Skip to Content

Dissecting the interface between Klebsiella pneumoniae and lung immune cells in vivo and the effect of new therapeutics.

School of Medicine, Dentistry and Biomedical Sciences | PHD

Applications are now CLOSED
Funding
Funded
Reference Number
SMED-2241-1040
Application Deadline
22 April 2024
Start Date
1 June 2024

Overview

Klebsiella pneumoniae is one of the pathogens sweeping the World in the pandemic of antibiotic resistant infections. Klebsiella infections are associated with high mortality rates and prolonged hospitalisation. Not surprisingly, the World Health Organisation includes K. pneumoniae in the ‘critical’ group of pathogens for which new therapeutics are urgently needed. Less obvious but critical for pathogenesis are K. pneumoniae adaptations to the human immune system allowing the pathogen to flourish in human tissues such as the airways. Notably, the current knowledge on the interface between immune cells and K. pneumoniae is based mostly on in vitro and in vivo studies that still lack breath to decipher the effect of K. pneumoniae on different immune populations, particularly to define cell subpopulations associated with the clearance of the infection, those cells linked to histopathology, and those cells not necessary. This knowledge is critical when considering vaccinology and the effect of therapeutics such as antibody-based approaches and cell-based approaches, to develop anti-infective measures.

This collaborative PhD between GSK-Siena and the laboratory of Professor Jose Bengoechea at Queen’s University Belfast, is aimed at undertaking a multidisciplinary approach bridging molecular microbiology and immunology, in vitro respiratory models (including tissue culture), and in vivo pneumonia mouse models of innate receptors and cytokines (IL10, type I IFN, type II IFN, and type III IFN) showing differential effect on Klebsiella survival to address three connected questions: (i) which are the subsets of lung immune cells governing K. pneumoniae clearance, (ii) which is the relevance of the K. pneumoniae virulence factors and antigen targets, i.e. the capsule and the lipopolysaccharide, and the type VI secretion nanoweapon, in counteracting immune cells (iii) how the immune response to the pathogen will be shaped by novel immunotherapies developed by GSK.

The project leverages the distinct but complementary international expertise on K. pneumoniae infection biology (Bengoechea, UK), and vaccines and infectious diseases therapeutics (GSK). In particular, the project builds up upon preliminary data generated by the Bengoechea laboratory exploiting a new technique developed by the team termed Bac-CyTOF (Calderon-Gonzalez et al PlosPathogens 2024). Bac-CyTOF leverages the power of mass cytometry to immuno profile cells while tracking their interactions with bacteria. Bac-CyTOF allowed to establish for the first the time the dynamic atlas of immune cells upon Klebsiella infection. We uncovered cell populations with different roles on Klebsiella infection among interstitial (permissive for Klebsiella infection) and alveolar macrophages (restrict Klebsiella infection), the effect of infection on the recruitment of cells from the bone marrow, and subbpopulations of neutrophils possibly implicated in bacterial clearance. This initial information will be integrated with the unique expertise of GSK on immunotherapy against Klebsiella and other infections, particularly antigen isolation and purification, 3D respiratory models and transcriptomics. In this project, we will provide mechanistic insights into the interplay of Klebsiella with these populations, and explore GSK therapeutics to facilitate clearance of the Klebsiella.

As part of the collaborative, the student will spend three months at Siena GSK R&D hub, one of the global leaders on bacterial vaccines and monoclonal antibodies, to run experiments, benefiting from from cutting-edge technological platforms and protocols developed by the company. Therefore, within the project the student will benefit from intersectorial training, providing the student with the experience of the working atmosphere at two complementary environments (company/academia) as well as different codes of practice

Funding Information

Terms and conditions for CAST awards are provided at the link below:
https://www.economy-ni.gov.uk/sites/default/files/publications/economy/Postgraduate-Studentships-Terms-Conditions-2023-24.pdf
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 includes an enhanced stipend of £2,000 per year in addition to the standard rates. 2024/25 rates are still to be confirmed (current rates for 2023/24 are Fees £4,712, Stipend £18,622). 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.
Any offer is subject to contract.

Project Summary
Supervisor

Professor Jose Bengoechea

More Information

j.bengoechea@qub.ac.uk

Research Profile


Mode of Study

Full-time: 3 Years


Funding Body
DfE CAST Award
Apply now Register your interest