Understanding The Mechanisms Underlying Airway Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$451,716.00
Summary
Changes in the structure of the lung contribute to the development of disease, but are not responsive to our current therapies. I have found two key structural proteins that are altered in asthma. This research will characterise the regulation and role of these proteins in the disease process. In addition, it will determine if these proteins also contribute to the development of other serious fibrotic diseases, for which there are no current treatments.
Elucidation Of The Aetiology Of Airway Remodelling In COPD
Funder
National Health and Medical Research Council
Funding Amount
$626,979.00
Summary
This project grant aims to discover how cigarette smoking induces the development of Chronic Obstructive Pulmonary Disease (COPD) by understanding how smoking drives the key pathological charges in the airways, airway remodelling. Our research to-date has found that cells from people with COPD have an hightened response to cigarette smoke and we aim to uncover the molecular basis of this aberrant response.
Airway Extracellular Matrix And Smooth Muscle In Chronic Obstructive Pulmonary Disease (COPD)
Funder
National Health and Medical Research Council
Funding Amount
$828,849.00
Summary
In asthma the layer of airway smooth muscle is thicker, due to more muscle cells. Airway narrowing is excessive but reversible. In chronic obstructive pulmonary disease (due mainly to smoking) the layer of airway smooth muscle is also thicker but the airways cannot be induced to open, or close. Our data suggest that this fixed airway narrowing is likely to be due to an excess of matrix between cells rather than muscle. This project will comprehensively test this new finding.
Therapeutic Regulation Of Matrix Metabolism To Stabilise The Biomechanical Properties Of The Sclera In High Myopia
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily correctable with spectacles or contact lenses. However a small, but significant, group of individuals have excessively long eyes and extreme amounts of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light s ....Myopia (short-sightedness) is due to the eye being too long. It is a common refractive disorder, affecting some 25-30% of people in developed countries, and results in blurred distance vision. Most myopia is easily correctable with spectacles or contact lenses. However a small, but significant, group of individuals have excessively long eyes and extreme amounts of myopia. These enlarged eyes impose abnormal stresses on the structures inside, particularly affecting the retina which is the light sensitive part of the eye. Any damage that occurs to the retina in these eyes is, at present, untreatable and irreversible and can result in blindness. In fact, myopia is the 2nd leading cause of blindness amongst adults of working age. In order for the eye to grow so large its white, outer coat (the sclera) must expand without allowing any leaks of the delicate structures and fluids inside. Although the sclera gets very thin as it expands, it has been shown that this process of expansion is not just due to stretching. Before any stretching can occur the biochemical structure of the sclera must change. A complex process, involving the synthesis of structural components and the activity of enzymes that breakdown these structural components, is at work in the sclera of eyes that are rapidly enlarging. The aim of this project is to intervene in the biochemical processes that have already been shown to be involved in excessive eye enlargement. We will use both therapeutic agents and innovative gene therapy techniques to reverse the biochemical changes that occur in the sclera of rapidly enlarging eyes. We predict that these therapies will result in a sclera that is more resistant to being stretched and an eye that has less pathology. The results from this study will provide us with potential therapeutic strategies for the treatment of eyes that are enlarging excessively, thereby giving us the opportunity of preventing blindness in a number of highly myopic individuals.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
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.