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Novel pharmacological tools for P2X7 and implications for the immune system (STOKESU15SF)

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  • Full or part time
    Dr Stokes
  • Application Deadline
    No more applications being accepted
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

The P2X7 receptor is a ligand gated ion channel activated by extracellular ATP. It is highly expressed on immune cell populations where it regulates many cell signalling pathways. P2X7 may be involved in inflammatory responses and developing pharmacological tools to modulate P2X7 channel activity is important. My group recently discovered a novel series of allosteric modulators of P2X7, chemicals present in the herbal medicine Panax ginseng. These ginsenosides potentiate responses through P2X7 and in doing so, enhance intracellular calcium signalling and promote downstream events such as cell death through apoptosis. This PhD project will expand on these observations and investigate the effects of modulating P2X7 on immune cells. The PhD student will be trained in core techniques such as cell culture, primary cell isolation from peripheral blood, fluorescent dye uptake assays using a plate reader, patch clamp electrophysiology (optional), flow cytometry, microscopy and ELISA techniques.

Funding Notes

This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at http://www.uea.ac.uk/pgresearch/pgrfees.

A bench fee is also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. The amount charged annually will vary considerably depending on the nature of the project and applicants should contact the primary supervisor for further information about the fee associated with the project.

References

i) Helliwell RM, ShioukHuey C O, Dhuna K, Molero JC, Ye J-M, Xue CC, Stokes L. Selected ginsenosides of the protopanaxdiol series are novel positive allosteric modulators of P2X7 receptors. British Journal of Pharmacology 2015 172(13):3326-40. doi 10.1111/bph.13123
ii) Bartlett R, Stokes L, Sluyter R The P2X7 purinergic receptor: recent developments and the use of P2X7 antagonists in models of disease. Pharmacological Reviews. 2014 66(3):638-75. doi: 10.1124/pr.113.008003.
iii) Stokes L, Fuller SJ, Sluyter R, Skarratt KK, Gu B, Wiley JS. Two haplotypes of the P2X7 receptor containing the Ala-348 to Thr polymorphism exhibit a gain-of-function effect and enhanced interleukin-1 secretion. FASEB Journal. 2010 24(8): 2916-27.

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