Tackling the Bad Bugs: Chemical Tools to Study Bacterial Pathogenicity and Antimicrobial Resistance
An exciting PhD project in chemical biology is available in the group of Professor Gerd Wagner (Queen’s University Belfast). The project is concerned with the development of chemical tools to understand fundamental aspects of bacterial pathogenicity and antimicrobial resistance (AMR).
The project is ideally suited for students with a strong background in organic synthesis, who want to significantly expand their experimental skill set, and apply their chemistry knowledge to one of the most urgent healthcare challenges today. In collaboration with Public Health England (PHE), the project will provide extensive multidisciplinary training at the chemistry/microbiology interface, as well as placement opportunities at PHE.
TRACKING BACTERIAL PORIN SWITCHING: A CHEMICAL BIOLOGY APPROACH.
The goal of this project is to understand how porin switching drives the development of AMR in the nosocomial pathogen Klebsiella pneumoniae, the causative agent of pneumonia and a WHO “priority pathogen”.
Porins are water-filled open channels in the outer membrane (OM) of Gram-negative bacteria that allow the passive transport of small, hydrophilic molecules across the OM. Individual bacteria possess up to 8-10 different porin-encoding genes, whose expression is finely regulated in response to environmental factors, including antibiotics.
Switching between different porins allows pathogens to modulate the permeability of their cell envelope. Porin switching has been linked to the stepwise increase in AMR and the phenomenon of “MIC creep”, which plays a decisive role in the gradual increase in global resistance. Although porins have been directly implicated in a new form of carbapenem resistance in Klebsiella pneumoniae, a detailed understanding of the factors that drive porin switching, and how this is linked to resistance development and bacterial pathogenicity, is currently lacking.
We have recently discovered a chemical probe for the labelling of bacterial porins. From this starting point, the student will develop a novel bioanalytical tool for bacterial porin tracking and use this tool to identify critical environmental factors that drive porin switching in Klebsiella pneumoniae. This novel tool will also form the basis for the development of a novel, point-of-care diagnostic for resistant bacterial infections.
Applicants should have a 1st or 2.1 honours degree (or equivalent) in a relevant subject. Relevant subjects include Chemistry, Pharmacy, Pharmaceutical Sciences, Biochemistry, Biological/Biomedical Sciences, Engineering, or a closely related discipline. Students who have a 2.2 honours degree and a Master’s degree may also be considered, but the School reserves the right to shortlist for interview only those applicants who have demonstrated high academic attainment to date. Home/EU applicants only