Investigators: Alexander Larcombe, Anthony Bosco, David Martino, Deb Strickland, Laith Harb
Plain language summary:
In newborns, the immune system and the lung are not fully developed and are highly sensitive to the environment. Exposure to environmental insults (e.g. severe respiratory viral infection) during this crucial period can damage the airways resulting in impaired lung development and function. The aim of this project is to discover the molecular processes that link environmental exposures in early life with impaired lung function in adult life, and determine if repurposed drugs can reprogram these processes and restore normal lung development and function.
Project description:
Environmental exposures in early life can have dramatic consequences for development and physiological function in adulthood. To study this phenomenon, we have developed a model of respiratory viral infection, in which infected neonates have impaired lung function as adults, long after the infection has cleared. Using this model, we seek to identify the molecular changes (set of genes) that are altered by viral infection, which in turn lead to impaired lung development and function. Then, we seek to identify Food And Drug Administration-approved drugs that can reverse these molecular changes, to determine if we can restore normal lung development and function. Our hypothesis proposes that the molecular changes which are brought on by viral infection causing developmental and physiological changes are reversible with FDA-approved drugs. In 2015 we received The Kids Research Institute Australia Blue Sky funding to explore this hypothesis. Initially, we infected with Influenza A and then at specific time-points after infection we harvested lung tissue for gene expression profiling studies (RNA-Seq). RNA-Seq is a powerful tool for transcriptomics, which employs next generation sequencing technologies to measure gene expression levels at single base resolution. In 2015 we collected and purified our samples and sent them to the Australian Genome Research Facility for RNA-Seq analysis on the Illumina platform (HiSeq 50-bp single end reads, 20 – 30 million reads per sample). In 2017 we received an NHMRC Project Grant on this topic, and recruited PhD candidate Laith Harb. Laith is undertaking the in vivo arm of the study.