Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100157
Funder
Australian Research Council
Funding Amount
$600,000.00
Summary
Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information th ....Confocal and single molecule microscopes for systems microscopy. This project aims to establish Australia’s first system microscopy facility with dedicated live-cell confocal and single-molecule fluorescence microscopes. In systems microscopy, the imaging workflow is automated so that large and unbiased data sets of the spatiotemporal organisation of molecules and cells can be generated. Combined with statistical and bioinformatics analyses, image-derived data provides system-wide information that is not easily obtainable with other approaches. The project will enable Australian researchers to image and analyse the full complexity of biological systems, potentially transforming cell biology, drug development and understanding the molecular basis of disease. It will also demonstrate how the capacity of microscopy facilities can be enhanced and bias in imaging data reduced by automating data acquisition and mining of image-based data.Read moreRead less
Novel mechanisms of early growth response-1 activation through the epidermal growth factor receptor. This project will expand our knowledge of how cytokines and growth factors switch on signalling pathways from the cell surface to the nucleus. Unique antibodies will characterise regulatory routes, state-of-the-art microscopy will define dynamic patterns of receptor co-assembly, and in vivo studies will show receptor crosstalk in animal models.
Cardiac a1-adrenergic receptors in survival of the fittest. This project aims to determine the role of alpha1A-adrenergic receptor inactivation, a receptor/signalling pathway, in mediating cardiac contraction and survival in response to stressors fight-or-flight response triggers.Higher organisms’ ability to respond to environmental changes is central to the survival of the fittest, and is mediated by the release of catecholamines that stimulate adrenergic receptors. The precise receptor and sig ....Cardiac a1-adrenergic receptors in survival of the fittest. This project aims to determine the role of alpha1A-adrenergic receptor inactivation, a receptor/signalling pathway, in mediating cardiac contraction and survival in response to stressors fight-or-flight response triggers.Higher organisms’ ability to respond to environmental changes is central to the survival of the fittest, and is mediated by the release of catecholamines that stimulate adrenergic receptors. The precise receptor and signalling pathways underlying these adaptive responses remain unclear. This project’s research could improve contractility, reduce cardiomyocyte death and define organismal adaptation to extreme environmental changes.Read moreRead less
Statistical analyses for spatial organisation in T cell signalling networks. This project aims to reveal how nanoscale spatial organisation encodes plasticity in the T cell signalling network, and how T cells exploit this plasticity to regulate sensitivity to antigens. In adoptive immunity, T cells respond appropriately to any given antigen, but how they make decisions is unclear. This project will define how nanoscale spatial organisation of signalling molecules shapes signalling strength and p ....Statistical analyses for spatial organisation in T cell signalling networks. This project aims to reveal how nanoscale spatial organisation encodes plasticity in the T cell signalling network, and how T cells exploit this plasticity to regulate sensitivity to antigens. In adoptive immunity, T cells respond appropriately to any given antigen, but how they make decisions is unclear. This project will define how nanoscale spatial organisation of signalling molecules shapes signalling strength and plasticity in the T cell antigen receptor (TCR) network; and infer rules linking spatial organisation and signalling activities in intact T cells. Contextualising the TCR signalling network is expected to reveal the origin and use of network plasticity for T cell decision-making. Such information could be invaluable for the design of vaccines and immune-modulating drugs.Read moreRead less
DNA nanotechnology for controlled antigen presentation to T cells. The project aims to present individual antigens to T cells and to image T cell receptor signalling with single molecule microscopy. Combining DNA origami nanotechnology with single molecule imaging should reveal the sensitivity of T cell signalling. A DNA force sensor will determine whether mechanical forces contribute to antigen discrimination. The project will use the nanotechnology strategy to identify antigen-specific T cells ....DNA nanotechnology for controlled antigen presentation to T cells. The project aims to present individual antigens to T cells and to image T cell receptor signalling with single molecule microscopy. Combining DNA origami nanotechnology with single molecule imaging should reveal the sensitivity of T cell signalling. A DNA force sensor will determine whether mechanical forces contribute to antigen discrimination. The project will use the nanotechnology strategy to identify antigen-specific T cells in tissue. The project is expected to advance understanding of T cell biology, and contribute to DNA nanotechnology and super-resolution microscopy whilst providing fundamental insights into antigen recognition by T cells and ultimately derive clinically relevant practical applications.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100011
