Role of Tau and Synapsin in clustering distinct synaptic vesicle pools. Neurotransmitter-containing synaptic vesicles (SVs) are highly enriched in specific locations of brain cells, called nerve terminals via an unknown mechanism. The clustering of SVs depend on the phosphorylation of an unknown set of proteins. Two key proteins have been identified for their phosphorylation pattern and their potential to form membraneless compartments: tau and synapsin. Using highly innovative single-molecule s ....Role of Tau and Synapsin in clustering distinct synaptic vesicle pools. Neurotransmitter-containing synaptic vesicles (SVs) are highly enriched in specific locations of brain cells, called nerve terminals via an unknown mechanism. The clustering of SVs depend on the phosphorylation of an unknown set of proteins. Two key proteins have been identified for their phosphorylation pattern and their potential to form membraneless compartments: tau and synapsin. Using highly innovative single-molecule super-resolution microscopy, this grant will uncover how tau and synapsin phosphorylation controls the clustering of SVs thereby regulating neurotransmitter release. This project uses improved nanoscopic technologies and international
collaborations to unveil novel avenues in our understanding of brain communication.Read moreRead less
Click chemistry to reveal how neurons and glia shape perineuronal nets . The extracellular matrix (ECM) and its perineuronal nets (which are net-like structures with holes wrapped around neurons) are largely underexplored, despite representing a remarkable 20% of the brain’s total volume and having been suggested to be involved in many brain functions. Interestingly, digestion of the ECM improves learning and memory, but deficits return once the ECM has reformed. However, how this ECM remodellin ....Click chemistry to reveal how neurons and glia shape perineuronal nets . The extracellular matrix (ECM) and its perineuronal nets (which are net-like structures with holes wrapped around neurons) are largely underexplored, despite representing a remarkable 20% of the brain’s total volume and having been suggested to be involved in many brain functions. Interestingly, digestion of the ECM improves learning and memory, but deficits return once the ECM has reformed. However, how this ECM remodelling is organised at a cell-type level is not understood. Here we aim to close this knowledge gap, using cutting-edge technology including bioconjugation and ultrasound-mediated cargo delivery. Together, this project aims to contribute to a deeper understanding of this major brain compartment in neuronal function. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100561
Funder
Australian Research Council
Funding Amount
$462,237.00
Summary
Understanding how platelets mediate new neuron formation in the adult brain. Exercise boosts the generation of new nerve cells from adult neural stem cells in the part of the brain responsible for learning and memory, the hippocampus. This project aims to investigate the mechanisms behind this effect, in particular, how blood cells known as platelets mediate this process. The expected outcomes include the discovery of new communication pathways between platelets and the brain following exercise ....Understanding how platelets mediate new neuron formation in the adult brain. Exercise boosts the generation of new nerve cells from adult neural stem cells in the part of the brain responsible for learning and memory, the hippocampus. This project aims to investigate the mechanisms behind this effect, in particular, how blood cells known as platelets mediate this process. The expected outcomes include the discovery of new communication pathways between platelets and the brain following exercise and will determine the importance of these blood cells in mediating brain function. This will help to explain how exercise affects the brain and may benefit Australian society through the implementation of new methods to support learning and memory in schools and workplaces, thereby enhancing performance and productivity.Read moreRead less
Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cel ....Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cell migration with relevance to the basic biology of inflammation, repair and regeneration and new innovations for cell imaging. Significant benefits are expected to arise from this new knowledge and from advanced skills training and improved national capabilities in bio-imaging and analysis.Read moreRead less
Molecular basis of glutamate receptor trafficking in neuronal plasticity . Neurons communicate via synapses, where chemicals (such as glutamate) are released to transmit neuronal signals. This proposal is aimed at understanding the molecular mechanisms of neuronal communication and adaptive plasticity, which are essential for normal brain function. The proposed research will combine biophysical, biochemical, molecular and cell biological assays to elucidate how the trafficking of glutamate recep ....Molecular basis of glutamate receptor trafficking in neuronal plasticity . Neurons communicate via synapses, where chemicals (such as glutamate) are released to transmit neuronal signals. This proposal is aimed at understanding the molecular mechanisms of neuronal communication and adaptive plasticity, which are essential for normal brain function. The proposed research will combine biophysical, biochemical, molecular and cell biological assays to elucidate how the trafficking of glutamate receptors is regulated in neurons during plasticity and learning. The outcomes will enhance our understanding of how neural plasticity is generated and maintained, knowledge that is critical for our understanding of the cellular correlates of information, sensory and motor processing, as well as learning, memory and cognition.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
Uncovering a novel energy-sensing mechanism in the brain. This project aims to investigate a novel regulator of energy homeostasis in the brain, a protein kinase called SIK3. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This project intends to generate new knowledge about molecular switches to regulate energy homeostasis by using innovative gene technologies and transgenic animal models. The expected outcomes include generating fundament ....Uncovering a novel energy-sensing mechanism in the brain. This project aims to investigate a novel regulator of energy homeostasis in the brain, a protein kinase called SIK3. Energy homeostasis is essential for life as it ensures an adequate supply of fuel to cells of the body. This project intends to generate new knowledge about molecular switches to regulate energy homeostasis by using innovative gene technologies and transgenic animal models. The expected outcomes include generating fundamental insights into how SIK3 in the hypothalamic neurons regulates energy homeostasis. Benefits include improving population health and wellbeing, informing the development of new bio-medical technologies, and expanding the capabilities of Australia’s next generation of researchers.
