PhD Studentship - Exploiting Pharmacology of Ion Channels to Control Macrophage Immune Responses (STOKESL_U26SCI)

Project Supervisor - Dr Leanne Stokes

Macrophages are part of the innate immune system which protects us from infection by bacterial, fungal and parasitic pathogens. Treatments targeting pathogens have been the mainstay of infection control but with resistant strains on the increase, alternative strategies need to be considered such as host-directed therapies. These focus on how to modulate protective physiological immune responses.

This project will investigate a macrophage ion channel called P2X7 as a novel host-directed target. We will elucidate how chemicals that act as positive allosteric modulators of P2X7 (facilitating ion channel opening) can engage with the protein and alter downstream cell signalling pathways. We will use a newly developed method from our group called on-cell saturation transfer difference NMR spectroscopy [1] to investigate how positive allosteric modulators interact with P2X7 and we will explore binding sites using a mutagenesis approach. We will further investigate downstream signalling consequences in macrophages following activation of P2X7 by positive allosteric modulators building on alteration of cell death signalling [2] to explore apoptosis and PANoptosis pathways. We will also use NMR spectroscopy to determine effects on cell metabolic pathways and secretory events in response to P2X7 stimulation. The student will gain skills in cell biology, pharmacological assays, computational docking, NMR spectroscopy, site-directed mutagenesis, macrophage biology, and cell death assays.

This project would suit a graduate in Pharmacology, Biomedicine, Biomedical Science, Immunology or Pharmacy, with curiosity and a passion for learning. We will provide additional training in transferable skills, critical thinking, problem solving, science communication and opportunities to attend national and international conferences to present work. The School of Chemistry, Pharmacy and Pharmacology at UEA has a growing postgraduate community with many opportunities for involvement in scientific events and outreach. We welcome applications from all backgrounds in line with our commitment to equality, diversity, and inclusivity. 

[1] doi.org/10.1021/jacs.5c02985

[2] www.nature.com/articles/s41419-019-2110-3

Entry Requirements

Acceptable first degree - Pharmacology, Biomedical Science, Biomedicine, Pharmacy.

The standard minimum entry requirement is 2:1.

Mode of study: Full-time

Start date: 1 October 2026

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.

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