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  Iron storage and detoxification in human ferritins (LEBRUNU21DTP1)


   School of Chemistry

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  Prof N Le Brun, Dr A M Hemmings  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Iron is an essential micronutrient for life, but its reactivity also means that it is potentially extremely toxic, and uncontrolled reactions with O2 can generate reactive oxygen species, which cause cellular damage and death. Indeed, breakdown in cellular iron metabolism is linked, directly or indirectly, to many disease states. Thus, organisms/cells must carefully regulate the amount and form of iron. This is, in part, achieved through storage of iron as a ferric mineral solubilised within ferritin proteins, which are found in all types of cells, from bacteria to humans.

Ferritins are composed of 24 subunits arranged in a highly symmetric fashion to form a football-shaped molecule, in which a rust-like iron mineral is formed and solubilised. Animal ferritins are composed of a mixture of two types of subunits, H-chain and L-chain, and the H-chain type contains an active site that catalyses the formation of the mineral. The aim of the project is to understand how human ferritins store/detoxify iron, and what the consequences of variable H/L subunit proportions are for this mechanism. New fundamental insight gained through the project will impact on understanding of human cellular iron metabolism and its importance for health.
This multi-disciplinary project will be based in the Le Brun lab at UEA, and will involve protein purification, biochemistry, mass spectrometry, spectroscopy, crystallography and rapid kinetic methods, offering excellent training potential for the appointed student within a supportive and stimulating environment. Informal enquiries to Prof Nick Le Brun ([Email Address Removed]) are welcome.

For more information on the supervisor for this project, please go here https://people.uea.ac.uk/n_le-brun

This is a PhD programme.

The start date is 1st October 2021.

The mode of study is full time.

The studentship length is 4 years.


About NRP DTP:

The Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) is open to UK and international candidates for entry October 2021 and offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three-month professional internship placement (PIPS) during their study. The placement offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second class honours degree, or equivalent, are invited to apply.

This project has been shortlisted for funding by the NRPDTP programme. Shortlisted applicants will be interviewed on Thursday 7th January, Friday 8th January and Monday 11th January 2021.

Visit our website for further information on eligibility and how to apply: https://biodtp.norwichresearchpark.ac.uk/

Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background.


Funding Notes

This project is awarded with a 4-year Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) PhD studentship. The studentship includes payment of tuition fees (directly to the University), a stipend for each year of the studentship (2020/21 stipend rate: £15,285), and a Research Training Support Grant for each year of the studentship of £5,000 p.a..

Entry Requirements

At least UK equivalence Bachelors (Honours) 2:1 or UK equivalence Master's degree. English Language requirement (Faculty of Science equivalent: IELTS 6.5 overall, 6 in each category).

References

Bradley, J. M., Pullin, J., Moore, G. R., Svistunenko, D. A., Hemmings, A. M. and Le Brun, N. E. (2019) Routes of iron entry into, and exit from, the catalytic ferroxidase sites of the prokaryotic ferritin SynFtn. Dalton Trans., 49, 1545 – 1554.

Bradley, J. M., Svistunenko, D. A., Pullin, J., Hill, N., Stuart, R. K., Palenik, B., Wilson, M. T., Hemmings, A. M., Moore, G. R. and Le Brun, N. E. (2019) Reaction of O2 with a di-iron protein generates a mixed valent Fe2+/Fe3+ center and peroxide. Proc. Natl. Acad. Sci. U.S.A., 116, 2058-2067.

Bradley, J. M., Svistunenko, D. A., Moore, G. R. and Le Brun, N. E. (2017) Tyr25, Tyr58 and Trp133 of Escherichia coli bacterioferritin transfer electrons between iron in the central cavity and the ferroxidase centre. Metallomics 9, 1421-1428.

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