NHMRC Early Career Fellowship (CJ Martin - Overseas Biomedical Fellowship): The role of inflammation in viral pathogenesis and exacerbations of asthma (2013-2017)
Abstract
The research proposed here addresses the role of viral induced inflammation in the pathogenesis of influenza virus and exacerbation of asthma. This proposal will thus harness the unique expertise available at Erasmus Medical Center (viral pathogenesis & pathology) and the University of Queensland (asthma immunology). Specifically, I will use a novel cloning strategy to create a fluorescently tagged human strain of influenza virus. I will then use this strain in mouse and ferret models of disease to study the role of inflammation in influenza virus pathogenesis, with a particular focus on the role of neutrophils and neutrophil extracellular traps (NETs). The use of a fluorescently tagged virus strain will enable me to perform both in vivo and ex vivo imaging on infected animals, in order to maximise our understanding of disease development in vivo. Upon return to Australia I will then use this tagged virus strain and skills obtained in virology, imaging and pathology to investigate the role of influenza virus in asthma exacerbation. These studies employ a mouse model of asthma previously developed in the laboratory of Dr. Phipps. This research will be performed with a particular focus on the role of neutrophils, NETs and toll like receptor 7 (TLR7) in influenza virus induced asthma exacerbation. The outcomes of this research will significantly inform the use of therapeutics for severe influenza infections and viral-induced exacerbations of asthma. Thus, this research will play an important role in improving Australian public health.