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Tuning the activating stimulus of voltage-gated sodium channels. This proposal aims to advance fundamental knowledge about how proteins (ion channels) found on the surface of neurons (brain cells and nerves) function as molecular conduits of cell-to-cell electrical communication. We aim to study how molecular probes and structural parts of these proteins affect the local chemical environment of ion channels, and how this leads to fine tuning of the ion channel's sensitivity to the stimulus that ....Tuning the activating stimulus of voltage-gated sodium channels. This proposal aims to advance fundamental knowledge about how proteins (ion channels) found on the surface of neurons (brain cells and nerves) function as molecular conduits of cell-to-cell electrical communication. We aim to study how molecular probes and structural parts of these proteins affect the local chemical environment of ion channels, and how this leads to fine tuning of the ion channel's sensitivity to the stimulus that activates them (cell membrane voltage).
The conceptual knowledge gained from this project would advance our understanding of a fundamental physiological process and facilitate the development of drugs that regulate ion channel function, such as anti-epileptics, analgesics and insecticides.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
How do apicomplexan parasites steal amino acids from their hosts? The single-celled parasites that cause malaria and toxoplasmosis are adept at stealing nutrients from the host animals that they infect. How they do this is, however, poorly understood. This project seeks to identify the processes by which these parasites scavenge amino acids, an essential class of nutrient, from their hosts. Using innovative experimental approaches, the project aims to identify and characterise the parasite prote ....How do apicomplexan parasites steal amino acids from their hosts? The single-celled parasites that cause malaria and toxoplasmosis are adept at stealing nutrients from the host animals that they infect. How they do this is, however, poorly understood. This project seeks to identify the processes by which these parasites scavenge amino acids, an essential class of nutrient, from their hosts. Using innovative experimental approaches, the project aims to identify and characterise the parasite proteins that mediate the uptake of different amino acids into the parasite. The intended outcomes of the project are to provide comprehensive insights into a fundamental aspect of parasite biology, and inform strategies to treat the diseases caused by these parasites by cutting off their nutrient supply.Read moreRead less
New Frontiers in Innate Immunity. This program aims to define how the immune system senses and responds to environmental cues. By combining interdisciplinary approaches with cutting-edge imaging and spatial biology technologies, this program expects to reveal how immune sensor proteins are regulated at the molecular, cellular and tissue level. Outcomes of this program include unparalleled insights into molecular mechanisms that underpin effective functioning of the immune system, training of fut ....New Frontiers in Innate Immunity. This program aims to define how the immune system senses and responds to environmental cues. By combining interdisciplinary approaches with cutting-edge imaging and spatial biology technologies, this program expects to reveal how immune sensor proteins are regulated at the molecular, cellular and tissue level. Outcomes of this program include unparalleled insights into molecular mechanisms that underpin effective functioning of the immune system, training of future scientists, and strengthening international collaborations across academia and industry. This will contribute to a high-quality workforce for research and innovation, and secure Australia’s position at the forefront of immunology research driven by cutting-edge technologies. 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
Discovery Early Career Researcher Award - Grant ID: DE230101681
Funder
Australian Research Council
Funding Amount
$457,139.00
Summary
Cryo-electron microscopy determination of G protein-coupled receptor states. This project aims to address fundamental knowledge gaps in understanding of the molecular mechanisms of peptide hormone G protein-coupled receptor activation. This will be achieved through cryo-electron microscopy determination of the structure and dynamics of key intermediate states in activation. Novel biochemical approaches will be applied to capture these states, using as exemplar the glucagon receptor that has a br ....Cryo-electron microscopy determination of G protein-coupled receptor states. This project aims to address fundamental knowledge gaps in understanding of the molecular mechanisms of peptide hormone G protein-coupled receptor activation. This will be achieved through cryo-electron microscopy determination of the structure and dynamics of key intermediate states in activation. Novel biochemical approaches will be applied to capture these states, using as exemplar the glucagon receptor that has a broad range of pharmacological tools to facilitate isolation of distinct functional states. The knowledge gained from these studies will advance fundamental understanding of physiologically important receptor activation and efficacy, while the approaches developed will enable similar investigation of other receptor classes.Read moreRead less
Elucidating the molecular mechanisms of dual function transporter/channels. This project aims to understand how a membrane protein that transports chemical messengers in the brain functions and how it is influenced by the membrane in which it is embedded. Cells from all life forms have a lipid membrane that separates them from their external environment. These membranes contain proteins that control the movements of molecules into and out of cells and are vital for a plethora of physiological pr ....Elucidating the molecular mechanisms of dual function transporter/channels. This project aims to understand how a membrane protein that transports chemical messengers in the brain functions and how it is influenced by the membrane in which it is embedded. Cells from all life forms have a lipid membrane that separates them from their external environment. These membranes contain proteins that control the movements of molecules into and out of cells and are vital for a plethora of physiological processes including cell-to-cell communication. The outcomes of this study will include new knowledge of this process and chemical modifiers of this transport protein. This project will benefit structural biology and biophysics training and may lead to the development of novel compounds that can be used to explore function. Read moreRead less
Understanding T cell trafficking and function during antigenic interference. Science generally studies antigenic stimulation in isolation, by measuring immunity towards antigens derived from a single pathogen. However, as mammals can harbour more than one infection at any given time, we established a model of antigenic interference using different antigens derived from two unrelated pathogens, influenza A (IAV) and Semliki Forest virus (SFV). Our data show that prior exposure to either IAV or SF ....Understanding T cell trafficking and function during antigenic interference. Science generally studies antigenic stimulation in isolation, by measuring immunity towards antigens derived from a single pathogen. However, as mammals can harbour more than one infection at any given time, we established a model of antigenic interference using different antigens derived from two unrelated pathogens, influenza A (IAV) and Semliki Forest virus (SFV). Our data show that prior exposure to either IAV or SFV greatly perturbs T cell dynamics. This proposal will study, at cellular and molecular levels, T cell trafficking, function and clonal distribution during antigenic interference, thus advance fundamental knowledge on T cell immunity during antigenic competition, and provide a new paradigm on how we research T cell immunity.Read moreRead less
Structure of the essential Commander protein trafficking complex. This project aims to provide a fundamental understanding of the structure and function of Commander, a large protein complex that controls export and recycling of internalised receptors. Commander is highly conserved throughout evolution and is essential for maintaining the homeostasis of hundreds of transmembrane receptors required for cell function and survival, regulating processes as diverse as lipid metabolism and cell adhesi ....Structure of the essential Commander protein trafficking complex. This project aims to provide a fundamental understanding of the structure and function of Commander, a large protein complex that controls export and recycling of internalised receptors. Commander is highly conserved throughout evolution and is essential for maintaining the homeostasis of hundreds of transmembrane receptors required for cell function and survival, regulating processes as diverse as lipid metabolism and cell adhesion. Despite advances in the understanding of Commander function, little is known about how Commander is assembled and interacts with other essential proteins. This project will use multidisciplinary cellular and structural biology approaches to reveal the architecture of Commander at an atomic level.Read moreRead less