Deciphering Mycobacteria-Phage Regulatory Interactions for Bovine Tuberculosis Control

Project (Students Worldwide) Visit institution website About the Project Tuberculosis remains a major global health threat affecting both humans and livestock. Bovine tuberculosis (bTB), caused by Mycobacterium bovis, has a devastating impact on animal welfare, farm productivity, and farmers' wellbeing. The Midlands is affected by bTB, with several areas reporting particularly high incidence, increasing the risk of disease transmission. Thus, bTB eradication is a global, national, and regional priority. M. bovis survives within macrophages by overcoming host-imposed stresses, including nitric oxide, acidic pH, and reactive oxygen species. Detection of M. bovis DNA in environmental samples further suggests an ability to persist outside the host, highlighting its remarkable resilience. Adaptation to environmental change is coordinated by transcriptional regulators such as Lsr2 and WhiB proteins. Homologues of these regulators are also encoded by many mycobacteriophages. Lsr2 is required for adaptation to hypoxia, persistence in macrophages and productive phage infection, while WhiB proteins contribute to virulence, antimicrobial tolerance, and redox homeostasis. However, the functions of phage-derived Lsr2 and WhiB proteins and their impact on phage-host interactions remain poorly understood. The student will investigate the interplay between mycobacterial and phage transcriptional regulation with the following objectives: (i) characterise the diversity, distribution and evolution of mycobacteriophage - encoded Lsr2 and WhiB proteins; (ii) determine their effects on mycobacterial physiology, stress adaptation, and antimicrobial susceptibility; (iii) investigate their roles during phage infection and phage-host interactions; (iv) define the transcriptional networks controlled by these proteins. The project will employ genetic manipulation of mycobacteria and bacteriophages, phage infection assays, antimicrobial susceptibility testing, transcriptomics (RNA-sequencing), DNA binding assays, microscopy, imaging, and bioinformatic analyses. Techniques that will be undertaken during the project 1. Cultivation and phenotypic analysis of mycobacteria, including viability and antimicrobial susceptibility assays. 2. Genetic manipulation of mycobacteria and bacteriophages, including generation of M. bovis BCG overexpression strains. 3. Bacteriophage infection assays and characterisation of phage-host interactions. 4. Transcriptomic analyses (RNA-seq) and DNA-binding studies, including electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation sequencing (ChIP-seq). 5. Fluorescence and electron microscopy, protein localisation studies using reporter fusion proteins, and antibody-based labelling techniques. 6. Bioinformatic analysis of transcriptomic, genomic, and protein datasets. Enquiries Project Enquiries to gvm4@leicester.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.