Expression And Function Of Fatty Acid Binding Proteins In Asthmatic Airway Epithelium
Funder
National Health and Medical Research Council
Funding Amount
$226,500.00
Summary
Asthma is an inflammatory disease of the lungs that affects over 10% of all Australians. It ranges in severity from mild to life-threatening. Although a number of drugs are currently available for the treatment of asthma, there are many people whose asthma does not respond very well to treatment. We have recently identified a gene called aP2 that is important in the development of asthma. Drugs targeted against this gene may be very useful in the treatment of asthma. In this project, we aim to u ....Asthma is an inflammatory disease of the lungs that affects over 10% of all Australians. It ranges in severity from mild to life-threatening. Although a number of drugs are currently available for the treatment of asthma, there are many people whose asthma does not respond very well to treatment. We have recently identified a gene called aP2 that is important in the development of asthma. Drugs targeted against this gene may be very useful in the treatment of asthma. In this project, we aim to understand how aP2 is turned on during asthma, and how it contributes to disease development. This information will be essential for designing optimal strategies for drug targeting of the aP2 pathway in asthma.Read moreRead less
Functional Analysis Of The Ym2 Chitinase-like Lectin In Allergic Airways Disease
Funder
National Health and Medical Research Council
Funding Amount
$283,767.00
Summary
The prevalence of asthma is widespread and nationally affects over two million Australians. Consequently, one of the Country s National Health Priorities is to improve our understanding of this condition. Analyses of the asthmatic lung reveal an airway wall that is thickened, an airway lumen that is obstructed and abnormal spasmogenicity of the airway smooth muscle: processes that collectively contribute to both acute and chronic respiratory dysfunction. Asthmatics develop an immune response tha ....The prevalence of asthma is widespread and nationally affects over two million Australians. Consequently, one of the Country s National Health Priorities is to improve our understanding of this condition. Analyses of the asthmatic lung reveal an airway wall that is thickened, an airway lumen that is obstructed and abnormal spasmogenicity of the airway smooth muscle: processes that collectively contribute to both acute and chronic respiratory dysfunction. Asthmatics develop an immune response that is biased toward production of allergy-related T helper 2 cytokines of which interleukin (IL)-13 is a potent mediator of disease. However, the molecular processes linking IL-13 with abnormal airway wall changes are unclear. To identify previously uncharacterised IL-13-related molecules, we used a protein profiling approach that identified a novel lectin (carbohydrate-binding protein) termed Ym2, which is secreted abundantly into the airway fluid of mice in which allergic airways disease has been induced. Preliminary studies suggest that Ym2 is an intermediary of IL-13 that is involved in respiratory dysfunction. This project aims to work out how Ym2 interacts with the molecules and cells of the respiratory tract to regulate allergic disease. Specific inhibitors of Ym2 will be developed to examine what happens to allergic responses when Ym2 can t function; transgenic mice will be developed to determine if we see features of allergy when Ym2 is over-expressed in the normal lung, and human samples will be screened to identify the human counterpart of Ym2 and whether this counterpart is secreted into the lung fluid of asthmatics. Defining the mechanism by which Ym2 regulates the pathogenesis of allergic disease will not only contribute to our basic understanding of the processes underlying asthma pathology, but also generate new information for better design of therapeutics directed against specific mediators of this debilitating and widespread disease.Read moreRead less
Mechanism Of Exacerbations In Cystic Fibrosis Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$254,876.00
Summary
Cystic Fibrosis lung disease is characterised by infeciton with a bug called Pseudomonas aeruginosa. Patients ultimately die in their mid-30's as a result of this infection, but lung decline is accelerated by episodes of exacerbation when patients cough up large volumes of mucky sputum. We are studying the casue of exacerbations by looking at bacterial behaviour and the response of the immune system. We will use this information to try and develop early warning signals and better treatments.
Evolution And Function Of A Novel Lateral Flagellar Locus, Flag-2, In Pathogenic Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$465,158.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified a novel genetic region that allows E. coli to survive and persist in the intestine. Similar genes are also present in closely related organisms. This project will help us to undestand how new diseases evolve and emerge and may lead to the development of new vaccines to protect against infant diarrhoea.
Contribution Of Nuclear Targeting Of The NleE-OspZ Family Of Proteins To Escherichia Coli And Shigella Virulence
Funder
National Health and Medical Research Council
Funding Amount
$542,462.00
Summary
This project will study how the bacteria that cause infant diarrhoea colonize the intestine and induce disease. We have identified new bacterial proteins that allow E. coli to manipulate the normal host cell processes involved in killing an invading bacterium. Similar proteins are also present in the closely related organism, Shigella which causes dysentary. We will determine how these proteins act by finding the host cell proteins they bind.
THE INTERFACE BETWEEN INNATE AND ADAPTIVE IMMUNITY
Funder
National Health and Medical Research Council
Funding Amount
$4,905,420.00
Summary
Allergic disorders including asthma are amongst the most prevalent diseases in Australia afflicting up to 25% of the population and costing the Australian Government in excess of $600 million annually. This program aims to understand the molecular and cellular mechanisms controlling airway inflammation, focusing on the cross-talk between scavenger cells at airway surfaces and circulating cells of the immune system. These studies will combine sophisticated mouse models of airway inflammation in t ....Allergic disorders including asthma are amongst the most prevalent diseases in Australia afflicting up to 25% of the population and costing the Australian Government in excess of $600 million annually. This program aims to understand the molecular and cellular mechanisms controlling airway inflammation, focusing on the cross-talk between scavenger cells at airway surfaces and circulating cells of the immune system. These studies will combine sophisticated mouse models of airway inflammation in the laboratory with clinical investigation and analysis of human tissue. Understanding these processes will translate into better treatments for patients suffering from life-threatening allergy and asthma.Read moreRead less
Regulatory Roles Of Mast Cells In Cutaneous Dermatitis In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$586,965.00
Summary
Allergic conditions that can affect the skin, such as contact dermatitis or eczema are common amongst Australians. Although not life threatening, these common skin conditions can cause considerable physical diability and be expensive to treat. The major focus of our research is to define how dermal mast cells can be modulated to help limit the tissue changes and damage associated with these skin conditions, and ultimately develop improved treatments in the future.
Understanding The Immune Mechanisms Leading To Resolution Of Peanut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$602,472.00
Summary
Food allergy affects up to 10% of children and rates are rising. The greatest rise has been in peanut allergy which is the commonest cause of life threatening reactions. Currently, there is no cure for food allergy. Management relies on food avoidance which is impossible to achieve. Recent deaths in children from food allergy highlight the need for an effective treatment. This project will examine what happens when you grow out of peanut allergy. New information will lead to possible cures.
Regulation Of Skin Inflammation By Mechanosensor YAP
Funder
National Health and Medical Research Council
Funding Amount
$612,566.00
Summary
Atopic diseases are a significant public health burden in the developed world. The economic cost of care and reduced quality of life for asthmatics necessitates that greater action and resources be directed toward the treatment and prevention of the atopic march. This project aims to identify molecular regulators of this disease process which may identify novel targets for therapy and early intervention.
Human CD4+ T-cell Epitope-based Therapeutic For Peanut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$403,121.00
Summary
Peanut allergy affects ~2% of the population and peanuts are the major cause of fatal food-induced anaphylaxis. Peanut allergy usually appears in infancy and persists indefinitely. At present, unlike grass pollen allergy, there is no preventative treatment. Using blood cells from peanut-allergic patients, we will identify the components of major peanut allergens to use in _allergy shots� to develop tolerance on peanut exposure without risking anaphylaxis.