Inflammasome Function In Protection Against Infectious Disease And Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Inflammation, characterised by swelling, heat, pain and redness, is a normal response to injury and infection. Many human diseases such as gout, athersclerosis, diabetes and Alzheimer’s disease involve some inflammation, mediated through a common pathway termed the inflammasome. This project will investigate the proteins involved in this pathway and how they interact in their normal role of combatting infections, as well as a possible defect in this pathway in autoimmune patients.
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.
Unconventional Mechanisms For Activating The NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$747,031.00
Summary
Many inflammatory driven diseases such as arthritis, atherosclerosis and septic shock are also associated with cell death. This project will identify, at the molecular level, how cell death signalling specifically acts to trigger pathological inflammation. As such, it will identify novel targets for the development of next generation anti-inflammatory drugs.
A Study Of The Function Of Neuronal Apoptosis Inhibitory Proteins (NAIP) In Innate Immunity.
Funder
National Health and Medical Research Council
Funding Amount
$242,696.00
Summary
The innate immune system is the first line of defence against infection and cancer. Regulation of the immune system is extremely important as too little response can lead to severe infections, whilst too much response can lead to chronic inflammatory disease. This project will examine the role of �neuronal apoptosis inhibitory protein� in the immune system, which should provide information on regulation of innate immunity, as well as provide insight to neurodegenerative diseases and cancer.
Mechanisms connecting diet, metabolism, gut microbiota and immunity. This project will identify the role of short chain fatty acids and the G-protein coupled receptor (GPR43) in regulating immune responses. This could explain how diet affects immune responses and also how certain bacteria in the gut provide benefits for immune defence.
Nuclear alarmins escalate tissue immune responses. Humans and other animals are constantly exposed to potential threats, including microbes on and near the body. Animals can live with such dangers because these everyday encounters are made harmless by the immune system. It is unclear how cells distinguish low-danger threats from high-danger threats. This proposal seeks to reveal how immune cells identify increasing levels of threat and appropriately escalate their responses. Expected outcomes in ....Nuclear alarmins escalate tissue immune responses. Humans and other animals are constantly exposed to potential threats, including microbes on and near the body. Animals can live with such dangers because these everyday encounters are made harmless by the immune system. It is unclear how cells distinguish low-danger threats from high-danger threats. This proposal seeks to reveal how immune cells identify increasing levels of threat and appropriately escalate their responses. Expected outcomes include new insights into how immune cells and tissues respond according to the posing threat. Project benefits include understanding how to manipulate danger responses for future basic research and commercial applications, and fundamental understanding of how animals flourish in a dangerous world.Read moreRead less
A novel mechanism of host defence via macrophage extracellular traps. Animal health relies upon innate immune cells to rapidly detect invading microbes and induce inflammatory and antimicrobial responses to clear infection. Mechanisms of inflammation and immune defence are only partly understood. This project aims to elucidate a novel innate immune pathway (the inflammasome) that drives inflammatory cell death and antimicrobial defence. Using innovative multidisciplinary methods, this project wi ....A novel mechanism of host defence via macrophage extracellular traps. Animal health relies upon innate immune cells to rapidly detect invading microbes and induce inflammatory and antimicrobial responses to clear infection. Mechanisms of inflammation and immune defence are only partly understood. This project aims to elucidate a novel innate immune pathway (the inflammasome) that drives inflammatory cell death and antimicrobial defence. Using innovative multidisciplinary methods, this project will yield exciting new knowledge of mechanisms of inflammation and anti-microbial responses, and new paradigms for inflammasome action. Expected outcomes and benefits include high-impact publications, international collaboration, world-class training for young scientists, and new knowledge for future commercialisation.Read moreRead less
Cytoplasmic DNA As A Danger Signal For Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$592,661.00
Summary
DNA in mammalian cells is contained within a structure known as the nucleus. The presence of DNA outside the nucleus in the cytoplasm of the cell is a sure sign that something is wrong, and may indicate the presence of a viral invader. In this case, the cell initiates anti-viral responses, including production of anti-viral proteins and death of the infected cell to stop replication of the virus. Lack of proper control of these responses may contibute to the autoimmune disease lupus.
Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic un ....Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic understanding of cell death, and build interdisciplinary collaborations. This work should provide significant benefit to the economy and health of Australians, as it is expected to identify molecules that will be of interest to the pharmaceutical and biotechnology industries.Read moreRead less
Combating invading DNA: a process conserved in evolution? Cells of our body defend against foreign genetic material, or DNA, which indicates an infection or invading DNA capable of causing mutation. These defences are so important that several layers have developed during evolution, and this project compares the responses of different organisms to foreign DNA.