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A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.
Molecular interactions in cell membranes. Cell membranes are a complex composite of proteins and lipids and we have only a rough idea about how they perform their many functions. Together with Leica Microsystems, this project will develop a new microscope that can map the molecular interactions within the membrane revealing details that have never been seen before.
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.
Breaking through the Gram-negative cell barrier. This project aims to develop fundamental knowledge of the cell envelope in Gram-negative bacteria, which functions as a permeability barrier to small molecules. Combining innovative functional genomics with biochemistry, this project will determine how small molecules can pass across the cell envelope, and the chemical properties that they need to do so. Some Gram-negative bacteria are human pathogens and cause serious infections, whereas others a ....Breaking through the Gram-negative cell barrier. This project aims to develop fundamental knowledge of the cell envelope in Gram-negative bacteria, which functions as a permeability barrier to small molecules. Combining innovative functional genomics with biochemistry, this project will determine how small molecules can pass across the cell envelope, and the chemical properties that they need to do so. Some Gram-negative bacteria are human pathogens and cause serious infections, whereas others are used in biotechnology for biosynthetic chemical production or bioremediation. This project expects to help the future development of new antibiotics and assist in the design of strains to be used in biotechnological applications.Read moreRead less
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
Discovery Early Career Researcher Award - Grant ID: DE240101055
Funder
Australian Research Council
Funding Amount
$448,737.00
Summary
How blood vessel stiffness regulates their growth and maintenance. This project aims to reveal an unidentified molecular mechanism of how endothelial cells in the walls of blood vessels detect stiffness of the surrounding environment in order to regulate blood vessel growth and maintenance. The results are expected to advance the emerging field of mechanobiology by combining cutting-edge cell biology and microscopy techniques carried out in novel 3D cell culture and unique quail models. The bene ....How blood vessel stiffness regulates their growth and maintenance. This project aims to reveal an unidentified molecular mechanism of how endothelial cells in the walls of blood vessels detect stiffness of the surrounding environment in order to regulate blood vessel growth and maintenance. The results are expected to advance the emerging field of mechanobiology by combining cutting-edge cell biology and microscopy techniques carried out in novel 3D cell culture and unique quail models. The benefits of these outcomes include generation of knowledge on the impact of tissue stiffness on the signalling mechanisms that drive formation and maintenance of blood vessels. In the long term, this fundamental understanding could give rise to major developments in emerging industries such as organ bioengineering.Read moreRead less
Sensing biomechanical forces in the heart. Mechanosensitive ion channels are key molecules that define how each heart cell interacts with their physical environment. Yet how they enable cells to decode biomechanical cues remains poorly understood. At the heart of this problem is a lack of tools to quantify the force required for activation. This project aims to develop novel technologies to record the activity of these essential channels in a critical cell type within the heart, and use this inf ....Sensing biomechanical forces in the heart. Mechanosensitive ion channels are key molecules that define how each heart cell interacts with their physical environment. Yet how they enable cells to decode biomechanical cues remains poorly understood. At the heart of this problem is a lack of tools to quantify the force required for activation. This project aims to develop novel technologies to record the activity of these essential channels in a critical cell type within the heart, and use this information in addition to micro-engineering approaches to fully understand the role of these channels in force sensing and generation, at both the single cell and micro-tissue levels. This knowledge and technology has broad utility that extends far beyond cardiac biology into multiple fields.Read moreRead less
Nutritional and bacterial influences on gut and peripheral homeostasis. Nutritional and bacterial influences on gut and peripheral homeostasis. This project aims to understand the role of macronutrients on gut homeostasis. While the understanding of what factors affect gut homeostasis is still in its infancy, scientists know that its disruption contributes to a broad range of inflammatory diseases, including type 1 diabetes and asthma. This project will determine the role of specific macronutrie ....Nutritional and bacterial influences on gut and peripheral homeostasis. Nutritional and bacterial influences on gut and peripheral homeostasis. This project aims to understand the role of macronutrients on gut homeostasis. While the understanding of what factors affect gut homeostasis is still in its infancy, scientists know that its disruption contributes to a broad range of inflammatory diseases, including type 1 diabetes and asthma. This project will determine the role of specific macronutrients on gut microbiota, gut epithelium, and immunity in mice, and the receptors involved. This research could ultimately lead to significant decreases in the cost of healthcare.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101128
Funder
Australian Research Council
Funding Amount
$444,154.00
Summary
Decode Neuro-Mechanobiology:mechanosensitive ion channels in proprioception. Human bodies are densely covered with numerous mechanosensory neurons that provide us with the sense of touch and pain. However, the molecular force sensors remain poorly identified. This project aims at defining the fundamental roles of mechanosensitive ion channels to sense and respond to various mechanical stimuli, and how their responses may encode mechanical cues.The ultimate goal is to provide a fundamentally new ....Decode Neuro-Mechanobiology:mechanosensitive ion channels in proprioception. Human bodies are densely covered with numerous mechanosensory neurons that provide us with the sense of touch and pain. However, the molecular force sensors remain poorly identified. This project aims at defining the fundamental roles of mechanosensitive ion channels to sense and respond to various mechanical stimuli, and how their responses may encode mechanical cues.The ultimate goal is to provide a fundamentally new understanding of proprioception and motion sensing. The new multimodality approach generated in this project is expected to evolve as a national facility for neuro-mechanobiology, and future research may lead to the inspiration of novel bionic sensor design and brain-computer interface for future neuroengineering industry.Read moreRead less