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Mast Cell Proteases Suppress Respiratory Viral Infections And Alleric Inflammation Of The Airways
Funder
National Health and Medical Research Council
Funding Amount
$665,532.00
Summary
Severe RSV infection and asthma accounts for poor quality of life in our community and current treatments have limited effects. Although the factors regulating these disorders are poorly understood, mast cells (MCs) may play important roles. We have shown MC protease-6 protects against viral infection. Here we will identify how MC and their factors are involved in the control of severe respiratory infections and allergic disease of the lung, and identify potential new ways to treat these conditi ....Severe RSV infection and asthma accounts for poor quality of life in our community and current treatments have limited effects. Although the factors regulating these disorders are poorly understood, mast cells (MCs) may play important roles. We have shown MC protease-6 protects against viral infection. Here we will identify how MC and their factors are involved in the control of severe respiratory infections and allergic disease of the lung, and identify potential new ways to treat these conditions.Read moreRead less
Targeting MicroRNA (miRNA) As A Unified Therapeutic Approach To The Treatment Of Asthma And Allergic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$675,030.00
Summary
Approximately 30% of our community suffers from allergic inflammation (asthma/rhinitis/dermatitis) that results in poor quality of life. The factors regulating these disorders are poorly understood and current treatments only target the symptoms and not the cause of disease. MicroRNA control gene expression and are emerging as potential regulators of inflammation. This project will identify the role of microRNA in the regulation of allergic diseases and their potential as new therapeutic targets ....Approximately 30% of our community suffers from allergic inflammation (asthma/rhinitis/dermatitis) that results in poor quality of life. The factors regulating these disorders are poorly understood and current treatments only target the symptoms and not the cause of disease. MicroRNA control gene expression and are emerging as potential regulators of inflammation. This project will identify the role of microRNA in the regulation of allergic diseases and their potential as new therapeutic targets.Read moreRead less
Airway Inflammation In Allergic Aspergillosis: Characterisation, Immunologic Mechanisms And Treatment.
Funder
National Health and Medical Research Council
Funding Amount
$242,562.00
Summary
Aspergillus fumigatus is a fungus that commonly occurs in our community. In some people with asthma, this fungus causes the asthma to become severe and chronic. It may also be associated with a severe form of lung destruction called bronchiectasis. There is little known about the chemicals produced by the body which contribute to inflammation in this condition. Similarly, it is not known why only some people with asthma develop an allergic disease to this fungus. In this project we will examine ....Aspergillus fumigatus is a fungus that commonly occurs in our community. In some people with asthma, this fungus causes the asthma to become severe and chronic. It may also be associated with a severe form of lung destruction called bronchiectasis. There is little known about the chemicals produced by the body which contribute to inflammation in this condition. Similarly, it is not known why only some people with asthma develop an allergic disease to this fungus. In this project we will examine 2 important inflammation chemicals (called cytokines) to examine what their role is in aspergillus associated allergy. We will also examine 2 genetic markers to establish whether these predispose to people developing allergy to aspergillus. The treatment of aspergillus lung disease is also problematic. In this project we will examine whether a new medication called itraconazole is effective in removing this fungus from the airway and improving asthma.Read moreRead less
Targeting MiRNA To Inhibit Leukocyte Differentiation: A Novel Anti-inflammatory Approach For The Treatment Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$601,386.00
Summary
In asthma, the symptoms are caused by an allergic reaction in the lung and the production of inflammatory cells whose maturation is guided by tiny molecules called “microRNAs”. The critical microRNAs will be identified and strategies to block their function developed and tested for their ability to inhibit allergic inflammation to evaluate this approach as a new treatment for asthma.
