In the asthmatic lung structural changes, such as increased deposition of proteins which form the scaffolding of the airways (the extracellular matrix proteins), and an increased mass of bronchial smooth muscle cells occur. Many of these critical structural changes are not reversed or prevented with current asthma therapy, thus we need to investigate, by using lung cells and tissues , why they happen and how we can prevent them.
MKP-1 As A Novel Anti-inflammatory Strategy In Asthma And Airway Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$461,528.00
Summary
Asthma is a chronic disorder where airways are remodelled, or thickened, resulting in poor lung function. Airway remodelling is a consequence of long-term inflammation after multiple episodes of asthma. As the current drugs to treat remodelling have side effects, the aim of this grant is to investigate a novel anti-inflammatory strategy to reverse the development of airway remodelling by increasing the anti-inflammatory protein - MKP-1.
The Role Of Reduced Lung Volume In The Pathogenesis Of Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$275,095.00
Summary
Asthma is a disease for which the cause is not understood. This project is designed to examine the possibilty that breathing at low volumes causes an abnormality in the smooth muscle of the airways that predisposes them to the airway hyperresponsiveness of asthma.
Genetic Dissection Of The Function Of The Src Family Tyrosine Kinase Hck In Inflammatory Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$323,750.00
Summary
This project aims to identify better and safer treatments for serious, life-threatening inflammatory lung diseases, such as Chronic Obstructive Lung Disease (COPD), which affect over 600 million people worldwide and are a major health problem in Australia. There are no effective treatments that can reverse or slow these diseases. The research is based on our recent discovery that an enzyme called Hck might play a very important role in lung disease. We used mice in which a genetic method had bee ....This project aims to identify better and safer treatments for serious, life-threatening inflammatory lung diseases, such as Chronic Obstructive Lung Disease (COPD), which affect over 600 million people worldwide and are a major health problem in Australia. There are no effective treatments that can reverse or slow these diseases. The research is based on our recent discovery that an enzyme called Hck might play a very important role in lung disease. We used mice in which a genetic method had been used to change Hck into its active form. The mice appeared normal when they were born but developed a progressive lung inflammation that resembled serious human lung diseases. Surprisingly, the mice also displayed enhanced responses to substances from bacteria that can infect the lung - a so-called innate immune response. This led us to conclude that the main problem in the mice was actually enhanced innate immunity - which is usually protective - turning against the lung to cause disease. To understand exactly what controls this fine balance between protection and lung damage, we will use new and sophisticated gene modification methods that allow us to target changes in Hck activity to specific cells that we suspect are the main cause of the disease. In doing so we will add special tags into these cells, so that we can isolate the controlling molecules in the disease process. We are particularly interested in a cell called the macrophage, a major defensive cell in the lung that is also known to be capable of causing lung disease. Our aim is to find disease-controlling molecules that could be blocked with new drugs that would suppress disease but spare defenses against lung infections.Read moreRead less
The Role Of Src Family Tyrosine Kinases In Inflammatory Lung Disease And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
We aim to learn why some people develop COPD, a serious lung disease, and adenocarcinoma, a common fatal lung cancer. COPD is mostly caused by cigarette smoke which induces lung inflammation. Lung inflammation, which involves macrophage activation, is a major cancer risk. Macrophages can destroy lung tissue, and they may promote cancer development. We will study the role of Src kinases, which can regulate macrophage activation, which may lead to new treatments for these diseases.
Is Lyn Tyrosine Kinase A Predictor Of Severe, Persistent Multi-trait Asthma And Allergy?
Funder
National Health and Medical Research Council
Funding Amount
$250,250.00
Summary
Asthma is a major health problem in Australia affecting over 10% of the population at any time, and more than 25% of the population at one stage in their lives. Although the public perception is that asthma treatments have improved management of the disease, more than 700 people die from severe asthma each year and hospitalisation from exacerbation (sudden worsening) is one of the most costly components of the health care burden in Australia and most developed countries. Currently there are no m ....Asthma is a major health problem in Australia affecting over 10% of the population at any time, and more than 25% of the population at one stage in their lives. Although the public perception is that asthma treatments have improved management of the disease, more than 700 people die from severe asthma each year and hospitalisation from exacerbation (sudden worsening) is one of the most costly components of the health care burden in Australia and most developed countries. Currently there are no molecular markers that can predict who will get severe asthma and there are no specific treatments to reverse severe exacerbations. This project will use advanced molecular biology methods to examine whether a molecule called Lyn may be important. The Lyn tyrosine kinase is a member of a family of genes that participate in transmitting information across the cell membrane. This enzyme is expressed in blood cells, and is involved in mechanisms pertaining to infection, immunity and allergic responses. To further our understanding of the role of this enzyme in the context of the whole animal, we have generated mice that are unable to make Lyn protein (Lyn-deficient mice). In animal models of asthma we know that if Lyn is not functioning, severe and persistent asthma develops. We have also made preliminary studies that suggest that Lyn does not work properly in people who have been admitted to the emergency ward with life threatenting asthma. In this study we will examine in detail the role that Lyn plays in asthma and allergy, and we intend to identify the pathways that give rise to asthma in Lyn-deficient mice. We will also investigate our hypothesis that Lyn activity may be reduced or disregulated in patients with asthma and allergy. This research should lead to better predictive markers for severe asthma and also to improved and specific treatments.Read moreRead less