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Combining biophysical and synthetic chemistry to decipher a key enzyme in respiration

About the project

Biocatalysis underpins metalloenzyme chemistry and is essential for processes such as respiration and photosynthesis. The Roessler group studies the biochemical and biophysical reactions of metalloenzymes at the nanoscale, using spectroscopy, electrochemistry and biochemical methods. Gaining insight into these reactions is not only of great value to our fundamental understanding of how biological systems carry out some of the most difficult chemical transformations known, but are also essential for guiding medical studies and providing technological inspiration. We are interested in deciphering how electrons travel through these metalloenzymes in order to effectuate catalysis efficiently and prevent unwanted side-reactions. In particular, unpaired electrons - spins – can provide detailed insight into the structure-function properties that underlie the mechanisms of very large and complex enzymes such as mitochondrial complex I, an enzyme that we all rely on for the production of ATP. The Jones group is interested in developing new synthetic organic chemistry methodology and are experienced in the design and synthesis of a range of small organic molecules, notably heterocycles that can form the core of myriad pharmaceutical and agrochemical compounds.

In this project we will be combining the expertise in the Roessler and Jones groups to investigate a key step in the mechanism of mitochondrial complex I (one of the largest and most enigmatic enzymes known) from a new perspective. We will design and synthesise small organic molecules that serve as substrate mimics for the enzyme and are capable of stabilising unpaired electrons in a mechanistically key location, allowing for the interrogation of their environment using electron paramagnetic resonance (EPR) spectroscopy, a technique whose fundamental concepts are analogous to NMR.

Research environment

The PhD student will join two vibrant and well-funded growing research groups that share a common lab space in a modern building and work in a collaborative, international and multi-disciplinary research environment. The student will receive training in a number of biochemical and biophysical techniques as well as synthetic organic chemistry, and will be given the opportunity to attend international conferences. Moreover, the Roessler laboratory will host a major international EPR conference in 2018 that the candidate would have the opportunity to be involved in. Find out more about the work of the Roessler group and the Jones group.

Queen Mary University of London (QMUL)

As a member of the prestigious Russell group, QMUL is one of UK’s leading research-focused higher education institutions, where multidisciplinary research is carried out at the highest level. The university is unique in London by providing a completely integrated residential campus. All researchers are part of the QMUL Doctoral College, which provides high quality training in transferable key skills and free English language courses are also available through the Queen Mary Language Centre.

The School of Biological and Chemical Sciences at QMUL is a highly interdisciplinary environment and home to state-of-the-art facilities, including EPR spectrometers at multiple microwave frequencies, high field NMR and mass spectrometers. The School holds an Athena SWAN Silver Award and is committed to supporting equality and diversity for all staff and students.

Eligibility

Outstanding students with, or expecting to receive, at least an upper-second class honours degree (or equivalent) and preferably as Masters degree in chemistry or a chemistry-related subject. International students are required to provide evidence of their proficiency in English language skills.

How to apply

Candidates should e-mail Dr Roessler or Dr Jones with cover letter and CV, explaining how they intend to fund their project. Informal enquiries about the project are welcome.

Applicants wishing to apply for PhD funding through Ciência sem Fronteiras, CONACYT, the China Scholarship Council, the Pakistani Higher Education Commission or the Islamic Development Bank are welcomed. The project is also open to applicants who can self-fund, however, these applicants should be able to demonstrate that they can cover the cost of living expenses and tuition fees for a minimum of 3.5 years.

References

  • M. M. Roessler et al, PNAS, 2010, Vol. 107, pp. 1930-1935
  • M. M. Roessler et al, JACS, 2012, Vol. 134, pp. 15581-15594
  • J. Hirst & M. M. Roessler, BBA Bioenergetics, 2016, Vol. 1857, pp. 872-883
  • T. J. Donohoe, C. R. Jones, A. F. Kornahrens, L. C. A. Barbosa, L. J. Walport, M. R. Tatton, M. O’Hagan, A H. Rathi and D. B. Baker, J. Org. Chem. 2013, 78, 12338.
  • T. J. Donohoe, C. R. Jones and L. C. A. Barbosa, J. Am. Chem. Soc. 2011, 133, 16418
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