Evolution inspired design of new antibiotics to address antimicrobial resistance

WILKINSON_J23DTP1

The discovery and development of penicillin sparked ‘The Golden Age of Antibiotics’ which spanned the 1940’s to 1960’s when most major classes of antibiotics were discovered. Indeed, most antibiotics in clinical use today are derived from natural products made by bacteria. Alarmingly, however, the pipeline of new antibiotics has dried up at a time when the continued evolution of antimicrobial resistance (AMR) presents a significant threat to global health and new antibiotics with novel mechanisms of action are urgently needed.

The aim of this project is to use principles learned from evolutionary studies, in combination with gene editing tools and methods developed in our lab, to engineer antibiotic producing bacteria to produce new antibiotics that can be used for the treatment of drug resistant pathogens.

The successful candidate will have access to cutting-edge research facilities as well as a stimulating research and training environment. They will be part of an interdisciplinary team focussed on antibiotic discovery and the project provides an exceptional training opportunity in antibiotic function and biosynthesis, molecular microbiology including gene editing, enzymology and protein purification, protein modelling, bioinformatics, and analytical chemistry.

The successful candidate also will be supported in acquiring transferable skills such as written and spoken communication, problem solving and critical thinking and to help train students that visit the lab so they can gain skills in knowledge exchange. The combination of skills and experience provided by this studentship will make the successful candidate highly employable in both academia and industry.

References

[1] K. A. J. Bozhueyuek, J. Micklefield & Barrie Wilkinson (2019) Engineering enzymatic assembly lines to produce new antibiotics. Curr. Opin. Microbiol. 51:88-96.

[2] T. J. Booth et al (2022) Bifurcation drives the evolution of assembley-line biosynthesis. Nat. Commun. 13:3598.

[3] M. I. Hutchings, A. W. Truman & Barrie Wilkinson (2019) Antibiotics: past, present and future. Curr. Opin. Microbiol. 51:72-80.

[4] J-P. Gomez-Escribano et al (2021) Genome editing reveals the pSCL4 is required for chromosome linearity in Streptomyces clavuligerus. Microbial Genomics 7:000669.

All these publications are freely available online.