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Investigation of phage-host and human cell interactions via the biochemical and structural analysis of host cell receptors

Primary Supervisor: Dr Antonia Sagona, SLS

Secondary supervisor: Dr Allister Crow

PhD project title: Investigation of phage-host and human cell interactions via the biochemical and structural analysis of host cell receptors

University of Registration: University of Warwick

Project outline:

Bacteriophages or phages are viruses that have the ability to target their host bacteria efficiently and can be used as therapeutics of infection, in a process that is known as phage therapy.

The interest of phage-host and human cells interactions has grown over the last years, due to re-emergence of phage therapy, as an alternative to antibiotics and to the problem of antimicrobial resistance1. One important characteristic of bacteriophages is their specificity towards their host. This is an area well studied and it is known that this specificity can be attributed to the structure of receptors in the surface of the host bacterial cells, that are specifically recognized by specific bacteriophages. These receptors could include protein receptors (OmpA and OmpC), lipopolysaccharide (LPS) receptors, receptors located in capsular polysaccharides (Vi-antigen), pili and flagella 2,3.

When it comes to the interaction between phages and human cells, even though more and more studies support this4 (via adherence of bacteriophages to mucus5, phage transcytosis6, phagocytosis7 or via the interaction of the cell surface polysialic acid of the phage with human cells in the case of PK1A28), it still remains a field that requires further investigation.

In this project, using phage biology, human cell biology, confocal microscopy, biochemistry and structural biology, we wish to investigate further the interactions between phage-host and human cells, using bacteriophage T4 as a model phage.

The objectives of the project are:

  1. To screen for important receptors between bacteriophage T4 and its host coli, based on the current literature and using a library of mutants.
  2. To perform biochemistry and structural biology experiments in order to understand the specificity between T4 phage and its bacterial host via receptors.
  3. Using the T4-GFP phage constructed in Sagona lab, to perform confocal microscopy and electron microscopy experiments as well as biochemistry experiments in epithelial human cells, in order to identify potential receptors between T4 phage and epithelial human cells.
  4. To characterize with the use of structural biology, the potential receptors between T4 phage-host and human cells.

The methods to be used in this project are the following: Human cell biology, confocal microscopy, electron microscopy, biochemistry, phage biology/microbiology and X-ray crystallography.

BBSRC Strategic Research Priority: Understanding the Rules of Life: Microbiology & Structural Biology

    Techniques that will be undertaken during the project:

    • Human cell culture
    • Confocal microscopy
    • Biochemistry
    • Structural biology
    • Microbiology/phage biology methods

    Contact: Dr Antonia Sagona, University of Warwick