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Novel approaches to detect and treat Pseudomonas aeruginosa antibiotic resistant biofilms in cystic fibrosis

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  • Full or part time
    Prof M Camara
    Dr L Martinez-Pomares
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Project Overview:
Cystic fibrosis patients are regularly colonised by Pseudomonas aeruginosa (P. aeruginosa) which avoids the impact of the immune system and antibiotic therapy through the formation of biofilms. Under certain conditions P. aeruginosa "transforms" into a virulent state through the production of quorum sensing signal molecules (QSSMs). This results in increase damage to the lung and likely to play a key role in the exacerbation process. P. aeruginosa uses quorum sensing (QS), a widespread bacterial intercellular communication system based on the production of these QSSMs, the extracellular concentration of which is related to the population density of the producing bacterial strain. QS systems control diverse phenotypes including the production of virulence determinants, biofilm formation and antibiotic resistance hence representing an important therapeutic target.

Current P. aeruginosa diagnostic methods are not suitable for point-of-care (POC), as in some cases they incorrectly report the presence of P. aeruginosa, and do not detect virulence status. We have recently generated antibodies against quorum sensing molecules and in this PhD project we will evaluate the potential of these antibodies for their incorporation into POC diagnostic test to specifically detect P. aeruginosa infections with high sensitivity but also their therapeutic potential to treat biofilms produced by this organism by sensitising them to antibiotics.
This studentship will be imbedded within the Nottingham branch of the National Biofilm Innovation Centre (https://biofilms.ac.uk ) and hence will benefit from the highly multidisciplinary training including entrepreneurial and the participation in industrial engagement events of this Centre.

Techniques:
Amongst the techniques to be used in this project will be, immunoassays, molecular biology techniques, protein purification, confocal microscopy, use of a range of biofilm and disease models and analytical chemistry.

About the School of Life Sciences:
The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers.

Applying:
Applicants should send a CV and cover letter to Charlotte May ([Email Address Removed]) before applying to the School of Life Sciences.

Funding Notes

Project Funding: Cystic Fibrosis Trust and The University of Nottingham under the umbrella of the National Biofilms Innovation Centre

References

1. Soukarieh, F., Williams, W., Stocks, M. J., & Cámara, M. (2018). Pseudomonas aeruginosa Quorum Sensing Systems as Drug Discovery Targets: Current Position and Future Perspectives. Journal of Medicinal Chemistry, 1–18. http://doi.org/10.1021/acs.jmedchem.8b00540
2. Rampioni, G., Falcone, M., Heeb, S., Frangipani, E., Fletcher, M.P., Dubern, J-F., Visca, P., Leoni, L., Cámara, M. and Williams, P. (2016) Unravelling the Genome-Wide Contributions of Specific 2-Alkyl-4-Quinolones and PqsE to Quorum Sensing in Pseudomonas aeruginosa. PLoS Pathogens. 16;12(11):e1006029
3. Barr, H.L., Halliday, N., Barrett, DA., Williams, P., Forrester, DL., Peckham, D., Williams, K., Smyth, AR., Honeybourne, D., Whitehouse, JL., Nash, EF., Dewar, J., Clayton, A., Knox, AJ., Cámara, M. and Fogarty, AW.(2017)Diagnostic and prognostic significance of systemic alkyl quinolones for P. aeruginosa in cystic fibrosis: A longitudinal study; response to comments.J Cyst Fibros. 2017 S1569-1993(17)30887-1.
4. Barr, H.L., Halliday, N., Cámara M., Barrett, D.A.,Williams, P., Forrester, D.L., Simms, R., Smyth, A.R., Honeybourne, D., Whitehouse, J.L.,Nash, E.F., Dewar, J., Clayton, A., Knox, A.J. and Fogarty, A.W.(2015) P. aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis. Eur Resp J. doi: 10.1183/09031936.00225214
5. LiuY-C., Hussain, F., Negm, O., Pavia, A., Halliday, N., Dubern, J-F., Singh, S., Muntaka, S., Wheldon, L., Luckett, J., Tighe, P., Bosquillon, C., Williams, P., Cámara, M. and Martinez-Pomares, L. Contribution of the alkylquinolone quorum sensing system to the interaction of Pseudomonas aeruginosa with bronchial epithelial cells. Front. Microbiol. (in press)

How good is research at University of Nottingham in Biological Sciences?

FTE Category A staff submitted: 90.86

Research output data provided by the Research Excellence Framework (REF)

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