Lung transplantation is an increasingly used treatment for individuals with advanced lung disease. Despite a marked improvement over the last two decades, lung transplantation remains associated with a lower survival rate (54% at 5 years post-transplantation in 2013), compared to the heart, kidney, liver and pancreas. Long-term success following lung transplantation is still limited by chronic lung allograft dysfunction (CLAD), an umbrella term used to describe different phenotypes of chronic rejection. There is an urgent need for increasing our understanding of CLAD pathophysiology and identifying prognostic biomarkers. The airways harbour a microbiota that changes in its constituents depending upon the health status of an individual. This microbiota consists of bacteria, viruses and fungi, which are in intimate contact with cells in the lung providing tonic stimuli to our immune system. There is a disconcerting lack of knowledge concerning how the microbiota influences lung health. Moreover, the field is largely focused upon the bacterial component of the microbiota, even though they represent only one aspect of the microbiome. We recently found that the constituents of bacterial communities in the transplanted lung influence macrophage functionality, and in particular, influence the type of tissue remodelling that they promote. Now we have discovered that changes in the bacterial communities and macrophage tissue remodelling capacity are linked with the subclinical presence of viruses. Currently, little is known about the normal fungal constituents of the transplanted lung. The overarching goal of this project is to determine the impact and interaction of bacteria, viruses and fungi in the transplanted lung, in order to inform the development of novel biomarkers and improve treatment and prevention of CLAD. This highly translational project involves close collaboration with the Lung transplantation unit of the Alfred Hospital, high throughput sequence analysis of microbial populations, bioinformatics and development of cell culture models of macrophage-microbe interactions.
microbiota, lung, transplantation, immunology, translational
Central Clinical School
Masters by Research