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Structural insights into ligand binding and channel gating in ATP-gated P2X7 receptor


Faculty of Biological Sciences

About the Project

P2X7 receptor, belonging to the ATP-gated ion channel P2X receptor family, exhibits distinct functional and pharmacological properties that are crucial for its role in innate immunity and inflammatory diseases and cancers (Jiang et al., 2013; Caseley et al., 2014; Roger et al., 2014; Wei et al., 2018). This research project is, using structural modelling, ligand docking, EM imaging, electrophysiology, site-directed mutagenesis, to elucidate the structural basis that governs ligand binding (Caseley et al., 2016), channel gating and pore formation in the P2X7 receptor, and to develop novel P2X7 receptor antagonists for treatment of inflammatory and cancer diseases.

Funding Notes

(1) We have a strong track record of home and international applicants to succeed in their application for various scholarships at University of Leeds (View Website). For those presently studying in reputed universities in China, we are eligible to support their applications for University of Leeds/China Scholarship Council Scholarships.
(2) We also warmly welcome strong international applicants with funding support from their own governmental scholarship schemes; a bench fee of £8000 per year is required.
(3) Informal enquiry regarding the project can be made to: .

References

(1) Jiang, L.-H. et al, (2013) Insights into the Molecular Mechanisms Underlying Mammalian P2X7 Receptor Functions and Contributions in Diseases, Revealed by Structural Modeling and Single Nucleotide Polymorphisms. Front Pharmacol 4: 55;
(2) Jelassi, B. et al., (2013) Anthraquinone emodin inhibits human cancer cell invasiveness by antagonizing P2X7 receptors. Carcinogenesis 34: 1487-96;
(3) Caseley, E.A. et al., (2014) Non-synonymous single nucleotide polymorphisms in the P2X receptor genes: association with diseases, impact on receptor functions and potential use as diagnosis biomarkers. International Journal of Molecular Science 15: 13344-71;
(4) Roger, S. et al., (2014) Understanding the roles of the P2X7 receptor in solid tumour progression and therapeutic perspectives. BBA Biomembranes
(5) Caseley, E. A. et al., (2016) Structure-based identification and characterisation of structurally novel human P2X7 receptor antagonists. Biochemical Pharmacology 116: 130-139
[6] Wei, L. et al (2018) ATP-activated P2X7 receptor in the pathophysiology of mood disorders and as an emerging target for the development of novel antidepressant therapeutics. Neuroscience & Biobehavioral Reviews 87:192-205

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