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.
How membrane-sensing proteins regulate synaptic vesicle endocytosis. This project aims to elucidate the molecular basis of how membrane-sensing proteins regulate synaptic vesicle endocytosis in mammalian central neurons. Nerve cells’ ability to transmit cellular information to one another is important for normal brain function. Efficient communication between neurons through sustained neurotransmitter release relies on the continuous supply of synaptic vesicles in presynaptic nerve terminals. Ke ....How membrane-sensing proteins regulate synaptic vesicle endocytosis. This project aims to elucidate the molecular basis of how membrane-sensing proteins regulate synaptic vesicle endocytosis in mammalian central neurons. Nerve cells’ ability to transmit cellular information to one another is important for normal brain function. Efficient communication between neurons through sustained neurotransmitter release relies on the continuous supply of synaptic vesicles in presynaptic nerve terminals. Key to this process are membrane dynamics during synaptic vesicle retrieval, but the precise underlying mechanisms are not well understood. The intended outcome of this project is insights into the molecular mechanisms of synaptic transmission, the fundamental process of brain function, increasing understanding of physiological processes such as muscle movement, vision, hearing, touch, learning and memory.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100078
Funder
Australian Research Council
Funding Amount
$800,000.00
Summary
Live molecular imaging using super resolution microscopy, two photon and spinning disk confocal microscopy. With recent developments of super-resolution microscopy it is now feasible to image single molecules within the cellular environment in living cells. Such insight is key to understanding basic biological interactions that govern the wiring of our brain, communications between cells and neurons and cell-cell adhesion.
Nuclear functions of the microtubule-associated protein tau. The important neuronal protein, tau, has cellular functions that go far beyond its established role in stabilising microtubules. This project will determine which tau species are nuclearly localised, what the consequences are for nuclear functions, and how phosphorylation regulates this localisation.
Unveiling the nanoscale organisation and dynamics of synaptic vesicle pools. This project aims to uncover the role of key molecules in allowing brain cells to actively communicate with each other. Communication between neurons relies on the fusion of synaptic vesicles containing neurotransmitters with the presynaptic plasma membrane. The addition of vesicular membrane is transient as the vesicles quickly reform from the plasma membrane and refill with neurotransmitter ready for subsequent rounds ....Unveiling the nanoscale organisation and dynamics of synaptic vesicle pools. This project aims to uncover the role of key molecules in allowing brain cells to actively communicate with each other. Communication between neurons relies on the fusion of synaptic vesicles containing neurotransmitters with the presynaptic plasma membrane. The addition of vesicular membrane is transient as the vesicles quickly reform from the plasma membrane and refill with neurotransmitter ready for subsequent rounds of fusion. This recycling process ensures that neurons communicate efficiently, however the underpinning mechanism is unknown. This project aims to use a recently developed single synaptic vesicle super-resolution tracking method to establish how Myosin-VI and Synapsin-IIa orchestrate this recycling in central and peripheral neurons. It will explain how neurons manage to preserve their ability to communicate.Read moreRead less
Trafficking inside the cell for effective immunity. This project aims to investigate how cargo is trafficked to the right destination inside cells. The project will investigate the trafficking routes and the critical machinery required. This project is expected to generate fundamental new knowledge in the areas of cell biology and immunology. Expected outcomes of this Project include scholarly publications and highly-trained personnel in cell biology and immunology. This project will provide sig ....Trafficking inside the cell for effective immunity. This project aims to investigate how cargo is trafficked to the right destination inside cells. The project will investigate the trafficking routes and the critical machinery required. This project is expected to generate fundamental new knowledge in the areas of cell biology and immunology. Expected outcomes of this Project include scholarly publications and highly-trained personnel in cell biology and immunology. This project will provide significant benefits such as advances to fundamental knowledge, training for higher research degree students, opportunities for the biotechnology sector and strengthened international (research collaborations.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
Discovery Early Career Researcher Award - Grant ID: DE140101626
Funder
Australian Research Council
Funding Amount
$394,179.00
Summary
Flotillin link membrane microdomains to signalling endosome during T cell activation. This project aims to determine the mechanisms that connect signalling microdomains at the cell surface to intracellular signalling endosomes to regulate T cell activation. A T cell immune response begins with the reorganisation of the plasma membrane to yield two-dimensional signalling microdomains that must be connected to the three-dimensional microarchitecture of the endocytic matrix for full T cell activati ....Flotillin link membrane microdomains to signalling endosome during T cell activation. This project aims to determine the mechanisms that connect signalling microdomains at the cell surface to intracellular signalling endosomes to regulate T cell activation. A T cell immune response begins with the reorganisation of the plasma membrane to yield two-dimensional signalling microdomains that must be connected to the three-dimensional microarchitecture of the endocytic matrix for full T cell activation. This project hypothesises that Flotillin form distinct signalling microdomains in the plasma membrane that internalise to constitute an independent endocytic pathway. Using single-molecule and ultra-fast fluorescence imaging, the project will demonstrate that Flotillin represent a unique two-dimensional to three-dimensional regulatory mechanism for T cell signalling.Read moreRead less
Novel tools and nanotechnology to navigate intracellular trafficking. This project aims to investigate how material accesses different compartments inside cells, also known as trafficking. Using immunology, cell biology and nanotechnology, the project will manipulate intracellular trafficking to achieve specific cellular functions. Outcomes will also form the basis of intellectual property development for new products by Australian biotechnology companies. These products will improve veterinary ....Novel tools and nanotechnology to navigate intracellular trafficking. This project aims to investigate how material accesses different compartments inside cells, also known as trafficking. Using immunology, cell biology and nanotechnology, the project will manipulate intracellular trafficking to achieve specific cellular functions. Outcomes will also form the basis of intellectual property development for new products by Australian biotechnology companies. These products will improve veterinary and human health services, leading to increased productivity.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100165
Funder
Australian Research Council
Funding Amount
$250,000.00
Summary
Electron microscopy cryopreparation facility for biomedical research. The proposed cryopreparation facility will allow cell and molecular biologists and material scientists in the region to prepare samples for ultrastructural research not currently possible due to insufficient local resources, and will thus significantly boost their research. The facility will support a wide range of world class medical and material scientists, including those visiting the Australian Synchrotron, whose research ....Electron microscopy cryopreparation facility for biomedical research. The proposed cryopreparation facility will allow cell and molecular biologists and material scientists in the region to prepare samples for ultrastructural research not currently possible due to insufficient local resources, and will thus significantly boost their research. The facility will support a wide range of world class medical and material scientists, including those visiting the Australian Synchrotron, whose research in health sciences and advanced materials characterisation facilitates the goals of promoting and maintaining good health and frontier technologies. The instrumentation will enhance training capacity in the region and provide young Australian scientists with direct experience of modern electron microscopy techniques.Read moreRead less