Fyn-STEP-Tau axis: the nanoscale mechanisms of synaptic plasticity. This project investigates how brain cells use their molecular machinery to communicate with one another. At the heart of this process lies the synapses, the contact points that connect brain cells. This project will employ an innovative combination of quantitative microscopy techniques, gene knockout mouse models, and advanced computational and mathematical analyses to generate new knowledge on how a crucial set of proteins orga ....Fyn-STEP-Tau axis: the nanoscale mechanisms of synaptic plasticity. This project investigates how brain cells use their molecular machinery to communicate with one another. At the heart of this process lies the synapses, the contact points that connect brain cells. This project will employ an innovative combination of quantitative microscopy techniques, gene knockout mouse models, and advanced computational and mathematical analyses to generate new knowledge on how a crucial set of proteins organises in space and time to regulate synaptic connectivity. This will provide significant benefits, including molecular-level insight into the inner workings of the brain and interdisciplinary training for students. The expected outcomes include a deeper understanding of brain functions, such as learning and memory.Read moreRead less
The Role of Lck/CD8 Association in Negatively Regulating T cell Activation. This proposal aims to advance our fundamental understanding of how T cell recognition of antigens translates into a T cell activating signal. The proposal will establish whether the major T cell coreceptor also acts as a negative regulator of T cell activation in vivo when antigen recognition is unorthodox. It will also determine whether certain subsets of T cells naturally lack coreceptors in order to facilitate unortho ....The Role of Lck/CD8 Association in Negatively Regulating T cell Activation. This proposal aims to advance our fundamental understanding of how T cell recognition of antigens translates into a T cell activating signal. The proposal will establish whether the major T cell coreceptor also acts as a negative regulator of T cell activation in vivo when antigen recognition is unorthodox. It will also determine whether certain subsets of T cells naturally lack coreceptors in order to facilitate unorthodox antigen recognition. Thus, the proposal will significantly advance our understanding of, and establish new paradigms around, the regulation of T cell activation. Expected long term benefits outside the scope of this proposal include improved immunotherapies and vaccines designed to elicit or suppress T cell responses.Read moreRead less
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
Defining how cells relay mechanical signals to changes in cell architecture. Mechanical signals play crucial roles in shaping organs and entire organisms during development, though how these signals are relayed to changes in cell architecture is a major unanswered question. Within vascular networks, mechanical signals including fluid flow, tension and stretch play key roles in vessel patterning, identity and maturation. This application aims to employ cutting-edge technologies to determine how t ....Defining how cells relay mechanical signals to changes in cell architecture. Mechanical signals play crucial roles in shaping organs and entire organisms during development, though how these signals are relayed to changes in cell architecture is a major unanswered question. Within vascular networks, mechanical signals including fluid flow, tension and stretch play key roles in vessel patterning, identity and maturation. This application aims to employ cutting-edge technologies to determine how the atypical cadherin FAT4 relays mechanical signals including flow and tension to the lymphatic endothelial cell skeleton, thereby enabling changes in cell shape important for building lymphatic vessels. This project will increase our understanding of how cells sense touch and may be applied for tissue engineering purposes.
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Characterising a novel stress-sensing signalling factor. Aim: To understand how phosphorylation regulates signalling pathways to allow metabolic adaptations in response to energetic stress. Significance: A fundamental understanding of the activation of signalling pathways via phosphorylation is vital for our knowledge of homeostasis and the mechanisms controlling cell survival. Expected outcomes: To generate new systems biology and physiology data to understand how the stress response is regulat ....Characterising a novel stress-sensing signalling factor. Aim: To understand how phosphorylation regulates signalling pathways to allow metabolic adaptations in response to energetic stress. Significance: A fundamental understanding of the activation of signalling pathways via phosphorylation is vital for our knowledge of homeostasis and the mechanisms controlling cell survival. Expected outcomes: To generate new systems biology and physiology data to understand how the stress response is regulated and characterise new stress-sensing pathways. Benefits: A greater understanding of the molecular mechanisms controlling metabolism in response to stress has extremely broad applications to improve metabolic efficiency in fields ranging from exercise- and life-sciences to agriculture.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
Mitochondria as sensors of environmental threats. This project aims to understand how energy-generating mitochondria control immune responses, both in immune cells called macrophages and in the nematode Caenorhabditis elegans (a free-living roundworm used as a model organism to study gene function and evolutionary biology). The project expects to advance knowledge of how a process called mitochondrial fission enables cells to respond to environmental threats. Expected outcomes include important ....Mitochondria as sensors of environmental threats. This project aims to understand how energy-generating mitochondria control immune responses, both in immune cells called macrophages and in the nematode Caenorhabditis elegans (a free-living roundworm used as a model organism to study gene function and evolutionary biology). The project expects to advance knowledge of how a process called mitochondrial fission enables cells to respond to environmental threats. Expected outcomes include important conceptual advances in cell biology and genetics, new international and national collaborations, and improved methods for cell biology research. Anticipated benefits include a knowledge base that can be indirectly applied in the long term in the development of new strategies to combat infections.Read moreRead less
Countdown to death: defining new signalling events preceding cell death . This proposal aims to understand how programmed cell death molecular machineries promote innate immune responses and proliferation by identifying new molecules that regulate these fundamental biological processes. This project expects to enhance our basic understanding of cell death, cell proliferation and innate immunity using innovative approaches and to build interdisciplinary collaborations. The new generated knowledge ....Countdown to death: defining new signalling events preceding cell death . This proposal aims to understand how programmed cell death molecular machineries promote innate immune responses and proliferation by identifying new molecules that regulate these fundamental biological processes. This project expects to enhance our basic understanding of cell death, cell proliferation and innate immunity using innovative approaches and to build interdisciplinary collaborations. The new generated knowledge in these critical processes will be fertile ground to develop innovative applications in biomedical industries. This this will have a positive impact on the health and economy of Australian society.Read moreRead less
Pyroptotic macrophages posthumously sculpt immune responses. The life of an organism relies on the timely birth and death of its cells. Importantly, it is crucial for cells to die not only at the right time, but also in an appropriate manner. This proposal investigates a cell death pathway that triggers potent immune responses. This proposal seeks to reveal precisely how cell death sculpts immune responses. Expected outcomes include new insights into how immune cells die, and how they instruct i ....Pyroptotic macrophages posthumously sculpt immune responses. The life of an organism relies on the timely birth and death of its cells. Importantly, it is crucial for cells to die not only at the right time, but also in an appropriate manner. This proposal investigates a cell death pathway that triggers potent immune responses. This proposal seeks to reveal precisely how cell death sculpts immune responses. Expected outcomes include new insights into how immune cells die, and how they instruct immune responses from beyond the grave. Project benefits include a fundamental understanding of how cell death signalling sculpts tissue immune responses, and knowledge of how to manipulate cell death responses for future basic research and commercial applications beyond this project.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