ProfessorDoryen Bubeck

My research group explores fundamental mechanisms in immunity and how pathogens hijack cellular pathways during infection. We create and apply novel membrane systems to understand how information is relayed across cellular membranes and use cryo electron microscopy to visualize protein complexes in a lipid environment.



One of the key questions we are trying to answer is how an immune pore called the membrane attack complex (MAC) forms on lipid membranes and kills bacterial pathogens. Our lab solved the first MAC structure and discovered molecular drivers underpinning its sequential assembly. We explore how immune activation changes biophysical properties of the membrane to provide a general mechanism for how proteins cross lipid bilayers.



Although a potent weapon of immune defence, MAC formed on human cells can cause disease. We are fascinated by the interplay between immune activation and cellular pathways. Using cryo electron microscopy, we have solved structures of inhibited MAC and now aim to explore their impact on cell signalling and membrane remodelling. Our structural models may then underpin the discovery of new therapeutics that regulate inflammatory and disease pathways.

We are currently recruiting for a PhD studentship

Engineering Synthetic Tissues for Targeted Antimicrobial Delivery Against Resistant Biofilms

 

Antimicrobial resistance (AMR) represents one of the most pressing global health challenges, with biofilm-forming Gram-negative pathogens causing recurrent and difficult-to-treat urinary tract infections (UTIs). This interdisciplinary PhD project aims to develop a groundbreaking solution: synthetic tissues (SynTissues) capable of delivering antimicrobial payloads directly to infection sites while preserving the host microbiome. This project will engineer 3D-printed networks of synthetic cells organized into tissue-like architectures (100-500 µm) that enable precise, localized delivery of combination antimicrobials. By integrating large bacterial-derived membrane pores inspired by gut symbionts, these SynTissues will release both small molecule antibiotics and large antimicrobial peptides/bacteriocins directly onto biofilms, minimizing off-target effects and reducing dosage requirements. This research has the potential to transform AMR treatment strategies by enabling site-specific antimicrobial delivery, reducing systemic antibiotic use, and preserving microbial homeostasis. The SynTissues platform could extend beyond UTIs to other biofilm-associated infections, representing a paradigm shift in precision antimicrobial therapy.

 

This project is a collaboration between the Krishna Kumar and Bubeck laboratories, offering access to state-of-the-art facilities and expertise in synthetic cell engineering, membrane protein characterization, and antimicrobial research. The student will receive comprehensive training in advanced microscopy, protein purification, biofilm assays, and 3D printing technologies.

For more details on how to apply visit Imperial's EPSRC University Doctoral Lanscape Award page.