Bacteriophage-derived antimicrobial proteins

About the Project

Antimicrobial resistance is a global health challenge and there is an urgent need for precision antimicrobials that can eradicate pathogens and biofilms without driving broad-spectrum resistance. This project develops and evaluates bacteriophage-derived proteins (endolysins, depolymerases, and receptor-binding proteins/tail fibre derivatives) as next-generation antimicrobials. The successful candidate will:

1. Mine phage and prophage genomes and metagenomes to identify candidate enzymes.
2. Design modular variants (e.g. engineered catalytic and cell-wall binding domains, chimeric depolymerases) for broadened spectrum and biofilm penetration
3. Express and purify proteins and characterise activity against clinically relevant Gram-negative and Gram-positive pathogens.
4. Test efficacy in biofilm and relevant ex vivo models (e.g. skin/wound, device-associated surfaces, blood serum)
5. Explore delivery/formulation routes (e.g. hydrogels, microneedles, liposomes) to enhance stability and localisation.

The outcome will be a portfolio of protein biopharmaceuticals with clear translational potential and a mechanistic understanding of their anti-biofilm action.

Briefly describe the training that will be provided through the research project

The student will be trained in: genomic/mining pipelines for enzyme discovery; molecular cloning, genetic engineering, heterologous expression and purification of recombinant proteins; biochemical/biophysical characterisation (enzyme kinetics, stability, binding); antimicrobial and biofilm assays (MIC/MBC, time-kill, confocal/live-dead imaging, flow-cell systems); ex vivo model development (skin/wound, device-associated biofilms); and formulation/delivery (hydrogels, microneedles, lipid-based carriers).

Complementary skills include structural protein modelling (AlphaFold-Multimer), data analysis, visualisation, and reproducible research (Python/R, Git), statistics, research integrity and governance, project management, science communication, IP/commercialisation awareness.

Briefly outline the expected impact activities

Some of the potential impact activities include:

• Presentation of findings at leading conferences (e.g. Microbiology Society, Viruses of Microorganisms)
• Preparation of open-access publications and preprints
• Development of databases of antimicrobial proteins and/or software for their analysis
• Generation of IP where appropriate (disclosure and patent scoping for lead proteins/formulations) and engagement with the the commercialisation arm of Queen’s University, QUBIS
• Engagement with clinicians and industry for translational pathways
• Contributions to policy and public-engagement initiatives on AMR
• Release of curated datasets/protocols to accelerate adoption by the wider community