I am a group leader at the Sir William Dunn School of Pathology, funded by a Medical Research Council Career Development Award. I did my Undergraduate degree in Biology at the University of Bath (BSc Hons, 2012), followed by a PhD at the Institute of Microbiology and Infection at the University of Birmingham (PhD, 2017). I then spent over 4 years at New York University Langone School of Medicine as a postdoctoral researcher, returning to the UK to set up my lab at the University of Oxford in 2022.
Antimicrobial resistant (AMR) bacteria cause a major global threat to modern medicine. I am interested in understanding the fundamental mechanisms by which bacteria are antimicrobial resistant. Gram-negative, double-membraned bacteria are particularly difficult to treat, in part because their outer membrane (OM) acts as a barrier against antibiotics. Therefore, it is critical to understand how bacteria build and maintain their OM, potentially allowing for novel therapeutic approaches that disrupt this barrier.
The Gram-negative bacterial cell envelope consists of an inner membrane (IM) and an OM separated by an aqueous periplasmic space. To build and maintain this OM, bacteria must transport lipids and hydrophobic proteins across the aqueous periplasm. Increasingly, evidence suggests that membrane components are transported via protein pathways that form shuttles or direct bridges between the IM and OM. We use a combination of structural biology, biochemistry and bacterial genetics to gain important insights into how bacteria build the OM.
C Vieni, N Coudray, GL Isom, G Bhabha, DC Ekiert (2022). Role of Ring6 in the Function of the E. coli MCE Protein LetB. PMID: 35077766
N Coudray*, GL Isom*, MR MacRae*, MN Saiduddin, G Bhabha and DC Ekiert (2020). Structure of bacterial phospholipid transporter MlaFEDB with substrate bound. eLife. PMID: 33236984
LR Kolich*, Y Chang*, N Coudray*, SI Giacometti, MR MacRae, GL Isom et al. (2020). Structure of MlaFB uncovers novel mechanisms of ABC transporter regulation. eLife. PMID: 32602838
GL Isom*, N Coudray*, et al. (2020). LetB structure reveals a tunnel for lipid transport across the bacterial envelope. Cell. PMID: 32359438
GW Hughes, SC Hall, CS Laxton, P Sridhar, AH Mahadi, C Hatton, TJ Piggot, PJ Wotherspoon, AC Leney, DG Ward, M Jamshad, V Spana, IT Cadby, C Harding, GL Isom et al. (2019). Evidence for phospholipid export from the bacterial inner membrane by the Mla ABC transport system. Nature Microbiology. PMID: 31235958
GL Isom, et al. (2018). Mammalian Cell Entry domains are required for bile resistance and virulence in Salmonella. Biorxiv
CA Antunes, EJ Richardson, J Quick, P Fuentes-utrilla, GL Isom et al. (2018). Complete closed genome sequence of nontoxigenic invasive Corynebacterium diptheriae bv. mitis strain ISS 3319. Genome Announcements. PMID: 29437107
FC Morris, TJ Wells, JA Bryant, AE Shager, YR Sevastsyanovich, DJP Squire, J Marshall, GL Isom, et al. (2018). YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella enterica Serovar Typhimurium. Infection and Immunity. PMID: 30201701
GL Isom et al. (2017). MCE domain proteins: conserved inner membrane lipid-binding proteins required for outer membrane homeostasis. Scientific reports
DC Ekiert, G Bhabha, GL Isom, et al. (2017). Architectures of lipid transport systems for the bacterial outer membrane. Cell. PMID: 28388411