clinical Klebsiella pneumoniae strain with two prophage like elements that are induced by some external phages but not others. This provides an excellent starting model, alongside other suitable prophage-host systems, to investigate how resident phages influence therapeutic phage infection.
The student will determine how prophages alter phage infection, bacterial phenotype and the evolutionary outcome of treatment. Sequencing and electron microscopy will be used to characterise selected prophage systems and the particles they produce. Isogenic bacterial strains carrying different prophage complements will be created and challenged with diverse panels of lytic phages from the Becky Mayer Centre collection. Plate-based assays, plaque assays, adsorption measurements and one-step growth experiments will quantify how prophage status changes bacterial susceptibility, phage replication and bacterial survival.
Repeated phage exposure will then test whether resident prophages alter the routes by which bacteria evolve resistance and whether this produces trade-offs in growth, capsule, metabolism or virulence. Whole-genome sequencing and targeted gene-expression experiments will identify underlying mechanisms, while computational prophage analysis across wider bacterial collections will test how general these relationships are. The project will reveal an overlooked layer of phage interaction biology and establish broad principles for understanding and selecting reliable phage treatment.
Techniques that will be undertaken during the project
- Bacterial culture and Klebsiella genetics
- Prophage curing/ targeted genome engineering
- PCR, primer design and qPCR / RT-qPCR
- Prophage induction assays
- Plaque assays and efficiency-of-plating measurements
- Plate based phage susceptibility and kill-curve assays
- Phage adsorption assays and one-step growth experiments
- Experimental evolution/ serial phage exposure
- Bacterial fitness, metabolic/physiological, capsule and virulence phenotyping
- Plaque-2-seq and Oxford Nanopore sequencing
- Whole-genome sequencing and comparative genomics
- Prophage prediction, annotation and comparative genomics
- Integration of genomic and phenotypic datasets using machine-learning approaches to identify predictors of phage susceptibility and treatment outcome
- Transmission electron microscopy
- Quantitative statistics, time-series analysis and data visualisation
Enquiries
Project Enquiries to mrjc1@le.ac.uk
Programme enquiries to mibtp-admin@leicester.ac.uk
To apply please refer to
https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp
Funding Notes
All MIBTP students will be provided with a 4 year studentship. This includes: Tuition fees at the UK fee rate*, a tax free stipend which for 2026/7 is £21,805 per year (2027/8 stipend to be confirmed), a travel allowance over years 1-3, a travel/conference budget, a generous consumables budget, use of a laptop for the duration of the programme. The University of Leicester will provide full overseas fee waivers for the duration of their study to all international students accepted at Leicester. The funder, UKRI, allows us to appoint up to 30% overseas students.
