Project Title: Studying the trafficking of Nav1.7

Supervisor: Dr Mohammed A Nassar

Sensory neurons of the Dorsal Root ganglia (DRG) detect noxious stimuli and transmit sensory information to regions of the CNS that perceive pain. DRG neurons express multiple subtypes of voltage-gated sodium channel (VGSC) that are essential for their ability to fire the action potentials. Tissue inflammation and nerve damage result in changes in pain thresholds, which are associated with changes in the expression of VGSCs.

The aim of this project is to study the regulation of a particular subtype of VGSC that is essential for pain signaling. The project will use biochemical methods to study trafficking of VGSCs to membrane of cultured neurons following exposure to inflammatory conditions. Then, the project will attempt to identify the part(s) of the channel that mediates the trafficking. Finally, the project will identify proteins that interact with VGSCs and regulate or take part in their trafficking. The project will rely on primary culture of sensory neurons and will involve a range of techniques like molecular biology and biochemical methods. It can also involve recording of VGSC from neurons.  

References:

• Nassar MA, Stirling LC, Forlani G, Baker MD, Matthews EA, Dickenson AH and Wood JN.
  Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain.
  Proc Natl Acad Sci U S A. 2004. Aug 24;101(34):12706-11.
• Minett MS, Nassar MA, Clark AK, Passmore G, Dickenson AH, Wang F, Malcangio M, Wood JN.
  Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons.
  Nat Commun. 2012 Apr 24;3:791. doi: 10.1038/ncomms1795.

Contact Details:

Mohammed Nassar

http://www.shef.ac.uk/bms/research/nassar

Email: m.nassar@sheffield.ac.uk