Centre for Discovery Brain Sciences
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Dr Matthew Livesey

Human stem cell models of neurological disease.

Dr Matthew Livesey

Royal Society of Edinburgh Personal Research Fellow

  • The Chancellors Building
  • 49 Little France Crescent
  • EH16 4SB

Contact details

Personal profile

  • 2015 - Present: Royal Society of Edinburgh Personal Research Fellow funded by the Caledonian Research Fund. Centre for Discovery Brain Sciences, University of Edinburgh.
  • 2011 - 2015:  Postdoctoral Research Associate. Centre for Integrative Physiology, University of Edinburgh.
  • 2010 - 2011:  Postdoctoral Research Associate. University of Dundee.
  • 2005 - 2009:  PhD University of Dundee.
  • 2001 - 2005:  B.Sc (Hons) Edinburgh

Research Theme

Synapses, Circuits and Behaviour 

Research 

The primary research focus of the laboratory is to explore the physiological properties of neurons and glia derived from human pluripotent stem cells (hPSCs) in both healthy and disease scenarios using electrophysiological and pharmacological approaches. In vitro populations of hPSC-neurons and glia are an increasingly utilised pre-clinical experimental resource to study human physiology and disease. Research emanating from the laboratory has told us that while these cells display largely immature physiological properties, they do recapitulate some key hallmarks of mammalian physiological maturation. This information is key for disease modelling where it is important to be working with material that can recapitulate adult mammalian physiology as close as possible. Recently, this work is focused on the development and characterisation of an in vitro model of human synaptic plasticity at the single-cell level.

Directly related to this, the research in the laboratory concurrently investigates neurons and glia derived from patients with neurodevelopmental and adult-onset neurodegenerative diseases. Recently, in collaboration with Professors Siddharthan Chandran, David Wyllie and Giles Hardingham, work has recently identified novel physiological impairments in neurons derived from amytrophic lateral sclerosis and frontotemporal dementia patients that harbour C9ORF72 repeat expansion mutations. Increased understanding of such impairments may lead to novel therapeutic targets

Funding

Collaborations

Selected Publications 

  • Selvaraj BT*, Livesey MR*, Zhao C, Gregory JM, James OT, Cleary EM, Chouhan AK, Gane AB, Perkins EM, Dando O, Lillico SG, Lee YB, Nishimura AL, Poreci U, Thankamony S, Pray M, Vasistha NA, Magnani D, Borooah S, Burr K, Story D, McCampbell A, Shaw CE, Kind PC, Aitman TJ, Whitelaw CBA, Wilmut I, Smith C, Miles GB, Hardingham GE, Wyllie DJA, Chandran S. (2018) C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity. Nat. Comms. 9:347.
  • Sances S, Bruijn LI, Chandran S, Eggan K, Ho R, Klim JR, Livesey MR, Lowry E, Macklis JD, Rushton D, Sadegh C, Sareen D, Wichterle H, Zhang SC, Svendsen CN. (2016) Modeling ALS with motor neurons derived from induced pluripotent stem cells. Nature Neuroscience. 16: 542-553.
  • Livesey MR*, Magnani D*, Cleary E, Vasistha NA, James OT, Selvaraj BT, Burr K, Story D, Shaw CE, Hardingham GE, Wyllie DJ, Chandran S. (2016). Maturation and electrophysiological properties of human pluripotent stem cell-derived oligodendrocytes. Stem Cells. 34: 1040-1053.
  • Livesey MR, Magnani D, Hardingham GE, Chandran S, Wyllie DJ. Functional properties of in vitro excitatory cortical neurons derived from human pluripotent stem cells. (2015). J. Physiol. 594:6573-6582.
  • James OT*, Livesey MR*, Qiu J, Dando O, Bilican B, Haghi G, Chandran S, Kind PC, Wyllie DJ. (2014). Characterisation of GABAA and strychnine-sensitive glycine receptors in human pluripotent stem cell-derived cortical neurones. J. Physiol. 592: 4353-4363.
  • Livesey MR*, Bilican B*, Qiu J, Rzechorzek NM, Haghi G, Burr K, Hardingham GE, Chandran S, Wyllie DJ. (2014). Maturation of AMPAR composition and the GABAAR reversal potential in hPSC-derived cortical neurons. J. Neurosci. 34: 4070-4075.

  • Bilican B*, Livesey MR*, Haghi G, Burr K, Siller R, Hardingham GE, Wyllie DJA, Chandran S. (2014). Physiological oxygen levels and EGF withdrawal are required for scalable generation of functional cortical neurones from human pluripotent stem cells. PLoS One. 9: e85932.

  • Livesey MR, Cooper MA, Lambert JJ, Peters JA. (2011). Rings of charge in the extracellular vestibule influence ion permeation within the 5-HT3A receptor. J. Biol. Chem. 286: 16008-17.

  • Livesey MR, Cooper MA, Deeb TZ, Carland JE, Kozuska J, Hales TG, Lambert JJ, Peters JA. (2008). Structural determinants of Ca2+ permeability and conduction in the human 5-hydroxytryptamine type 3A receptor. J. Biol. Chem. 283: 19301-13.