About the Project
This project opportunity is offered as part of the Queen's Doctoral Training Programme - Multi-dimensional approaches to understanding microbe/host interactions in the context of disease, therapeutics and community resilience. For more information, please visit: https://www.findaphd.com/phds/program/queen-s-doctoral-training-programme-multi-dimensional-approaches-to-understanding-microbe-host-interactions-in-the-context-of-disease-therapeutics-and-community-resilience/?p4840
The glycosylation of host protein substrates by pathogenic bacteria is a common feature of microbe/host interactions. In this project, we will develop novel and generally applicable chemical tools to study the role of host protein glycosylation for infection. We will focus on the bacterial pathogen Legionella pneumophila, the causative agent of Legionnaires’ disease, a severe form of pneumonia. We have recently shown that L. pneumophila uses a novel type of glycosyltransferase effector called LtpM to subvert host defence mechanisms. We will develop chemical inhibitors and activity-based probes of LtpM – currently lacking – and use these chemical tools to establish the catalytic mechanism of LtpM, to identify host targets of LtpM and their role for Legionella virulence in vivo, and to identify new LtpM-like glycosyltransferase toxins. Outcomes of the project will also establish if LtpM and related glycosyltransferase toxins may be suitable targets for a novel anti-virulence therapeutic strategy. The project will provide training in a wide range of techniques at the interface of chemistry, chemical biology and microbiology, including chemical probe design and synthesis, protein biochemistry, assay development, and the application of infection models. It will also offer exciting opportunities for collaboration both nationally and internationally, including with research groups at Public Health England and the Complex Carbohydrate Centre (Georgia, USA).
Applicants must have an excellent background in chemical biology, medicinal/organic chemistry, biochemistry, pharmaceutical sciences, or a closely related subject.
Start Date: October 2021, Duration: 3.5 years
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