Loading content

Dr John Chilton

Senior Lecturer in Cell Biology

01392 408267

RILD Building 4.04

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.

Qualifications

  • M.A.(Hons.) Natural Sciences
  • M.Sc. Neuroscience
  • D.Phil. Developmental neurobiology
  • Postgraduate Certificate in Clinical Education
  • Fellow of the Higher Education Academy

Links

Research

Research interests

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. 

Research projects

Grants

  • 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

Links


Key publications | Publications by category | Publications by year

Key publications


Chilton JK, Ferrario JE, Baskaran P, Clark C, Hendry A, Lerner O, Hintze M, Guthrie S (2013). Axon guidance in the developing ocular motor system and Duane's Retration Syndrome depends on Semaphorin signalling via alpha2-chimaerin. PNAS
Dun X-P, Bandeira de Lima T, Allen J, Geraldo S, Gordon-Weeks P, Chilton JK (2012). Drebrin controls neuronal migration through the formation and alignment of the leading process. Mol Cell Neurosci, 49(3), 341-350. Abstract.  Author URL.  Full text.

Publications by category


Journal articles

Dun X-P, Chilton JK (In Press). Control of cell shape and plasticity during development and disease by the actin-binding protein Drebrin. Histol Histopathol, 25(4), 533-540. Abstract.  Author URL.
Chilton JK, Guthrie S (2017). Axons get ahead: Insights into axon guidance and congenital cranial dysinnervation disorders. Dev Neurobiol, 77(7), 861-875. Abstract.  Author URL.
Gasperini RJ, Pavez M, Thompson AC, Mitchell CB, Hardy H, Young KM, Chilton JK, Foa L (2017). How does calcium interact with the cytoskeleton to regulate growth cone motility during axon pathfinding?. Mol Cell Neurosci, 84, 29-35. Abstract.  Author URL.
Ketschek A, Spillane M, Dun XP, Hardy H, Chilton J, Gallo G (2016). Cover Image. Developmental Neurobiology, 76(10).
Ketschek A, Spillane M, Dun X-P, Hardy H, Chilton J, Gallo G (2016). Drebrin coordinates the actin and microtubule cytoskeleton during the initiation of axon collateral branches. Developmental Neurobiology, 76(10), 1092-1110. Full text.
Gutowski NJ, Chilton JK (2015). The congenital cranial dysinnervation disorders. Archives of Disease in Childhood, 100(7), 678-681. Abstract.
Gutowski NJ, Chilton JK (2015). The congenital cranial dysinnervation disorders. Arch Dis Child, 100(7), 678-681. Abstract.  Author URL.
Chilton JK, Ferrario JE, Baskaran P, Clark C, Hendry A, Lerner O, Hintze M, Guthrie S (2013). Axon guidance in the developing ocular motor system and Duane's Retration Syndrome depends on Semaphorin signalling via alpha2-chimaerin. PNAS
Dun X-P, Bandeira de Lima T, Allen J, Geraldo S, Gordon-Weeks P, Chilton JK (2012). Drebrin controls neuronal migration through the formation and alignment of the leading process. Mol Cell Neurosci, 49(3), 341-350. Abstract.  Author URL.  Full text.
Ketschek A, Spillane M, Dun X-P, Chilton J, Gallo G (2012). Regulation of axonal filopodia and collateral branches by the actin filament binding protein drebrin. MOLECULAR BIOLOGY OF THE CELL, 23 Author URL.
Allen J, Chilton JK (2009). The specific targeting of guidance receptors within neurons: who directs the directors?. Dev Biol, 327(1), 4-11. Abstract.  Author URL.
Miyake N, Chilton J, Psatha M, Cheng L, Andrews C, Chan W-M, Law K, Crosier M, Lindsay S, Cheung M, et al (2008). Human CHN1 mutations hyperactivate alpha2-chimaerin and cause Duane's retraction syndrome. Science, 321(5890), 839-843. Abstract.  Author URL.
Geraldo S, Khanzada UK, Parsons M, Chilton JK, Gordon-Weeks PR (2008). Targeting of the F-actin-binding protein drebrin by the microtubule plus-tip protein EB3 is required for neuritogenesis. Nat Cell Biol, 10(10), 1181-1189. Abstract.  Author URL.
Lee S, Faux C, Nixon J, Alete D, Chilton J, Hawadle M, Stoker AW (2007). Dimerization of protein tyrosine phosphatase sigma governs both ligand binding and isoform specificity. Mol Cell Biol, 27(5), 1795-1808. Abstract.  Author URL.
Chilton J (2006). Molecular mechanisms of axon guidance. Developmental Biology, 292(1), 13-24.
Chilton J, Faure J, Peris L, Thery M (2006). Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends. The Journal of Cell Biology, 174(6), 839-849.
Osborne NJ, Begbie J, Chilton JK, Schmidt H, Eickholt BJ (2005). Semaphorin/neuropilin signaling influences the positioning of migratory neural crest cells within the hindbrain region of the chick. Dev Dyn, 232(4), 939-949. Abstract.  Author URL.
Chilton J, Hammond R, Naeem A, Vivancos V (2005). Slit-mediated repulsion is a key regulator of motor axon pathfinding in the hindbrain. Development, 132(20), 4483-4495.
Chilton J, Guthrie S (2004). Development of the oculomotor axon projections in the chick embryo. The Journal of Comparative Neurology, 472(3), 308-317.
Chilton JK, Guthrie S (2003). Cranial expression of class 3 secreted semaphorins and their neuropilin receptors. Dev Dyn, 228(4), 726-733. Abstract.  Author URL.
Sajnani-Perez G, Chilton JK, Aricescu AR, Haj F, Stoker AW (2003). Isoform-specific binding of the tyrosine phosphatase PTPsigma to a ligand in developing muscle. Mol Cell Neurosci, 22(1), 37-48. Abstract.  Author URL.
Chilton JK, Stoker AW (2000). Expression of receptor protein tyrosine phosphatases in embryonic chick spinal cord. Mol Cell Neurosci, 16(4), 470-480. Abstract.  Author URL.
Chilton JK, Stoker AW (2000). Spatiotemporal distribution of the ligands for both isoforms of the protein tyrosine phosphatase crypalpha in embryonic chick spinal cord and limbs. EUROPEAN JOURNAL OF NEUROSCIENCE, 12, 266-266. Author URL.
Smith AL, Akerman CJ, Baker GE, Dempster AC, Smyth D, Chilton J, Thompson ID (1998). Sustained and reversible cortical blockade by Elvax-encapsulated muscimol. EUROPEAN JOURNAL OF NEUROSCIENCE, 10, 242-242. Author URL.

