Airway Epithelial Barrier Function, Asthma And Aero-allergen Sensitization.
Funder
National Health and Medical Research Council
Funding Amount
$527,886.00
Summary
There is a strong association between allergy and asthma. This association been almost universally assumed to be causative. However, recent evidence suggests an alternative explanation ie., that the abnormal epithelium in asthma allows or facilitates sensitization to airborne allergens. This project will test this alternative hypothesis using human lung tissue and an animal model.
Defective Cell Migration As A Mechanism Of Dysregulated Asthmatic Airway Repair
Funder
National Health and Medical Research Council
Funding Amount
$616,712.00
Summary
Injury of the airway epithelium (cells lining the airways) is normally repaired by a process involving the deposition of specific proteins by the airway epithelial cells, promoting them to attach and migrate to cover the injury. These cells appear to be abnormal in asthmatics, in that they fail to repair. By studying specimens from healthy, allergic and asthmatic children we will determine the factors that influence the ability of these cells to repond to an injury in a normal manner specificall ....Injury of the airway epithelium (cells lining the airways) is normally repaired by a process involving the deposition of specific proteins by the airway epithelial cells, promoting them to attach and migrate to cover the injury. These cells appear to be abnormal in asthmatics, in that they fail to repair. By studying specimens from healthy, allergic and asthmatic children we will determine the factors that influence the ability of these cells to repond to an injury in a normal manner specifically through their ability to migrate.Read moreRead less
Fibroblast Senescence As A Driver Of Pulmonary Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$845,611.00
Summary
Idiopathic pulmonary fibrosis (IPF) has no cure. Currently we think that IPF develops like normal wound healing, but the normal “braking” mechanisms in the myofibroblasts (the cells that produce the connective tissue) don’t work, such that too much connective tissue is produced and oxygen transfer to the blood is stopped. We have identified a protein we think stops, the myofibroblasts from dying. Reducing the activation of this protein should return the myofibroblasts function to normal.
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.
Epithelial Regeneration As A Novel Therapeutic Target In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$633,228.00
Summary
While allergies are very common, affecting ~40% of the population in Western countries, only a proportion of allergic people develop asthma, highlighting the importance of cell specific mechanisms that contribute to the disease. We will address how the structure and function of cells that line the airways, called epithelial cells contribute to asthma. We believe that in asthma, certain types of epithelial cells do not go through normal stages of development and differentiation and remain immatur ....While allergies are very common, affecting ~40% of the population in Western countries, only a proportion of allergic people develop asthma, highlighting the importance of cell specific mechanisms that contribute to the disease. We will address how the structure and function of cells that line the airways, called epithelial cells contribute to asthma. We believe that in asthma, certain types of epithelial cells do not go through normal stages of development and differentiation and remain immature.Read moreRead less
Herpesviruses infect us all and cause cancer, blindness, and congenital disability. Developing vaccines requires information from both patients and experimental animals. CD4 T cells seem to suppress directly virus replication, and cells in the nose provide an important way for herpesviruses to get in. We will test whether CD4 T cells can clear nasal infection; what targets they recognize; and how they act. Thus we can establish whether CD4 T cell-directed vaccines might protect against disease.
Mapping The Dynamics Of Corneal Stem Cell During Aging And After Wounding And Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$548,403.00
Summary
Restoring vision in patients with corneal blindness is our focus. Before this can be achieved we need to understand how corneal stem cells function. For many reasons these studies cannot be performed in man, so we engineered a mouse in which the location, migration, division, differentiation, death of these cells can be followed indefinitely. This information will allow us to improve current therapeutic options and develop new clinical solution for patients with blinding corneal disease.
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.
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.