Unravelling the molecular mechanisms of prophage lifecycle regulation in Staphylococcus aureus
University of St Andrews
Supervisors: Dr Andreas Haag, Prof matt Holden
Deadline: 31st March 2023
Phages are viruses of bacteria. They are the most abundant biological entities on the planet and are found in almost all microbial communities. Phages play vital roles in the ecology of biological ecosystems and are crucial agents of horizontal gene transfer (HGT), including the rapid spread of antimicrobial resistance (AMR) genes. Additionally, phages can be directly responsible for or contribute to a bacterium’s ability to cause disease by carrying and disseminating fitness and virulence factors or by altering the bacterial genome and gene regulation through integration. For example, human-associated prophages in the notorious pathogen Staphylococcus aureus encode immune evasion factors and toxins that play fundamental roles in subverting the host’s immune response and establishing serious infections.
Virulent phages infect their host, replicate, and lyse their host cell to release new phage particles that can infect more host cells (lytic cycle). By contrast, temperate phages infect and can also integrate the phage genome into the bacterial chromosome as prophages, thus converting the receiving bacterium into a lysogen. Prophage dormancy is maintained by a master repressor that blocks replicative phage functions but can be released upon specific environmental cues. During prophage induction, the master repressor is inactivated allowing the expression of genes of the lytic phage cycle. Different phages encode a range of different lifecycle regulatory elements and different types of master repressors. Despite phages having first been identified more than a century ago, the function of most phage genes and their roles in the prophage lifecycle remains unknown.
This project aims to close a fundamental knowledge gap in our understanding of how the lifecycle of staphylococcal prophages is regulated by phage and host factors. The student will use state of the art molecular microbial genetics, biochemistry, molecular biology, next generation sequencing, etc. techniques to decipher and characterize the molecular mechanisms controlling the lifecycles of prophages in S. aureus. This research will uncover the complexity of lifecycle regulation of staphylococcal prophages, identify key host factors and shed light onto their role in bacterial pathogenesis and the spread of AMR.
Training will be further enhanced by participation in GRADskills, an award-winning skills development programme for researchers. The student will work primarily in Dr Haag’s laboratory, situated in the state-of-the-art Medical and Biological Sciences Building in St Andrews. Dr Haag’s research focuses on the role of mobile genetic elements and their interactions on bacterial evolution, pathogenicity and the spread of AMR.
How to apply
Full applications should be made via the University’s online portal: https://www.st-andrews.ac.uk/study/apply/postgraduate/research/
Applications should include:
A covering letter
A full curriculum vitae (CV)
Supporting document including a list of refereed publications and key conference contributions
Application enquiries can be made to Rachel Horn at [email protected]
This is a 3-year funded PhD studentship, covering fees and stipend (matched to UKRI)
School of Medicine, University of St Andrews
The successful applicant will join a thriving research laboratory and will have the opportunity to work in an exciting and collaborative research environment, equipped to the highest international standards. The School of Medicine is located at the core of a highly interactive and vibrant research campus at the forefront of cell signalling and molecular medicine research with a focus on understanding and combating disease.
The School is committed to equal opportunities and values all applicants. The School currently has Athena SWAN bronze accreditation.