Manipulating electron spins to explore structure in biomacromolecules.
Knowledge of the structure of and structural changes within biomacromolecules such as proteins or oligonucleotides (DNA, RNA) leads to advancing our understanding of the underlying mechanisms of function. Ultimately this is not only fundamentally interesting but will lead to improved drug targets and better biotechnology.
Electron paramagnetic resonance (EPR) spectroscopy is capable of measuring nanometre distances between stable radicals, such as nitroxyl-containing spin labels.1 These spin labels can be attached site-selectively to proteins or nucleic acids, though naturally occurring paramagnetic centres can also be used.2,3 For example, double electron electron resonance (DEER) is a pulsed EPR experiment that has proved useful for studying the structure of a range of biomacromolecules.1,4 Many of these experiments have been carried out in frozen glassy solutions. Your project would be to work on methods to expand the scope of the environment that biopolymers can be studied in through development of high-pressure,5 room temperature6 and in-cellular methods.7 You will also work on biological systems to answer questions about their structure.
The PhD will be run through the School of Physics and Astronomy at the University of St Andrews and you will also be a member of the Biological Sciences Research Complex. You must have a good scientific degree such as in physics, chemistry, biochemistry or biology, and be motivated to work across the disciplines.
The facilities at St Andrews for EPR, protein preparation and chemistry are outstanding. Informal enquires are encouraged prior to application and should be made to Dr Janet Lovett (email@example.com).
1. Klare, J. P. and Steinhoff H.-J., (2009) Photosynth. Res. 102 377-390.
2. Haugland, M. M., El-Sagheer, A. H., Porter, R. J., Pena, J., Brown, T., Anderson, E. A., Lovett, J. E., (2016) J. Am. Chem. Soc. 138 9069-9072.
3. Motion, C. L., Lovett, J. E., Bell, S., Cassidy, S. L., Cruickshank, P. A. S., Bolton, D. R., Hunter, R. I., El Mkami, H., Van Doorslaer, S. and Smith, G. M., (2016) J. Phys. Chem. Lett. 7 1411-1415.
4. Jeschke, G., (2012) Annu. Rev. Phys. Chem. 63 419-446.
5. Lerch, M. T., López, C. J., Yang, Z., Kreitman, M. J., Horwitz, J. and Hubbell, W. L., (2015) Proc. Natl. Acad. Sci. E2437–E2446.
6. Meyer, V., Swanson, M. A., Clouston, L. J., Boratyński, P. J., Stein, R. A., Mchaourab, H. S., Rajca, A., Eaton, S. S. and Eaton G. R., (2015) Biophys. J. 108 1213-1219.
7. Igarashi, R., Sakai, T., Hara, H., Tenno, T., Tanaka, T., Tochio, H. and Shirakawa, M., (2010), J. Am. Chem. Soc. 132 8228-8229.
The studentship will be funded by EPSRC through the School of Physics and Astronomy. Successful applicants from the UK can be fully supported for 3.5 years though there are exceptions. Funding is allocated depending upon availability and candidate quality so early applications are encouraged.
We would love to hear from you if you are interested in a PhD position. In addition to the post above, opportunities across the spectrum of research are possible, from development of EPR spectroscopy to chemical synthesis of spin labels and preparing proteins or nucleic acids for structural investigation.
Undergraduate projects and summer internships
Please get in touch to discuss options for projects.
While we do not have any positions available at present JEL is happy to advise with applications for fellowships. Some relevant links are below. Other schemes exist, particularly internationally. Please contact JEL.