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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100089
Funder
Australian Research Council
Funding Amount
$700,000.00
Summary
Super-resolution fluorescence microscopy. The prestigious journal Nature Methods named super-resolution fluorescent microscopy as the Method of the Year 2008. This recognition is justified because fluorescent imaging on the molecular scale will revolutionise biological sciences. It will literally change the way we see the smallest building blocks of life and this allows researchers to identify the function of proteins and lipids in health and disease. This breakthrough technology is currently no ....Super-resolution fluorescence microscopy. The prestigious journal Nature Methods named super-resolution fluorescent microscopy as the Method of the Year 2008. This recognition is justified because fluorescent imaging on the molecular scale will revolutionise biological sciences. It will literally change the way we see the smallest building blocks of life and this allows researchers to identify the function of proteins and lipids in health and disease. This breakthrough technology is currently not available to researchers in Australia. Super-resolution fluorescence microscopy would extend Australia's leading position in the fundamental biological sciences, bio- and nano-technologies as well as imaging and microscopy.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100224
Funder
Australian Research Council
Funding Amount
$250,000.00
Summary
Multi-mode fluorescence microscope for visualising the dynamics of cellular processes at the single-molecule level. Fluorescence is the emission of light by a substance that has absorbed light of a different wavelength. This fluorescence microscopy facility will allow the visualisation of the dynamic processes that define life at the molecular level. This insight will help us understand cellular function and how it is impaired in various diseases including cancer and neurodegenerative disorders ....Multi-mode fluorescence microscope for visualising the dynamics of cellular processes at the single-molecule level. Fluorescence is the emission of light by a substance that has absorbed light of a different wavelength. This fluorescence microscopy facility will allow the visualisation of the dynamic processes that define life at the molecular level. This insight will help us understand cellular function and how it is impaired in various diseases including cancer and neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease.Read moreRead less
Assembly and stability of human voltage-gated potassium channels. The Kv11.1 voltage-gated potassium channel is an important regulator of cardiac function and a problem for the pharmaceutical industry due to its promiscuity with respect to drug binding. This project aims to investigate how Kv11.1 channels fold and assemble into tetramers and what stabilizes them in the cell membrane. Borrowing from insights gained from the structural analysis of G-Protein coupled receptors, the project intends t ....Assembly and stability of human voltage-gated potassium channels. The Kv11.1 voltage-gated potassium channel is an important regulator of cardiac function and a problem for the pharmaceutical industry due to its promiscuity with respect to drug binding. This project aims to investigate how Kv11.1 channels fold and assemble into tetramers and what stabilizes them in the cell membrane. Borrowing from insights gained from the structural analysis of G-Protein coupled receptors, the project intends to apply a novel protein stabilization strategy to facilitate the structural analysis of Kv11.1 channels. The successful completion of the project could reveal important insights into how these molecular machines work as well as enable atomic level studies of how drugs interact and bind to these channels.Read moreRead less
Defining systems that clear dangerous misfolded proteins from body fluids. The project intends to establish how the human body defends itself against protein-folding related disease and loss of quality of life. Exposure to everyday physical and chemical stresses can cause proteins to lose their normal shape and become misfolded. Misfolded proteins are causally involved in human ageing and serious diseases (for example, Alzheimer's disease). However, the body does have a protective system that cl ....Defining systems that clear dangerous misfolded proteins from body fluids. The project intends to establish how the human body defends itself against protein-folding related disease and loss of quality of life. Exposure to everyday physical and chemical stresses can cause proteins to lose their normal shape and become misfolded. Misfolded proteins are causally involved in human ageing and serious diseases (for example, Alzheimer's disease). However, the body does have a protective system that clears dangerous misfolded proteins from body fluids. Using cutting-edge approaches and a novel animal model, the project aims to establish how this system works. The outcomes are expected to improve understanding of the molecular processes affecting human ageing and disease and strengthen the framework needed to develop better strategies to combat these.Read moreRead less
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