Polymer based inhibition of bacterial biofim formation

This is an opportunity to work on an exciting interdisciplinary project which is part of work currently shortlisted for the prestigious Newton Prize. Bacterial biofilms are complex mixed communities of bacteria which can form on almost any surface. They are a particular problem in the biomedical field as they frequently colonise medical devices such as indwelling catheters and prosthetics, and they are difficut to treat with conventional therapies as they are not sensitive to traditional treatments such as antibiotics, due to their complex architechture.
In order to form biofilms, bacteria use a communication process known as Quorum Sensing (QS), which involves the use of molecular signals sent and received by the bacteria forming and maintining the biofilm. Gram negative organisms, such as Pseudomonas aeruginosa which frequently colonises chronic wounds and is also the main pathogen in the lungs of cystic fibrosis patients, use a signalling molecule known as homoserine lactone (HSL) in the QS process. HSL is released by bacteria and binds to a receptor-type molecule (LasR) both internally and in neighbouring bacteria, initiating further signalling and cascades of pathogenic factors involved, for example, with bacterial adhesion on the surface and release of virulence factors.

The objective of our project is to use synthesized polymers with HSL homologues attached, that will bind to LasR without initiating any biological effect and effectively blocking LasR for any other binding. The polymers will be produced by colleagues at the University of Bradford, and the project based at Sheffield will test these polymers for anti-biofilm effectiveness and also use them to investigate mechanisms of biofilm formation. The polymers will be used on bacteria and to treat infected and non-infected 2D and 3D human cell cultures, to investigate both their anti-biofilm activity and potential cytotoxicity. Using this method we could decrease QS in important Gram-negative disease causing bacteria and therefore reduce incidence of biofilm, without contributing to antibiotic resistance.

The project will involve microbiology, molecular biology techniques, microscopy, and mammalian cell culture.