Dr John Chilton
Senior Lecturer in Cell Biology
RILD Building 4.04
University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK
John was in the first cohort of students on the Wellcome Trust four year program in neuroscience at Oxford University, where he began his DPhil with Dr. Andrew Stoker on the role of receptor tyrosine phosphatases in axon guidance. During this time the group moved to the Institute of Child Health at University College London, to become part of the Neural Development Unit.
He moved to the MRC Centre for Developmental Neurobiology at King’s College London to join the group of Prof. Sarah Guthrie, where he studied the development of the oculomotor system and began a collaboration that continues today. During this time he was awarded an EMBO short-term fellowship to work in the lab of Dr. Alain Chédotal in Paris. He stayed at KCL for a second post-doc, this time with Prof. Phillip Gordon-Weeks, working on the growth cone cytoskeleton.
In 2005 he was awarded a RCUK Fellowship in Clinical Neuroscience and Molecular Biology at the newly-founded Peninsula Medical School and has remained there, now part of the University of Exeter Medical School.
Broad research specialisms
His fundamental interest is in understanding how the incredible complexity of the nervous system arises. They start from the point at which a rudimentary nervous system has been laid down and neurons have begun to acquire their identity. They study two overlapping aspects of their development – axon guidance, the extension of long neuronal protrusions to contact their target and neuronal migration, the movement of neurons to their correct position within the brain.
These processes are interdependent; a cell must be in the appropriate place to both send and receive information. If either of them goes wrong then it can result in a range of neurological disturbances. His group makes extensive use of fluorescent proteins to visualise nerves and their axons as they form circuits. They want to understand what signals orchestrate the wiring up of the brain and how these can be harnessed to prevent or repair nervous system disorders.
- M.A.(Hons.) Natural Sciences
- M.Sc. Neuroscience
- D.Phil. Developmental neurobiology
- Postgraduate Certificate in Clinical Education
- Fellow of the Higher Education Academy
His work focuses on a class of proteins called semaphorins which can both inhibit and promote neuronal growth. In collaboration with Prof. Sarah Guthrie at King’s College London, he has shown that strabismus (squint) results from defective semaphorin signalling causing miswiring of the oculomotor system that controls eye movements.
To exert their action, semaphorins bind to extracellular receptors which send signals to modulate the neuronal cytoskeleton, an intracellular scaffold responsible for cell shape, growth and motility. We have demonstrated that a protein called drebrin which regulates the actin component of the cytoskeleton is necessary for neuronal migration and morphology. The research group believes that drebrin may be a crucial link between semaphorin signalling and the actin network. Levels of drebrin are reduced in Alzheimer Disease and Down Syndrome so our work is also relevant to the regeneration of circuits later in life by reactivating developmental mechanisms.
The oculomotor system is among the few motor nerves that are relatively spared in motor neuron diseases. Uncovering the reasons behind this resistance to degeneration could open new avenues to restore function. Calcium ions are a key intracellular messenger in neurons but must be tightly regulated to avoid overloading and ultimately killing nerve cells. The group has begun to study the role of a class of proteins called neuronal calcium sensors which may form part of the protective mechanism.
Dr Chilton gives an overview of this research in the video below, filmed at the Living Systems Institute Symposium in March 2016.
- 2012 Wellcome Trust/University of Exeter Institutional Strategic Support Fund
Calcium sensor proteins in neurodegeneration – are they the solution...or the problem?
- 2012 Northcott Devon Medical Foundation
Identification of changes in gene expression mediated by the SIM2 transcription factor
- 2011 BBSRC
Interpretation of guidance cues by the actin-binding protein Drebrin to direct collective neuronal migration
- 2010 Wellcome Trust
Alpha2-chimaerin as a molecular switch which regulates motor axon growth and guidance
- 2010 Peninsula Medical School PhD studentship
Identifying the basis of the resistance of ocular motor neurons to degeneration in Motor Neuron Disease
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