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Glyco-microbubbles – a new strategy for biofilm imaging and destruction

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  • Full or part time
    Dr Turnbull
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Uropathogenic E. coli are responsible for 85% of urinary tract infections. Adhesins on the bacteria bind to carbohydrates on the bladder surface creating biofilms that lead to persistent infections.[1] Once embedded in biofilms, the bacteria become 100–1000-fold less susceptible to antibiotics, increasing the probability of recurrent infection and genetically resistant strains emerging as a result of sub-lethal drug doses. If biofilms were prevented/dispersed, the bacteria would be more susceptible to standard therapies.

In this project we will develop a new method for imaging and disrupting biofilms based on microbubbles: lipid-coated gas bubbles commonly used for contrast-enhanced ultrasound imaging.[2] You will make carbohydrate-coated microbubbles that can bind to the adhesins on the surface of uropathogenic E. coli and a range of other pathogenic bacteria. The glyco-microbubbles will be targeted to biofilms for enhanced ultrasound imaging, biofilm disruption and delivery of antibiotics.[3]

The project will be very interdisciplinary and you will learn a broad range of techniques that combine the expertise of the supervisory team in clinical microbiology (Dr Jon Sandoe);[4] synthetic chemistry and biophysical assays of protein-carbohydrate interactions (Dr Bruce Turnbull);[5] and microbubble fabrication and characterization (Prof Steve Evans).[2-3] You will learn to synthesise simple ligands for bacterial adhesins. The ligands will then be incorporated into microbubbles using state of the art microfluidic technologies before characterisation of their interactions and activity against clinically-relevant bacterial biofilms.

Funding Notes

This imaging project is available as part of the Faculty of Medicine Leeds Anniversary Research Scholarships competition. The supervisor team will be led by Dr Jon Sandoe (Medicine), and co-supervised by Dr Bruce Turnbull (Chemsitry) and Prof Steve Evans (Physics).
For more information see: https://www.findaphd.com/search/PhDDetails.aspx?CAID=2980
Faculty of Medicine: http://medhealth.leeds.ac.uk/info/1450/scholarships/1528/leeds_anniversary_research_scholarships/1
Project description: http://medhealth.leeds.ac.uk/download/2541/sandoe_turnbull_evans_lars

References

1. A. Bernardi, J. Jiménez-Barbero, A. Casnati, C. De Castro, T. Darbre, F. Fieschi, J. Finne, H. Funken, K.-E. Jaeger, M. Lahmann, T. K. Lindhorst, M. Marradi, P. Messner, A. Molinaro, P. V. Murphy, C. Nativi, S. Oscarson, S. Penadés, F. Peri, R. J. Pieters, O. Renaudet, J.-L. Reymond, B. Richichi, J. Rojo, F. Sansone, C. Schäffer, W. B. Turnbull, T. Velasco-Torrijos, S. Vidal, S. Vincent, T. Wennekes, H. Zuilhof and A. Imberty, Multivalent glycoconjugates as anti-pathogenic agents. Chem. Soc. Rev. 2013, 42, 4709-4727.

2. Abou-Saleh, R. H.; Swain, M.; Evans, S. D.; Thomson, N. H. Poly(Ethylene Glycol) Lipid-Shelled Microbubbles: Abundance, Stability, and Mechanical Properties. Langmuir 2014, 30, 5557–5563.

3. Peyman, S. A.; Abou-Saleh, R. H.; McLaughlan, J. R.; Ingram, N.; Johnson, B. R. G.; Critchley, K.; Freear, S.; Evans, J. A.; Markham, A. F.; Coletta, P. L.; Evans, S. D. Expanding 3D Geometry for Enhanced on-Chip Microbubble Production and Single Step Formation of Liposome Modified Microbubbles. Lab Chip 2012, 12, 4544–4552.

4. Kanaa M, Wright MJ, Akbani H, Laboi P, Bhandari S, Sandoe JA. Cathasept line lock and microbial colonization of tunneled hemodialysis catheters: A multicenter randomized controlled trial. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2015, 66, 1015-1023

5. T. R. Branson, T. E. MCAllister, J. Garcia-Hartjes, M. A. Fascione, J. F. Ross, S. L. Warriner, T. Wennekes, H. Zuilhof and W. B. Turnbull, A protein-based pentavalent inhibitor of the cholera toxin B-subunit, Angew. Chem. Int. Ed. 2014, 53, 8323-8327.

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