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Understanding the biology of how a promiscuous vibriophage, pirates host metabolism

Primary Supervisor: Dr Andrew Millard, Department of Genetics and Genome Biology

Secondary supervisor: Prof Martha Clokie

PhD project title: Understanding the biology of how a promiscuous vibriophage, pirates host metabolism

University of Registration: University of Leicester

Project outline:

BACKGROUND: Bacteriophages are the most abundant biological entity on the planet, with 1031 in the biosphere. Despite a recent resurgence in phage research, we still do not know the function of the majority of phage genes and how they are involved in phage replication. Recently we have isolated a very large vibriophage (~380 kb) that has limited genomic similarity to any other bacteriophages. Genomic analysis reveals ~80% of its genes have no predicted function, which is a high percentage even for bacteriophage. For the genes that have a predicted function, a number fall into the category of auxiliary metabolic genes (AMGs). AMGs are thought to augment the metabolism of the host, overcoming metabolic bottlenecks that might otherwise limit phage replication.

Initial characterisation of the phage has shown it has a number of interesting biological characteristics:

  • A broad host range, infecting multiple different species in the genus Vibrio. Including the shellfish and human pathogen Vibrio parahaemolyticus
  • Different infection dynamics on different Vibrio species
  • Change in infection dynamics with altered host growth temperature

We propose the large genome contains a number of genes that allow it to subvert host metabolism in different hosts and contributes to its broad host range. Furthermore, it is known that phages with very large genomes carry genes to protect themselves from host anti-phage systems. This can include anti-CPISPR proteins that protect against host CRISPR-CAS systems by inhibiting different steps of CRISPR system. Alternatively, phages carry genes that encode for proteins that produce a nucleus like structure. The nucleus like structure is comprised of a proteinaceous structure, containing phage DNA, which excludes CRISPR-CAS complexes. Currently, our newly isolated vibriophages doesn’t not contain any known homologues of anti-CRISPR proteins or nucleus-like forming proteins. Given the phage infects Vibrio spp, that contain CRISPR-CAS systems, it seems likely it also carries an as yet undetermined anti-CRISR system.

PROPOSED WORK:

The project will have a broad remit to understand the fundamental biology of this novel vibriophage BBSRC Strategic Research Priority: Sustainable Agriculture and Food: Animal Health and Welfare & Microbial Food Safety & Understanding the Rules of Life: Microbiology

    Techniques that will be undertaken during the project:

    • Molecular biology techniques

    • Phage engineering

    • Protein expression and analysis

    • Transcriptomics

    Contact: Dr Andrew Millard, University of Leicester