Conferences

Walker JMV, Malhi A, Hardy H, Chilton J, Beall C (2016). A769662 regulates intracellular calcium and extracellular ATP independent of AMPK.  Author URL.

Publications by year


In Press

Dun X-P, Chilton JK (In Press). Control of cell shape and plasticity during development and disease by the actin-binding protein Drebrin. Histol Histopathol, 25(4), 533-540. Abstract.  Author URL.

2017

Chilton JK, Guthrie S (2017). Axons get ahead: Insights into axon guidance and congenital cranial dysinnervation disorders. Dev Neurobiol, 77(7), 861-875. Abstract.  Author URL.
Gasperini RJ, Pavez M, Thompson AC, Mitchell CB, Hardy H, Young KM, Chilton JK, Foa L (2017). How does calcium interact with the cytoskeleton to regulate growth cone motility during axon pathfinding?. Mol Cell Neurosci, 84, 29-35. Abstract.  Author URL.

2016

Walker JMV, Malhi A, Hardy H, Chilton J, Beall C (2016). A769662 regulates intracellular calcium and extracellular ATP independent of AMPK.  Author URL.
Ketschek A, Spillane M, Dun XP, Hardy H, Chilton J, Gallo G (2016). Cover Image. Developmental Neurobiology, 76(10).
Ketschek A, Spillane M, Dun X-P, Hardy H, Chilton J, Gallo G (2016). Drebrin coordinates the actin and microtubule cytoskeleton during the initiation of axon collateral branches. Developmental Neurobiology, 76(10), 1092-1110. Full text.

2015

Gutowski NJ, Chilton JK (2015). The congenital cranial dysinnervation disorders. Archives of Disease in Childhood, 100(7), 678-681. Abstract.
Gutowski NJ, Chilton JK (2015). The congenital cranial dysinnervation disorders. Arch Dis Child, 100(7), 678-681. Abstract.  Author URL.

