[john innes centre, norwich]

Ghilarov Lab

We study bacterial molecular machines to make better antibiotics
We stand with Ukraine. Aggressor must be stopped. Нет войне!

Based at the John Innes Centre, Norwich, the world-renowned place for antibiotic research. We apply cryo-electron microscopy to discover how bacteria make, transport and acquire resistance to antibiotics to deliver better healthcare for the future world. Promoting fair, kind and inclusive academic culture.

News
Research
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ANTIBIOTIC TRANSPORT

To make an effective drug, we need to know how to deliver it to the target cell.
Bacterial outer and inner membrane transporters are key to the sensitivity to antibacterial peptides. In collaboration with the groups of Konstantinos Beis, Christos Pliotas and Jonathan Heddle we study the molecular mechanisms of antibiotic transport and determinants for the compound selectivity. We use lipid membrane mimetics (nanodiscs) and cryo-electron microscopy to look at the transporters in the conditions most close to native.

Escherichia coli inner membrane transporter SbmA [https://doi.org/10.1126/sciadv.abj5363]
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Microcin B17 biosynthesis complex McbBCD [https://doi.org/10.1016/j.molcel.2018.11.032]
BIOSYNTHESIS OF RIBOSOMALLY SYNTHESIZED ANTIBIOTICS

A large group of bacterial antibiotics are produced by enzymatic transformations of ribosomally-synthesized precursors. Such compounds are termed "RiPPs" for ribosomally-synthesized post-translationally modified peptides.

YcaO enzymes are responsible for peptide backbone modifications in RiPPs: conversion of amino acids into heterocycles and thioamidation (replacement of peptide bond oxygen by sulfur). Peptide bonds are generally very stable and difficult to chemically modify, but YcaOs do so easily. YcaOs are capable of modifying virtually any substrate peptide bearing a correct recognition sequence, making them highly valuable for industry.

We work with microcin B17 and klebsazolicin RiPP systems to unravel the mechanistic details of YcaO-catalysed reactions.
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DNA GYRASE & NEW ANTIBIOTICS

Mode of action of microcin B17 and many other peptide antibiotics targeting DNA gyrase is not known. By determining cryo-EM structures of DNA gyrase in complex with these compounds, we are preparing grounds for the development of new antimicrobials targeting different enzyme pockets and thus avoiding existing resistance.

E.coli DNA gyrase cryo-EM map determined in the lab
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Srtucture of K. pneumoniae QnrB1 determined by cryo-EM in the lab
DNA GYRASE & FLUOROQUINOLONE RESISTANCE

DNA gyrase inhibitors fluoroquinolones are one of the most prescribed antibiotics. Bacterial genomes encode special proteins to endow gyrase with a degree of resistance to these drugs. We are applying cryo-EM to study molecular mechanisms of this process.
People
Yinghong Gu
Postdoctoral Scientist
Yinghong comes from Chongqing, a municipality in southwest China. He has deep expertise in membrane protein structural biology. He will use cryo-EM methods to reveal the modification mechanisms of a class of natural peptides, RiPPs, and develop them into novel antimicrobial agents.
Dmitry Ghilarov
Group Leader, Wellcome Trust Sir Henry Dale Fellow
Dmitry did his PhD in Russia and worked as visiting scientist at the John Innes Centre before moving to Poland and now returning to the UK to set up his own lab. Throughout his career, Dmitry studied RiPPs microcin B17 and klebsazolicin, their biosynthesis and target of microcin B17 - DNA gyrase.
Funding
Publications
Join Us!
We are looking forward to meet inspired people who are not afraid to address global challenges.

PhD students are normally expected to apply for one of Norwich Research Park DTPs or JIC Rotation Programme

We will welcome researchers wishing to apply for Postdoctoral Fellowships such as EMBO, BBSRC Discovery or Marie Curie

6 month research assistant post is now available in the Lab!
Contact Us:
Dmitry.Ghilarov@jic.ac.uk

Address
John Innes Centre, Norwich Research Park
Norwich NR4 7UH United Kingdom
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