Understanding microbe-pathogen interactions in a clinically relevant model of the cystic fibrosis lung

Cystic fibrosis is a genetic disease hallmarked by an accumulation of mucus in the lungs which results in an active and diverse respiratory microbiome.

A subset of the microbiome - termed canonical cystic fibrosis pathogens - contribute to episodes of increased respiratory symptoms known as pulmonary exacerbations which account for much of the morbidity and mortality in people with cystic fibrosis. A better, wider range of therapeutic options to inhibit these pathogens will help mitigate cystic fibrosis disease.

My research group has identified a number of microbes that are able to inhibit the growth of cystic fibrosis pathogens in vitro.

In this proposal, we build upon this work to characterize these microbe-pathogen interactions in a realistic model of the cystic fibrosis lung.

This work was not possible until the recent innovation of my colleague, Prof Alvaro Mata, to use hydrogels in a novel way.

In this new collaboration with Alvaro Mata, we will use hydrogels to build multi-species biofilms in an artificial sputum media, previously shown to mimic the physiological characteristics of the cystic fibrosis lung.

We will characterize the interaction between microbe and pathogen using transcriptomic and metabolic techniques with the long-term goal of identifying how microbes inhibit pathogens so that we can co-opt similar techniques in the clinic.