Summary
MEMBRANE PROTEIN STRUCTURAL BIOLOGY
The lab is based at the Research Complex at Harwell, Oxfordshire (https://www.rc-harwell.ac.uk/research-groups/beis-group/).
Membrane proteins represent around 30% of the proteomes of most organisms and more than 40% of drug targets and yet few structures of these molecules have been solved by x-ray crystallography. Drug resistance of bacterial pathogens is a rising crisis. Bacterial membrane proteins are essential for resistance since they are involved in the export of the drugs from the cell. My group is interested to determine the structure and function of these proteins in order to elucidate the molecular mechanism of drug resistance.
The lab is also interested to exploit novel antibacterials as treatments for bacterial infections by understanding how bacteria secrete antibacterial peptides and hijack membrane transporters of other bacteria to inhibit their growth under nutrient starvation.
We are also investigating the mechanism and dynamics of ABC transporters by employing a multidisplinary approach of protein crystallography, transport assays and biophysical methods such as PELDOR/EPR and smFRET.
Publications
Journals
Wong JLC, Romano M, Kerry LE, et al., 2023, Author Correction: OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo., Nat Commun, Vol:14
Mathavan I, Liu LJ, Robinson SW, et al., 2022, Identification of inhibitors of the Schistosoma mansoni VKR2 kinase domain, Acs Medicinal Chemistry Letters, Vol:13, ISSN:1948-5875, Pages:1715-1722
Wong J, David S, Sanchez Garrido J, et al., 2022, Recurrent emergence of Klebsiella pneumoniae carbapenem resistance mediated by an inhibitory ompK36 mRNA secondary structure, Proceedings of the National Academy of Sciences of Usa, Vol:119, ISSN:0027-8424, Pages:1-12
David S, Wong JLC, Sanchez-Garrido J, et al., 2022, Widespread emergence of OmpK36 loop 3 insertions among multidrug-resistant clones of Klebsiella pneumoniae., Plos Pathogens, Vol:18, ISSN:1553-7366, Pages:1-23
Low WW, Wong J, Beltran L, et al., 2022, Mating pair stabilization mediates bacterial conjugation species specificity, Nature Microbiology, Vol:7, ISSN:2058-5276, Pages:1016-1027