Edinburgh Research Explorer

Prof Peter Brophy

Professorial Fellow

Profile photo

Willingness to take PhD students: Yes

Education/Academic qualification

Bachelor of Science
Doctor of Philosophy (PhD)

Professional Qualifications

Fellow of the Academy of Medical Sciences, FMedSci
Fellow of the Royal Society of Biology, FRSB
Fellow of the Royal Society of Edinburgh, FRSE

Biography

Peter Brophy received his BSc from King's College, London University and PhD from Guy's Hospital Medical School (now King's College Medical School), London University. He was the Chair of Anatomy from 2009 to 2014 and was the Director of the Centre for Neuroregeneration (formerly the Centre for Neuroscience Research) from 2002 to 2014.

He has served on the research panels of a variety of bodies, including Action Research, the MS Society and the Neurosciences and Mental Health Panel at the Wellcome Trust. In 2008, Brophy served as the Chair of the International Gordon Conference on Myelin.

Research Overview

In the developing vertebrate nervous system oligodendrocytes and Schwann cells not only play a vital role in promoting neuron survival, but they also produce the myelin sheath, which is essential for the normal function of the nervous system, a fact underscored by the debilitating consequences of demyelination in multiple sclerosis in the CNS and in peripheral neuropathies of the Charcot-Marie-Tooth (CMT) type.

The discovery of the Periaxin (Prx) gene and its role in forming the Cajal bands (first described by Santiago Ramon y Cajal) in Schwann cells led to the identification of the cause of a severe demyelinating neuropathy-CMT 4F-in humans. This work also permitted the first experimental proof of the proposal by Huxley and Stämpfli (1949) that internodal distance can regulate nerve conduction velocity.

A second project has been focused on the assembly of the node of Ranvier in response to myelination. Three isoforms of neurofascin, one glial, and two neuronal, have been shown to play distinct but vital roles in the clustering of voltage-gated sodium channels at the node of Ranvier.

Studies on the role of these proteins during both normal development and during nerve repair exploit live imaging using both conventional and super-resolution microscopy.

Qualifications

BSc (First class hons) University of London, 1970

PhD University of London, 1974

Websites

http://www.cnr.ed.ac.uk/Research/brophy.html

Research Interests

Myelination and the mechanisms of saltatory conduction.

Visiting and Research Positions

Honorary Professor, Heriot Watt University

My research in a nutshell

Oligodendrocytes are the cells in the human brain and spinal cord (central nervous system) that produce the myelin sheath around nerves. Schwann cells do the same job in the rest of the nervous system (peripheral nervous system). These cells myelinate nerve fibres by extending processes which encircle the nerves many times to form a multi-layered sheath. Each nerve fibre has many myelin segments and in humans each segment can be over a millimeter in length, with gaps between the segments of about a thousandth of a millimeter. Myelin promotes rapid communication not only between different groups of nerve cells within the central nervous system, but also between nerve cells and muscles. This is because

wrapping myelin around nerves causes specialized pores at the nerve surface called sodium channels to become concentrated in the gaps between successive myelin wraps. These gaps are called nodes of Ranvier and their high concentration of sodium channels is crucial for the rapid electrical conduction of nerve impulses.

When myelin is destroyed, as in multiple sclerosis (MS) in the central nervous system, or Charcot-Marie-Tooth (CMT) disease in the peripheral nervous system, we lose functions for two reasons. First, the speed of nerve conduction slows because sodium channels diffuse away from the node, and secondly, without a myelin sheath the nerves start to degenerate. It is believed that nerve degeneration is linked to the disruption of the nodal sodium channels, and their dispersion is also believed to be at the root of other distressing aspects of these diseases such as pain. Demyelinating diseases are relatively common: there are about 80,000 people in the UK with MS and about 30,000 with CMT. Thus far there are no cures and no therapy halts disease progression.

There has been considerable progress in identifying the accessory proteins that persuade sodium channels to go to the node and remain there, primarily by knocking the genes that encode the proteins out in mice. This is how we discovered a group proteins that are encoded by a gene called Neurofascin which have a key role in "clustering" sodium channels. However, we have no idea how they do it. Therefore, two key question need to be answered. The first is, how does myelination cause Neurofascin proteins to assist in concentrating sodium channels at nodes of Ranvier? Secondly, why does loss of myelin cause sodium channels to disperse?

Teaching

Undergraduate: Honours Neuroscience, Developmental and Clinical Neuroscience

Postgraduate: MSc

Administrative Roles

Role 1, Chair, UK MS Society Grant Review Panel 1

Role 2, Member UK MS Society Strategy Review Committee

Role 3, Member MRC Non-Clinical  Training and Career Development Panel

Role 3, Chair, Scientific Advisory Board, INSERM Institute for Molecular and Cellular Neuroscience, Institut du Fer a Moulin, Paris, France

Role 4, Member, National Committee, British Neuroscience Association

Role 5, Member, Wellcome Trust Peer Review College

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