Targeting the Biofilm for Drug Design: Modelling the roles and impacts of extracellular matrix composition in a mixed species bacterial biofilm.

About the Project

Bacterial biofilms are an evolved strategy used by bacteria to protect themselves in large colonies. The biofilm, which is composed of an extracellular mixture of sugars, proteins, DNA, ions and lipids, acts as a sophisticated barrier, preventing therapeutic molecules, such as antibiotics, from reaching the bacterial cells. The major components of most bacterial biofilms are polysaccharides (sugars), and each bacterial species has a different type or range of polysaccharides that it employs for this purpose. In this project we will look at the polysaccharide extracellular matrices (glycocalyx) of multi-species biofilms, for example Pseudomonas aeruginosa and Staphylococcus aureus, which are two dangerous pathogens linked to poor human health and the rapid development of antimicrobial resistance (AMR). Previous work has revealed an ambiguity with these two bacteria, showing both that they work cooperatively and, alternatively, antagonistically.

For this PhD we will model the polysaccharide structures of the multi-species biofilm, exploring the interactions and partitioning behaviour of the biofilm components. We will also examine how quorum sensing (the messages sent between bacteria to ensure positive collective behaviour) and nutrient components move through this overlapping matrix; for example, can the quorum sensing molecules of one species navigate their way through the extracellular matrix of the other? This knowledge will then inform the rational design and modification of antibiotics, targeted against extracellular enzymes that maintain the glycocalyx.

The project, based at the University of Leeds, will be entirely computational in nature, using computer-aided drug design and working on the University of Leeds’ new High-Performance Computer, Aire. It would suit a student with a chemistry, physics, materials or maths background, or equally someone with a background in biology or microbiology who is also interested in exploring computational methods.

Funding Notes

This is not a funded project, but you can apply for funding separately. Self-funding students are also welcome to apply.

For more information please visit the institution website.