Integrative omics analyses of lung microbiome in health and disease

The airways are a key barrier between the outside world and a host, and are regularly bombarded with external particulates and pathogens. In the last decade, it has become clear that the airways have a distinct microbiome in healthy individuals which can become altered in a disease state. Therefore, this project will focus on the respiratory microbiome as characterisation of the selection pressures and interactions that shape this environment is a topical area.
Previous proteomics analysis of Pseudomonas aeruginosa indicates that a novel toxin is induced in nutrient limited culture and is significantly reduced in a metallophosphatase mutant. This toxin may have implications on the lung microbial community during infection and promote the establishment of P. aeruginosa biofilms. Therefore, the first aim of the project is to determine the role of the toxin in P. aeruginosa and determine how a pathogen, such as P. aeruginosa, can colonise and outcompete the lung microbiome. This will be investigated using wild type and mutant strains, with a range of isolates and in varying conditions.
The second aim of this project is to develop a macrophage phagocytosis assay. This model will enable the study of macrophage selectivity. There is evidence that macrophages show selectivity towards pathogenic bacteria in chronic illnesses such as Chronic Obstructive Pulmonary Disease (COPD). This may have implications on the composition of the respiratory microbiome. This model will be tested with a variety of pathogens, including those used in the first aim of this project, in order to allow analysis of microbial community interactions in the context of host immunity.