The Role Of MicroRNAs As New Anti-inflammatory Targets For The Treatment Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$625,655.00
Summary
Asthma is a significant health and economic burden to our society and its prevalence has increased over the last 25 years. New ways of treating asthma are urgently required as current therapeutics treat the symptoms and not the cause of the disease. Asthma is widely thought to be due to the abnormal accumulation of white blood cells (inflammation) in the lungs of diseased individuals. In this project we are exploring new advanced ways to inhibit inflammation and the development of disease.
Role Of IL-3 In Allergic Inflammation: Modulation Of Basophils, Mast Cells, Eosinophils And Remodelling In Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$495,380.00
Summary
Asthma is an important disease in the Australian community. We will investigate how the underlying inflammation in this disease is controlled and will focus our studies on a hormone-like regulator of the immune system called interleukin-3. Our hypothesis is that interleukin-3 regulates basophils, mast cells and remodelling of the airways which are central features of asthma. This study will give a better understanding of how the inflammation is caused and information for new drug targets.
The Role Of MicroRNAs In The Regulation Of Antiviral And Inflammatory Responses During Experimental Rhinovirus Infection
Funder
National Health and Medical Research Council
Funding Amount
$605,096.00
Summary
Asthma exacerbations due to viral infections are a major health and economic burden to our society. Treatment of asthma exacerbations focuses on reducing the symptoms rather than the cause of the disease. Virus-induced asthma exacerbation are widely thought to be due to an abnormal influx of white blood cells into the lungs (inflammation) and an altered anti-viral responses. In this project we will explore novel strategies to inhibit inflammation and to promote the anti-viral response.
Negative Modulators Of Leucocyte Recruitment In The Kidney. The Role Of Slit And Robo.
Funder
National Health and Medical Research Council
Funding Amount
$368,100.00
Summary
Kidney failure is a major health problem in our community, affecting the lives of several thousand individuals and their families. Every year in Australia, about 2,000 new individuals commence dialysis and require ongoing treatment for the rest of their lives. The significant negative impact kidney failure has on quality of life and on life expectancy added to the major shortage of transplant organs, makes the development of effective therapies for kidney diseases an important goal. Our current ....Kidney failure is a major health problem in our community, affecting the lives of several thousand individuals and their families. Every year in Australia, about 2,000 new individuals commence dialysis and require ongoing treatment for the rest of their lives. The significant negative impact kidney failure has on quality of life and on life expectancy added to the major shortage of transplant organs, makes the development of effective therapies for kidney diseases an important goal. Our current therapies have major limitations in terms of their effectiveness and side effects. New therapies which can prevent the progression of kidney disease or prolong the survival of transplanted kidneys may, therefore, have enormous benefits. In order for this to occur, an improved understanding of the common factors underlying kidney disease is required. Our recent studies have been examining the factors influencing kidney inflammation. This process is a significant cause of long term damage in various kidney diseases and in kidney transplants. Our work has identified a potentially major role for recently discovered molecules known as Slit proteins in preventing or decreasing inflammation in the kidney. The level of expression of these molecules in the kidney appears to be rapidly decreased in kidney inflammation and their protective effect is then lost. This imbalance appears to promote the disease process and may be a useful target for the treatment of certain kidney diseases. Our work has found that Slit proteins are able to decrease the movement of white cells (the cells which cause inflammation) out of the blood circulation and into the kidney. The proposed studies aim to better understand the role of these molecules in the kidney as naturally expressed anti-inflammatory agents and to test their potential as therapeutic agents. We hope that the information obtained from these studies will help in the development of new therapies to manage various forms of kidney disease.Read moreRead less
The Role Of Pulmonary Macrophages In The Pathogenesis Of An Acute Exacerbation Of Chronic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$495,710.00
Summary
We will examine the role of lung defence cells, known as macrophages, in triggering the inflammation of acute severe asthma. The experimental work will use unique mouse models of mild chronic asthma and of an acute exacerbation of the illness, which have been developed in our laboratories. We will study the mechanisms of activation of the asthmatic response and assess whether treatment with drugs that suppress the function of macrophages can help to control steroid-resistant exacerbations.
Regional Mechanisms Of Ventilator Induced Lung Injury: Insights From Dynamic Lung Imaging
Funder
National Health and Medical Research Council
Funding Amount
$623,323.00
Summary
Mortality rates due to acute respiratory distress syndrome (ARDS) are high (>30%). While ARDS requires mechanical ventilation as a lifesaving intervention, it is clear that mechanical ventilation itself can contribute to the high mortality rates. We will use a new lung imaging technology (CTXV) to visualize the damage that occurs to the lung as a result of mechanical ventilation in order to design better ventilation strategies and reduce mortality rates in these critically ill patients.
Role Of Myeloperoxidase In Endothelial Barrier Dysfunction During Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$302,123.00
Summary
The release of the enzyme myeloperoxidase (MPO) within blood vessels is thought to affect their ‘leakiness’ during periods of inflammation, leading to fluid associated swelling (oedema). We propose that MPO produces oxidant chemicals that increase blood vessel leakage. The aim of our work is to study how these chemicals increase vascular leakage by studying the biochemical pathways involved. These studies could lead to new intervention strategies targeting MPO to reduce excessive tissue oedema.
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
Influence Of Early-life Viral Infection On Severity Of Murine Chronic Asthma And Acute Exacerbations
Funder
National Health and Medical Research Council
Funding Amount
$508,528.00
Summary
This project examines the relationship between certain childhood infections with respiratory viruses and the progression of asthma later in life. The experimental work will use mouse models of mild chronic asthma and of an acute exacerbation of the illness -- these unique models have been developed in the laboratories of the chief investigators. It will employ the most appropriate mouse models of infection by the relevant group of viruses. We expect to obtain new information about mechanisms of ....This project examines the relationship between certain childhood infections with respiratory viruses and the progression of asthma later in life. The experimental work will use mouse models of mild chronic asthma and of an acute exacerbation of the illness -- these unique models have been developed in the laboratories of the chief investigators. It will employ the most appropriate mouse models of infection by the relevant group of viruses. We expect to obtain new information about mechanisms of airway inflammation and airway hyper-reactivity, which are characteristic features of chronic asthma and of acute exacerbations. This could help to identify candidate signalling molecules and pathways that could be targeted by new treatments. The findings might also provide a basis for development of ways to modify the immune response after respiratory viral infection in childhood.Read moreRead less