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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.
Understanding and implications of formation of lipid nanostructures in milk. This project aims to deliver new understanding of the processes of milk digestion. Milk is the most important food for human survival, providing all the essential nutrition to newborn infants and constituting a major part of the adult diet. The recent discovery that nanostructure is formed during the digestion of both cow and breast milk, but not of vegetable 'milk', has opened a large number of questions to answer in t ....Understanding and implications of formation of lipid nanostructures in milk. This project aims to deliver new understanding of the processes of milk digestion. Milk is the most important food for human survival, providing all the essential nutrition to newborn infants and constituting a major part of the adult diet. The recent discovery that nanostructure is formed during the digestion of both cow and breast milk, but not of vegetable 'milk', has opened a large number of questions to answer in this project. Specifically, the project plans to link nanostructure formation in milk with composition during digestion, and the subsequent delivery of nutrients. The project plans to use synchrotron and microscopy techniques to address these questions. Project outcomes may improve our understanding of digestion and drive innovation in products delivering nutrients to infants.Read moreRead less
The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of ....The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of macropinocytosis at a molecular level. The project is relevant to understanding the functioning of normal cells and the means by which some pathogens can enter cells and also understanding processes involved in tumour progression and metastasis.Read moreRead less
Designing new generation adjuvants for allergy and parasite vaccines. Allergy vaccines have the potential to provide a permanent cure against many allergic diseases, currently affecting 20-30 per cent of people in developed countries. This project will study how allergy vaccines work and how we can improve their effectiveness and safety.
Investigation of the fundamental roles of class Ib MHC (major histocompatibility complex) molecules in immunity. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide insight into the roles of a poorly understood class of immune molecules. This will improve our understanding of the regulation of immunity, and the knowledge gained will increase Australia's international research profile.
Real-time imaging of the initiation of adaptive immunity in vivo. Understanding the first few hours of an immune response is fundamental to understanding how the human immune system functions. The immune system mounts our responses to infectious diseases, but can also cause autoimmune disease, allergy, and organ graft rejection. We will study how naive antigen-specific T cells first contact antigen in lymph nodes using 2-photon intravital microscopy. The research has the potential to change the ....Real-time imaging of the initiation of adaptive immunity in vivo. Understanding the first few hours of an immune response is fundamental to understanding how the human immune system functions. The immune system mounts our responses to infectious diseases, but can also cause autoimmune disease, allergy, and organ graft rejection. We will study how naive antigen-specific T cells first contact antigen in lymph nodes using 2-photon intravital microscopy. The research has the potential to change the way we think about the clonal selection of lymphocytes, the fundamental theory underlying our understanding of the immune system.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
Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek ....Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek to establish, an integrated model that incorporates new findings to explain how the distinctive functions of specialised receptors can be orchestrated to achieve this function. A successful outcome to the project will provide new knowledge of value to human health.Read moreRead less
A structural investigation into the peptide-loading complex molecular machine. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide fundamental insight into a process central to immunity, namely antigen presentation. Investigating the process of Antigen presentation is important, as it will further our understanding how a cell is "ear-marked" for being infected by viruses or bacteria. Such knowledge will increase Australia's international research ....A structural investigation into the peptide-loading complex molecular machine. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide fundamental insight into a process central to immunity, namely antigen presentation. Investigating the process of Antigen presentation is important, as it will further our understanding how a cell is "ear-marked" for being infected by viruses or bacteria. Such knowledge will increase Australia's international research standing.Read moreRead less
Regulation of MHC-I and ICAM-1 by flavivirus, West Nile. This project investigates the intracellular signalling pathway responsible for the expression of genes which are critical to our immune response. We have demonstrated in a mouse model that high levels of expression of two of these genes in flavivirus encephalitis are associated with a survival advantage. We would expect this project to provide basic new information about the mechanisms of expression of these genes as well as information ab ....Regulation of MHC-I and ICAM-1 by flavivirus, West Nile. This project investigates the intracellular signalling pathway responsible for the expression of genes which are critical to our immune response. We have demonstrated in a mouse model that high levels of expression of two of these genes in flavivirus encephalitis are associated with a survival advantage. We would expect this project to provide basic new information about the mechanisms of expression of these genes as well as information about the interaction of this family of viruses, flavivirus with the host.Read moreRead less