Development Of An In Vitro Immunodiagnostic Test For Serum IgE Specific To The Major Pollen Allergen, Pas N 1, Of The Subtropical Bahia Grass
Funder
National Health and Medical Research Council
Funding Amount
$349,435.00
Summary
Treatment of grass pollen allergy by immunotherapy reduces the risk of asthma but most reagents for diagnosis and treatment are based on cool climate grasses. We will develop a more specific diagnostic blood test for people with hay fever and allergic asthma triggered by subtropical Bahia grass pollen. This test based on the major allergen of Bahia grass pollen, Pas n 1, will help people who need improved accuracy of diagnosis and more effective treatment outcomes for hay fever and allergic asth ....Treatment of grass pollen allergy by immunotherapy reduces the risk of asthma but most reagents for diagnosis and treatment are based on cool climate grasses. We will develop a more specific diagnostic blood test for people with hay fever and allergic asthma triggered by subtropical Bahia grass pollen. This test based on the major allergen of Bahia grass pollen, Pas n 1, will help people who need improved accuracy of diagnosis and more effective treatment outcomes for hay fever and allergic asthma.Read moreRead less
Towards Reducing The Susceptibility Of “high Risk” Infants To Allergic Asthma By Therapeutic Modulation Of Immunoregulatory Functions In The Pregnant Mother.
Funder
National Health and Medical Research Council
Funding Amount
$445,681.00
Summary
This project will deliver information in relation to the potential use and underlying modes of action of a therapeutic agent fed to pregnant mothers at high risk for atopic children, to protect against allergic asthma development in their offspring. Furthermore, the project will address the benefits of this therapeutic agent in relation to protection against inflammation induced preterm birth.
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
The Significance Of Aeroallergens In Eosinophilic Esophagitis
Funder
National Health and Medical Research Council
Funding Amount
$117,331.00
Summary
Eosinophilic esophagitis is an allergic condition that causes difficulty swallowing food and chest discomfort.Current diagnostic methods are inaccurate, and treatments are not curative. This project aims to clarify the role of promising new diagnostic techniques and to delineate the significance of aeroallergens (e.g. pollens) with a view to improving the treatment of eosinophilc esophagitis in the future. It is possible that simply avoiding pollens or treating hayfever in the future may be all ....Eosinophilic esophagitis is an allergic condition that causes difficulty swallowing food and chest discomfort.Current diagnostic methods are inaccurate, and treatments are not curative. This project aims to clarify the role of promising new diagnostic techniques and to delineate the significance of aeroallergens (e.g. pollens) with a view to improving the treatment of eosinophilc esophagitis in the future. It is possible that simply avoiding pollens or treating hayfever in the future may be all that is required to manage this condition.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
Immunomodulatory Effects Of Omega-3 Polyunsaturated Fatty Acids : Role In Allergy Prevention In Infancy
Funder
National Health and Medical Research Council
Funding Amount
$537,600.00
Summary
The dramatic increase in asthma and allergic disease over the last 20-30 years has highlighted the urgent need to identify associated environmental changes that may also be logical targets for disease prevention. Although this is likely to be multifactorial, one significant change during this period has been a progressive decline in the intake of dietary anti-inflammatory n-3 polyunsaturated fats (PUFA) in Western diets, with a corresponding increase in n-6 PUFA fatty acids. We recently showed f ....The dramatic increase in asthma and allergic disease over the last 20-30 years has highlighted the urgent need to identify associated environmental changes that may also be logical targets for disease prevention. Although this is likely to be multifactorial, one significant change during this period has been a progressive decline in the intake of dietary anti-inflammatory n-3 polyunsaturated fats (PUFA) in Western diets, with a corresponding increase in n-6 PUFA fatty acids. We recently showed for the first time that n-3 PUFA may have more significant effects in very early life before immune responses are fully established. We confirmed that maternal fish oil supplementation (n-40) resulted in significantly higher n-3 PUFA levels in newborns (compared to those with no supplements, n-43), and this was related to reduced immune responses to allergens (such as house dust mite, cat and egg). These observations suggest that n-3 PUFA can modify early immune development. Although this previous study was designed to assess immune outcomes (rather than clinical outcomes) we collected preliminary clinical data for the purposes of this application. We observed a consistent trend for less allergic symptoms and sensitisation in the supplementation group. These observations clearly warrant this proposed study to confirm these clinical effects, and to assess the mechanisms of action in considerably more detail. In this proposed study we will compare the effects of fish oil (n-165) or placebo (n-165) in early infancy (from 0-6 months of age). This much larger population will allow us to determine if increasing dietary n-3 PUFA is a way of reducing the chance of allergy in families where there is a high genetic risk. Approximately 40% of infants in Australia will go on to develop asthma or allergies. Strategies such as this that reduce the risk (even slightly) or the severity of disease expression could have enormous impact in this global context at relatively little cost.Read moreRead less
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.
Defective Toll-like Receptor 7 Signalling In Plasmacytoid Dendritic Cells Underlies The Inception Of Virus-associated Asthma
Funder
National Health and Medical Research Council
Funding Amount
$552,301.00
Summary
In genetically susceptible individuals, respiratory virus infections are a risk factor for asthma inception and are the most common cause of acute exacerbations. Using a clinically relevant mouse model of disease, this study will investigate whether the altered expression of toll-like receptor 7, a host protein that senses viral invasion, causes the host to mount an inappropriate pro-allergic immune response to the virus.
Investigation Of The Association Between Chlamydial Infection And Asthma In Different Age Groups
Funder
National Health and Medical Research Council
Funding Amount
$382,117.00
Summary
Asthma is a common and severe lung disease that results from inflammation due to allergy and has symptoms of breathing difficulties, wheezing, chest tightness, and cough. Asthma is clinically characterised by the presence of certain types of responses from the immune system. We are looking for ways of preventing and curing asthma. There is a well known link between certain types of bacteria, called Chlamydia, and asthma but it is not known whether people develop asthma first and then get chlamyd ....Asthma is a common and severe lung disease that results from inflammation due to allergy and has symptoms of breathing difficulties, wheezing, chest tightness, and cough. Asthma is clinically characterised by the presence of certain types of responses from the immune system. We are looking for ways of preventing and curing asthma. There is a well known link between certain types of bacteria, called Chlamydia, and asthma but it is not known whether people develop asthma first and then get chlamydial infection or are infected first and this leads to asthma. We have shown that if adult mice are exposed to an allergen during chlamydial infection then the asthma gets worse. However, if newborn mice have a chlamydial infection then asthma is prevented when they are adults. These are preliminary observations, which we need to expand and understand the immune mechanisms that result in infection and allergy so that we can target them with antibiotics or vaccines. We will investigate how the timing of chlamydial infection relative to exposure to allergens (before, during or after) affects the development of asthma in adult mice. Newborns and young children have different immune systems to adults, so we will investigate what effects the infection of young mice has on infection and allergy later in life. We will also test a new vaccine we have developed against chlamydial infection to see if it can prevent chlamydial infection and infection-induced asthma. We will then examine if there is the same association between chlamydial infection and asthma in human asthmatics that present to hospital with exacerbation of their asthma. This work will help us develop new strategies for preventing and curing asthma, which may vary in different age groups. We will identify whether prevention of chlamydial infection by vaccination (or antibiotics) can be used to prevent and treat asthma.Read moreRead less