To experimentally determine the environmental influences acting on P. aeruginosa virulence factor expression in biofilms and understand the catalytic mechanism of one of them (the surface tethered aminopeptidase AaaA)
Fact file
| Duration |
Three to four years full-time |
|---|
| Eligibility |
Self-funded; Home, EU or International Students |
|---|
| Supervisor(s) |
Dr Kim Hardie |
|---|
| Application deadline |
No deadline |
|---|
About the project
Pseudomonas aeruginosa is an important opportunistic pathogen. It is a problem for the immunocompromised and has attained superbug notoriety since it is evident in hospitals and has inherent resistance to antibiotics. P. aeruginosa is a major cause of morbidity in cystic fibrosis sufferers and also causes infections of burns and trauma wounds. This can cause a problem after surgical procedures. Many of the P. aeruginosa virulence factors are secreted or found on the cell surface where they are ideally located to contact host cells. We have recently characterized one of these and found that it is an arginine-specific aminopeptidase (AaaA). We know that this protein is required for full virulence in a mouse chronic wound model, and also for colonisation of reconstructed human skin where it can influence the innate immune response. However, we do not know the target or regulatory control of AaaA. We will use our collection of clinical strains, defined mutants, reporter strains and overproduction strains to understand what factors control AaaA, and how it functions.
The group you will join is funded by the EU and Industry, and is integrating a range of novel technological platforms through active collaborations to uncover the complex regulatory pathways at work and deliver this exciting data. Techniques include novel optical nanosensors (in collaboration with Jonathan Aylott), Mass Spectroscopy (in collaboration with Morgan Alexander) and Raman Sectroscopy (in collaboration with Ioan Notingher).
Funding notes
This project is available to self-funded students. Home applicants should contact the supervisor to determine the current funding status for this project. EU applicants should visit the Graduate School webpages for information on specific EU scholarships. International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University.
References
-
Luckett, J.C.A, Darch, O., Watters, C., AbuOun, M., Wright, V., Paredes-Osses, E., Ward, J., Goto, H., Heeb, S,, Pommier, S., Rumbaugh, K., Camara, M., and Hardie, K.R. (2012) A novel virulence strategy for Pseudomonas aeruginosa mediated by an autotransporter with arginine-specific aminopeptidase activity. Plos Pathogens. 8(8):e1002854.
-
Ruparell A., Dubern JF., Ortori C., Harrison, F., Halliday N., Emtage A., Ashawesh, M., Laughton C., Diggle, SP., Williams P., Barrett D., and Hardie K.R (2016) The fitness burdens imposed by synthesising quorum sensing systems. Nature Scientific Reports. 6, 33101 http://biorxiv.org/content/early/2016/04/26/050229.
See this project on FindaPhD
To experimentally determine the environmental influences acting on P. aeruginosa virulence factor expression in biofilms and understand the catalytic mechanism of one of them (the surface tethered aminopeptidase AaaA)