Project Title: Studying the trafficking of Nav1.7 channel, a key pain target in nociceptive neurons

Supervisor: Dr Mohammed A Nassar

Application deadline: Friday 14 December 2012.

Project description:

Chronic pain has a significant socioeconomic effect on the society. In a recent survey about 19% of European complained of chronic pain which negatively impacted their life and wellbeing. This project is aimed at studying the trafficking of Nav1.7, a voltage-gated sodium channel (VGSC) subtype that is crucial for pain signalling. Loss of function mutations of Nav1.7 leads to complete insensitivity to pain whereas gain of function mutations results in painful conditions. The findings of this project may lead to novel analgesic drug targets and thus has an immense clinical relevance and significance.

The project will use biochemical methods to study trafficking of Nav1.7 to membrane of cultured neurons following exposure to inflammatory conditions. We have found that inflammatory mediators promote the trafficking of Nav1.7. The project will attempt to identify the part(s) of the channel that mediates the trafficking. The project will also identify proteins that interact with Nav1.7 and regulate or take part in its trafficking. The project will use primary culture of sensory neurons and whenever possible cell lines. The project will involve a range of techniques like molecular biological, biochemical and imaging methods. It can also involve recording of sodium currents from cultured neurons. 

References:

• 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.
• 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.
• Cox JJ, Reimann F, Nicholas AK, Thornton G, Roberts E, Springell K, Karbani G, Jafri H, Mannan J, Raashid Y, Al-Gazali L, Hamamy H, Valente EM, Gorman S, Williams R, McHale DP, Wood JN, Gribble FM, Woods CG.
  An SCN9A channelopathy causes congenital inability to experience pain.
  Nature. 2006 Dec 14;444(7121):894-8

Contact Details:

Dr Mohammed Nassar

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

Email: m.nassar@sheffield.ac.uk