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PhD: A Hub-and-spoke Approach for Electron Paramagnetic Resonance of Proteins and Model Systems

The University of Manchester - School of Chemistry

Qualification Type: PhD
Location: Manchester
Funding for: UK Students, EU Students, International Students
Funding amount: Not Specified
Hours: Full Time
Placed On: 19th June 2019
Closes: 31st July 2019

Project Summary: Manchester University hosts the EPSRC National Research Facility (NRF) for Electron Paramagnetic Resonance (EPR). EPR is an invaluable tool for the structural characterization of large chemical and biochemical assemblies. In particular, the ability of Pulsed Dipolar Spectroscopy (PDS) methods to measure distances on a nanometer length scale has facilitated structural studies of large protein complexes.

This studentship will be highly interdisciplinary and is focused on the development of new PDS sequences to study hub-and-spoke systems; formed when a single spin-centre of one type (hub) is surrounded by a number of spincentres of a second type (spokes). Spin-centres that will be studied include Nitroxide (NO●), EPR-active metals and triplet states, formed by laser excitation.

The project has been inspired by the protein p7 viroporin, a small viral protein from Hepatitis C, which assembles into channels in membranes (collaboration with Prof. Nicole Zitzmann, Oxford University). p7 channels are believed to play a role in the viral infection pathway, therefore understanding the structure of these channels may allow the development of new antiviral drugs. p7 channels are known to bind EPR-active Cu(II) (hub) and NO● spin-centres (spokes) can be added to the peptide chains, forming a hub-and-spoke system.

Initial work on the project will involve design and synthesis of hub-and-spoke model systems with Dr. Louise Natrajan and design, development and testing new EPR methodologies with Dr Alice Bowen.

The project has significant scope for a student to gain a broad range of skills including synthesis, spectroscopic measurements, sample preparation, computational modelling and data analysis. The exact balance between these can be tailored to the strengths and interests of the student. EPR is a growing field, both in industry and academic settings. Students familiar with EPR have a wide variety of future career paths open to them in many varied disciplines, for example, from analysing in vivo samples in EPR imaging through to quantum computing.

About you: You are an enthusiastic person with a first degree (at 2.1 level or above) in Chemistry or a related discipline (for example Natural Sciences, Physics, Materials, Biochemistry etc.). You are interested in a multidisciplinary project that can be tailored to your interests, which will include a mix of spectroscopy (Electron Paramagnetic Resonance, UV-vis and others), synthesis of model systems, computational modelling (e.g. Density Functional Theory and simulations of spectroscopic data) and working with biological systems (including viroporin p7). No prior experience of Electron Paramagnetic Resonance or other forms of spectroscopy is necessary, but a willingness to learn new techniques and an interest in problem solving are required. The project described below is an outline and there will be opportunities for the student to have significant input into the direction of research over the course of the work.

Research environment: The University of Manchester provides world-class facilities for research and skills training. In particular it is the location of the National EPR facility, holding one of the largest numbers of EPR instruments in the country. The student will be part of an active EPR community. The funding offered will enable the student to attend several international conferences during the course of their doctorate, allowing them to make connections in the wider
EPR and magnetic resonance communities.

Funding: fees will only be paid at the Home/EU rates, so international students would need to make up the difference themselves.

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