Elucidating the mechanisms of mitochondrial DNA escape. The human body is powered by mitochondria, microscopic components of living cells that make the energy they need to function. Mitochondrial damage is linked to a wide spectrum of human diseases, from devastating syndromic illnesses to neurodegeneration and autoimmunity. This project is focused on 1) how stresses such as cancer therapy or infection cause mitochondrial damage, and 2) understanding the biological processes that are triggered i ....Elucidating the mechanisms of mitochondrial DNA escape. The human body is powered by mitochondria, microscopic components of living cells that make the energy they need to function. Mitochondrial damage is linked to a wide spectrum of human diseases, from devastating syndromic illnesses to neurodegeneration and autoimmunity. This project is focused on 1) how stresses such as cancer therapy or infection cause mitochondrial damage, and 2) understanding the biological processes that are triggered inside the cell as it tries to recover. It will give a much greater understanding of mitochondrial damage at the microscopic level, and has the potential to unlock new avenues of investigation into the causes of inflammatory and immune disorders.Read moreRead less
Androgen receptor: A master regulator of lipid metabolism. This project aims to understand how male sex hormones, or androgens, affect the amount and metabolism of fats in normal body tissues. By integrating our multi-disciplinary expertise in androgen action, molecular biology, metabolism and bioinformatics with novel techniques and instrumentation, this collaboration expects to generate the first detailed picture of how fat metabolism is controlled by androgens in humans, and how closely this ....Androgen receptor: A master regulator of lipid metabolism. This project aims to understand how male sex hormones, or androgens, affect the amount and metabolism of fats in normal body tissues. By integrating our multi-disciplinary expertise in androgen action, molecular biology, metabolism and bioinformatics with novel techniques and instrumentation, this collaboration expects to generate the first detailed picture of how fat metabolism is controlled by androgens in humans, and how closely this relates to mice. Expected outcomes and benefits will be a new understanding of which aspects of fat metabolism are most influenced by androgens, and an ability to anticipate potential metabolic impacts of natural or pharmacological fluctuations in androgen levels in humans, laboratory animals and livestock.Read moreRead less
Discovery and directed evolution of small molecule biosensors. This project aims to address the need for novel small molecule biosensing capability in diverse fields including food and wine production, environmental monitoring, biocatalysis, and diagnostics using a synthetic biology approach. The significance of this work is the development of new biosensors by a strong interdisciplinary team contributing bioinformatics to identify new biosensors, innovative protein engineering approaches, and c ....Discovery and directed evolution of small molecule biosensors. This project aims to address the need for novel small molecule biosensing capability in diverse fields including food and wine production, environmental monitoring, biocatalysis, and diagnostics using a synthetic biology approach. The significance of this work is the development of new biosensors by a strong interdisciplinary team contributing bioinformatics to identify new biosensors, innovative protein engineering approaches, and cutting-edge directed evolution methodologies. Intended outcomes include enhanced institutional capacity for interdisciplinary collaboration; discovery of fundamentally important bacterial sensors; and development of synthetic regulatory circuits enabling outgrowth of non-biological biocatalysis industries.Read moreRead less
Structure and metabolism of bioactive carbohydrates from brown algae. Brown algae produce a diversity of species-specific carbohydrates in their cell walls that exhibit a variety of biological activities that can be exploited for the development of functional food and biopharmaceutical formulations. However, the metabolic pathways responsible for the biosynthesis of these carbohydrates are poorly characterised. This multidisciplinary project aims to understand the molecular events that control t ....Structure and metabolism of bioactive carbohydrates from brown algae. Brown algae produce a diversity of species-specific carbohydrates in their cell walls that exhibit a variety of biological activities that can be exploited for the development of functional food and biopharmaceutical formulations. However, the metabolic pathways responsible for the biosynthesis of these carbohydrates are poorly characterised. This multidisciplinary project aims to understand the molecular events that control the structure and metabolism of bioactive carbohydrates in the prominent Australian brown alga Ecklonia radiata, with particular focus on alginates and fucoidans. This knowledge will be used to produce in yeast bioactive oligosaccharides that are of high commercial interest to the biopharmaceutical industry.Read moreRead less
