This project seeks to advance our understanding of infectious disease by examining the role that bacteriophages might play in the context of clinical diagnostics. We seek to test whether clinical specimens of non-tuberculous mycobacteria [NTM] harbour mycobacteriophages and to determine if their presence is associated with altered phenotypes or modulated responses to chemotherapeutics. From the larger context, this study will provide essential insight into the complex relationship between bacteriophages, their targets and human health. As a recent report of the presence of prophages in a variety of type and clinical strains of Mycobacterium abscessus suggests [1], we deem it likely that the multiple species classified as NTM also contain genetic evidence of phage infection. Induction of phages from species that comprise NTM have been reported using UV light or treatment with mitomycin C [2]. Induction of phages from and sensitivity to infection has been proposed for use as a species typing approach for some of the species classified as NTM [3].
This project will experimentally test whether clinical isolates from non-tuberculous mycobacterial infections collected from pulmonary sources, such as those acquired during biopsy or bronchiolar wash, from sputum, or from other sampled tissues contain evidence of bacteriophage(s). Based on Oxford Nanopore sequencing performed in-lab, the student will perform genomic sequence analysis of the clinical isolates for signatures of prophage and will sequence all induced phage. Critically, this informatic analysis will investigate any genetic payload incorporated into the phage as a potential mechanism for horizontal transfer of virulence determinates or disease modulating genes.
Among the techniques available for this project are confocal microscopy and flow cytometry for the determination of bacterial membrane potential, cryo-electron microscopy for visualization of enzymatic complexes, bioreactors of various capacities with a range of features, real-time and quantitative PCR and various methods for extracting RNA and DNA, as well as other intracellular materials from mycobacteria.
We expect the project to generate at least one peer-reviewed publication and to significantly contribute to on-going efforts to combat the emergence of antibiotic resistance and to mitigate clinical chemotherapeutic failure.
Start date: As soon as possible
Eligibility:
International applicants only please.
Entry requirements:
Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject or overseas equivalent.
The University of Leicester English language requirements may apply.
To apply
Please refer to the information and How to Apply section on our web site
https://le.ac.uk/study/research-degrees/research-subjects/respiratory-sciences
Please ensure you include the Self Funded Project - supervisor's name and project title on your application.
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