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Asthma is a significant burden to the health care system and to individual sufferers. Currently we can treat asthma with corticosteroids to reduce inflammation in the lung but the side effects of these medications, particularly in children, make them less than ideal treatments. In order to design a more specific treatment for asthma, which would only target the inflammatory cells which are involved in the lung, we need to understand how these cells behave and what initiates the cascade of events ....Asthma is a significant burden to the health care system and to individual sufferers. Currently we can treat asthma with corticosteroids to reduce inflammation in the lung but the side effects of these medications, particularly in children, make them less than ideal treatments. In order to design a more specific treatment for asthma, which would only target the inflammatory cells which are involved in the lung, we need to understand how these cells behave and what initiates the cascade of events in the lung. This project is designed to investigate how chemical mediators, cytokines, are produced by various cells in the lung and how they induce lung cells to make structural changes to the lung tissue and increase the inflammation. The source and specific types of cytokines released are being investigated to provide important information regarding the disease process of asthma. From this new knowledge, design of specific new treatments, with fewer unwanted side-effects, should be possible.Read moreRead less
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.
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.
Understanding The Role Of Th22 Cells In Regulating Respiratory Immune Responses In Health And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$870,476.00
Summary
T cells that produce the cytokine IL-22 (Th22 cells) are found in infectious and inflammatory lung disease. However, the role of Th22 cells in promoting or preventing disease remains largely unknown. We have discovered how to grow Th22 cells and have generated a unique strain of IL-22 reporter mice, which will allow us to identify their role in infectious and inflammatory diseases. Our investigations will provide new insights into therapeutic approaches for these diseases of the lung.
Targeting An Epigenetic Silencing Pathway To Treat Allergic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Asthma affects around 11% of the Australian population and costs the health care system around $28 billion. Unfortunately there is still no cure and treatments have not changed for decades. This project aims to discover new drugs to treat asthma by re-wiring the cells of the immune system which cause the disease.
Anti-viral Immunity In Asthma: A Detailed Assessment Of TLR7 Function And The Regulation Of Interferon ?/? Synthesis.
Funder
National Health and Medical Research Council
Funding Amount
$517,156.00
Summary
Many people with asthma are unusually vulnerable to viral infections. This study will carefully examine different components of immune function in people with asthma, including the receptors that respond to viral nucleic acids and the reasons why people with asthma do not produce normal quantities of anti-viral interferons. This research may lead to novel methods for prevention and treatment of virus infections in people with asthma.
Airway Inflammation In Asthma And Chronic Obstructive Pulmonary Disease
Funder
National Health and Medical Research Council
Funding Amount
$390,509.00
Summary
In chronic diseases of the airway such as asthma and airway narrowing due to cigarette smoking - chronic obstructive pulmonary disease (COPD), the airways show inflammation (increased numbers of cells and their products) and remodelling (increased thickness and scarring) which persist for many years, possibly indefinitely. The exact mechanisms by which inflammation persists in the airway wall in asthma and COPD are unknown. We and others have shown that greater numbers of memory T-lymphocytes (T ....In chronic diseases of the airway such as asthma and airway narrowing due to cigarette smoking - chronic obstructive pulmonary disease (COPD), the airways show inflammation (increased numbers of cells and their products) and remodelling (increased thickness and scarring) which persist for many years, possibly indefinitely. The exact mechanisms by which inflammation persists in the airway wall in asthma and COPD are unknown. We and others have shown that greater numbers of memory T-lymphocytes (T-cells) are present in the airway wall in asthma and COPD. T-cells orchestrate the processes involved in inflammation. We have hypothesised that the persistence of airway inflammation in asthma and COPD results from the proliferation of memory T-cells within the airway wall. Unlike na ve T-cells, memory T-cells have previously been stimulated and can easily be activated to proliferate and promote inflammation by other cells which are fixed in the airway. Data from our current work examining this process suggests that, although cells fixed in the airway such as fibroblasts and macrophages are activated in asthma and COPD and may activate T-cells, they do not seem to be causing T-cell proliferation. We now wish to extend these studies by determinimg if memory T- lymphocytes are proliferating in the airway wall within aggregations of lymphoid cells which act like lymph nodes and promote T-cell growth. To do this we will compare the number of these aggregations and the types of T-cells they contain in mild and severe cases of asthma and COPD with those in normal subjects. This work will provide new knowledge to help understand the mechanisms for the persistance of airway inflammation in asthma and COPD and may thereby also provide a focus for effective treatments of these condition.Read moreRead less
Asthma Prevention And Treatment Using UVB Radiation-induced Immunomodulation
Funder
National Health and Medical Research Council
Funding Amount
$496,446.00
Summary
The prevalence of asthma is increasing despite the adoption of modern expensive drugs. Our studies suggest that exposure of skin to an erythemal dose of the wavelengths of UVB radiation found in sunlight can suppress responses to allergens encountered in the airways. We are requesting support to study the mechanisms in mice by which exposure to UVB radiation on their shaved backs can reduce inflammation in the airway mucosa upon allergen exposure. Whole body immunomodulatory effects of UVB radia ....The prevalence of asthma is increasing despite the adoption of modern expensive drugs. Our studies suggest that exposure of skin to an erythemal dose of the wavelengths of UVB radiation found in sunlight can suppress responses to allergens encountered in the airways. We are requesting support to study the mechanisms in mice by which exposure to UVB radiation on their shaved backs can reduce inflammation in the airway mucosa upon allergen exposure. Whole body immunomodulatory effects of UVB radiation have been previously described but have not been scientifically linked with asthma development. This is a very new and novel research area which supports century-old anecdotal reports that holidays at beach and mountain resorts associated with increased UVB exposure are beneficial in asthma treatment. This is a proof of principle study. If we can confirm that UVB is immunomodulatory and better understand the mechanisms by which UVB suppresses inflammation in the airways, we will investigate the potential of non-carcinogenic, UVB-induced, skin-derived intermediary molecules to have the same regulatory effects.Read moreRead less