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  Resolving coarse-grained dynamic distance constraints of the transport cycle of NSS transporters using EPR spectroscopy (MACMILLANFU20MCNTF)


   School of Chemistry

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  Dr F MacMillan  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

An H2020 Marie Sklodowska-Curie Action funded PhD studentship is available in the School of Chemistry at the University of East Anglia (UEA) working with Fraser MacMillan within the Henry Wellcome Unit for Biological EPR Spectroscopy. You will be part of a cohort of international early stage researchers within the NeuroTrans Innovative Training Network (ITN). This ITN combines a group of world-leading laboratories and organisations, where early stage researchers benefit from academic and industrial collaboration and research skill training.

The aim of the NeuroTrans ITN is an improved understanding of neurotransmitter: sodium symporter (NSS) function ranging from the molecular level to human pathologies; to investigate how psychoactive substances target these transporters and to elucidate how disruption of transporter function contributes to neuropsychiatric disease pathobiology. NeuroTrans will make use of cutting-edge methods in biochemistry, biophysics and molecular and structural biology to reach this goal.

This post focuses on the biophysical characterisation of ligand-bound protein complexes and aims to derive dynamic structural and mechanistic insights into their structures. This will be achieved using advanced magnetic resonance techniques in combination with site-directed spin labelling, as part of ongoing collaborations with other members of the ITN. Accessing different conformational states during the transport cycle remains challenging. You will employ advanced EPR spectroscopy to derive structural information in form of distances and angles constraints for state-specific structural ensembles. The use of multiple labels and integration of both NMR and EPR techniques and their application to membrane proteins is a novel and innovative aspect of this project. You will be expected to develop and deploy sophisticated spectroscopic approaches, be involved with data interpretation and development of mechanistic models describing the mode of action of these transporters via collaborative research.
Further informal enquiries welcome to Dr. MacMillan ([Email Address Removed]).

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For more information on the project’s supervisor, please visit: https://people.uea.ac.uk/fraser_macmillan
Type of programme: PhD
Start date of project: October 2020.
Mode of study: full time.
Studentship length: 3 years. (3 year studentships have a (non-funded) 1 year ‘registration only’ period).
Location: UEA.
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ENTRY REQUIREMENTS:
Acceptable first degree: BSc (Hons) degree in a Chemistry, Biochemistry, Biophysics, Physics, or a related field equivalent to 2:1 or preferably a 1st class classification.

If English is not your first language or you are form a country that is not in the UKVI list of English speaking countries you may be required to provide evidence of proficiency in English language. Further information can be found at https://www.uea.ac.uk/study/postgraduate/research-degrees/how-to-apply/entry-requirements
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HOW TO APPLY
Applications must be submitted to the NeuroTrans consortium ([Email Address Removed]), including the completed Application Form available through the NeuroTrans Application page: https://www.neurotrans.org/recruitment/application-to-neurotrans

The successful applicant will also be required to submit a full application to the University of East Anglia (details to given post-interview).


Funding Notes

This project is awarded with a 3-year PhD scholarship through the Horizon 2020 Marie Skłodowska-Curie Actions - Innovative Training Networks (ITN) Programme (No. 860654). EU applicants are eligible to apply who have not been based in the UK for more than 12 months in the last 3 years. Remuneration will be in line with the Marie Skłodowska-Curie guidelines (Early Stage Researchers, ITN). For programme, funding information and eligibility criteria please visit: https://ec.europa.eu/research/participants/data/ref/h2020/other/guides_for_applicants/h2020-guide-appl-msca-itn_en.pdf

References

i) Anna Mullen, Jenny Hall, Janika Diegel, Isa Hassan, Adam Fey, Fraser MacMillan,
Membrane transporters studied by EPR spectroscopy: structure determination and elucidation of functional dynamics. Biochem. Soc. Trans., 44, 905–915 (2016) .

ii) Shiran Barber‐Zucker, Jenny Hall, Sivasubramanyan, Venkata Mangapuram, Itamar Kass, Sofiya Kolusheva, Fraser MacMillan*, Raz Zarivach*, Arnon Henn*,
Metal binding to the dynamic cytoplasmic domain of the cation diffusion facilitator (CDF) protein MamM induces a 'locked-in' configuration
FEBS Journal 286, 2193-2215 (2019)

iii) D.P. Claxton, K. Kazmier, S. Mishra, S., H.S. Mchaourab,
Navigating Membrane Protein Structure, Dynamics, and Energy Landscapes Using Spin Labelling and EPR Spectroscopy. Meth. Enzymol., 564, 349–387 (2015)

iv) T.D.W. Claridge, Protein Ligand Screening by NMR
in High-Resolution NMR techniques, Chapter 11, Elsevier, Amsterdam (2016)

v) J van Wonderen, D.N. Kostrz, C. Dennison & F. MacMillan
REFINE’d Distances Between Paramagnetic Centres of a Multi-Copper Nitrite Reductase Determined by Pulsed EPR (iDEER) Spectroscopy
Angewandte Chemie, 52, 1990-1993 (2013)

Where will I study?