Dr A Bowen, Prof Sam Hay, Dr Muralidharan Shanmugam
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
Electron Paramagnetic Resonance is a rapidly expanding suit of techniques used for the study of complex (bio)molecules that possess spin-active moieties with unaired electrons. In particular distance measurements, and in some cases orientation information, measured between two spin-active moieties using EPR pulsed dipolar spectroscopy (PDS) can be aid the determination of the three dimensional structure of bio-assemblies. This is important for the understanding of their function. While EPR PDS measurements have formally relied on the placement of spin-active nitroxide moieties (spin-labels) into the biological structure, recent developments in EPR PDS have shown that it is possible to use innate cofactors, such as flavins, as spin-labels. These must be carefully prepared to be spin-active; either through chemical, electrochemical or photochemical preparation in this type of measurement.
Use of such innate spin-active moieties for this type of technique has the potential to be very beneficial as it is allows EPR measurements to be conducted on native proteins, without the need to introduce non-native spin-active moieties which may distort the structure. This project aims to investigate the possible mechanisms of forming EPR active cofactors and compare the PDS EPR datasets obtained to evaluate the best methodologies. We will use the different techniques to study proteins of interest to the bio-technology industry, including Mono Amine Oxidases and diflavin reductases.
Furthermore the rigid binding of co-factors within a protein structure makes the determination of both distance and orientation information from PDS measurements possible, increasing the amount of data that can be obtained from a single protein sample. To fully interpret the orientation and distance information present in EPR PDS datasets, simulation of the data and models of the spin density must be calculated computationally.
The PhD student will be based in Department of Chemistry and the Manchester Institute of Biotechnology (MIB) and will be co-supervised by Dr Alice Bowen, Dr Sam Hay and Dr Muralidharan Shanmugam. The project is interdisciplinary, with a specific focus on Electron Paramagnetic Resonance Spectroscopy, a growing field in structural biology. The student will have the opportunity to gain broad experience in modern experimental biophysics and spectroscopic techniques, alongside biochemically-relevant computational chemistry and data analysis.
https://www.chemistry.manchester.ac.uk/epr/
https://www.chemistry.manchester.ac.uk/
http://www.mib.ac.uk
https://www.research.manchester.ac.uk/portal/Sam.Hay.html
Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
Funding Notes
This project is to be funded under the BBSRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP website www.manchester.ac.uk/bbsrcdtpstudentships
As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.
References
1) C. Altenbach et al. Biochemistry, (1989), 28, 7806-7812.
2) Y. Yang et al. J. Phys. Chem. Lett, (2018), 920, 6119-6123.
3) A.D. Milov et al., Soviet Physics, Solid State, (1981), 23(4), 565-569; M. Pannier et al., JMR, (2000), 142(2), 331-340; S. Milikisyants et al., JMR, (2009), 201(1), 48-56.
4) Hay et al. JACS, (2010), 132(28), 9738-9745.
5) M. Di Valentin et al., JACS, (2014), 136, 6582-6585. C. Hintze et al., Phys. Chem. Lett., (2016), 7(12), 2204–2209. 6) A.M. Bowen et al. JACS, (2018), 140(7), 2514-2527. 7) D.E. Edmondson et al., Biochemistry. (2009), 48(20), 4220–4230. 8) A.T. Murray et al. Angew. Chem. Int. Ed. (2015), 54, 8997 –9000.
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