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PhD studentship in bioinorganic chemistry - design and build a sensor for quantification of heme concentrations in cells

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Applications are invited for a PhD studentship starting in October 2019 to work with Prof. Emma Raven. The aim of the project is to design and build a sensor for quantification of heme concentrations in cells. This will involve the construction of fluorescently-labelled proteins which can bind heme under certain conditions; quantification (using spectroscopy/imaging) of this heme binding will be used to build heme sensors under a range of heme concentrations using different protein scaffolds.

The project will involve training and use of the following methods: enzyme kinetics, various spectroscopes (uv-visible, EPR), X-ray crystallography, and protein expression. No extensive prior experience of these methods is required, merely an ability and enthusiasm to apply chemical/biophysical principles to the study of metalloproteins. The project is a collaboration with Dr Andrew Hudson, University of Leicester (https://www2.le.ac.uk/departments/chemistry/people/academic-staff/andrew_j_hudson ) and it will involve working with the Wolfson Bioimaging Centre in Bristol (http://www.bristol.ac.uk/wolfson-bioimaging/ ).

The student will join the Raven group in Bristol (more information here: http://www.bris.ac.uk/chemistry/people/emma-raven/index.html), which are hosted in brand new laboratories in the School of Chemistry. The student will receive a wide-ranging, interdisciplinary training in protein chemistry with particular focus on heme proteins, and will be invited to participate in other external-facing activities (conferences, seminars) as part of the overall Raven group activities in this country and internationally.

Candidate Requirements

Applicants must have obtained, or be about to obtain, a First or Upper Second Class UK first degree, or the equivalent qualifications gained outside the UK, in chemistry or in a related discipline (biochemistry, biological sciences, biophysics).

How to Apply

Please make an online application for this project at http://www.bris.ac.uk/pg-howtoapply. Please select Chemistry (PhD) on the Programme Choice page. You will be prompted to enter details of the studentship in the Funding and Research Details sections of the form. Applicants are encouraged to get in contact with Prof. Emma Raven before making an application.

Funding Notes

The successful applicant will receive a full studentship will cover UK/EU tuition fees, a training support fee and a stipend (£14,777 p.a. for 2018/19, updated each year) for 3 years and 6 months.

References

See for example the following papers for a broad introduction to the work of the Raven group.

Moody, P. C. E.; Raven, E. L. The Nature and Reactivity of Ferryl Heme in Compounds I and II. Acc. Chem. Res. 2018, 51, 427-435 (DOI: 10.1021/acs.accounts.7b00463).

Raven, E. L.; Bren, K. Locked and loaded for apoptosis: switching between respiration and apoptosis in cytochrome c is finely balanced. Science 2017, 356, 1236

Kapetanaki, S. M.; Burton, M. J.; Basran, J.; Uragami, C.; Moody, P. C. E.; Mitcheson, J. S.; Schmid, R.; Davies, N. W.; Dorlet, P.; Storey, N. M.; Raven, E. L. A mechanism for CO regulation of ion channels. Nature. Comm. 2018, 9, 907. DOI: 10.1038/s41467-018-03291-z.

Kwon, H.; Basran, J.; Casadei, C. M.; Fielding, A. J. Schrader, T. E.; Ostermann, A.; Devos, J.; Aller, P.; Blakeley, M. P.; Moody, P. C. E.; Raven, E. L. Direct visualisation of a Fe(IV)-OH intermediate in a heme enzyme. Nature Comm. 2016, 7, Article number: 13445 (doi:10.1038/ncomms13445).

Yuan, X.; Rietzschel, N.; Kwon, H.; Da Dilva, A. B. W. N.; Hanna, D.; Phillips, J.; Raven, E. L.; Reddi, A. R.; Hamza, I. Regulation of intracellular heme trafficking revealed by subcellular reporters. Proc. Natl. Acad. Sci. 2016, 113, E5144-5152.

Casadei, C. M.; Gumiero, A.; Clive L. Metcalfe; Murphy, E. J.; Basran, J.; Concilio, M. G.; Teixeira, S. C. M.; Schrader, T. E.; Fielding, A. J.; Ostermann, A.; Blakeley, M. P.; Raven, E. L.; Moody, P. C. E. Neutron cryo-crystallography captures the protonation state of ferryl heme in a peroxidase. Science, 2014, 345, 193-197.

Chauhan, N.; Thackray, S. J.; Rafice, S. A.; Eaton, G.; Lee, M.; Efimov, I.; Basran, J.; Jenkins, P. R.; Mowat, C. G.; Chapman, S. K.; Raven, E. L. Reassessment of the Reaction Mechanism in the Heme Dioxygenases. J. Amer. Chem. Soc., 2009, 131, 4186-4187.

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