Circulatory Biomarkers For Idiopathic Pulmonary Fibrosis: Improving Patient Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$841,625.00
Summary
We are going to find molecules in the blood that would improve the diagnosis and treatment of a lung condition called Idiopathic Pulmonary Fibrosis (IPF). The project brings together well characterized patients from the Australian IPF registry, blood samples we have collected from them and cutting edge technologies to complete this project.
Asthma causes wheeze and shortness of breath via airway narrowing, with asthma attacks commonly caused by virus infections. We plan to investigate how airway narrowing during an asthma attack decreases the body’s ability to fight off a viral infection, causing prolonged infection, worse asthma symptoms, more airway inflammation and long-term damage within the airways. We will attempt to use current and novel treatments to reverse these problems, and improve treatment for asthma.
Identification Of Epigenetic Regulators Of Lung Development
Funder
National Health and Medical Research Council
Funding Amount
$625,036.00
Summary
Adaptation to air breathing at birth is dependent on the generation of normal lung structure. Failure of lung formation and surfactant function results in respiratory failure at birth. Although progress has been made in identifying genes and pathways critical for lung function, the factors that control their expression, so called epigenetic factors, are not known. In this proposal, we will seek to identify these factors controlling lung formation.
Investigating The Effects Of Macrolides On Excessive Synthesis And Secretion Of Airway Mucins Using Novel Ex Vivo And In Vivo Approaches
Funder
National Health and Medical Research Council
Funding Amount
$520,821.00
Summary
Many people have difficulty breathing because the airway tubes that move air in and out of their lungs are blocked by excessive amounts of sticky mucus. Our project will use new techniques developed in our laboratories to investigate whether a group of medicines called “macrolides” can prevent the excessive production and release of mucus in the airways, and thus be beneficial in treating asthma, and potentially other lung diseases.
Stephen Stick Practitioner Fellowship In Paediatric Respiratory Medicine
Funder
National Health and Medical Research Council
Funding Amount
$542,272.00
Summary
Fellowship will facilitate the further study of mechanisms of chronic childhood respiratory disease and strategies for intervention to reduce morbidity and improve quality of life for patients and families.
Regulation Of Lung Stem Cells In Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$470,143.00
Summary
Breathing air at birth depends on the generation of normal lung structures. Using multiple approaches, we aim to identify factors that control embryonic lung development and adult lung remodeling by stem cells. This will define the molecular events that are critical in normal lung formation that may be altered in lung disorders such as respiratory distress syndrome of prematurity, and will have a significant impact on the future management of lung diseases.
Consequences Of Waveform Composition For Epithelial Integrity And Homogeneous Ventilation During HFOV
Funder
National Health and Medical Research Council
Funding Amount
$409,483.00
Summary
High-frequency oscillation (HFO) delivers up to 900 breaths/minute to newborn babies. In theory, the tiny HFO breaths decrease ventilator induced lung injury whilst efficiently delivering oxygen to and removing waste gas from the blood. However, HFO may damage the large airways due to the high gas flows. We will use mathematical models and studies in preterm lambs to assess how to optimise distribution of fresh gas to the lung while minimising any airway damage. Our findings will help doctors tr ....High-frequency oscillation (HFO) delivers up to 900 breaths/minute to newborn babies. In theory, the tiny HFO breaths decrease ventilator induced lung injury whilst efficiently delivering oxygen to and removing waste gas from the blood. However, HFO may damage the large airways due to the high gas flows. We will use mathematical models and studies in preterm lambs to assess how to optimise distribution of fresh gas to the lung while minimising any airway damage. Our findings will help doctors treat preterm babies with lung disease.Read moreRead less
Long-lasting Correction Of The Basic Defect In Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$458,500.00
Summary
The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special ....The airway disease caused by the genetic disease cystic fibrosis (CF) is not yet preventable. Current treatments can only limit the gradually-increasing lung disease and is costly. Our new gene therapy technique introduces a correcting gene into affected airway cells, and it has already worked in the first tests in mice bred with CF. Airways in mice are used to test whether the effect is reliable, effective, and lasts long enough to be useful. The gene is introduced into the airway using special virus delivery-particles, after conditioning the airway to make it receptive to the particles. The method works in normal mice and in CF mice; it gives long lasting gene transfer from a single dose and seems to affect all airway cell types. The gene transfer may also be occurring in airway stem cells, i.e. the mother cells from which grow all the cells of the airway surface. Until now, no-one else has been able to produce prolonged gene transfer in this way, nor arrange gene transfer into stem cells in live airways. There are now a number of things that we must investigate before we could conduct safety and effectiveness trials in larger animals, or consider moving into clinical trials in humans. We need to understand exactly how our conditioning agent works and is it safe; measure how long the gene correction can last actually in our animals; decide if we can we re-dose animals (if needed) without losing effectiveness because of inflammation or immune responses that might occur; and decide how important the airway stem cells are in producing the length of the gene transfer. Because it has been difficult to measure gene correction in CF airways, we will also test new ways we have developed to measure how well the gene correction works in CF airways. The findings of this project will allow us to develop our method to where we can test it in larger animals, to provide a strong, long-lasting gene correction that will be safe for testing in human clinical trials.Read moreRead less
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