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
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
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
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
Imaging the T cell signalling machinery . The conversion of external stimuli to the interior of a cell is a fundamental process that underpins many unique facets of biology, including cellular movement, nerve transmission, response to hormones and immune recognition. However, the basic mechanism by which such signals are transmitted across cellular membranes is poorly understood. This proposal will seek to bridge this gap in our knowledge by imaging a multi-component “decision-making” machine th ....Imaging the T cell signalling machinery . The conversion of external stimuli to the interior of a cell is a fundamental process that underpins many unique facets of biology, including cellular movement, nerve transmission, response to hormones and immune recognition. However, the basic mechanism by which such signals are transmitted across cellular membranes is poorly understood. This proposal will seek to bridge this gap in our knowledge by imaging a multi-component “decision-making” machine that controls whether or not the immune system becomes activated. Accordingly, this proposal will provide far-reaching insights into molecular events that are of central importance to the initiation of immunity, and thus will ultimately benefit society via improvements in health.Read moreRead less
Investigation of the mechanisms underlying successful placentation. The overall aim of this project is to provide novel insights into the basic cellular processes that underpin placental development and to improve our ability to manipulate mammalian reproduction, both human and animal. The placenta is critical for intrauterine development because it determines the level of nutrition, oxygenation and maternal tolerance to the developing foetus. The project intends to explore the role of prorenin ....Investigation of the mechanisms underlying successful placentation. The overall aim of this project is to provide novel insights into the basic cellular processes that underpin placental development and to improve our ability to manipulate mammalian reproduction, both human and animal. The placenta is critical for intrauterine development because it determines the level of nutrition, oxygenation and maternal tolerance to the developing foetus. The project intends to explore the role of prorenin and its receptor as a novel mechanism driving placentation. Applications for expected project outcomes may include improved breeding of threatened animal species and economically valuable domestic animals as well as improved health care and fertility control for domesticated pets and feral animals. Read moreRead less
Nano-scale organisation of cellular adhesions. Cell migration is a key aspect of many normal processes but also of diseases such as cancers. This project will use a novel fluorescence microscope that can see single proteins to identify how cell adhesions are formed, remodelled and disassembled. This knowledge will help to design better drugs against cancers and novel implantable materials.
Discovery Early Career Researcher Award - Grant ID: DE130100251
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Biophysical mechanisms regulating early T cell signalling events. T cell activation in response to foreign pathogens or cancer cells requires a complex set of protein interactions which must be controlled in space and time. This project will use new microscopy methods with single-molecule sensitivity to determine how the cell membrane and protein clustering regulate these interactions.