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Adrenomedullin: a specific regulator of venous vessel integrity. Arteries and veins display different adhesive properties, which enable them to fulfil their physiological roles. We are yet to understand the mechanisms that establish and maintain adhesive function in different vessel types. We have discovered that signalling by the peptide Adrenomedullin (ADM) is a key mediator of adhesion, only in veins but not arteries. This project aims to utilise innovative models (zebrafish, mouse and bioeng ....Adrenomedullin: a specific regulator of venous vessel integrity. Arteries and veins display different adhesive properties, which enable them to fulfil their physiological roles. We are yet to understand the mechanisms that establish and maintain adhesive function in different vessel types. We have discovered that signalling by the peptide Adrenomedullin (ADM) is a key mediator of adhesion, only in veins but not arteries. This project aims to utilise innovative models (zebrafish, mouse and bioengineered vessels) to identify the biochemical and mechanical mechanisms by which ADM controls venous adhesion. Outcomes will improve our understanding on how vessel integrity is controlled across vessel types and will expand the scope of Australian research by informing efforts to vascularise engineered tissues.Read moreRead less
Microbiome Regulation of the Host Mitochondrial Genome. This project aims to describe newly discovered processes by which bacteria that reside in the gut of an animal influences host mitochondria, the powerhouses of the cell. Using advanced genetic and molecular methodologies, this project aims to generate new knowledge on improving mitochondrial function as well as advance our understanding of the emerging field of microbiome research. Expected outcomes include a novel and universal technology ....Microbiome Regulation of the Host Mitochondrial Genome. This project aims to describe newly discovered processes by which bacteria that reside in the gut of an animal influences host mitochondria, the powerhouses of the cell. Using advanced genetic and molecular methodologies, this project aims to generate new knowledge on improving mitochondrial function as well as advance our understanding of the emerging field of microbiome research. Expected outcomes include a novel and universal technology platform in which to engineer small molecules and probiotics to improve mitochondrial health and enhance fitness in a range of animals. This should provide significant benefits, through both scientifically relevant outcomes and economic benefits through technological advancements.Read moreRead less
What drives the Anterior Expansion of the Central Nervous System? A striking and highly conserved feature of the central nervous system is that the brain is larger than the spinal cord. Despite the manifest implications this has for nervous system function, the underlying drivers are largely unknown. This project aims to investigate the mechanisms controlling anterior expansion of the central nervous system, and will generate new knowledge in the areas of nervous system development and evolution ....What drives the Anterior Expansion of the Central Nervous System? A striking and highly conserved feature of the central nervous system is that the brain is larger than the spinal cord. Despite the manifest implications this has for nervous system function, the underlying drivers are largely unknown. This project aims to investigate the mechanisms controlling anterior expansion of the central nervous system, and will generate new knowledge in the areas of nervous system development and evolution. This project aims to impact on our understanding of nervous system function, develop bioinformatics tools with broad utility within the biosciences field, strengthen Australia’s international standing in the developmental neuroscience, and enhance the capacity for interdisciplinary international collaborations.Read moreRead less