Functional Significance Of Subcellular Localisation Of Viral 3C Protease In Rhinovirus Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$613,513.00
Summary
Rhinovirus (RV) infections are the major cause of virus induced asthma attacks and common colds, causing significant morbidity and mortality. The incidence of asthma is increasing worldwide with new strategies urgently needed to reduce RV-associated disease. We have observed RV 3C protease in the nuclear compartment of infected host cells and propose to determine its significance in RV pathogenesis with relevance to asthma therapies.
Antiviral Defects Of The Airway Epithelium Associated With Wheeze And Atopy In Children
Funder
National Health and Medical Research Council
Funding Amount
$658,571.00
Summary
Asthma affects 10-15% of Australian. Repeated respiratory viral infections increase the risk of developing asthma, and are also the principal cause of asthma attacks. Asthmatics may be more susceptible to respiratory viral infections due to a defect in the innate antiviral response to infection. Here we aim to identify defects in the antiviral response of children who are at risk of developing asthma, and understand how they occur so that future therapies may be developed.
Development Of New Therapies For Respiratory Diseases And Infection
Funder
National Health and Medical Research Council
Funding Amount
$847,490.00
Summary
Prof Hansbro’s group have developed world 1st experimental models of emphysema, severe asthma infection and lung cancer. He uses them to further our understanding of these untreatable diseases. This has led to the development of new potential therapeutic approaches. Now, in discovery programs he will expand studies of pathogenesis to identify new therapeutic targets these diseases. In development and translational programs he will progress new therapies towards clinical application.
Influence Of Early-life Viral Infection On Severity Of Murine Chronic Asthma And Acute Exacerbations
Funder
National Health and Medical Research Council
Funding Amount
$508,528.00
Summary
This project examines the relationship between certain childhood infections with respiratory viruses and the progression of asthma later in life. The experimental work will use mouse models of mild chronic asthma and of an acute exacerbation of the illness -- these unique models have been developed in the laboratories of the chief investigators. It will employ the most appropriate mouse models of infection by the relevant group of viruses. We expect to obtain new information about mechanisms of ....This project examines the relationship between certain childhood infections with respiratory viruses and the progression of asthma later in life. The experimental work will use mouse models of mild chronic asthma and of an acute exacerbation of the illness -- these unique models have been developed in the laboratories of the chief investigators. It will employ the most appropriate mouse models of infection by the relevant group of viruses. We expect to obtain new information about mechanisms of airway inflammation and airway hyper-reactivity, which are characteristic features of chronic asthma and of acute exacerbations. This could help to identify candidate signalling molecules and pathways that could be targeted by new treatments. The findings might also provide a basis for development of ways to modify the immune response after respiratory viral infection in childhood.Read moreRead less
Mechanisms Of Induction And Progression Of Childhood Asthma: Investigations In A Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$517,586.00
Summary
This project investigates how certain respiratory viral infections in very young children might predispose to developing asthma, and how inflammation in the airways in asthma might then worsen. The experimental work, which will use unique mouse models developed in the laboratories of the chief investigators, will focus on changes in genes that control the pattern of immune response to allergens and that regulate the progression of inflammation.
In the asthmatic lung structural changes or remodelling occur, which are thought to contribute to the abnormal functioning of the airways. These remodelling events which occur in the asthmatic airway include increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix ECM proteins), and an increased mass of bronchial smooth muscle cells. Many of these critical structural changes are not reversed or prevented with current asthma therapy. Remodelling is an i ....In the asthmatic lung structural changes or remodelling occur, which are thought to contribute to the abnormal functioning of the airways. These remodelling events which occur in the asthmatic airway include increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix ECM proteins), and an increased mass of bronchial smooth muscle cells. Many of these critical structural changes are not reversed or prevented with current asthma therapy. Remodelling is an important process in both the development and progression of asthma. The reason why remodelling occurs in the lungs of people with asthma is not known. It is thought that persistent inflammation drives the remodelling process; however remodelling can perpetuate inflammation, thereby creating a cyclic series of events. Furthermore we have shown that cells from non-asthmatic volunteers which are grown on asthmatic ECM change to become more like cells from asthmatic subjects. Viruses which infect the lungs may play a role in the development of asthma, and in the increased remodelling which is observed. Many common respiratory viruses are capable of infecting lung cells, eg epithelial cells, which evokes an inflammatory response. I will investigate if viral infection can alter the remodelling process, using lung cells isolated from asthmatic and non-asthmatic volunteers. Furthermore, I will assess if current and novel treatments are effective in reducing the remodelling process. We have preliminary evidence that infection of lung epithelial cells with rhinovirus (the common cold virus) alters the amount of ECM deposited by these cells. I hypothesise that this process will be increased in cells from volunteers with asthma compared to non-asthma. As current therapeutics are unlikely to be able to reverse these remodelling events these experiments will enable the development of new therapeutics which can target this important aspect of airway disease.Read moreRead less
The Mechanisms Underlying Pneumoviral-induced Angiogenesis Of The Lung And Its Impact On The Asthmatic Response.
Funder
National Health and Medical Research Council
Funding Amount
$564,625.00
Summary
Asthma, is a serious respiratory disease resulting in structural changes to the lung and breathing difficulties, and is often compounded by respiratory viruses. We have shown that viral infection of newborn mice causes the growth of new blood vessels in the lungs (a feature seen in human asthmatics). This project will investigate the mechanisms involved and determine the potential of this feature as a therapeutic target.
Mechanisms Underlying Acute Changes In Lung Function And Airway Responsiveness Following Respiratory Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$444,878.00
Summary
This study will investigate the mechanisms responsible for the increased airway responsiveness seen during respiratory viral infections to the common viruses of influenza (flu) and respiratory syncytial virus (RSV). Respiratory viral infections alter lung function and increase airway responsiveness in man. In addition, respiratory viral infections early in life are a risk factor for the subsequent development of asthma. The mechanisms responsible for this are unknown. Both the infecting virus an ....This study will investigate the mechanisms responsible for the increased airway responsiveness seen during respiratory viral infections to the common viruses of influenza (flu) and respiratory syncytial virus (RSV). Respiratory viral infections alter lung function and increase airway responsiveness in man. In addition, respiratory viral infections early in life are a risk factor for the subsequent development of asthma. The mechanisms responsible for this are unknown. Both the infecting virus and host factors, such as age of infection, gender and genetic predisposition, are likely to be important. OUTCOMES and SIGNIFICANCE: These studies will provide a comprehensive assessment of the effects of acute viral respiratory infections on lung function and airway responsiveness using cutting edge techniques developed in our labs. The results will provide new insights into how these infections cause lung disease and may provide clues for new approaches to prevent the adverse effects of these common respiratory viral infections.Read moreRead less