Developmental-associated Dysregulation Of Innate Anti-microbial Immunity In Early Life As A Determinant Of Susceptibility To Atopic Asthma
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
Previous NHMRC-sponsored research from the applicants has demonstrated that one of the strongest risk factors for subsequent development of asthma is having chest infections during infancy that are so severe that they trigger symptoms of fever and wheeze. It is not known what predisposes susceptible infants to these severe infections, and this project will attempt to define the mechanisms of susceptibility.
Epigenetic Regulation Of Lymphoid Cell Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$631,950.00
Summary
Inflammatory diseases such as multiple sclerosis, inflammatory bowel disease and asthma are caused by unregulated white blood cells called CD4 T cells. Why certain people develop hyperactive CD4 T cells is not clear but a understanding how CD4 T cells are regulated will help inform future therapies. Our research focuses on one enzyme called G9a that modifies proteins that control immune cell function. Our goal is to define the role of this enzyme in inflammation to aid in drug development.
Role of antibodies and their receptors in chronic inflammation: The activation of inflammatory white blood cells is a major mechanism of tissue destruction in certain autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. It is well known that destructive chemicals, enzymes and hormones are released by these cells into affected tissues, for example joints and kidneys. What is lacking is knowledge of the earliest steps in the immune system that activate the inflammator ....Role of antibodies and their receptors in chronic inflammation: The activation of inflammatory white blood cells is a major mechanism of tissue destruction in certain autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. It is well known that destructive chemicals, enzymes and hormones are released by these cells into affected tissues, for example joints and kidneys. What is lacking is knowledge of the earliest steps in the immune system that activate the inflammatory white blood cells and drive this inflammation cascade to the point where chemicals are released and tissued destroyed. This project investigates the role of one of the major receptor families involved in the activation of inflammation. These are receptors for antibodies called FcR. The binding to these receptors of unusual antibodies produced in autoimmune disease initiate events that stimulate white blood cells leading to their activation and the secretion of inflammatory substances. Our work leading up to this project has been very exciting and has shown that one receptor in particular, FcgammaRIIa is unique to humans, is the most widespread FcR in the body and is the most potent activator of inflammatory substance release. We will be studying animal models to precisely define how this human receptor works. Mice have been generated which contain this uniquely human receptor and these mice develop many features of human autoimmune disease such as the joint destruction, kidney destruction and lung destruction seen in both rheumatoid arthritis and lupus. The principal aim of our study is to define the role of this human receptor in the development of inflammatory conditions with the ultimate goal of using this information to generate new treatments for these diseases.Read moreRead less
Taking The First Steps From Promise To Product: Exploration Of The Newly Discovered Interleukin 37 Receptor Complex And Its Signaling Pathways
Funder
National Health and Medical Research Council
Funding Amount
$694,623.00
Summary
Cytokines are messenger proteins used by most cells of the body. They function as master regulators of many biological processes and as such play an important role in a wide spectrum of diseases. Anti-inflammatory cytokines attenuate the potentially destructive force of other cytokines and the immune system as a whole, and are therefore coveted as drug targets. We discovered the formidable anti-inflammatory properties of IL-37 and will now explore how these activites can be utilised in clinical ....Cytokines are messenger proteins used by most cells of the body. They function as master regulators of many biological processes and as such play an important role in a wide spectrum of diseases. Anti-inflammatory cytokines attenuate the potentially destructive force of other cytokines and the immune system as a whole, and are therefore coveted as drug targets. We discovered the formidable anti-inflammatory properties of IL-37 and will now explore how these activites can be utilised in clinical medicine.Read moreRead less
Influence Of TCR Signals From Contact With Self-MHC Ligands On Naive T Cell Survival
Funder
National Health and Medical Research Council
Funding Amount
$418,658.00
Summary
A diverse repertoire of naive T cells constitutes a critical part of the adaptive immune system and protects hosts from various infections and cancer. T cells are stably maintained at a constant number in the periphery by mechanisms that are not clearly understood. This proposal will shed light on how the immune system preserves a diverse na�ve T cell pool able to respond against various foreign antigens, while preventing their harmful auto-reactivity to self antigens.
Toll-like receptors in infectious and inflammatory diseases: the double-edged sword of innate immunity. The innate immune system is the first line of defence against invading microorganisms. This project will explore the role of specific innate immune genes in the control of infections and the development of inflammatory diseases.
Understanding The Role Of Innate Immune Cells In Regulating Gut-associated Lymphoid Tissues At Steady-state And In Disease
Funder
National Health and Medical Research Council
Funding Amount
$365,126.00
Summary
The intestine is the largest surface area forming a protective barrier between the external environment and the body. It represents the first line of defence against invading pathogens. The immune system of the intestine is critical to protect this tissue -any breakdown leads to profound and progressive inflammatory disease of the gut such as chronic inflammatory bowel disease. Our work will determine the critical the mechanisms that protect the gut opening the door to targeted intestinal immuno ....The intestine is the largest surface area forming a protective barrier between the external environment and the body. It represents the first line of defence against invading pathogens. The immune system of the intestine is critical to protect this tissue -any breakdown leads to profound and progressive inflammatory disease of the gut such as chronic inflammatory bowel disease. Our work will determine the critical the mechanisms that protect the gut opening the door to targeted intestinal immunotherapeutics.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100398
Funder
Australian Research Council
Funding Amount
$410,507.00
Summary
How T cells modulate stem cells and tissue regeneration. The project aims to determine how T cells modulate tissue repair and regeneration in mammals. Most of the mechanisms modulating the healing of tissues are elusive. This research is expected to reveal unknown mechanisms controlling the processes of tissue repair and regeneration, particularly the nexus between the stem cells involved in the tissue healing process and the immune response .
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100217
Funder
Australian Research Council
Funding Amount
$450,000.00
Summary
In-Vivo Multispectral and X-ray Micro-CT Imaging: Founding a Western Australian small animal imaging core facility. The Western Australian Small Animal Imaging facility will provide wide access for the West Australian research community to a multimodality functional and dynamic core bioimaging facility to characterise in-vivo animal models, including extensive postgraduate research training. Wide-ranging research outcomes of national and community benefit include imaging tumour development, bone ....In-Vivo Multispectral and X-ray Micro-CT Imaging: Founding a Western Australian small animal imaging core facility. The Western Australian Small Animal Imaging facility will provide wide access for the West Australian research community to a multimodality functional and dynamic core bioimaging facility to characterise in-vivo animal models, including extensive postgraduate research training. Wide-ranging research outcomes of national and community benefit include imaging tumour development, bone metabolism (osteoporosis), neural function (Alzheimer's disease) and regeneration, and infection mechanisms in live animals, which will result in improvements in human health. Imaging and monitoring coral growth, fish age, and soil structure will improve the economics and sustainability of Australia's marine ecosystems and agricultural food production.Read moreRead less