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Dissecting how antibiotic resistant pathogens rewire macrophages to overcome host immunity

School of Medicine, Dentistry and Biomedical Sciences | PHD

Applications are now CLOSED
Funding
Funded
Reference Number
SMED-2221-1163
Application Deadline
7 February 2022
Start Date
1 October 2022

Overview

*Application closing date has been extended* The strategies deployed by antibiotic resistant bacteria to counteract the immune system to flourish in the tissues are poorly understood. This project will demonstrate that Klebsiella pneumoniae, a global threat to human health, leverages the type VI secretion nanoweapon to disarm macrophages, and to overcome host restriction during pneumonia.

The control of bacterial infections is one of the most important achievement of modern medicine. However, we have failed to keep pace with microbes becoming increasingly resistant to available treatments. This threat is exemplified by Klebsiella pneumoniae, resistant to all major front line antibiotic compounds.
An attractive approach to develop new antimicrobial therapeutics is to boost protective immune responses. This is particularly difficult in the case of Klebsiella infections because we lack a complete understanding of the strategies deployed by Klebsiella to avoid the attack of our defenses.
In this project, we will expose a hitherto unknown Klebsiella evasion strategy directed to counteract the microbicidal function of macrophages. This project builds up upon a landmark discovery of the laboratory showing that Klebsiella survives within a unique compartment in mouse and human macrophages (Cell. Microbiol. 17, 1537-1560 (2015). However, the Klebsiella factor(s) needed for this are unknown. This research will uncover that Klebsiella exploits a trans kingdom type VI secretion effector (T6SS) to manipulate the phagolysosome fusion and to govern inflammatory responses. Previous research from our laboratory demonstrated that the role of the T6SS nanoweapon in antimicrobial warfare (PlosPathogens 16(3):e1007969 (2020); this project will expand our knowledge on how microbes utilized the T6SS beyond antimicrobial warfare to control macrophage biology.
The project has three aims: (i) to define the role of Klebsiella T6SS in the pathogen’s macrophage life style; (ii) to dissect the role of the T6SS in macrophage responses, and (iii) to characterize the role of the T6SS in vivo.
The successful candidate will join the Bengoechea laboratory at the Wellcome-Wolfson Institute for Experimental Medicine and will acquire unique skills assessing the microbial-host pathogen interface including single-cell approaches leveraging cellular microbiology, imaging, and mass cytometry techniques.

Funding Information

Please note that this is a Competition Award - 3 advertised projects for 2 Award.

Funded by the Department for the Economy (DfE). For UK domiciled students the value of an award includes the cost of approved tuition fees and maintenance support (Fees £4,500, Stipend £15,609 – 2022 TBC). To be considered eligible you must have been ordinarily resident in the UK for the full 3 year period prior to the start of the studentship and you must be ordinarily resident in Northern Ireland on the first day of the start of the studentship. For further information about eligibility criteria please refer to the DfE Postgraduate Studentship Terms and Conditions 2021-22 at https://go.qub.ac.uk/dfeterms

Funding eligibility: ROI (and EU applicants with pre-settled/settled) status may be eligible for funding. Please review the DfE T&C’s.

Project Summary
Supervisor

Professor Jose Bengoechea

More Information

j.bengoechea@qub.ac.uk

Research Profile

Mode of Study

Full-time: 3 Years

Funding Body
Department for the Economy (DfE).
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