Discovering the next generation of antibiotics (WILKINSON_J27DTP)

The continued evolution of antibiotic-resistant bacteria presents a significant threat to global health and new compounds with novel mechanisms of action are urgently needed. Most clinical antibiotics are derived from the specialised metabolites of Streptomyces strains, and on average a single Streptomyces strain encodes between 25-50 biosynthetic gene clusters (BGCs) which encode for their production; many of these molecules will have antibiotic activity. However, more than 90% of these encoded specialised metabolites are not produced under laboratory conditions, meaning many new compounds remain to be discovered. To access the full metabolic potential of Streptomyces species, cryptic pathways encoding new molecules must be switched on under laboratory conditions.

In this crossdisciplinarity project the successful candidate will use genetic methods to systematically target the regulatory networks controlling specialised metabolite production. This will lead to new methods for accessing the silent arsenal of cryptic antibiotics encoded in bacterial genomes. They will develop an understanding of antibiotic function, discovery & development in addition to cutting edge training in molecular microbiology, natural products chemistry, antimicrobial resistance, biochemical analysis, and bioinformatics. These skills are essential to the next generation of bioscientists, and the candidate will be further supported in acquiring transferable skills such as written and spoken communication, problem solving and critical thinking and will help train visitors to the lab so s/he can gain skills in knowledge exchange. This combination of skills and experience will make the successful candidate highly employable in both academia and industry.