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Gdansk University of Technology Featured PhD Programmes
Life Science Zurich Graduate School Featured PhD Programmes

Disarming antimicrobial responses: how Klebsiella pneumoniae controls inflammasome activation

   School of Medicine, Dentistry & Biomedical Sciences

  Prof J Bengoechea, Dr Rebecca Coll  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Microbial infection triggers assembly of inflammasome complexes that promote caspase-1–dependent antimicrobial responses. This project will dissect how the antibiotic resistant pathogen Klebsiella pneumoniae evades inflammasome activation to overcome host restriction during pneumonia. The project bridges molecular microbiology and immunology and leverages state-of-the-art in vivo models and human iPSC cells. 

 Inflammasome activation and subsequent production of caspase-1–dependent cytokines is important for both innate and adaptive antimicrobial responses, as IL-1 family cytokines released upon inflammasome activation promote neutrophil migration to infected tissues and drive TH17 and TH1 responses against mucosal pathogens. How bacteria evade the activation of inflammasomes is still poorly understood.  

K. pneumoniae is recognized as a global threat to human health due to multidrug resistant strains. We lack a complete understanding of the strategies deployed by Klebsiella to avoid our immune defences. In this project, we will expose how the pathogen counteracts the activation of inflammasomes to limit inflammation. The project builds up upon exciting data showing that Klebsiella does not activate the NLRP3 inflammasome like many other pathogens, but specifically the AIM2 inflammasome (Feriotti bioRxiv 2021). The project has four aims: (i) to dissect Klebsiella-governed NLRP3 inhibition; (ii) to delineate the basis of AIM2 activation; (iii) to identify how Klebsiella activates inflammasomes in human cells; and (iv) to demonstrate the role of inflammasomes in host defense against Klebsiella

The successful candidate will join the Bengoechea and Coll laboratories 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. 

Start Date: October 2022

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