Are you an ambitious researcher looking for your next challenge? Do you have an established background in protein structure and function analysis? Do you want to further your career in one of the UKs leading research intensive Universities? 

Antibiotic resistance is projected to cause 10 million deaths per year by 2050, with gram-negative (diderm) pathogens comprising 9 of the 12 bacteria that pose the greatest threat to human health (World Health Organisation). These pathogens have a unique outer membrane (OM) that acts as a first line of defence against an assault from potentially harmful molecules to the bacteria, such as antibiotics. Finding ways to prevent correct assembly of the OM may therefore produce new routes to kill gram-negative bacteria, or make them more susceptible to existing antibiotics. Recently, we have been studying the mechanism by which beta-barrel outer membrane proteins (OMPs) reach the OM, how chaperones facilitate OMP delivery across the periplasm, and how the β-barrel assembly machinery (BAM) folds/inserts its clients into the OM, yielding new insights into the mechanism of OM assembly (e.g. Schiffrin et al, Commun Biol, 2022; White et al., Nat Commun, 2021; Calabrese et al, Nat Commun, 2020).

In this project we aim to gain new information about a key player in OMP assembly, the periplasmic chaperone SurA. This work builds on our previous studies, in which we have identified two key hotspot regions on SurA that are critical for OMP recognition and we are looking for a new team member to help us address the following important questions, using biochemical and biophysical tools:

Given that deletion of SurA results in OM defects, including impaired virulence factor assembly, reduced pathogenicity, induction of cell envelope stress responses, and loss of OM integrity (heightened sensitivity to antibiotics), SurA could be a good target for the development of new antimicrobial agents. However, this is hampered by a lack of mechanistic knowledge about SurA function. This project aims to address this gap in our understanding, by combining cutting edge biophysical, structural, and biochemical approaches to target this fascinating chaperone machinery.

You will be based in the laboratories of Dr Antonio Calabrese, Prof Sheena Radford and Dr Anastasia Zhurvaleva, and work closely with collaborators within the Astbury Centre at Leeds. In order to answer these vital questions we will apply integrative structural biology methods, giving you an opportunity to enhance you skills and to learn different methods to study biological mechanisms in our collaborative and supportive team. You should have a PhD (or be close to completion) in Chemistry, Biochemistry, Biophysics or a related discipline. You should have significant experience in protein structure/function analysis and training in any techniques that you lack experience in will be provided.

To explore the post further or for any queries you may have, please contact: 

Dr Antonio Calabrese, Sir Henry Dale Fellow and University Academic Fellow

Email: a.calabrese@leeds.ac.uk 

Prof Sheena Radford, Astbury Professor of Biophysics

Email: s.e.radford@leeds.ac.uk

Dr Anastasia Zhurvaleva, Lecturer in Biological NMR Spectroscopy

Email: a.zhuravleva@leeds.ac.uk