About the Project
The regulation of genes crucially determines the fitness and function of all organisms. This is particularly relevant for bacteriophages, the viruses that infect bacteria, as they rely on a tightly scheduled program for a successful infection. After entering a bacterial host cell, phages use the host cell machinery to produce new phage virions and lyse the cell to release these virions. The timing of lysis shows little variation as it must allow for enough time to produce new virions but also minimize the time until infection of other bacterial cells1. Therefore, the production of lysis proteins is likely to be tightly regulated but the diversity and function of lysis protein regulation has rarely been studied so far2.
This project will combine synthetic engineering, single-cell microscopy, biophysics, and phylogenetic analysis to understand regulatory evolution in phage lysis systems and their impact on phage ecology. We will first use bioinformatic and phylogenetic analyses to investigate the diversity and relatedness of regulatory structures controlling lysis of E. coli and P. aeruginosa phages. These regulatory structures consist of short DNA sequences (promoters) and proteins that bind to those promoters (transcription factors). Once we know these structures, we will use DNA microarrays and synthetic constructs to study the strength and dynamics of promoter – transcription factor interactions using population and single-cell measurements. Based on the experimental data, we will build a biophysical model of lysis protein regulation and predict how different regulatory structures affect the ability of phages to kill bacterial cells.
This project provides a unique opportunity to obtain training in a wide range of interdisciplinary skills, including experimental microbiology, synthetic engineering techniques, bioimaging and biophysical modelling. We are looking for a student who is either coming from a biological background with a keen interest in learning mathematical modelling or from a mathematical / physics / computer science background with a genuine interest in doing microbiology experiments.
Training
This project will provide multidisciplinary training in synthetic engineering (e.g. molecular cloning), experimental microbiology (e.g. phage and bacteria handling), bioimaging techniques (e.g. single-cell microscopy), ecology and evolution (e.g. phage-bacteria population dynamics) and mathematical modelling (e.g. differential equation models in R or Python). The student will gain a broad skillset highly relevant to industry/academia (including laboratory techniques, data analysis and mathematical modelling tools) and will be integrated into MERMan, the UK’s largest cluster of microbial evolution research groups, providing a supportive and stimulating research environment.
Eligibility
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in microbiology, biophysics, mathematics or computer science. Candidates with experience in microbiological lab skills or biophysical modelling skills with a keen interest in interdisciplinary work are encouraged to apply.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit https://www.bmh.manchester.ac.uk/study/research/international-phd/
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
Funding Notes
References
2. Dennehy, J. J. & Wang, I.-N. Factors influencing lysis time stochasticity in bacteriophage λ. BMC Microbiol. 11, 174 (2011).
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