Evolution Of Airway Function And Inflammation In Early Cystic Fibrosis Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$494,447.00
Summary
Our goal is to evaluate if lung function can identify the onset of early lung disease in infants with cystic fibrosis (CF). We aim to evaluate: - Changes in lung function in infants with CF. - Associations between lung function and lung inflammation and infection. - Links between infant lung function and disease severity at 2 years of age. The long term aims are to determine how useful lung function will be in trials of novel treatments for the early treatment of CF.
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
Economic, social and cross cultural issues in non-pharmaceutical protection of front line responders to pandemic influenza and emerging infections. The protection of front line responders in a pandemic is essential to underpin an effective response. This research is the only work internationally which will address a key gap in evidence. This research has major implications for the national stockpile and for management of front line responders in a pandemic. These data are urgently needed, not ju ....Economic, social and cross cultural issues in non-pharmaceutical protection of front line responders to pandemic influenza and emerging infections. The protection of front line responders in a pandemic is essential to underpin an effective response. This research is the only work internationally which will address a key gap in evidence. This research has major implications for the national stockpile and for management of front line responders in a pandemic. These data are urgently needed, not just in Australia, but globally to inform pandemic planning and disease control policy around emerging infections and bioterrorism.Read moreRead less
Assessing a model of the physiological changes at arousal from sleep. Arousals from sleep are common in the elderly and have adverse consequences. This project will investigate a model of the changes in bodily processes (muscle, brain and cardiovascular activation) that occur when humans awaken from sleep.
Increasing the utility of tetanus toxins by protein engineering. There are a variety of common diseases that are the result of muscular defects. Some of these may be able to be treated with an agent that increases muscle tone, thereby giving benefit to the patient in the alleviation of symptoms. This project aims to use some of the most potent substances known, bacterial toxins, and engineer them to be valuable agents for treatment of certain muscular disorders.
Breathing disturbances and reflexes in sleep and effects on sleep and daytime function. This project will investigate protective reflexes in sleep and the impact of breathing disturbances and frequent arousal on markers of brain functioning and health. This will also significantly advance the understanding of key mechanisms promoting unstable breathing in sleep and ill health and functioning from disturbed sleep.
Rhinovirus impairs physiological and immunological lung development and causes exacerbation of allergic airways disease. Rhinovirus (RV) infections account for around 90 per cent of asthma exacerbations, yet the mechanisms behind this are unknown. This project will use mouse models to study the effects of early life RV infection and allergic sensitisation on respiratory and immunological development, with the expectation that early life RV infection disrupts anitgen presenting cell function.
Understanding the biology of reactive oxygen species. This project will utilise forefront technologies to identify and characterise fundamental biological processes involving toxic free radicals that cause infectious disease and cancer. The approach synergises with researchers across disciplines and universities to ultimately identify future drugs to improve and maintain health.
Identifying New Therapeutic Targets For Preventing The Induction And Progression Of COPD
Funder
National Health and Medical Research Council
Funding Amount
$649,314.00
Summary
Smoking leads to lung inflammation that causes emphysema, which is a major health problem in Australia. Once induced there is a progressive decline in health, which continues even after stopping smoking. There are no treatments that halt this decline. Recently small genes have been discovered that control inflammation. We may be able to control these small genes and stop the induction and progression of emphysema. This project may lead to a completely new way of preventing and treating emphysema ....Smoking leads to lung inflammation that causes emphysema, which is a major health problem in Australia. Once induced there is a progressive decline in health, which continues even after stopping smoking. There are no treatments that halt this decline. Recently small genes have been discovered that control inflammation. We may be able to control these small genes and stop the induction and progression of emphysema. This project may lead to a completely new way of preventing and treating emphysema.Read moreRead less