Exposure Of Bronchial Epithelial Cells To Inflammatory Stimuli Impairs Their Innate Immune Response To Rhinovirus.
Funder
National Health and Medical Research Council
Funding Amount
$325,966.00
Summary
Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory conditions in Australia, both of these conditions are characterised by acute attacks precipitated by respiratory virus infections. The most common trigger for these acute attacks is the usually innocuous common cold virus, rhinovirus. The reason for this susceptibility remains poorly understood. We have previously shown that the cells lining the airways of asthmatics are more susceptible to infection with rhi ....Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory conditions in Australia, both of these conditions are characterised by acute attacks precipitated by respiratory virus infections. The most common trigger for these acute attacks is the usually innocuous common cold virus, rhinovirus. The reason for this susceptibility remains poorly understood. We have previously shown that the cells lining the airways of asthmatics are more susceptible to infection with rhinovirus and fail to react to this infection effectively. We propose to further elucidate this defect and for the first time determine if it is also present in subjects with COPD. We will examine the airway cells of subjects with asthma and COPD and look for evidence of a defective immune response, relating this to the presence of persistent bacterial infection. We will then grow these and infect them with rhinovirus, carefully examining the mechanisms behind this impaired response to infection and then see if we can induce such impairment in these cells with chronic exposure to infection and inflammatory stimuli. Our laboratory is well placed to investigate these problems with an established track record in investigating patients with inflammatory airways disease and virus infection, unparalleled access to sufficient well characterised clinical samples and have demonstrated the ability to study virus epithelial cell interactions. This work will highlight those at risk of developing frequent debilitating exacerbations along with the reasons for this and identify areas to target novel therapeutic interventions.Read moreRead less
Novel Interventions For The Diverse Population Of Australians With Bronchiectasis
Funder
National Health and Medical Research Council
Funding Amount
$726,822.00
Summary
Bronchiectasis is a chronic lung condition in which infection causes wheeze, breathlessness, fatigue and sputum production - markedly reducing quality of life and requiring repeated hospital admissions. Risk of hospitalisation due to the disease is up to 9-fold higher in Indigenous vs other Australians. This research will examine two new, low-cost therapies with excellent potential to treat bronchiectasis: a new antibiotic, Azithromycin, and a mucus-clearance agent, hypertonic saline.
Bronchoscopic Applications Of Anatomical Optical Coherence Tomography.
Funder
National Health and Medical Research Council
Funding Amount
$408,366.00
Summary
This research proposal aims to investigate the potential utility of a novel, Australian designed dianostic laser system. A tube positioned in the lungs takes real-time images of the shape and size inside the airways. This can have both clinical and research benefits. It may help doctors choose the right size hardware when opening up cancerous airways and it will help us understand disease mechanisms of lung diseases by studying parts of the airways not previously able to be measured.
Serum Mesothelin-related Protein As An Early Marker Of Mesothelioma
Funder
National Health and Medical Research Council
Funding Amount
$354,750.00
Summary
The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of individuals per year and its incidence is increasing. It is expected to cost communities hundreds of billions of dollars in compensation. This disease is usually already quite advanced by the time a patients presents to a doctor with symptoms so we have been working on methods of early detection. This project studies a new, exciting method of diagnosis using blood levels of a molecule called 'SMRP'. Late l ....The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of individuals per year and its incidence is increasing. It is expected to cost communities hundreds of billions of dollars in compensation. This disease is usually already quite advanced by the time a patients presents to a doctor with symptoms so we have been working on methods of early detection. This project studies a new, exciting method of diagnosis using blood levels of a molecule called 'SMRP'. Late last year we published a paper in the prestigious journal Lancet showing that SMRP was a good test to help diagnose mesothelioma and this became a lead news item around the world because of widespread concern about this disease. In those studies we found strong clues that this test was very sensitive and could detect mesothelioma a year or so before a patient develops symptoms. In this grant we will evaluate whether this test could be useful for screening asbestos-exposed individuals for early detection of this cancer. We will also study ways of improving the test using laboratory methods. This would provide a foundation for studies aimed at determining if early treatment could improve patient survival.Read moreRead less
Diagnostic Markers For Malignant Mesothelioma And Other Respiratory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$467,315.00
Summary
The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of individuals per year. We have been working on improving the tests available to detect this cancer and to follow the course of the disease with the aim of reducing patients' anxiety and health-care costs.
Investigatin The Causes Of Failed Efferocytosis In COPD-emphysema With A View To Identifying Novel Theraputic Targets
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
COPD is a leading cause of death. Smoking is the major cause of COPD and many sufferers are left with permanent damage and need ongoing treatment even after smoking cessation. Current treatments for COPD generally have limited efficacy. The project will identify the reason for the large number of dying cells and defective clearance of these cells that we have identified in the airways in COPD and study novel treatments that we hope will improve the health and well being of those with COPD.
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
Is MUC1 A Viable Therapeutic Target For Patients With The Asbestos-induced Tumour Malignant Mesothelioma?
Funder
National Health and Medical Research Council
Funding Amount
$465,068.00
Summary
The deadly asbestos-induced cancer mesothelioma is continuing to kill tens of thousands of people each year. Most patients are diagnosed with advanced disease. We are investigating the use of a specific marker, called MUC1, to improve mesothelioma diagnosis. Improved diagnosis will reduce the time taken to commence treatment. It will also reduce hospital costs and the number of surgical procedures a patients must undergo.
Preventing Complications Of Chronic Obstructive Pulmonary Disease
Funder
National Health and Medical Research Council
Funding Amount
$310,914.00
Summary
Chronic obstructive pulmonary disease (COPD) is a devastating lung disease that affects smokers. Lung complications and complications in other organs occur commonly. This study will examine factors that lead to exacerbations of COPD, and test the effectiveness of early diagnosis of coronary artery disease using CT scans.