PhD Research Project: The role of the intracellular parts of the Nav1.7 channel in its membrane exp

Sensory neurons detect and transmit painful stimuli to the CNS. Inflammation and nerve injury sensitise sensory neurons in vivo which results in a decrease of pain thresholds. This can be due, at least in part, to an enhanced trafficking of voltage gated sodium channels to the plasma membrane which would result in increased excitability of sensory neurons. The VGSC subunit Nav1.7 has been shown to be crucial for pain signaling in mouse and human. Three genetic pain disorders have been mapped to Nav1.7 in humans; these are primary erthromyalgia, familial rectal pain and complete insensitivity to pain. However and despite its importance in pain signaling, little is known about Nav1.7 transport to nerve terminals, insertion into the membrane and endocytosis from the membrane. Investigation of these processes may lead to new druggable targets for pain relief. Drugs will be directed to inhibit insertion in membrane and increase endocytosis form membrane. Therefore, the aim of this project is to identify the contribution of the intracellular parts of Nav1.7 channel to its membrane expression.
The project will involve using molecular biology methods to generate fusion protein constructs, transfection of DNA into cell lines and primary DRG neurons, immunocytochemistry and Western blotting. Functional effect of transfected fusions on Nav1.7 will be assessed by calcium imaging and patch clamping.

For further details and informal discussion please feel free to contact Dr Nassar

Funding Notes

Applications from self-funded students or students with secured funding are also welcome.
Entry requirements
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD Studentship, you must complete the University's application form using the following link: http://www.sheffield.ac.uk/bms/prospective_pg/how_to_apply
*All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information*.
 

References

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