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Structural studies of membrane proteins: Structure and function of ion channels and transporters

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Research in the Pliotas group focuses on the investigation of molecular mechanisms, which underlie the gating and function of integral membrane proteins, in particular ion channels and transporters. These systems are pore-forming proteins embedded in lipid bilayers, allow the passage of solutes and molecules, and are the first point of attack for antimicrobial therapies. Most genetically studied human diseases are due to malfunctions of these proteins, and the majority of drugs, target them.
A multi-disciplinary approach combining biology, chemistry and physics will be engaged to address fundamental and challenging scientific problems. X-ray crystallography and Electron Paramagnetic Resonance (EPR) spectroscopy will be the main methodologies used to obtain high quality structural information. Complimentary techniques, such as lipid mass spectrometry and single molecule electrophysiology will be also facilitated to investigate the role of lipids on protein function and ion channel regulation.

We are seeking a highly motivated and talented individual interested in undertaking a very challenging and exciting PhD project in the laboratory of Dr Christos Pliotas. The project aims at obtaining and solving novel high-resolution 3D x-ray crystal structures of ion channels in distinct conformational states. Emerging structures will be interrogated by EPR spectroscopy for their validity within lipid/native environment and will be subsequently linked to function with the use of single molecule methodologies.

X-ray protein crystallography facilities in St Andrews are world-class including state-of-the-art crystallization robots for multiple pipetting, both hanging drop and lipidic cubic phase (LCP). In-house x-ray facilities, and regular visits to both Diamond (Oxford) and ESRF (Grenoble) synchrotrons for on-site or remote data collection are planned. Multiple purifiers for membrane protein purification, large-scale protein production, SEC-MALLS, ultracentrifuges, are all located in the same building complex while the EPR infrastructure available in St Andrews is truly world-leading (Bruker EMX cw-X-Band, Bruker E580 pulse X-Band, Bruker E580 pulse X/Q-band and a home-built pulse W-band (HIPER).

Interested and eligible candidates should directly contact Dr Christos Pliotas () for informal enquiries. More information about research interests in the group can be found at the Pliotas Group website: http://synergy.st-andrews.ac.uk/pliotas/

Founded in the early 15th century, St Andrews is Scotland’s first university and the third oldest in the English speaking world. The University of St Andrews is a diverse and international community of over 9000, comprising students and staff of over 100 nationalities. It has 7,500 students, 6,000 of them undergraduates, and employs approximately 2,460 staff. The University is one of Europe’s most research intensive seats of learning. It is the top rated University in Scotland and among the top three rated in the whole of UK.

Funding Notes

Candidates should usually hold a Bachelor's degree from a prestigious university with an overall mark of 85% or above, or a Masters degree.
Experience in chemical and/or structural biology of membrane proteins is highly desirable

References

(1) Pliotas et al, Nature Structural and Molecular Biology. “The Role of Lipids in Mechanosensation” (advance online publication) (2015). doi:10.1038/nsmb.3120
(2) Pliotas & Naismith, Current Opinion in Structural Biology. "Spectator no more, the role of the membrane in regulating ion channel function". (2017). doi:10.1016/j.sbi.2016.10.017
(3) Ward, Pliotas et al., Biophysical journal. “Probing the Structure of the Mechanosensitive Channel of Small Conductance in Lipid Bilayers with Pulsed Electron-Electron Double Resonance.” (2014). doi:10.1016/j.bpj.2014.01.008.
(4) Branigan, Pliotas et al., Nature Protocols. “Quantification of Free Cysteines in Membrane and Soluble Proteins Using a Fluorescent Dye and Thermal Unfolding.” (2013). doi:10.1038/nprot.2013.128.
(5) Pliotas et al., Proceedings of the National Academy of Sciences of the United States of America. “Conformational State of the MscS Mechanosensitive Channel in Solution Revealed by Pulsed Electron – Electron Double Resonance ( PELDOR ) Spectroscopy” (2012). doi:10.1073/pnas.1202286109.

How good is research at University of St Andrews in Biological Sciences?

FTE Category A staff submitted: 50.45

Research output data provided by the Research Excellence Framework (REF)

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