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Understanding cell wall-anchored protein function during human colonisation and infection

Primary Supervisor: Dr Joan Geoghegan, Institute of Microbiology and Infection

Secondary supervisor: Professor Willem van Schaik, University of Birmingham, Professor Julie Morrissey, University of Leicester.

PhD project title: Understanding cell wall-anchored protein function during human colonisation and infection.

University of Registration: University of Birmingham

Project outline:

Staphylococcus aureus is an important pathogen of humans. Methicillin resistant S. aureus (MRSA) cause infections that are extremely challenging to treat, posing a major threat to public health. An important factor in the success of S. aureus as a pathogen is its ability to asymptomatically colonise the nasal cavity of humans. The bacterium possesses a vast repertoire of cell wall-anchored proteins (CWAPs) that mediate interactions with the host and underpin the versatility of S. aureus as a commensal and a pathogen. CWAPs promote bacterial adhesion, invasion of host cells, immune evasion and biofilm formation (Geoghegan & Foster, 2016). Research in Dr Geoghegan’s lab focuses on understanding how CWAPs contribute to colonisation and infection and understanding the relationship between CWAP structure and function. For example, interactions with fibrinogen and fibrin allow the bacteria to aggregate with fibrin networks in plasma or to recruit soluble fibrinogen to the bacterial surface during infection, while CWAP-mediated interaction with the cornified envelope protein loricrin facilitates adhesion of S. aureus to corneocytes during nasal colonisation. The aim of this project is to investigate the influence of the nasal microbiota, other pathogens and host factors on CWAP activity. Studying CWAP function in complex environments that mimic those encountered at colonisation and infection sites will advance our knowledge of the S. aureus-host interaction.

The key objectives will be to:

  1. Investigate the influence of the microbiota, and bacterial pathogens that colonise the nasal cavity, on the regulation of S. aureus CWAP expression.
  2. Study the activity of host- and bacteria-derived proteases that cleave CWAPs and alter their function.
  3. Establish how the activity of CWAPs is modulated by the complexity of the host environment and how this influences the microbe-host interaction.

The student will join a collegiate interdisciplinary research group within the Institute of Microbiology and Infection (IMI) at University of Birmingham and benefit from an established collaborations with the University of Leicester. The student will be trained in a range of molecular microbiology techniques, transcriptome profiling, proteomics, recombinant protein production and mammalian cell culture.

Reference:

  1. Geoghegan & Foster (2016). Cell Wall-Anchored Surface Proteins of Staphylococcus aureus: Many Proteins, Multiple Functions. Current Topics in Microbiology and Immunology. 409:95-120.
    Relevance to BBSRC and Approvals

BBSRC Strategic Research Priority: Understanding the Rules of Life: Microbiology

    Techniques that will be undertaken during the project:

    • Molecular microbiology techniques
    • Transcriptome profiling using next generation sequencing
    • Proteomics
    • Recombinant protein production
    • Cutting-edge cell culture models

    Contact: Dr Joan Geoghegan, University of Birmingham