PhD Studentship in Biosciences and Pharmacy (PhD Studentship)
Reference Number: R2296
Project title: Structure-based design of human P2X4-selective small-molecule modulators
This project aims to use structure-based drug design to discover and develop small-molecule modulators of human P2X4, a member of the P2X receptor family known to play roles in neuropathic pain and blood-pressure regulation.
P2X receptors are a family of ATP-gated ion channels which play important roles in pain and inflammation. They are drug targets for the treatment of chronic inflammatory and neuropathic pain, thrombosis and hypertension, so the potential value of new P2X-selective compounds is highly significant, but to date, few have been discovered.
Recently, the 3D-structure of a fish P2X receptor bound to its ligand (ATP) was published. We have used this structure to make models of human P2X4, and have searched a database of drug-like molecules to identify those which fit best into the ATP-binding site, and thus are likely to act as drugs.
We aim to test the effect of these compounds on the function of P2X4 using fluorescent calcium-uptake assays in mammalian cells stably expressing P2X4 receptors. Compounds which show activity (hits) will be characterised using patch-clamp electrophysiology, and molecular models of hits docked into the hP2X4 ATP-binding site will be used to design alterations to the molecules to increase potency and specificity.
Training: The student will receive training in a wide range of techniques including molecular modelling, PCR, mutagenesis, molecular cloning, mammalian cell culture, transfection and protein expression, fluorescence imaging, fluorescent calcium influx assays and patch-clamp electrophysiology. They will develop their skills in all aspects of data presentation, including preparing posters, giving oral presentations and writing reports and papers. Furthermore, the student will be encouraged to become involved in scientific engagement, by taking part in the School Open Day and giving practical demonstrations to school pupils.
Start date: 1 October 2014
Number of Studentships: 1
This studentship is generously funded by Ser Cymru and consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£13,863 p.a. for 2014/15, updated each year).
One studentship is available.
Residency: Full awards (fees plus maintenance stipend) are open to UK Nationals and EU students without further restrictions.
Academic criteria: Candidates should hold a First or Upper Second Class Honours BSc degree in Biomolecular sciences (Microbiology, Biochemistry, Molecular Biology or Biomedical Sciences) or Pharmacy; and/or a Masters degree with suitable background.
How to Apply
Consideration is automatic on applying for Doctor of Philosophy (Biosciences), with a start date of October via Cardiff University's Online Application Service. In the research proposal section of your application, please specify the project title and supervisors of this project and copy the project description in the text box provided. In the funding section, please select "I will be applying for a scholarship / grant" and specify that you are applying for advertised funding from Ser Cymru.
The deadline for applications is 11 July 2014.
Cardiff University reserves the right to close applications early should sufficient applications be received.
For further details on the project contact Dr Mark Young by emailing YoungMT@cardiff.ac.uk.