Using structural biology, biochemistry, and microbiology to study the molecular mechanisms by which Gram-negative bacteria build their outer membranes and protect themselves against antibiotics.
The Gram-negative bacterial cell envelope.
Antimicrobial resistant (AMR) micro-organisms cause a major global threat to modern medicine. Gram-negative 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. Membrane components (such as proteins, phospholipids and lipopolysaccharides) 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 investigate the function of these transport systems.
2025
Phospholipid Transport Across the Bacterial Periplasm Through the Envelope-spanning Bridge YhdP
Cooper, B.F., Clark, R., Kudhail, A., Dunn, D., Tian, Q., Bhabha, G., Ekiert, D.C., Khalid, S., Isom, G.
J Mol Biol. – 437(2):168891.
2020
Structure of bacterial phospholipid transporter MlaFEDB with substrate bound.
Coudray, N.,* Isom, G.L.,* MacRae, M.R.,* Saiduddin,M.N., Bhabha, G. and Ekiert, D.C.
eLife – 9: e62518
2020
LetB Structure Reveals a Tunnel for Lipid Transport across the Bacterial Envelope
Isom, G.L.,* Coudray, N.,* MacRae, M.R., McManus, C.T., Ekiert, D.C. and Bhabha, G.
Cell – 181(3): 653-664
2017
MCE domain proteins: conserved inner membrane lipid-binding proteins required for outer membrane homeostasis
Isom, G.L., Davies, N.J., Chong, Z.S., Bryant, J.A., Jamshad, M., Sharif, M., Cunningham, A.F., Knowles, T.J., Chng, SS., Cole, J.A. and Henderson, I.R.
Scientific Reports – 7(1): 8608
2017
Architectures of lipid transport systems for the bacterial outer membrane.
Ekiert, D.C., Bhabha, G., Isom, G.L., Greenan, G., Ovchinnikov, S., Henderson, I.R., Cox, J.S. and Vale, R.D.
Cell – 169(2): 273-285
Antimicrobial resistance research at the Dunn School receives 3-year funding boost
September 2025
The generous gift by Juliet and Andrew Wilkinson will allow the group of Georgia Isom to pilot an exciting new approach in the study of Gram-negative bacteria.
ERC success for Dunn School Researchers Studying Antibiotic Resistance
September 2024
Building on the Dunn School’s rich history as the birthplace of the antibiotic era, the Isom and Stracy labs have each been awarded ERC starting grants to work on antibiotic resistance.
Dunn School strengthens its research on bacterial pathogenesis
March 2022
Dr Georgia Isom and Dr Mathew Stracy lead two new research groups in the Dunn School. March marks the beginning of a new phase at the Dunn School with the arrival of two new research groups, led by Dr Georgia Isom and Dr Mathew Stracy. Both Dr Isom and Dr Stracy have secured highly competitive...