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 across the inner membrane and 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 (Cooper, Clark et al., 2025, De’Ath, Kumar et al., 2026). Understanding how these proteins function provide new insights into how bacteria build the OM and potentially enable us to design new drugs targeting this membrane.
This PhD project will take place in the group of Dr Georgia Isom, at the Sir William Dunn School of Pathology. The group focuses on understudied proteins/protein complexes that are implicated in transport of OM components in E. coli. This project will give you the opportunity to learn state-of-the-art techniques in structural biology, biochemistry and genetics, enabling you to answer some of the following important questions:
- How do proteins that transport OM components function mechanistically? To address this we will use a combination of cryo-EM and X-ray crystallography to solve the structure of proteins/protein complexes.
- What are the substrates of these proteins? Understanding which molecules the proteins interact with will allow us to determine what exactly they are transporting (e.g. lipids or proteins). To investigate this we will use a combination of biochemical approaches including protein-substrate binding assays, mass spectrometry, and in vivo crosslinking.
- What are the phenotypes of bacteria that lack these proteins? We will construct gene knockouts in E. coli and assess changes in cell morphology, sensitivity to OM stresses/antibiotics, and OM lipid and protein composition.
Funding Notes
4 Year DPhil Prize Studentships cover full University fees, a tax free enhanced stipend of ~£24,305 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.
References
C De’Ath*, S Kumar*, S Chhibber, BF Cooper, EK Taylor, E Jones, T Lanyon-Hogg, JR Bolla, C Redfield, N Ruiz# & GL Isom# (2026). YdbL directly modulates YdbH-YnbE bridge formation to maintain Escherichia coli outer membrane homeostasis. mBio
BF Cooper, R Clark, A Kudhail, D Dunn, Q Tian, G Bhabha, DC Ekiert, S Khalid, GL Isom# (2025). Phospholipid transport to the bacterial outer membrane through the envelope-spanning bridge YhdP. Journal of Molecular Biology.
