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Life’s ups and downs: probing the conformational dynamics of DASS transporters, a protein family associated with age-related diseases and lifespan determination (MACMILLANU20DTP)


Project Description

We study the architecture and functional dynamics of membrane proteins, especially many medically relevant membrane transport systems. There is increasing evidence that membrane proteins do not act alone, but that they are organised as nano-machineries which function through the concerted action of individual components with high precision and specificity observed in both time and space. We are seeking to unravel the principles underlying the architecture and dynamics of these protein nanomachineries as well as their function. Our experimental approach focuses on the use of magnetic resonance techniques specifically Electron Paramagnetic Resonance (EPR) and Nuclear Magnetic Resonance (NMR) spectroscopy in combination with molecular biological, and biochemical approaches.

This project will study a specific divalent anion sodium symporter (DASS) transporter VcINDY. In eukaryotes, reducing cytoplasmic citrate modulates the energy homeostasis of cells and induces caloric restriction-like benefits. Citrate enters the cytoplasm through the DASS transporter family. Disruption of DASS function can increase lifespan, protect against insulin resistance and adiposity, and inhibit cancer cell proliferation. Thus, human DASS transporters are prime drug targets to treat numerous chronic diseases and promote healthy ageing. However, DASS transporters are highly dynamic and the development of DASS inhibitors relies on understanding the distribution of conformational states. Recent structural studies have proposed large scale conformational changes and we aim to probe the functional dynamics of this protein using a combination of state-of-the-art magnetic resonance techniques as well as techniques to purify and stabilise the protein using novel SMA lipid particles.

Project supervisor: https://people.uea.ac.uk/fraser_macmillan
Project sponsor: Norwich Research Park Bioscience Doctoral Training Partnership
Type of programme: PhD
Start date: 1 October 2020
Mode of study: Full-time
Studentship length: 4 years


ELIGIBILITY REQUIREMENTS

- First degree (2:1 or above) in relevant subject
- English language (IELTS 6.5 overall, 6 in each section)


MORE INFORMATION

This project has been shortlisted for funding by the Norwich Biosciences Doctoral Training Partnership (NRPDTP). Shortlisted applicants will be interviewed as part of the studentship competition. Candidates will be interviewed on either the 7th, 8th or 9th January 2020.

The NRP DTP offers postgraduates the opportunity to undertake a 4-year research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three-month professional internship (PIPS) during their study. The internship offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second class honours degree, or equivalent, are invited to apply.

For further information and to apply, please visit our website: https://biodtp.norwichresearchpark.ac.uk/

Funding Notes

For funding eligibility guidance, please visit our website: View Website. Full Studentships cover a stipend (2019/0 rate: £15,009pa), research costs and tuition fees at UK/EU rate and are available to UK and EU students who meet the UK residency requirements.

Students from EU countries who do not meet the UK residency requirements may be eligible for a fees-only award. Students in receipt of a fees-only award will be eligible for a maintenance stipend awarded by the NRPDTP Bioscience Doctoral Scholarships. To be eligible students must meet the EU residency requirements.

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