James N. Sleigh

MBiol, DPhil

Sir Henry Wellcome Postdoctoral Fellow

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Research Summary

I am particularly interested in understanding the cause of neuronal susceptibility often observed in motor nerve disorders. Motor neurons are nerve cells that connect the brain and spinal cord to muscles providing a one-way message-delivery system for voluntary muscle contraction. These nerves appear to be highly susceptible cells, because mutations in numerous different genes that are important throughout the body manifest in a very specific detrimental effect on the motor nerves.

Charcot-Marie-Tooth type 2D (CMT2D) is a peripheral neuropathy caused by mutations in a gene that codes for a protein found in almost every cell. Dominant mutations in the GARS gene, which produces glycyl-tRNA synthetase (GlyRS), a protein that is indispensible for the production of many other proteins, causes the targeted dysfunction of motor neurons leading to muscle wasting and significant disability.

I intend to use my Wellcome Trust Fellowship to elucidate the disease mechanism underlying this peripheral nerve selectivity. Working with both Prof. Kevin Talbot at the NDCN and Prof. Giampietro Schiavo at University College London, I will implement live imaging of cellular dynamics, including axonal transport, to better understand the cause of neuronal fragility seen in CMT2D patients.


Originally from Nottingham, I received my undergraduate Masters in Biology (MBiol) from the University of Bath (2005-2009), which included a year at Harvard Medical School (2007-2008) researching the neuromuscular disease spinal muscular atrophy (SMA). I then completed my MRC-funded DPhil at the University of Oxford (2009-2012), extending my work on SMA, while studying a number of other peripheral nerve disorders. From 2012-2014, I worked in the laboratory of Dr. Zameel Cader on Charcot-Marie-Tooth type 2D (CMT2D). I am now a Sir Henry Wellcome Postdoctoral Fellow continuing my work on CMT2D both in Oxford at the NDCN and in London at the Institute of Neurology, UCL (2014-2018).

Hum Mol Genet 23: 2639-50 (2014)

Bioessays 33: 956-965 (2011)