray LM, Lamont DJ, Mutsaers CA, Ross J, Geldsetzer P, Ansorge O, Talbot K, Parson SH, Gillingwater TH (2010) SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy. Human Molecular Genetics 19:4216-4228.
Murray LM, Lee S, Baumer D, Parson SH, Talbot K, Gillingwater TH (2010) Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy. Human Molecular Genetics 19:420-433.
de Waard MC, van der Pluijm I, Zuiderveen Borgesius N, Comley LH, Haasdijk ED, Rijksen Y, Ridwan Y, Zondag G, Hoeijmakers JH, Elgersma Y, Gillingwater TH, Jaarsma D (2010) Age-related motor neuron degeneration in DNA repair-deficient Ercc1 mice. Acta Neuropathologica 120:461-475.
Bäumer D, Lee S, Nicholson G, Davies JL, Parkinson NJ, Murray LM, Gillingwater TH, Ansorge O, Davies KE, Talbot K (2009) Alternative splicing events are a late feature of pathology in a mouse model of spinal muscular atrophy. PLoS Genetics 5:e1000773.
Kielar C, Wishart TM, Palmer A, Dihanich S, Wong AM, Macauley SL, Chun C-H, Sands MS, Pearce D, Cooper JD & Gillingwater TH (2009) Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Human Molecular Genetics 18:4066-4080.
This article was published on Feb 5, 2014