The increase in bacterial infections which are resistant to all clinically approved antibiotics means that new treatments must be developed to overcome these resistance mechanisms. One way is by developing drugs that have a new mechanism of action in bacteria, against which resistance does not yet exist in the clinic. There are many difficulties in early-stage drug discovery, but a critical issue, for a completely novel compound in the antimicrobial resistance age, is to be able to show that any new lead compound does indeed have a novel mechanism of action.
When bacteria are treated with antibiotics which have different mechanisms of action, they respond differently, with different patterns in both gene expression and in the metabolites that they use and release. Using RNASeq and NMR metabolomics, we will catalogue (and better understand) existing antibiotics with known mechanisms of action into a database. We will also test novel antibacterial compounds using these methods and when they do not match any known mechanism of action, we will use these techniques to explore and define the new mechanism of action. Having this data set of existing antibiotics will reduce the amount of time and money spent on developing antibiotics which, even if initially effective, will have limited shelf-lives in the clinic due to them having the same mechanisms of action to which bacteria have already developed resistance in the clinic.
This PhD offers the opportunity to work as part of an established, long-running, interdisciplinary collaboration between UKHSA and King’s College London. The PhD will be supervised by Dr Charlotte Hind at UKHSA and Professor James Mason at KCL. Work will be carried out at Porton Down, UKHSA and within the Institute of Pharmaceutical Science, King’s College London. The student will be registered at KCL.
The project is funded by the UK Health Security Agency (UKHSA), an executive agency of the UK Department of Health & Social Care and is open to UK students only. The funding covers the tuition fees and provides an annual stipend for three years (currently at £18,062 for 2022-2023, regardless of geographic location).
We are looking for an enthusiastic, motivated candidate with a degree in a relevant STEM field. Prior experience in bioinformatics, working with ACDP2 level pathogens and/or biophysical chemistry will be beneficial. A desire to learn new skills, work as part of an interdisciplinary team and communicate clearly to the team and external collaborators are essential.
Target start date: Oct 2022.
Application instructions: Candidates are requested to send a one-page cover letter explaining your interest in the project plus CV (including referees) to firstname.lastname@example.org. The closing date for applications is 30th June 2022.
The selection process will involve a pre-selection of application documents; if selected, this will be followed by an invitation to interview.