Discovery Early Career Researcher Award - Grant ID: DE200100778
Funder
Australian Research Council
Funding Amount
$390,000.00
Summary
Mapping the neural circuits that underlie emotional learning. This project aims to understand the precise neural circuits that mediate the formation of emotional memories. Recent findings have identified a novel complexity in these circuits and the goal of this proposal is to resolve the underlying mechanism that drives emotional memories. In detail, this project will combine state of the art dual- optical stimulation techniques combined with behaviour-dependent tagging of neurons to investigate ....Mapping the neural circuits that underlie emotional learning. This project aims to understand the precise neural circuits that mediate the formation of emotional memories. Recent findings have identified a novel complexity in these circuits and the goal of this proposal is to resolve the underlying mechanism that drives emotional memories. In detail, this project will combine state of the art dual- optical stimulation techniques combined with behaviour-dependent tagging of neurons to investigate the precise brain circuits linked to emotional learning, an approach that also allows knowledge transfer to other research fields. Expected outcomes and benefits of the project is a significant shift in our understanding of the neural mechanisms that underlie emotional learning.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200101300
Funder
Australian Research Council
Funding Amount
$423,711.00
Summary
Lipopolysaccharide-induced macrophage extracellular traps in host defence. The innate immune system is the first line of defence against invading microbes. Macrophages are key innate immune cells that deploy antimicrobial responses to clear infection and restore health. There are many critical unanswered questions on the molecular mechanisms that drive macrophage inflammatory and antimicrobial pathways. This project aims to elucidate a novel inflammatory mechanism that immobilises and kills inva ....Lipopolysaccharide-induced macrophage extracellular traps in host defence. The innate immune system is the first line of defence against invading microbes. Macrophages are key innate immune cells that deploy antimicrobial responses to clear infection and restore health. There are many critical unanswered questions on the molecular mechanisms that drive macrophage inflammatory and antimicrobial pathways. This project aims to elucidate a novel inflammatory mechanism that immobilises and kills invading bacteria via newly discovered structures made by dying macrophages called extracellular traps. Insight we gain by interrogating this immune cell signalling pathway, called the non-canonical inflammasome, will add valuable knowledge to our fundamental understanding of mammalian inflammation and anti-microbial responses
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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
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
An active ion transport pathway exploited by coronaviruses. Cells have active transport “pumps” that are regulators of a variety of cellular processes. This project aims to understand how a specific ion pump is exploited by coronaviruses when they infect animal cells. These studies will provide new mechanistic insights into how coronaviruses alter calcium signalling in cells and how a specific ion pump regulates a variety of key processes during coronavirus infection. This work will greatly enha ....An active ion transport pathway exploited by coronaviruses. Cells have active transport “pumps” that are regulators of a variety of cellular processes. This project aims to understand how a specific ion pump is exploited by coronaviruses when they infect animal cells. These studies will provide new mechanistic insights into how coronaviruses alter calcium signalling in cells and how a specific ion pump regulates a variety of key processes during coronavirus infection. This work will greatly enhance our understanding of the intersection between ion pumps and viruses.Read moreRead less
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
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
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
Discovery Early Career Researcher Award - Grant ID: DE220100823
Funder
Australian Research Council
Funding Amount
$442,482.00
Summary
Elucidating ATPase function during NLRP3 inflammasome assembly. Humans and animals are constantly exposed to microbes, which inhabit their external environment as well as body surfaces such as the skin and gut. We are, however, able to co-exist with these microbes, because our immune system protects us from these everyday encounters. This proposal will reveal how an important immune protein called NLRP3 senses microbes and other physiological processes. When NLRP3 senses such factors and is acti ....Elucidating ATPase function during NLRP3 inflammasome assembly. Humans and animals are constantly exposed to microbes, which inhabit their external environment as well as body surfaces such as the skin and gut. We are, however, able to co-exist with these microbes, because our immune system protects us from these everyday encounters. This proposal will reveal how an important immune protein called NLRP3 senses microbes and other physiological processes. When NLRP3 senses such factors and is activated, it induces the release of messenger substances to alert other immune cells. This research will deliver fundamental knowledge of how animals normally co-exist with microbes.Read moreRead less
The molecular basis for efficacy at G protein coupled receptors. This project aims to investigate the molecular steps underlying the relationship between sensing by signal-transmitting proteins on the cell surface called G protein-coupled receptors and cellular response. The project aims to build on studies that have sought to understand the primary, molecular basis for this cellular volume control. This project seeks to use these novel approaches to fill this knowledge gap, providing a deeper u ....The molecular basis for efficacy at G protein coupled receptors. This project aims to investigate the molecular steps underlying the relationship between sensing by signal-transmitting proteins on the cell surface called G protein-coupled receptors and cellular response. The project aims to build on studies that have sought to understand the primary, molecular basis for this cellular volume control. This project seeks to use these novel approaches to fill this knowledge gap, providing a deeper understanding of how physiology and medicines work. The project expects to expand fundamental understanding of signal transmission at this receptor class. This project will deliver benefits including expanded basic knowledge and a contribution to future improvements in drug development.Read moreRead less