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Examining The Intracellular Pathways Regulated By GM-CSF In Macrophages And The Role In Diseases Such Arthritis.
Funder
National Health and Medical Research Council
Funding Amount
$63,567.00
Summary
A protein, termed GM-CSF, has been shown to be important in inflammatory conditions, like rheumatoid arthritis. GM-CSF can modify the properties of a key white blood cell, the macrophage, causing macrophages to produce factors harmful to host tissue. Various therapies are being developed to block GM-CSF, however discovering other drugs that block the intracellular actions of GM-CSF in macrophages are needed. Therefore the molecular pathways governing these actions need to be defined.
During injury or infection, our body’s immune system protects us by launching inflammation. But uncontrolled inflammation drives common diseases such as cancer, diabetes and Alzheimer’s. This project will reveal how the body produces interleukin-1? – a protein at the heart of inflammation and disease – so we can design better strategies for treating patients with inflammation-driven disease.
Inhibition Of Necroptosis As A Novel Strategy For The Prevention Of Bronchiolitis And Subsequent Asthma
Funder
National Health and Medical Research Council
Funding Amount
$658,015.00
Summary
Severe virus associated bronchiolitis is a major cause of infant mortality and a risk factor for asthma. Using a mouse model, we have shown that virus infection causes tissue damage, leading to the release of 'danger' molecules that promote excessive inflammation and tissue remodelling. We have identified an important mechanism by which the danger molecules are released. We will now assess whether blocking this process ameliorates viral bronchiolitis and breaks its nexus with subsequent asthma.
Excess inflammation is a major problem after injury and in many diseases. Upon injury molecules are release that act as danger signals to alert the immune system to start the repair process. However, high levels of these dangers signals can impair the final stages of healing. Understanding how to prevent the immune system being excessively stimulated by these danger signals is key to being able to dampen inflammation after injury improve the healing response.
The Use Of Positron Emission Tomography (PET), Novel Immune And Microbiological Biomarkers To Improve The Diagnosis And Prognostication Of Giant Cell Arteritis
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Giant cell arteritis (GCA) is an inflammatory condition of blood vessels. Diagnosing the condition and predicting which patients will develop complications is challenging. Undiagnosed, a significant proportion of patients experience sudden onset, permanent blindness. Our study aims to improve the diagnosis and risk assessment of patients with suspected GCA by following a group of 65 patients for two years with serial scans, blood tests and clinical reviews.
Innate Immune Signalling In Mycobacterium Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$562,857.00
Summary
Tuberculosis (TB) is a major global health threat that causes 1.5 million deaths every year. This study will characterise a new molecular control mechanism that optimises the immune response to the bacteria that cause TB and determine how it contributes to controlling the infection. Such knowledge is essential to help improve patient management and develop better treatments for this devastating disease.
Novel Mechanisms In Regulating Cytokine Secretion In The Inflammatory Response
Funder
National Health and Medical Research Council
Funding Amount
$323,160.00
Summary
Macrophages are key cells in the immune and inflammatory response. They play a role in many biological processes including wound healing and resistance to tumours and infections. It is also a major cell involved in mediating inflammation and tissue damage in chronic inflammatory diseases such as atherosclerosis and rheumatoid arthritis. The macrophage's role in these processes is achieved in large part by secreting enzymes and other proteins called cytokines to the outside of the cell. These cyt ....Macrophages are key cells in the immune and inflammatory response. They play a role in many biological processes including wound healing and resistance to tumours and infections. It is also a major cell involved in mediating inflammation and tissue damage in chronic inflammatory diseases such as atherosclerosis and rheumatoid arthritis. The macrophage's role in these processes is achieved in large part by secreting enzymes and other proteins called cytokines to the outside of the cell. These cytokines are synthesized by the macrophage and travel through a secretory pathway in the cell, in order to be released to the outside of the cell. There are various quality control mechanisms along the pathway which ensure only correctly made functional protein is secreted out of the cell. One cytokine, called macrophage inhibitory cytokine is produced by the immune cells called macrophages only when they become activated to mount an immune response against invading pathogens. The cell uses a novel mechanism to ensure the quality control of this cytokine. The propeptide of this cytokine targets incorrectly folded cytokine to a protein complex called the proteasome for degradation. This prevents secretion of inactive cytokine. Additionally, the propeptide of the cytokine helps secretion from macrophages by a novel mechanism. Because of these characteristics the cytokine provides a good model to study secretion from macrophages under pro- and anti-inflammatory conditions. In addition, demonstrating that activation of the macrophages causes a major upregulation in the synthesis and secretion of cytokines by novel mechanisms, will further our understanding of how the macrophage operates in fulfilling its role in the immune response.Read moreRead less
Recycling Endosomes Governing Cell Polarity And Cytokine Secretion.
Funder
National Health and Medical Research Council
Funding Amount
$958,412.00
Summary
Cytokines are chemical messengers released by cells to mount inflammatory responses to fight infections. The timing and direction of cytokine release must be tightly regulated. We investigate the cellular compartments and molecules that control cytokine secretion using sophisticated live cell imaging. Uncontrolled cytokine release is the main cause of ongoing inflammation in arthritis and inflammatory bowel disease and our studies aim to identify cellular targets for new drug development.
Regulating The Secretion Of Inflammatory Cytokines
Funder
National Health and Medical Research Council
Funding Amount
$558,441.00
Summary
Cytokines or chemical messengers released by cells are essential for controlling immune responses but, in excess, they cause Crohn's disease and arthritis. Our research aims to block cytokine release as a novel way to ameliorate disease. We have identified specific cellular proteins, called golgins, that can be targeted to reduce cytokines. Here, characterization of golgin mediated cytokine transport in cells and in a mouse disease model is necessary to translate these findings for human benefit