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Enzyme mechanism through advanced techniques

  • 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

This studentship is for up to 4 years and supported by a Royal Society Wolfson Fellowship

“Traditional” protein X-ray crystallography has contributed enormously to our understanding of enzyme mechanisms. However, hydrogen atoms are not often seen, and the X-rays induce changes that may alter the chemical state of key catalytic components; this is a problem especially for redox enzymes. A number of approaches can be used to avoid some of these difficulties. One is neutron crystallography, as neutrons can show hydrogen positions and another is to use X-ray free-electron lasers (XFELs) which produce femtosecond pulses of X-rays, allowing diffraction data to be collected before damage can take place. Developments and improvements at synchrotron sources now let us collect diffraction data from very small crystals in milliseconds at room temperature. Electron crystallography is advancing quickly and could lead to detailed description of the electrostatic surfaces in enzyme active sites.

Using single crystal spectroscopy and neutron crystallography we have been able to see the hydrogen positions in catalytic intermediates of heme peroxidases. This project aims to take advantage of the latest exciting developments in structural biology techniques to explore the catalytic mechanisms of these and other redox enzymes. LISCB is well equipped for structural biology (see https://www2.le.ac.uk/institutes/liscb/facilities-and-technologies ). We expect to undertake external experimental work at the Diamond Light Source synchrotron near Oxford, the Neutron sources in Grenoble, Munich or Tennessee, and the XFELs in Japan and Hamburg.

Entry requirements
Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject. The University of Leicester English language requirements apply where applicable.

Apply online at: https://www2.le.ac.uk/research-degrees/phd/applyphd

Apply for Molecular and Cell Biology

In the funding section, please state you are applying for the Royal Society Wolfson Fellowship.

In the proposal section, give the supervisor’s name and project title.

Include a personal statement stating why you should be considered for the studentship.

Funding Notes

The studentship will provide a UK/EU Fee waiver and stipend at RIUK rates which for 2019/0 will be £15,009 pa.for up to 4 years.

References

• Casadei CM, et al. (2014) 'Heme enzymes. Neutron cryocrystallography captures the protonation state of ferryl heme in a peroxidase.' Science, 345. Pp. 193–197.
• Kwon H, et al. (2016) 'Direct visualization of a Fe(IV)-OH intermediate in a heme enzyme.' Nat Commun, vol. 7. P. 13445.
Moody, PCE & Raven EL (2018) The Nature and Reactivity of Ferryl Heme in Compounds I and II Acc. Chem. Res. 51 (2), pp 427–435

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