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Targeting bacterial protein glycosylation in pathogenic bacteria as a novel anti-virulence strategy


Project Description

Antibiotic resistance is a global health problem of epidemic proportions, especially for infections by Gram-negative bacteria. Identifying novel microbial targets to develop new classes of antimicrobial molecules, which could work alone or in combination with existing antibiotics, is a must. The most effective antibiotics target central functions of bacterial cells (e.g. protein and cell wall synthesis).

However, post-translational protein modifications have not been explored as antimicrobial targets. Protein glycosylation is a post-translational modification widespread among bacteria. Our group has recently discovered that loss of protein glycosylation in our bacterial model, the opportunistic cystic fibrosis pathogen Burkholderia cenocepacia, dramatically reduces bacterial fitness and virulence. Thus, protein glycosylation is a potentially novel antimicrobial target.

This PhD project, underpinning fundamental studies at the forefront of microbial glycobiology and chemical biology will address the hypothesis that chemicals directed at the glycosylation-specific enzymes will recapitulate the same effects as found with genetic mutations and result in phenotypes associated with dramatic reduction in bacterial fitness, which in conjunction with standard antibiotics would result in more effective infection treatments.

This aims of the project include
(i) Developing proof of principle that molecules inhibiting protein glycosylation can provide antimicrobial activity, and
(ii) Utilising these molecules to probe the mechanism behind the physiological alterations due to loss of protein glycosylation in bacteria.

This an ideal project for a candidate looking for cross-disciplinary training in microbiology and chemical biology in a highly interdisciplinary research environment.

ENTRY REQUIREMENTS

We are looking for graduates who are enthusiastic and strongly motivated to use the most innovative approaches to address key global challenges in infectious diseases, antimicrobial resistance, animal health, climate change and sustainability. Applicants should have a degree in biological sciences or a related discipline.

The minimum academic requirement is an Upper Second Class Honours degree from a UK or ROI HE provider (or qualifications deemed equivalent by the University).

Students wishing to apply to Queen’s University Belfast (and for whom English is not their first language) must be able to demonstrate their proficiency in English in order to benefit fully from their course of study or research. For more information on English Language requirements see http://www.qub.ac.uk/EnglishLanguageReqs

Funding Notes

The studentship will be funded by the Department for the Economy (DfE). Please read the full information on eligibility criteria: View Website

However, there may be flexibility to fund a small number of exceptional International applicants.

General enquiries about the programme may be directed to

References

Please visit the School of Medicine, Dentistry and Biomedical Sciences, Centre for Experimental Medicine, website for further details about the Centre:

http://www.qub.ac.uk/research-centres/CEM/

When applying, please choose 'MEDICINE' as your subject area/School.

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