Funder
Australian Research Council
Funding Amount
$900,000.00
Summary
Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, ....Integrated Multimodal System for Multiplexed Imaging of Signal Transduction. This project will introduce a unique microscopy platform and associated technologies into the Australian research environment that will enable researchers to redefine our understanding of molecular signal transduction. The instrumentation will enable the multidimensional imaging of live cells with unprecendented speed and sensitivity. The featured imaging modalities will enable the integration of distinct biological, biochemical and chemical probes with a focus on minimizing phototoxicity. Expected outcomes include new fundamental knowledge on molecular signal transduction and cell heterogeneity; development of novel probes and methodologies and the development of new and existing interdisciplinary research collaborations. Read moreRead less
Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. T ....Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. This knowledge is highly relevant to any industry or research project utilising living organisms, as nutrient availability supports survival, cell growth and proliferation.Read moreRead less
How do cells survive nutrient stress? Insight into mechanisms. This project studies cell survival under nutrient stress in eukaryotes. Building on extensive preliminary data that identifies novel TOR (Target of Rapamycin) Complex 2 (TORC2) control points it expects to generate new knowledge of critical and conserved features of stress control of macroautophagy that ensures cell survival. It uses interdisciplinary and innovative approaches to validate and characterize nutrient-stress dependent si ....How do cells survive nutrient stress? Insight into mechanisms. This project studies cell survival under nutrient stress in eukaryotes. Building on extensive preliminary data that identifies novel TOR (Target of Rapamycin) Complex 2 (TORC2) control points it expects to generate new knowledge of critical and conserved features of stress control of macroautophagy that ensures cell survival. It uses interdisciplinary and innovative approaches to validate and characterize nutrient-stress dependent signaling. Expected outcomes include novel insights into environmental control of cell proliferation and forging cross institutional collaborations. This knowledge benefits basic and applied biology and is relevant to industries/projects utilizing living cells as nutrient supports cell survival and proliferation.Read moreRead less
Systemic regulation of neuronal circuits in cognition and behaviour. This project aims to understand systemic regulation of behaviour and cognition in the central nervous system (CNS). The adrenal gland (AG) is an endocrine organ that regulates behaviour and cognition, but the molecular mechanisms underlying the regulatory axis between the CNS and AG are poorly understood. The AG selectively and highly expresses p38, a member of the MAP kinase family, while mice that lack p38 suffer memory and b ....Systemic regulation of neuronal circuits in cognition and behaviour. This project aims to understand systemic regulation of behaviour and cognition in the central nervous system (CNS). The adrenal gland (AG) is an endocrine organ that regulates behaviour and cognition, but the molecular mechanisms underlying the regulatory axis between the CNS and AG are poorly understood. The AG selectively and highly expresses p38, a member of the MAP kinase family, while mice that lack p38 suffer memory and behavioural deficits. This project will study p38’s role in systemic CNS function. It aims to understand brain function and systemic regulation of cognition and behaviour, thereby contributing to a deeper understanding of brain function and paving the way for new preventive treatments and medical care strategies.Read moreRead less
Life at the nanometre scale: imaging immunological synapses with a novel super-resolution fluorescence microscope. This project aims to image individual proteins in activated white blood cells in order to understand how lymphocytes participate in an immune response. The problem is that current imaging modalities either lack resolution or are unsuitable for live cell and three-dimensional (3D) imaging. With the project’s industry partner, Carl Zeiss MicroImaging, the project will build and apply ....Life at the nanometre scale: imaging immunological synapses with a novel super-resolution fluorescence microscope. This project aims to image individual proteins in activated white blood cells in order to understand how lymphocytes participate in an immune response. The problem is that current imaging modalities either lack resolution or are unsuitable for live cell and three-dimensional (3D) imaging. With the project’s industry partner, Carl Zeiss MicroImaging, the project will build and apply a novel microscope that is capable of visualising single proteins in 3D and live cells. This technology will provide insights into signalling and lymphocyte function on a true molecular scale.Read moreRead less