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  Understanding Biocatalysis using Single Protein Biophysics


   Department of Chemistry

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  Prof Ismael Díez-Pérez, Dr Sarah Barry  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Cytochrome P450s are best known for their role in drug metabolism in cells but are of growing interest as biocatalysts due to their ability to activate inert C-H bonds and catalyse selective oxidation reactions e.g. hydroxylation . P450s contain many flexible regions and undergo conformational change during catalysis. However, the effect of these changes on catalysis are poorly understood. To investigate, we will exploit cutting-edge biophysical approaches to trap individual enzymes in a nanoscale junction as a unique way to interrogate force stimuli (including mechanical forces) along crystallographic directions of the protein backbone. Precise electrical measurements of the single protein junctions4 will allow detection of single enzyme turnover and generate insight into the relationship between protein dynamics/conformational change and catalytic function.

This strongly interdisciplinary proposal combining chemistry, molecular biology, enzymology, and biophysics makes sense only when two supervisory teams covering the very different disciplines of the project join forces; the Díez-Pérez group is leader in the emerging field of BioMolecular Electronics and internationally recognized for its pioneering nanobiotech approach in single-protein electrical detection. The Barry group has extensive experience in discovery and characterisation of novel enzymes with emphasis in cytochrome P450s . The student should have a background in chemistry, biophysics, biochemistry or similar and will have the opportunity to work in an emerging field with important applications to biotechnology.

For informal enquiries email: ismael.diez_perez(@)kcl.ac.uk; sarah.barry(@)kcl.ac.uk

Group site: https://www.kcl.ac.uk/research/diez-perez ; https://www.kcl.ac.uk/research/barry

Application Procedure

Send your CV and a research statement to PGR-chemistry(@)kcl.ac.uk

Your research statement must detail:

  1. Your previous research experience (final year projects, summer placements, year in industry etc).
  2. Why you want to do a PhD and why you chose this programme

Complete an online application on the King’s College myApplication system at apply.kcl.ac.uk/

  1. Register a new account/login
  2. Once logged in, select Create a new application
  3. Enter ‘Chemistry Research MPhil/PhD (Full-time/Part-time)' under Choose a programme. Please ensure you select the correct mode of study.

CV submission and online application MUST both be completed by the deadline.

At King’s, we are deeply committed to embedding good equality and diversity practice into all of our activities so that the university is an inclusive, welcoming and inspiring place to study, regardless of age, disability, gender reassignment, marital status, pregnancy and maternity, race, religion, sex or sexual orientation.

This position is now open to international Students.

Biological Sciences (4) Chemistry (6) Medicine (26) Physics (29)

Funding Notes

The studentships are funded for 4 years, with a stipend at the standard research council rate, which is presently £18,062 per annum including London Allowance, and cover the full cost of Home tuition fees. Income tax is not payable on the stipend.

References

[1] M. Girhard et al. in Cytochrome P450 451–520 (Springer International Publishing, 2015).
[2] Carter, P. & Wells, J. Nature 332, 564–568 (1988).
[3] Arieh Warshel et al. Chem. Rev. 106, 3210-3235 (2006).
[4] A.C.Aragones et al Nature 531, 88–91 (2016) & M. P. Ruiz et al. J. Am. Chem. Soc. 2017, 139, 43, 15337-15346.
[5] Alkhalaf, L. M et al J. Am. Chem. Soc. 2019, 141, 216.