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Targeting the P2X7 purinergic receptor in melanoma (STOKESLU19SF)


Project Description

There is much research into trying to regain control of cell proliferation or cell death (apoptosis) in cancer. Different strategies exist to do this and a multitude of individual receptor targets are being identified in tumour cell lines and primary cells. This PhD project aims to investigate the P2X7 receptor, an ion channel activated by extracellular nucleotides, in the regulation of proliferation/apoptosis in cancer cells. Originally identified as a cytolytic receptor on immune cells, activation of P2X7 by high concentrations of the nucleotide agonist ATP rapidly induces apoptosis, a type of cell death. In recent years it has been shown that P2X7 activation can also contribute to increased cell proliferation in cancer. This questions the role of P2X7 signalling in tumour cells and the balance between cell growth and cell death.

This project will test positive allosteric modulators of P2X7 from the natural product Panax ginseng in proliferation and apoptosis assays using a range of melanoma cell lines. The experimental work will involve cell biology, cell signalling and pharmacology plus molecular biology and drug discovery involving medicinal chemists in the School of Pharmacy. Techniques would include standard tissue culture and 3D spheroid cell culture, fluorescence assays (plate reader), proliferation and apoptosis assays, molecular biology, and flow cytometry.

The PhD may also start in January 2018, but start date should initially be discussed with Dr Stokes.

For more infomation on the supervisior for this project please visit: https://www.uea.ac.uk/pharmacy/people/profile/l-stokes
Type of programme: PhD
Start date: October 2019
Mode of Study: Full time
Acceptable first degree: Pharmacology, Biomedical Science, Immunology, Biological Sciences, Pharmacy
Application deadline: 31 May 2019, applications are processed as soon as they are received and the project may be filled before the closing date, so early application is encouraged.

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 View Website.

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)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.
ii) 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.

iii) Di Virgilio F & Adinolfi E. Extracellular purines, purinergic receptors and tumour growth. Oncogene 2016 doi: 10.1038/onc.2016.206

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