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P2X receptors in the peripheral nervous system: molecular pharmacology (FOUNTAINSU20SF)

  • Full or part time
  • Application Deadline
    Sunday, May 31, 2020
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

P2X receptors are ligand-gated ion channels activated by extracellular adenosine 5’-triphosphate (ATP). In the peripheral nervous system (PNS), ATP is a neurotransmitter acting in both autonomic and sensory nerve control of body tissue function and homeostasis. P2X receptors are a promising therapeutic target for conditions arising from dysfunction of the PNS including hypertension and chronic cough. Though some progress has been made, selective small molecule modulators of human P2X receptors remain much sought after and may provide scaffolds for future drug development.

This PhD project will investigate the structure-activity relationship of small molecules that positively or negatively regulate human P2X receptor function. Specifically, the project will identify novel compounds through high throughput screening and characterise the function of several compounds already identified in the laboratory. Compounds will be assays to investigate their activity on peripheral nerve function. You will receive training in patch-clamp electrophysiology, calcium imaging, site-directed mutagenesis, molecular modelling, neuronal culture and confocal microscopy.

We are seeking an enthusiastic student with a background in Pharmacology, Biochemistry or Biomedical Sciences to join our lively and internationally recognised research team. The laboratory is well funded by UK Research and Innovation, British Heart Foundation and Industrial Partners. The laboratory is situated in the state-of-the-art Biomedical Research Centre on the University campus.

A start date prior to October 2020 may be possible but this should be discussed with Dr Fountain in the first instance.


MORE INFORMATION

Project supervisor: https://people.uea.ac.uk/s_j_fountain
Mode of study: Full time
Start date: October 2020
Entry requirements: First degree (2:1 or above) in Pharmacology, Biochemistry, Biomedical Sciences or Neuroscience.

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. Applicants should contact the primary supervisor for further information about the fee associated with the project.

References

Richards D, Gever J, Ford AP and Fountain SJ (2019). Action of MK-7264 (Gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation (British Journal of Pharmacology)

Layhadi JA, Turner JO, Crossman DC and Fountain SJ (2018). ATP evokes Ca2+ responses and CXCL5 secretion via P2X4 receptor activation in human monocyte-derived macrophages (Journal of Immunology)

Stokes L, Layhadi JA, Bibic L, Dhuna K, Fountain SJ (2017). P2X4 receptor function in the nervous system and current breakthroughs in pharmacology (Frontiers in Pharmacology)

Pijacka et al (2016). Purinergic receptors in the carotid body as a novel target for controlling hypertension (Nature Medicine)

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