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Initiating Events In The Development Of Allergic Airway Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$452,545.00
Summary
Despite recent advances we still do not understand the basic mechanisms which underlie the development of allergic airway inflammatory diseases such as rhinitis and asthma. It has been previously shown that when pollen are exposed to water they release a large number of very small starch granules which contain a number of potent allergens as well as plant steroids. In addition house dust mite allergens which are strongly associated with asthma are mostly located in small faecal pellets. Both the ....Despite recent advances we still do not understand the basic mechanisms which underlie the development of allergic airway inflammatory diseases such as rhinitis and asthma. It has been previously shown that when pollen are exposed to water they release a large number of very small starch granules which contain a number of potent allergens as well as plant steroids. In addition house dust mite allergens which are strongly associated with asthma are mostly located in small faecal pellets. Both these particles are ideally sized to enter the respiratory tract and initiate inflammatory responses. We have shown that these responses appear to be of the type that is needed to initiate allergic reactions. We intend to further study the interactions of these small inhaled allergen containing particles with cells of the respiratory tract. In this proposal we will look at both alveolar macrophages and respiratory epithelial cells. These approaches will not only provide new information about the processes of airway inflammation caused by allergens but may also define new therapeutic approaches to the treatment of these diseases.Read moreRead less
Immunity To Colonising Bacteria Of The Respiratory Tract In Atopic And Non-atopic Children
Funder
National Health and Medical Research Council
Funding Amount
$246,478.00
Summary
Evidence that seemingly harmless and common bacterial infections have a role, in the development of allergic disease has been uncovered. The development of immune responses to these microbes will be studied in children with and without allergy to inhalant allergens.
Studies On The Effects Of RSV Infection During Infancy On Aeroallergen-specific T-cell Immunity And Lung Function
Funder
National Health and Medical Research Council
Funding Amount
$130,475.00
Summary
Many infants who develop transient severe wheezing in association with respiratory infections, go on to develop asthma which can persist throughout childhood and some times into adult life. It is not known whether the respiratory infections are a direct cause of later asthma, or whether they simply function as flag which identifies children who have a genetic predisposition to wheeze e.g. because they have abnormally narrow airways. This project will compare the effects of respiratory infection ....Many infants who develop transient severe wheezing in association with respiratory infections, go on to develop asthma which can persist throughout childhood and some times into adult life. It is not known whether the respiratory infections are a direct cause of later asthma, or whether they simply function as flag which identifies children who have a genetic predisposition to wheeze e.g. because they have abnormally narrow airways. This project will compare the effects of respiratory infection in infants with the RSV virus, who contract the disease at different ages, and who have varying levels of genetic risk for respiratory allergies. In particular, it will examine the possibility that in certain cases, infection of genetically susceptible individuals during early infancy will boost the development of allergies to airborne environmental allergens (such as house dust mite) which are known to trigger asthma attacks in older children and adults.Read moreRead less
Perioperative Administration Of Dexamethasone And Infection- The PADDI Trial
Funder
National Health and Medical Research Council
Funding Amount
$4,832,815.00
Summary
The PADDI Trial is a large (8,800 patients) international, multicentre, randomised, controlled, non-inferiority safety and effectiveness study that will run for five years. It will examine the benefits and complications of administering 8mg of a steroid drug (dexamethasone) to adult patients undergoing non-urgent surgical procedures who receive general anaesthesia. The main outcome is surgical site infection 30 days after surgery. The influence of diabetes will also be investigated.
Inhibition Of Allergic Airway Inflammation By Nanoparticles
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Inhaled air pollution particulate matter causes asthma exacerbations, with 'ultrafine' nanoparticles thought to play a major role. Unexpectedly, we recently found that, by contrast, administration of inert ultrafine nanoparticles prevents allergic airway inflammation. We will identify the key particle physical and chemical properties associated with this novel type of disease inhibition, study particle effects in clinically-relevant disease models and identify mechanisms of action.
Mechanisms And Treatment Of Early Life Chlamydial Infection And Associated Asthma
Funder
National Health and Medical Research Council
Funding Amount
$616,195.00
Summary
Asthma is a serious respiratory disease that results from certain immune responses to allergens and there are no cures. Immune responses and lung structure may be permanently altered by respiratory chlamydial infection early in life that leads to reduced lung function and asthma but how this occurs is unknown. In this project we will determine how early life infections affect immune responses, lung function and asthma and test novel treatments and preventions for infection-associated asthma.
This project will examine new ways in which the major effector cells of allergy migrate to sites of inflammation, such as the lung and the skin and are activated locally by a novel S100 protein mediator. We have found a natural protein of the innate immune system, present in macrophages and neutrophils in the lungs of patients with acute fatal asthma, which activates mast cells causing release of mediators that trigger asthma attack. We have identified a potential receptor for this protein on hu ....This project will examine new ways in which the major effector cells of allergy migrate to sites of inflammation, such as the lung and the skin and are activated locally by a novel S100 protein mediator. We have found a natural protein of the innate immune system, present in macrophages and neutrophils in the lungs of patients with acute fatal asthma, which activates mast cells causing release of mediators that trigger asthma attack. We have identified a potential receptor for this protein on human mast cells grown in culture. We will characterise the chemical nature of this receptor and verify that it is functionally important in mast cell activation. Because mast cells reside in almost all body tissues and are also important mediators of host responses to infection and in chronic inflammation such as rheumatoid arthritis and psoriasis, our studies may indicate novel and unexpected ways in which they are activated. Another key cell in allergic and parasitic diseases is the eosinophil. We have found that two other S100 proteins are expressed in eosinophils from the blood of normal individuals and that the genes that encode these proteins are regulated by mediators that regulate eosinophil migration and survival at allergic sites. However although the numbers these cells are high in lung biopsies from patients with asthma, we find that these proteins are generally not expressed. Because one of the S100 proteins, S100A9, was recently found to be important in the ability of other blood cells to migrate to signals that recruit them into tissues, we will examine whether this protein regulates the ability of eosinophils to migrate. Results from this project will provide new knowledge concerning mechanisms of allergy and may lead to the design of novel strategies to regulate the process. Results may have broader ramifications applicable to other inflammatory and infectious diseases.Read moreRead less