Understanding The Mechanisms Of Steroid Resistant Inflammatory Pathways In Mouse Models Of Asthma: Potential New Treatment Approaches
Funder
National Health and Medical Research Council
Funding Amount
$523,694.00
Summary
Steroids are used to treat asthma but some patients are resistant to therapy, and there is no effective treatment. Such patients suffer greater morbidity and mortality, and the heath care cost for clinical management is a significant economic burden. In this project we will obtain a better understanding of the mechanisms that regulate steroid-resistant components of disease, which control inflammation and narrowing of the airway. These studies will be central to the development of new therapies.
Australia has one of the highest asthma rates in the world. In this project we will study how natural regulatory T cells suppress asthma in a mouse model. We will determine where and when interactions between regulatory T cells and allergic T cells occur, and define the mechanisms used by regulatory cells to mediate their suppressive effects. Our findings will aid in understanding why asthma develops and how it may be controlled by the immune system itself.
Effects Of Allergens On Dendritic Cell Function In Allergic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
In recent decades, there has been a nearly three-fold increase in the prevalence of allergic diseases such as asthma. Although the reason these diseases have increased in prevalence remains unknown, we suspect the way in which the immune system responds to foreign proteins in the environment may be very important in determining whether an individual develops allergic disease or not. How and why individuals with allergic asthma respond excessively and inappropriately to inhalation of a small rang ....In recent decades, there has been a nearly three-fold increase in the prevalence of allergic diseases such as asthma. Although the reason these diseases have increased in prevalence remains unknown, we suspect the way in which the immune system responds to foreign proteins in the environment may be very important in determining whether an individual develops allergic disease or not. How and why individuals with allergic asthma respond excessively and inappropriately to inhalation of a small range of seemingly innocuous proteins (allergens) is a central question in respiratory medicine and allergy. We propose that investigating the way that antigen presenting dendritic cells (DC) respond directly to allergens will shed important light on this issue, as DC are fundamental to our ability to deal with foreign antigens and to generate an appropriate immune response. The overall hypothesis underpinning this proposal is that allergens induce specific responses in DC from individuals with allergic asthma, and that this contributes to the maintenance and amplification of allergic tissue inflammation in this disease. Understanding the ways in which DC respond to clinically relevant allergens will lead to significant progress in understanding the pathogenesis of allergic asthma. This project was recommended for funding last year, but was relinquished when one of the previous co-investigators on last year's grant was awarded a Program grant.Read moreRead less
Phenotypic And Functional Characterisation Of CD4 T Helper 22 Cells And Their Role In The Regulation Of Chronic Allergic Disease Of The Lung And Skin
Funder
National Health and Medical Research Council
Funding Amount
$714,061.00
Summary
Allergic inflammatory diseases such as asthma and allergic dermatitis are major health problems in our community that lead to poor quality of life. These diseases are induced by activation of immune cells known as T helper (Th) lymphocytes. Recently Th22 cells have been identified in patients with allergic diseases. In this study we will, for the first time, characterise these cells and determine their role in the processes that lead to chronic inflammation in asthma and allergic dermatitis.
Targeting The Shared Beta-chain Of The IL-3, IL-5 And GM-CSF Receptors As Therapy For Allergic Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$610,037.00
Summary
This research aims to develop new treatments for allergic diseases such as asthma and allergic rhinitis, which remain significant public health problems in Australia. We will develop therapies targeting a common receptor pathway with the potential to completely suppress acute and chronic disease whilst maintaining a single molecular target. We will perform preclinical testing of antibodies for treatment of allergic disorders using a novel mouse strain expressing the human form of this receptor
The Pathogenesis Of Distinct Endophenotypes Of Asthma Is Underpinned By The Collaborative Activation Of Specific PRRs.
Funder
National Health and Medical Research Council
Funding Amount
$678,754.00
Summary
Asthma is a chronic airway disease caused by inflammation. Although asthmatics can be sub-typed based on the type of inflammatory cells present in the lungs, medication specific for the treatment of these sub-types is not yet available. In this grant we will investigate the immune processes that orchestrate the development of the distinct inflammatory sub-types of asthma. This information will help us develop new therapies that will be tailored to target the appropriate type of inflammation.