University of Leeds

University of Leeds

Research Fellow in Biochemistry and Biophysics of Chaperone Function

United Kingdom

Closing in 10 days

Research Fellow in Biochemistry and Biophysics of Chaperone Function

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:

  • What are the sequence determinants for OMP recognition at the hotspot regions we have already identified?
  • How does SurA modulate the conformational ensemble of its different OMP clients and remodel them to ensure they remain folding-competent and ready for delivery to BAM?
  • How do mutations in key hotspots alter the range of OMPs found in the OM and are different hotspots on SurA responsible for binding different OMPs?
  • Can we target the OMP binding hotspots on SurA as a route to new antibacterials?
  • 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: [email protected]

    Prof Sheena Radford, Astbury Professor of Biophysics

    Email: [email protected]

    Dr Anastasia Zhurvaleva, Lecturer in Biological NMR Spectroscopy

    Email: [email protected]

    Location: Leeds - Main Campus

    Faculty/Service: Faculty of Biological Sciences School/Institute: School of Molecular & Cellular Biology / Astbury Centre for Structural Molecular Biology Category: Research Grade: Grade 7 Salary: £37,099 to £44,263 p.a. Due to funding limitations it is unlikely an appointment will be made above £40,521 Working Time: 100% FTE - We are open to discussing flexible working arrangements Post Type: Full Time Contract Type: Fixed Term (available for 39 months from 1st April 2024, subject to start date.) Release Date: Thursday 08 February 2024 Closing Date: Sunday 03 March 2024 Interview Date: To be confirmed Reference: FBSAS1073 Downloads: Candidate Brief

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    Job details

    Title

    Research Fellow in Biochemistry and Biophysics of Chaperone Function

    Employer

    University of Leeds

    Location

    United Kingdom

    Published

    February 09, 2024

    Application deadline

    March 03, 2024

    Job type

    Postdoc,Research

    Field

    Agricultural Science,Biology,Chemistry,Physics

    About the employer

    The University of Leeds is a public research university in Leeds, West Yorkshire, England. It was established in 1874 as the Yorkshire College of Science. In 1884 it merged with the Leeds School of Medicine (established 1831) and was renamed Yorkshire College. It became part of the federal Victoria University in 1887, joining Owens College (which became the University of Manchester) and University College Liverpool (which became the University of Liverpool). In 1904 a royal charter was granted to the University of Leeds by King Edward VII.

    The university has 36,330 students, the 5th largest university in the UK (out of 169). From 2006 to present, the university has consistently been ranked within the top 5 (alongside the University of Manchester, Manchester Metropolitan University, the University of Nottingham and the University of Edinburgh) in the United Kingdom for the number of applications received. Leeds had an income of £789.6 million in 2019/20, of which £139.9 million was from research grants and contracts. The university has financial endowments of £82.1 million (2019–20), ranking outside the top ten British universities by financial endowment.

    Notable alumni include current Leader of the Labour Party Keir Starmer, former Secretary of State Jack Straw, former co-chairman of the Conservative Party Sayeeda Warsi, Piers Sellers (NASA astronaut) and six Nobel laureates.

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