Poly(amino acids) as immune stimulators. This project aims to develop nanoparticles built from natural hydrophobic amino acids as an immune stimulatory delivery system for peptide antigens. Currently available immune stimulants (adjuvants) are often toxic and/or are poorly chemically defined fragments of bacteria or toxins and vary from batch-to-batch. New adjuvants are in high demand; especially to facilitate the use of optimal, but weakly immunogenic, peptide antigens. It is expected that the ....Poly(amino acids) as immune stimulators. This project aims to develop nanoparticles built from natural hydrophobic amino acids as an immune stimulatory delivery system for peptide antigens. Currently available immune stimulants (adjuvants) are often toxic and/or are poorly chemically defined fragments of bacteria or toxins and vary from batch-to-batch. New adjuvants are in high demand; especially to facilitate the use of optimal, but weakly immunogenic, peptide antigens. It is expected that the proposed project will develop a novel efficient, safe and notably biodegradable self-adjuvanting delivery system that can be fully customised to match an antigen of choice. This foundational research should provide important advances for commercial immune stimulatory applications.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100433
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Cortical layer specific functional imaging of the human brain. This project aims to record layer specific cortical activity in humans by leveraging ultra-high field magnetic resonance imaging. It expects to yield robust techniques for the general analysis of neuroimaging-based, layer-specific measurements. This project will progress the fields of cognitive neuroscience and neuroimaging as well as bring the field of neuroimaging closer to that of neurophysiology and thus facilitate collaboration ....Cortical layer specific functional imaging of the human brain. This project aims to record layer specific cortical activity in humans by leveraging ultra-high field magnetic resonance imaging. It expects to yield robust techniques for the general analysis of neuroimaging-based, layer-specific measurements. This project will progress the fields of cognitive neuroscience and neuroimaging as well as bring the field of neuroimaging closer to that of neurophysiology and thus facilitate collaboration among researchers.Read moreRead less
Determining principles for successful episode retrieval of repeated events. This project aims to develop the first-ever set of explanatory principles for how people successfully retain and retrieve individual episode memories from repeated experiences (e.g., one occurrence of a routine social encounter or job-related activity). By deepening our understanding of how memory works, this new knowledge is expected to lay the foundation for interview guidance and ongoing research aimed at enhancing th ....Determining principles for successful episode retrieval of repeated events. This project aims to develop the first-ever set of explanatory principles for how people successfully retain and retrieve individual episode memories from repeated experiences (e.g., one occurrence of a routine social encounter or job-related activity). By deepening our understanding of how memory works, this new knowledge is expected to lay the foundation for interview guidance and ongoing research aimed at enhancing the proficiency of investigations into matters that rely on detailed and accurate accounts of specific episodes. This includes workplace or traffic accident investigations, infectious disease contact tracing, as well as prosecution of repeated sexual offences.Read moreRead less
Can the Relational Account predict search in multiple-element displays? . This project provides evidence of a novel mechanism that guides visual attention. Our results confirm the existence of a mechanism that can rapidly and automatically assess the dominant feature(s) in a visual scene and radically change how attention is tuned to a target object. Moreover, this attention-guiding target template can change systematically as observers search through different items in visual search, possibly d ....Can the Relational Account predict search in multiple-element displays? . This project provides evidence of a novel mechanism that guides visual attention. Our results confirm the existence of a mechanism that can rapidly and automatically assess the dominant feature(s) in a visual scene and radically change how attention is tuned to a target object. Moreover, this attention-guiding target template can change systematically as observers search through different items in visual search, possibly due to a re-shaping and narrowing of the target template. These are both ground-breaking discoveries that have not been described before. Work on this project promises to lead to important theoretical breakthroughs, resolve current discrepancies in the literature and advance methods of Cognitive Psychology and Neuroscience.Read moreRead less
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
Super-resolving neurotransmitter release machinery during priming. Understanding how neurons communicate in the brain is one of the most challenging feats in neuroscience. The assembly of the molecular machinery involved in communication is unknown. This grant aims to understand how priming molecules Munc18 and Munc13, undergo a series of molecular steps leading to the release of neurotransmitter. Using innovative single-molecule super-resolution imaging we will uncover how Munc18 and Munc13 are ....Super-resolving neurotransmitter release machinery during priming. Understanding how neurons communicate in the brain is one of the most challenging feats in neuroscience. The assembly of the molecular machinery involved in communication is unknown. This grant aims to understand how priming molecules Munc18 and Munc13, undergo a series of molecular steps leading to the release of neurotransmitter. Using innovative single-molecule super-resolution imaging we will uncover how Munc18 and Munc13 are spatially and temporally organised to mediate communication. By elucidating how nanoclustering of these essential proteins enables key steps, this grant will reveal how brain cells communicate. This may then provide new opportunities to optimise underlying functions such as cognition, sensory and motor processing.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
Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the ....Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the degradation of proteins implicated in cell division and cell death. Expected outcomes include an increased understanding of how proteins are specifically selected for degradation. Protein degradation pathways operate with remarkable selectivity and this work is expected to illuminate the mechanisms of substrate targeting. The biochemical approaches will provide insight and impact in the areas of cell signaling, organelle biology and cell biology.Read moreRead less