New mechanisms regulating the biogenesis of extracellular vesicles. Extracellular vesicles are small packages that contain active components derived from the cell of origin. These vesicles, released by most cell types, are critical for communication between cells. However, the processes of their formation and release remain poorly understood. This project aims to explore how ubiquitination, a type of protein modification system, controls the production of extracellular vesicles. Using a strong c ....New mechanisms regulating the biogenesis of extracellular vesicles. Extracellular vesicles are small packages that contain active components derived from the cell of origin. These vesicles, released by most cell types, are critical for communication between cells. However, the processes of their formation and release remain poorly understood. This project aims to explore how ubiquitination, a type of protein modification system, controls the production of extracellular vesicles. Using a strong collaborative team and highly innovative approaches, the project will generate new knowledge to inform how cells communicate. Expected outcomes include knowledge of broad significance to cell biology, that can be leveraged to develop extracellular vesicles as tools for various biotechnology applications in the future.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101081
Funder
Australian Research Council
Funding Amount
$458,238.00
Summary
Developing CRISPR Prime Editing for highly efficient precise gene editing. This project will further develop a recent breakthrough in gene editing technology named CRISPR prime editing to improve its performance in generating specific genome modifications in cells and organisms. This project expects to generate new knowledge regarding optimal strategies for its deployment as well as create novel enhanced versions of the technology. This would significantly enhance our ability to perform precise ....Developing CRISPR Prime Editing for highly efficient precise gene editing. This project will further develop a recent breakthrough in gene editing technology named CRISPR prime editing to improve its performance in generating specific genome modifications in cells and organisms. This project expects to generate new knowledge regarding optimal strategies for its deployment as well as create novel enhanced versions of the technology. This would significantly enhance our ability to perform precise genome modification of organisms and lead to substantial benefits for a vast array of applications in fundamental and applied biology. Future applications will include generating mutations in cells and model organisms for basic research and creating genetically enhanced agricultural animals or plants.Read moreRead less
Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is ....Signaling in the crypt: a novel metabolic pathway in intestinal stem cells. The gut is the most rapidly renewing tissue in the body, driven by a highly active stem cell niche. Bile acids are emerging as critical regulators of this stem cell niche and disruption of bile acid homeostasis has profoundly adverse effects on intestinal renewal and hence gut health. We are addressing a critical gap in our understanding of how bile acids are controlled within stem cell niche. The aim of the project is to define the critical role of a novel enzyme called UGT8 in controlling intestinal stem cell response to bile acids; this is achieved by modulating UGT8 activity in intestinal stem cell models and determining the effects on stem cell function and the key signalling pathways that control intestinal homeostasis and renewal.Read moreRead less
EFR3: Novel gatekeeper of cell proliferation. This interdisciplinary, cross-institutional project uses leading-edge mass spectrometry and the yeast genetic model to enhance knowledge of fundamental signalling mechanisms common to cell proliferation of eukaryotic cells. Building on extensive preliminary data that identifies novel energy-stress control points, this research will generate insights into critical and conserved features of nutrient stress control of cell proliferation that ensures cel ....EFR3: Novel gatekeeper of cell proliferation. This interdisciplinary, cross-institutional project uses leading-edge mass spectrometry and the yeast genetic model to enhance knowledge of fundamental signalling mechanisms common to cell proliferation of eukaryotic cells. Building on extensive preliminary data that identifies novel energy-stress control points, this research will generate insights into critical and conserved features of nutrient stress control of cell proliferation that ensures cell survival. This project advances basic and applied biology. Its outcomes will be relevant to several research areas and industries, specifically to the propagation of cell cultures that nowadays contributes to the production of a myriad of biotechnical and pharmaceutical commodities.
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How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misf ....How do protein quality control mechanisms maintain neuronal ageing? This project aims to interrogate how mechanisms of protein quality control act in the brain - an organ that is particularly vulnerable to a high load of misfolded protein - to maintain normal physiology during ageing. This project expects to make advances in cellular biochemistry and neuroscience, using an innovative proximity labelling approach to identify quality control regulators in neurons that specifically engage with misfolded proteins during ageing, within the nervous system of a living animal. Expected outcomes of this project will generate new knowledge of brain physiology and ageing relevant to all animals. This should provide significant benefits, such as a greater understanding of long-term brain functions including memory.Read moreRead less