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Exploiting the protein O-glycosylation pathway in opportunistic bacteria as a novel antimicrobial target


Project Description

Antibiotic resistance is a global health problem of epidemic proportions, especially for infections caused by Gram-negative bacteria. It is imperative identify novel microbial targets to develop new classes of antimicrobial molecules, which could work alone or in combination with existing antibiotics. The most effective antibiotics target central func-tions of bacterial cells (e.g. protein and cell wall synthesis, DNA replication and transcription). However, post-translational protein modifications have not been explored as antimicrobial targets. Protein glycosylation is a post-translational modification widespread among microorganisms. Recent work by our group has revealed that loss of protein glycosylation in our Gram-negative model bacterium, 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, molecular biology, and glycochemistry research, will address the hypothesis that loss of protein glycosylation affects the stability of unglycosylated proteins in the bacterial cell envelope resulting in an unfolded protein response leading to stress, which in turn causes dramatic reduction in cell fitness. This hypothesis will be addressed by experiments elucidating the mechanism behind the physiological alterations due to loss of protein glycosylation in bacteria, and by developing proof of principle that molecules inhibiting protein glycosylation can provide antimicrobial activity.

ENTRY REQUIREMENTS

Candidates should have or expect to obtain a 2:1 or higher Honours degree or equivalent in a relevant biomedical or life sciences subject.

English Language

Candidates applying from countries where the first language is not English should produce evidence of their competence through a qualification such as IELTS or TOEFL score.

The minimum recommended score for the School of Medicine, Dentistry and Biomedical Science is:
• IELTS score of 6.0 with not less than 5.5 in each of the four component elements of listening, reading, speaking and writing taken within the last 2 years;
• TOEFL score of 80+ (internet basted test), taken within the last 2 years, with minimum component scores of; Listening 17, Reading 18, Speaking 20, Writing 17);
• A valid Certificate of Proficiency in English grade A or B;
• A valid Certificate of Advanced English grade A; or
• A first or upper second class honours degree from a university based in the UK, Republic of Ireland or other suitably quality assured location in a country deemed by the UK Border Agency to be majority English speaking.

For a list of English Language qualifications also accepted by the School and University please see the following link:
http://www.qub.ac.uk/International/International-students/Applying/English-language-requirements/#English

INTO Queen’s English Language Courses offers both pre-sessional and in-sessional courses in English for academic purposes and study skills. Courses vary in length and full information can be obtained at: https://www.qub.ac.uk/International/International-students/Applying/University-Preparation-Courses/INTOEnglishlanguagecoursesatQueens/

Funding Notes

*FUNDING CONFIRMED – Department for the Economy (DfE) Award*

Eligibility for both fees (£4,327 for 2019/20, 2020/21 TBC) and maintenance (£15,009 for 2019/20, 2020/21 TBC) depends on the applicants being either an ordinary UK resident or those EU residents who have lived permanently in the UK for the 3 years immediately preceding the start of the studentship.

Non UK residents who hold EU residency may also apply but if successful may receive fees only.

For further details re eligibility criteria (including academic, citizenship and residency criteria) please click on the following link: View Website

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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