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Dissecting how the human pathogen Klebsiella pneumoniae rewires macrophages to promote infection


Project Description

Macrophages represent play a critical role in host defence against pathogens. Therefore, pathogens should overcome macrophages’ antimicrobial programme to promote infection. In this project, we will uncover a hitherto unknown anti-macrophage strategy deployed by Klebsiella pneumoniae based on exploiting immune receptor(s)-regulated host metabolites to control cell intrinsic immunity. Cellular microbiology approaches (confocal microscopy, transcriptomics, Seahorse-based analysis, probing macrophages from knock-out mice) will lead to the identification of the receptor(s) and signalling pathways hijack by Klebsiella. We will also identify the bacterial factor(s) launching this anti-macrophage strategy. The in vivo relevance will be established probing the mouse pneumonia model. High-dimensional phenotypic and functional analysis of single cells will be done by mass cytometry (CyTOF), and transcriptomics of sorted macrophages associated with Klebsiella will comprehensively characterize Klebsiella-induced rewire in vivo.

Even though Klebsiella is included in the list of “critical pathogens” of the World Health Organization for which new therapeutics are urgently needed, our understanding of its pathogenesis is still elementary. Therefore, it is both urgent and necessary to better understand its immune evasion arsenal to design new strategies to treat Klebsiella infections. The results of this project shall be the foundation of new therapeutics antagonising Klebsiella anti-macrophage strategies.

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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