The goal of the Brophy laboratory is to understand how interactions between neurons and glia underpin rapid nerve impulse conduction in the vertebrate nervous system. Myelination of axons is a key event that stimulates the clustering of voltage gated sodium channels at nodes of Ranvier. The concentration of these sodium channels with associated proteins at nodes promotes rapid propagation of the action potential. A second key axonal domain is the axon initial segment (AIS). It has been assumed that the AIS initiates the action potential.
We are addressing three main questions:
1. What determines the site of node of Ranvier assembly?
2. How are voltage-gated sodium channels clustered at the node?
3. What is the role of the axon initial segment?
Please see also: http://www.cnr.ed.ac.uk/Research/brophy.html
Sherman DL., Krols M., Wu LM., Grove M., Nave KA., Gangloff YG., Brophy PJ. (2012) Arrest of myelination and reduced axon growth when Schwann cells lack mTOR. J. Neurosci., 32, 1817-1825 (Cover).
Wu LMN., Williams A., Delaney A., Sherman DL., Brophy PJ. (2012) Increasing internodal distance in myelinated nerves accelerates nerve conduction to a flat Maximum. Curr. Biol., 22 (20) : 1957-61.
Zonta B., Desmazieres A., Rinaldi A., Tait S., Sherman DL., Nolan MF., Brophy PJ. (2011) A critical role for Neurofascin in regulating action potential initiation through maintenance of the axon initial segment. Neuron., 69 (5) : 945-56.
Feinberg K., Eshed-Eisenbach Y., Frechter S., Amor V., Salomon D., Sabanay H., Dupree JL., Grumet M., Brophy PJ, Shrager P., Peles E. (2010). A glial signal consisting of gliomedin and NrCAM clusters axonal Na+ channels during the formation of nodes of Ranvier. Neuron., 65 (4) : 490-502.
Zonta B., Tait S., Melrose S., Anderson H., Harroch S., Higginson J., Sherman DL., Brophy PJ. (2008). Glial and neuronal isoforms of Neurofascin have distinct roles in the assembly of nodes of Ranvier in the central nervous system. J. Cell Biol., 181 (7) : 1169-77.
2011 Visiting Distinguished Professor at the École des Neurosciences de Paris
2008 Elected Chair, Gordon Conference on Myelin, Italy
2007 Elected to Fellowship, Royal Society of Edinburgh
2003 Elected to Fellowship, Academy of Medical Sciences
1982 Max-Planck-Society Fellow
1981 Fulbright-Hays Research Scholar