Boyan Bonev
Biography
Boyan Bonev is professor of biophysics at the University of Nottingham (United Kingdom), where he is also the Director of Research and Knowledge Exchange for the School of Life Sciences. During his USIAS Fellowship, he will be hosted by Professor Burkhard Bechinger at the Strasbourg Institute of Chemistry (IC).
Research in the Bonev lab is focused on the study of the organisation and composition of cell membranes, the interfaces of life, to understand their compositional variation and stability. Primary tools include solid state NMR (Nuclear Magnetic Resonance), molecular dynamics simulations and other advanced biophysical and computational techniques. The team is interested in the molecular mechanisms of infection and resistance to antibiotics. To understand and tackle bacteria, resistant to antibiotics, they study bacterial physiology and specific molecular targets, which they use to develop new approaches for antimicrobial intervention and bacterial control. Work is funded primarily by the UK Biotechnology and Biological Sciences Research Council (BBSRC), as well as the Medical Research Council (MRC) and the Engineering and Physical Sciences Research Council (EPSRC).
Dr. Bonev is the Chair of a Review Panel at the Diamond Light Source. He has served on the BBSRC Committee for Molecules, cells and Industrial Biotechnology, an MRC Panel on Antimicrobial Resistance and the EPSRC College. He is a member of the Royal Society of Chemistry and the Canadian Association of Physicists. He studied engineering physics and obtained his MSc degree at the University of Sofia (Bulgaria) and his PhD in physics from the Memorial University of Newfoundland (Canada), with Mike Morrow. He moved to the UK in 1996 and worked with Tony Watts at the University of Oxford before moving to Nottingham in 2002. He feels privileged to have had the opportunity to work with Alexander Petrov (Bulgarian Academy of Sciences), Mike Morrow, Tony Watts, Paul Williams (Nottingham), as well as many outstanding colleagues and collaborators over the years.
Fellowship 2024
Dates - 01/09/2024-31/08/2025
Other information and news (activities, project staff, publications...)
- Bardelang et al. (2023) 10.3389/fchem.2023.1113885
- Goode et al. (2021) 10.1039/D1FD00036E
- Bonev BB & Brown NM, Eds. (2020) Bacterial resistance to antibiotics DOI:10.1002/9781119593522
- Bonev et al. (2008) https://doi.org/10.1093/jac/dkn090
Project summary
STRUCTURAL INSIGHTS FROM STAPHYLOCOCCAL QUORUM SENSING MEMBRANE ENDOPEPTIDASE AGRB, A CONSERVED, NOVEL TARGET FOR VIRULENCE ATTENUATION
Staphylococci are bacteria commonly found in healthy human populations as skin or nasopharyngeal commensals and include a number of opportunistic pathogens. Staphylococcus aureus is an important human pathogen capable of causing a broad range of mild to severe infections ranging from skin and soft tissue to bacteraemia, endocarditis and toxic shock syndrome. S. aureus also includes clinically important variants with multi-antibiotic resistance, such as methicillin and vancomycin-resistant S. aureus (MRSA, VRSA). Staphylococci use pheromone-like communication signals to govern virulence and collective behaviour, known as quorum sensing. In this study, we investigate a key step in pheromone maturation as a druggable target, which will allow us to engineer pheromone-like decoy compounds that attenuate virulence and reduce patient morbidity during antibiotic treatment.
The accessor gene regulator in S. aureus is responsible for transcriptional control of the pro-peptide, AgrD, membrane endopeptidase AgrB responsible for maturation of AgrD into the autoinducer peptide (AIP), a two-component response system AgrAC, as well as a number of virulence factors. In this study we combine the expertise in solid state NMR, membrane biophysics, and methodological capability of partner labs at Nottingham and Strasbourg to investigate the conformational and orientational characteristics of AgrB and its complex with substrate AgrD, to obtain an experimentally validated structural model of the ternary membrane complex AgrB2/AgrD. We will use solid state NMR from oriented, strategically labelled peptide and protein membrane systems to describe substrate orientation and membrane protein conformation. We see leading structure from the 6-transmembrane domain endopeptidase AgrB as archetype of this class of proteins.
Targeting the agr processing system at the sensory kinase AgrC has already shown promise for Staphylococcal virulence attenuation. Modulating the autoinducer peptide pre-processing enzyme, AgrB, aims to interfere with AIP maturation at an unexploited part of the signalling pathway and offers a new druggable target for virulence attenuation. The longer-term aim is to use structure-informed approach to developing antibiotic adjuvants, which will attenuate virulence and reduce patient morbidity and mortality during antibiotic chemotherapy.
