P2X receptors are ligand-gated ion channels activated by extracellular ATP. The human genome encodes 7 pore-forming subunits (P2X1-7), from which functional P2X receptors assembly as homo- and heteromeric trimers (3 subunits). The P2X4 receptor is a drug target for the treatment of neuropathic pain, hypertension and cardiac failure. Despite this, the molecular composition of P2X4 containing ion channels in targets tissues is unclear, though evidence exists for homo- and heteromeric assembly of P2X4 in overexpressed systems. This PhD project will focus on understanding the molecular composition of P2X4-containing receptors in treatment-relevant tissues and in overexpressed systems. The student will explore how the presence of P2X4 heteromers influences receptor pharmacology, and the impact thereafter on cellular function.
Training will be provided in the areas of mammalian cell culture, immunoprecipitation, western blotting, confocal microscopy, FRET, calcium imaging and electrophysiology. This project is highly suited to a student with an interest in ion channel/receptor background in pharmacology and biochemistry. The successful candidate will join a world class, dynamic, and well-funded and laboratory. The laboratory is currently funded by BBSRC, British Heart Foundation and international industrial partners. PhD candidates are encouraged to present their research at domestic and international conferences.
The project may be available to start earlier than October 2018, but candidates should discuss this with the primary supervisor in the first instance.
Minimum 2:1 in BSc in Biomedical Sciences, Biological Sciences, Physiology or Pharmacology
For more information on the supervisor for this project, please go here: https://www.uea.ac.uk/biological-sciences/people/profile/s-j-fountain
Type of programme: PhD
Start date of project: October 2018
Mode of study: Full-time
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/study/postgraduate/research-degrees/fees-and-funding.
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.
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.
North RA (2002). Molecular physiology of P2X receptors. Physiological Reviews.
Yamamoto K, Sokabe T, Matsumoto T, Yoshimura K, Shibata M, Ohura N, Fukuda T, Sato T, Sekine K, Kato S, Isshiki M, Fujita T, Kobayashi M, Kawamura K, Masuda H, Kamiya A, Ando J (2006). Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. Nature Medicine.
Beggs S, Trang T, Salter MW (2012). P2X4R+ microglia drive neuropathic pain. Nature Neuroscience.