Autocyclases: A new class of self-cyclising proteins. The biotechnology sector is emerging as an important economic strength in Australia. While the improved efficacy and selectivity of biomolecules has seen them emerge as alternatives to existing chemicals in health and agriculture, the stability of biomolecules remains a major limiting factor. A general strategy for improving protein stability is by joining the ends of the peptide chain in a cyclisation reaction. While a wide range of cyclic p ....Autocyclases: A new class of self-cyclising proteins. The biotechnology sector is emerging as an important economic strength in Australia. While the improved efficacy and selectivity of biomolecules has seen them emerge as alternatives to existing chemicals in health and agriculture, the stability of biomolecules remains a major limiting factor. A general strategy for improving protein stability is by joining the ends of the peptide chain in a cyclisation reaction. While a wide range of cyclic peptides and proteins are being developed in Australia and around the world, the cyclisation reaction presents a significant challenge. In this proposal we detail a novel method for protein cyclisation as a general, low-cost and green production method for making a diverse range of biomolecules. 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
A humanised sensory neuron high-throughput screening platform . Sensory neurons are responsible for converting external stimuli such as touch or temperature into graded electrical signals that allow us to interact with the world around us. However, unlike other cell types, sensory neurons cannot proliferate and thus must be removed from human cadavers, or animals, in order to study their pharmacology and function. This limits our ability to understand neuronal signalling pathways. This project a ....A humanised sensory neuron high-throughput screening platform . Sensory neurons are responsible for converting external stimuli such as touch or temperature into graded electrical signals that allow us to interact with the world around us. However, unlike other cell types, sensory neurons cannot proliferate and thus must be removed from human cadavers, or animals, in order to study their pharmacology and function. This limits our ability to understand neuronal signalling pathways. This project aims to use sensory neurons derived from human stem cells to develop and optimise assays that can be used to study the pharmacology and function of human sensory neurons in vitro. This enhances access to critical model systems and technology platforms and removes the need for isolation of cells from cadavers. Read moreRead less
Regulation of activity-induced glutamate receptor trafficking in neurons. 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 the role of a calcium binding protein i ....Regulation of activity-induced glutamate receptor trafficking in neurons. 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 the role of a calcium binding protein in controlling glutamate receptor trafficking in neurons. The outcomes will enhance our understanding of how neural plasticity is generated and maintained, knowledge that is critical for our understanding of cellular correlates of information, sensory and motor processing, as well as learning, memory and cognition. 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
Metabolite regulation of mitochondrial fission. This project aims to understand how the function and health of mitochondria – the energy producing structures in cells - are controlled by fat molecules. The project expects to integrate cutting edge techniques and instrumentation to generate new knowledge of how fat molecules interact with, and influence, enzymes that control how cells maintain their mitochondria in response to nutrient state. An anticipated goal is to define a fingerprint for enz ....Metabolite regulation of mitochondrial fission. This project aims to understand how the function and health of mitochondria – the energy producing structures in cells - are controlled by fat molecules. The project expects to integrate cutting edge techniques and instrumentation to generate new knowledge of how fat molecules interact with, and influence, enzymes that control how cells maintain their mitochondria in response to nutrient state. An anticipated goal is to define a fingerprint for enzymes regulated by fat molecules that will be of great interest to researchers across many branches of life sciences. Expected outcomes and benefits will be deeper understanding of fat molecules as nutrient signalling metabolites, and how they influence cell metabolism, growth and development.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
Protecting cereal grain development at high temperatures. This project aims to investigate new temperature-responsive factors that regulate cereal grain development to protect grain production under heat stress. The new research will leverage international collaborations with access to cutting-edge genetic and technological resources, and refine novel X-ray imaging techniques in Australia, to observe how temperature affects flower structure and function in barley and rice. Favourable mutations t ....Protecting cereal grain development at high temperatures. This project aims to investigate new temperature-responsive factors that regulate cereal grain development to protect grain production under heat stress. The new research will leverage international collaborations with access to cutting-edge genetic and technological resources, and refine novel X-ray imaging techniques in Australia, to observe how temperature affects flower structure and function in barley and rice. Favourable mutations that optimise plant yield and fitness will be defined and explored in other, more complex, cereals such as wheat. Expected outcomes will be fundamental breakthroughs in understanding how plants respond to, and buffer, the effects of heat to lead to translational breeding strategies that bolster grain yield.Read moreRead less