2013

Chilton JK, Ferrario JE, Baskaran P, Clark C, Hendry A, Lerner O, Hintze M, Guthrie S (2013). Axon guidance in the developing ocular motor system and Duane's Retration Syndrome depends on Semaphorin signalling via alpha2-chimaerin. PNAS

2012

Dun X-P, Bandeira de Lima T, Allen J, Geraldo S, Gordon-Weeks P, Chilton JK (2012). Drebrin controls neuronal migration through the formation and alignment of the leading process. Mol Cell Neurosci, 49(3), 341-350. Abstract.  Author URL.  Full text.
Ketschek A, Spillane M, Dun X-P, Chilton J, Gallo G (2012). Regulation of axonal filopodia and collateral branches by the actin filament binding protein drebrin. MOLECULAR BIOLOGY OF THE CELL, 23 Author URL.

2009

Allen J, Chilton JK (2009). The specific targeting of guidance receptors within neurons: who directs the directors?. Dev Biol, 327(1), 4-11. Abstract.  Author URL.

2008

Miyake N, Chilton J, Psatha M, Cheng L, Andrews C, Chan W-M, Law K, Crosier M, Lindsay S, Cheung M, et al (2008). Human CHN1 mutations hyperactivate alpha2-chimaerin and cause Duane's retraction syndrome. Science, 321(5890), 839-843. Abstract.  Author URL.
Geraldo S, Khanzada UK, Parsons M, Chilton JK, Gordon-Weeks PR (2008). Targeting of the F-actin-binding protein drebrin by the microtubule plus-tip protein EB3 is required for neuritogenesis. Nat Cell Biol, 10(10), 1181-1189. Abstract.  Author URL.

2007

Lee S, Faux C, Nixon J, Alete D, Chilton J, Hawadle M, Stoker AW (2007). Dimerization of protein tyrosine phosphatase sigma governs both ligand binding and isoform specificity. Mol Cell Biol, 27(5), 1795-1808. Abstract.  Author URL.

2006

Chilton J (2006). Molecular mechanisms of axon guidance. Developmental Biology, 292(1), 13-24.
Chilton J, Faure J, Peris L, Thery M (2006). Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends. The Journal of Cell Biology, 174(6), 839-849.

2005

Osborne NJ, Begbie J, Chilton JK, Schmidt H, Eickholt BJ (2005). Semaphorin/neuropilin signaling influences the positioning of migratory neural crest cells within the hindbrain region of the chick. Dev Dyn, 232(4), 939-949. Abstract.  Author URL.
Chilton J, Hammond R, Naeem A, Vivancos V (2005). Slit-mediated repulsion is a key regulator of motor axon pathfinding in the hindbrain. Development, 132(20), 4483-4495.

2004

Chilton J, Guthrie S (2004). Development of the oculomotor axon projections in the chick embryo. The Journal of Comparative Neurology, 472(3), 308-317.

2003

Chilton JK, Guthrie S (2003). Cranial expression of class 3 secreted semaphorins and their neuropilin receptors. Dev Dyn, 228(4), 726-733. Abstract.  Author URL.
Sajnani-Perez G, Chilton JK, Aricescu AR, Haj F, Stoker AW (2003). Isoform-specific binding of the tyrosine phosphatase PTPsigma to a ligand in developing muscle. Mol Cell Neurosci, 22(1), 37-48. Abstract.  Author URL.

2000

Chilton JK, Stoker AW (2000). Expression of receptor protein tyrosine phosphatases in embryonic chick spinal cord. Mol Cell Neurosci, 16(4), 470-480. Abstract.  Author URL.
Chilton JK, Stoker AW (2000). Spatiotemporal distribution of the ligands for both isoforms of the protein tyrosine phosphatase crypalpha in embryonic chick spinal cord and limbs. EUROPEAN JOURNAL OF NEUROSCIENCE, 12, 266-266. Author URL.

1998

Smith AL, Akerman CJ, Baker GE, Dempster AC, Smyth D, Chilton J, Thompson ID (1998). Sustained and reversible cortical blockade by Elvax-encapsulated muscimol. EUROPEAN JOURNAL OF NEUROSCIENCE, 10, 242-242. Author URL.

  • BClinSci
    • Module Lead for Professional Training Year
    • Personal Tutor
  • BMBS
    • Research in Action SSU School Lead
    • Doctors as Teachers SSU
    • PBL
    • LSRC
    • Academic Tutor

Back | Edit Profile