This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths ....This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths in our society. We will use technology which is proven to provide precise information, the molecular and biochemical processes responsible for cell function (or malfunction). However in each individual project there will be a clear path to a clinical use, diagnostic or therapeutic. Indeed in a number of the components of the program there are already potential treatments and diagnostics in development and trial.Read moreRead less
Structural and functional studies of a Tripartite Motif-Containing Protein. This project will study a fundamental process that is crucial to the regulation of almost all cellular processes. The dysfunction of this process can lead to cancer, neurodegenerative and immunological disorders. The outcome will be an advancement in knowledgebase at the most fundamental level.
SNARE-mediated perforin and cytokine release in natural killer cells. Cytotoxic cells release toxic granules and cytokine messengers to kill pathogen infected and cancerous cells and to mount immune responses. This project will investigate different SNARE molecules that regulate the secretion of perforin from granules and cytokines from other carriers, assisting in the understanding of complex but essential cellular pathways.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100097
Funder
Australian Research Council
Funding Amount
$675,000.00
Summary
An Automated Protein Nano-Crystallisation Facility. An automated protein nano-crystallisation facility:
The project aims to establish a high throughput protein nanocrystallisation and imaging facility for protein crystallography. Protein crystallography is an important field of biological research, however there are many proteins, such as integral membrane proteins and transient molecular complexes that are more challenging to crystallise. The facility aims to use state-of-the-art imaging and c ....An Automated Protein Nano-Crystallisation Facility. An automated protein nano-crystallisation facility:
The project aims to establish a high throughput protein nanocrystallisation and imaging facility for protein crystallography. Protein crystallography is an important field of biological research, however there are many proteins, such as integral membrane proteins and transient molecular complexes that are more challenging to crystallise. The facility aims to use state-of-the-art imaging and crystallisation techniques, including second order nonlinear imaging of chiral crystals (SONICC) imaging and lipid cubic phase approaches, to enable structural studies to be undertaken on challenging proteins. This information is often used for the rational development of therapeutics. The facility would support cutting-edge biological research In Australia.Read moreRead less
A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Person ....A novel axis of cooperation between innate and adaptive immunity. The project aims to understand how two molecular components of the immune system, Complement and MHC, cooperate to protect the host. Further, these two molecules mediate trogocytosis, a little-studied form of intercellular communication, between two major immune cell types: dendritic cells and B cells. The project will be multidisciplinary, applying high-end microscopy, biochemistry, cell biology and immunology techniques. Personnel will be trained in cutting-edge techniques. The project will expand knowledge on basic immunology and cell-cell cooperation. It will generate intellectual property for the biotechnology sector to develop new commercial products that might improve the health of humans and also animals of economic importance.Read moreRead less
Nuclear plasticity during neutrophil migration and function. This project aims to discover how nuclear shape affects neutrophil function. Cell migration needs overall cellular plasticity and plasticity of internal structures such as the nucleus. The neutrophil, one of the most peripatetic cell types, has a specialised lobulated nucleus, thought to facilitate its mobility and function. Using zebrafish reporter lines that concurrently display the nucleus and cytoplasm, this project will display th ....Nuclear plasticity during neutrophil migration and function. This project aims to discover how nuclear shape affects neutrophil function. Cell migration needs overall cellular plasticity and plasticity of internal structures such as the nucleus. The neutrophil, one of the most peripatetic cell types, has a specialised lobulated nucleus, thought to facilitate its mobility and function. Using zebrafish reporter lines that concurrently display the nucleus and cytoplasm, this project will display the dynamic plasticity of neutrophil nuclei during neutrophil migration and function in vivo. This project seeks to use the spatiotemporal resolution of a lattice light sheet microscope to examine this further, and explore its effect on neutrophil function. The project seeks to establish morphological and mechanical principles applying not just to neutrophils, but to all migratory cell types.Read moreRead less
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
Cholesterol and Hydroxycholesterol Shaping Phagocytosis. Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. This project will also address the link between cholesterol synthesis, its storage in li ....Cholesterol and Hydroxycholesterol Shaping Phagocytosis. Reports now show that membrane cholesterol and 25-hydroxycholesterol (25HC) are required for immune cells to ingest and kill pathogens by phagocytosis. This project will measure phagocytosis in macrophages with genetically or pharmacologically varied cholesterol and 25HC, to compare and quantify the ingestion of different bacteria, fungi and particles. This project will also address the link between cholesterol synthesis, its storage in lipid bodies and its availability for phagocytosis, based on preliminary data showing such defects in the staggerer mouse model. Notably, cholesterol dysregulation is now a prevalent condition in society and our results will reveal at a fundamental, molecular level how this might compromise immune defenses.Read moreRead less