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Structural studies of the AgrB protease

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  • Full or part time
    Dr J Emsley
    Dr W Chan
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Staphylococci are extremely common human commensals, which have been implicated in systemic infections in hospitals, biofilm formation in surgical devices and implants, industrial fouling and food spoilage. The auxiliary gene regulation in staphylococci controls important bacterial functions, such as virulence and adhesion to surfaces (biofilm formation). AgrB is a key protein responsible for preprocessing of the signaling molecule, AIP, which mediates bacterial communications and quorum sensing. Pharmacological regulation of this protein can control bacterial behavior, attenuate virulence and inhibit biofilm formation. AgrB is a 22 kDa membrane protein with predicted six helical TMD topology and the 3D structure is unknown. The project involves crystallisation and X-ray diffraction analysis at the synchrotron (diamond or ESRF grenoble) to enable crystal structure determination. In addition AgrB complexes with substrate mimetic peptide or inhibitor will also be determined. The resulting complex structures are likely to prove most informative for identifying the key molecular features of the AgrB active site conformation and substrate/inhibitor recognition and ultimately facilitate the development of novel antimicrobials to combat antimicrobial resistance (J Med Chem. 2014 Mar 27;57(6):2813-9., Structure. 2013 Sep 3;21(9):1659-71, PLoS Pathog. 2013;9(7):e1003508.)

This is a University of Nottingham School of Pharmacy funded studentship (EU applicants only) as a collaboration between the groups of Jonas Emsley, Weng Chan and Paul Williams and is supported by a multidisciplinary team of postdoctoral researchers with complementary expertise in chemistry and microbiology.

Undergraduates holding or expecting to gain a Bachelor’s degree (or equivalent international qualification) with First Class or 2.1 honours in a relevant discipline including biophysics, biochemistry, biological sciences, chemistry, microbiology or relate. A 2:1 (upper second class) honours degree (or international equivalent) may be acceptable depending on the candidate’s academic background, including e.g. strong performance (predicted or achieved) in a Master’s degree.

For enquiries please contact [Email Address Removed] and send a cv.
Please apply as soon as possible as we expect the position will be filled at the deadline of Feb 6th.

Funding Notes

Phd Studentship available at the University of Nottingham to start in Oct 2016. This opportunity is available to UK and EU students to undertake a fully funded PhD (4 year) in protein crystallography.

How good is research at University of Nottingham in Allied Health Professions, Dentistry, Nursing and Pharmacy?

FTE Category A staff submitted: 44.10

Research output data provided by the Research Excellence Framework (REF)

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