Broadening the spectrum of antibacterial drugs to tackle multidrug resistant Gram-negative pathogens
Dr A O'Neill
Prof C Fishwick
No more applications being accepted
Funded PhD Project (UK Students Only)
The magnitude of the threat that antibiotic resistance poses to humanity is on a par with that of terrorism and climate change, and the WHO has declared antimicrobial drug resistance one of the three greatest problems currently facing human health. The situation is becoming particularly grave in the case of Gram-negative (G-VE) pathogens, which, in contrast to Gram-positive (G+VE) bacteria, are intrinsically insusceptible to many classes of antibacterial agents owing to the permeability barrier presented by the outer membrane (OM) and/or the action of efflux transporters.
This project will develop much-needed novel anti-G-VE agents through rational, structure-guided modification of two established antibacterial classes that currently only show clinically-useful activity against G+VE bacteria. Since our cutting-edge, joint chemistry-biology programme to antibacterial drug development takes as its starting point two clinically-used antibacterial classes, it circumvents many of the confounders evident in recent discovery programmes, which should serve to dramatically shorten the time to identification of new antibacterial drug candidates.
The successful candidate will have a background in synthetic chemistry, and will receive multidisciplinary training in a wide variety of aspects relevant to antibacterial drug discovery (including evaluation of antibacterial activity in vitro and in vivo, molecular microbiology, mode of action studies, etc). This training will include a working placement with the collaborative partner on this project (the Defence Science & Technology Laboratory at Porton Down).
This is an MRC Industrial CASE project that includes a full student stipend (UK students only).
The studentship will commence in October 2014.
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