Development of Carbon Monoxide Releasing Molecule (CO-RM) antimicrobials against Pseudomonas aeruginosa bacterial pathogen

The rise of antibiotic-resistant bacteria represents a significant threat to human health and therefore novel therapeutic agents are required to treat infections. Carbon monoxide-releasing molecules (CO-RMs) are a potentially highly effective new class of antibiotics. These are small-molecule compounds which, on exposure to suitable stimuli, release controlled amounts of carbon monoxide. In a range of experiments, we have shown than CO-RMs are highly effective at inhibiting the growth of a range of bacterial strains but at the concentrations used have little effect on mammalian cells. The observed activity is thought to be due to the CO-released by the compounds.

This project seeks to capitalise on these findings by exploring the activity of CO-RMs again P. aeruginosa, a pathogen which may readily develop high-levels of resistance. Initial work will involve screening the activity of CO-RMs against bacteria in vivo followed by investigation into how CO-RMs affect P. aeruginosa in bacterial communities. Such communities are often found in polymicrobial Cystic Fibrosis lung infections; therefore, these latter studies are vital if we are to translate CO-RMs from the laboratory to the clinic.

A key focus of the project will be to link the results from the microbiology experiments to the design and synthesis of novel CO-RM structures. In order to optimise the activity of the small molecules a range of species with different structure classes and triggers for the CO-release process will be employed and evaluated. These data will then be employed to rationally design subsequent generations of CO-RMs whose activity will, in turn, be assessed.
The student undertaking this project will develop a broad range of chemical and biochemical skills. These will include the skills required to identify new CO-RM structures and prepare them, coupled evaluating their behaviour in a microbiology laboratory.

8 four-year fully funded PhD studentships are available on this BBSRC White Rose Doctoral Training Partnership in Mechanistic Biology for entry in October 2018. To be considered you need to submit an application through the University of York online system stating which project you are applying for.

The studentships are available to UK and EU students who meet the UK residency requirements. Students from EU countries who do not meet the residency requirements may still be eligible for a fees-only award. Further information about eligibility for Research Council UK funding can be found at the following website: http://www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/

Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions.

Shortlisting will take place as soon as possible after the closing date and successful applicants will be notified promptly.
Shortlisted applicants will be invited for an interview to take place at the University of York on Tuesday 6 February 2018. Candidates will be asked to give a 10 minute presentation prior to their interview by an academic panel.

The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. This PhD project is available to study full-time or part-time (50%).