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Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels ....Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels, and will thereby lead to a greater understanding of the fundamental biological pathways controlling inflammation and defence against infection. This may ultimately lead to commercial opportunities for treating infection and chronic inflammation.Read moreRead less
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
Role Of PLZF In Regulating The Interferon Response
Funder
National Health and Medical Research Council
Funding Amount
$531,696.00
Summary
The Interferon (IFN) pathway is essential for immune defense against pathogens in vertebrates. IFNs both protect and alert cells about viral, bacterial, and other immune assaults and promote a cellular antiviral state, reduce proliferation, or induce apoptosis depending on the cell type and environment. Based on these properties, IFNs have been used clinically against a variety of diseases including viral infections, immunomodulatory disorders and hematologic and solid tumors including renal cel ....The Interferon (IFN) pathway is essential for immune defense against pathogens in vertebrates. IFNs both protect and alert cells about viral, bacterial, and other immune assaults and promote a cellular antiviral state, reduce proliferation, or induce apoptosis depending on the cell type and environment. Based on these properties, IFNs have been used clinically against a variety of diseases including viral infections, immunomodulatory disorders and hematologic and solid tumors including renal cell carcinoma. However, the factors determining outcome of IFN treatment, remain to be determined. We have identified a subset of interferon stimulated genes whose sustained expression was found to correlate with heightened antiviral sensitivity of renal cell carcinoma cell lines to IFN. Many of these genes were found to have binding sites for the transcriptional repressor promyleocytic zinc finger protein (PLZF). PLZF was first identified in a subset of Acute Promyelocytic Leukemia patients and is involved in maintenance of erythroid lineage stem cells and spermatogonial stem cells in male mice. PLZF has not previously been implicated in the IFN response. Accordingly, we investigated the expression of interferon stimulated genes and showed that increased expression of immune related genes depends on PLZF expression. PLZF was also found to directly associate with binding sites in promoters of interferon stimulated genes and that this requires histone deacetylation. Thus, we uncovered a novel function for PLZF in enhancement of IFN associated gene expression. We propose to test the hypothesis that PLZF is an essential component of the IFN response. As a corollary, we will also test whether PLZF expression can be linked to IFN responsiveness in renal cell carcinoma. These studies will establish the role of PLZF in the IFN response and define its utility in predicting IFN responsiveness in therapeutic applications.Read moreRead less
Human Dendritic Cell Subsets And Their Application For Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$443,946.00
Summary
Immunotherapy is a promising non-toxic strategy for the treatment of many cancers, viruses and other diseases. It works by teaching the patient's own immune system to recognize and destroy the cancer. Specialized blood cells called dendritic cells are essential to this process but they are poorly understood in humans. I aim to investigate the function these cells and use this information to develop new treatments for cancer and viruses.
In Vivo Imaging Of Protective And Malignant B Cell Function
Funder
National Health and Medical Research Council
Funding Amount
$431,412.00
Summary
B cells are responsible for producing antibody that protects us from infection. Disruption of healthy B cell function can lead to a myriad of diseases including immunodeficiency, autoimmunity and blood cancers such as leukaemia. The aim of my work is to use powerful microscopy to visualise how mutated B cells interact with their surrounding environment in real-time. These studies will allow the development of new treatments for cancer and immune conditions that target these interactions.
TARGETING THE HUMAN CROSS-PRIMING DENDRITIC CELLS FOR IMMUNOTHERAPY
Funder
National Health and Medical Research Council
Funding Amount
$589,544.00
Summary
Specialized white blood cells called dendritic cells (DCs) are essential to inducing the immune system to eradicate cancers and viral infections in mice. We have defined human DC subsets and related their functional capacities to the mouse DC subsets. We will now identify the human DC subsets involved in the induction of cancer and viral immune responses and use this information to develop clinical therapeutic cancer vaccination trials.
Investigating The Mechanism And Consequences Of Cytotoxic Lymphocyte Detachment
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Killer cells are white blood cells that destroy cancerous cells. To move to their next target they must quickly detach from a dying target. Failure of detachment results in excessive inflammation and tumour escape. This project will discover the detachment signals required to ‘release’ a locked-on killer cell. This will lead to a deeper understanding of immune pathology and new ways of treating cancer.