New pharmacological tools for targeting P2X receptors in cancer (STOKESL_U27SCI)
Key details
- Application Deadline
- 24 February 2027
- Location
- UEA
- Funding Type
- Competition funded project (Home students only)
- Start Date
- 1 October 2027
- Mode of Study
- Full-time
- Programme Type
- PhD
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Project Description
Primary Supervisor - Dr Leanne Stokes
There is a growing literature documenting the exploitation of ion channels by cancer cells. P2X receptors are ligand-gated ion channels (P2X1-7) activated by the extracellular signalling molecule ATP. Concentrations of ATP are known to be high within tumour microenvironments potentially driving cellular adaptations and exploiting downstream signalling associated with P2X receptors. This project will undertake two main lines of investigation; i) to characterise the expression of important P2X receptors and their variants within cancer cells under different conditions, and ii) to determine the benefit of blocking various P2X receptors (either individually or through dual antagonism) to cancer cell growth and survival.
Aberrant splicing events are common within cancer and novel splice isoforms have the potential to be neo-antigens (e.g. targets for immunotherapy or markers for diagnostic/prognostic purposes). At least 18 splice variants of P2X7 have been described but very little is known about their expression levels and functionality. Nothing is known about P2X4 variants as yet. We will explore RNAseq data from public databases and together with quantitative PCR data, we will assemble this information. Our recent work has discovered compounds that can act as dual antagonists of P2X7 and P2X4 receptors and we will compare their efficacy to individual blockade of either P2X7 or P2X4.
The aims of the project are to 1) characterise splice variant expression of P2X7 and P2X4 receptors across a range of cancer cell lines and conditions, 2) generate P2X7 and P2X4-null cancer cells using CRISPR/Cas9 gene editing to further understand how these ion channels contribute to cancer cell biology, and 3) testing of dual antagonists of P2X7/P2X4 in in vitro cancer cell survival and growth assays. Skills developed: cell culture, molecular biology, gene editing and pharmacology plus transferable skills. This project would suit a graduate from Biomedical Science or Pharmacology.
Entry Requirements
The standard minimum entry requirement is 2:1 in Pharmacology, MPharm, Biomedicine, Biomedical Science, Biological Sciences.
Funding
This PhD project is in a competition for a Faculty of Science funded studentship. Funding is available to UK applicants and comprises ‘home’ tuition fees and an annual stipend for 3 years. The current UEA / institutional PhD stipend rate is £21,805 and will be subject to any agreed inflationary uplift for 2027/28.