Understanding β-lactam antibiotic action and resistance with developments in dynamic structural biology

Project Code

MRCIIAR26Ba Tooke

Project Type

This project combines both wet and dry lab elements. The primary focus will be on wet-lab methods (enzyme purification, biochemical characterisation of enzymes, structural biology) but will feature dry lab approaches (biomolecular simulation).

Research Theme

Infection, Immunity, Antimicrobial Resistance and Repair

Project Summary Download

Summary

β-Lactams, including penicillins, are the world’s most commonly used antibiotics, but resistance is rising—particularly in opportunistic bacterial pathogens like Klebsiella pneumoniae. This project investigates how β-lactams bind and react with bacterial enzymes called penicillin-binding proteins PBPs and β-lactamases, which are key to both antibiotic action and resistance. Using advanced techniques—including time-resolved X-ray crystallography at synchrotrons/XFELs (X-ray Free-Electron Lasers), biomolecular simulations, molecular biology and structural biology—we aim to evaluate and capture “molecular movies” of these reactions in action. This project provides interdisciplinary training to understand antibiotic resistance mechanisms to ultimately support the design and evaluation of new drugs.

Lead Supervisor

Dr Catherine Tooke

Lead Supervisor Email

clt81@bath.ac.uk

University Affiliation

Bath