Augmenting the activity of glyoxalase-1 to increase dicarbonyl clearance . Reactive intermediates generated during our metabolism contribute to ageing. Glyoxalase-1 is a key defence enzyme against these toxic intermediates and therefore ageing itself. This project aims to investigate novel pathways how the expression and activity of glyoxalase-1 are regulated. This interdisciplinary project expects to generate new understanding by combining relevant cell and animal models, protein chemistry, epi ....Augmenting the activity of glyoxalase-1 to increase dicarbonyl clearance . Reactive intermediates generated during our metabolism contribute to ageing. Glyoxalase-1 is a key defence enzyme against these toxic intermediates and therefore ageing itself. This project aims to investigate novel pathways how the expression and activity of glyoxalase-1 are regulated. This interdisciplinary project expects to generate new understanding by combining relevant cell and animal models, protein chemistry, epigenetics and structural biology. It is expected that this work will improve understanding of this fundamental biological defence. This will allow us to identify the potential means to enhance the capacity of glyoxalase-1 to the future benefit of biological ageing.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100259
Funder
Australian Research Council
Funding Amount
$467,964.00
Summary
Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. T ....Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. This project will provide fundamental new knowledge in understanding how modifying muscle attributes influence successful ageing. This knowledge will improve resilience, productivity, and wellbeing of all Australians, with implications for reducing societal and economic burden.Read moreRead less
Unravelling the complexities of cell death pathways . This project aims to test if cells can flexibly rewire their cell death pathways to ensure that the absence or inhibition of one type of cell death can be compensated through the triggering of another. The project expects to generate new knowledge in the area of programed cell death, and more specifically will address why cells have multiple programmed ways to die. Expected outcomes of this project include the provision of unprecedented insig ....Unravelling the complexities of cell death pathways . This project aims to test if cells can flexibly rewire their cell death pathways to ensure that the absence or inhibition of one type of cell death can be compensated through the triggering of another. The project expects to generate new knowledge in the area of programed cell death, and more specifically will address why cells have multiple programmed ways to die. Expected outcomes of this project include the provision of unprecedented insights into the molecular regulation of how cells orchestrate and integrate cell death pathways. This should provide significant benefits, such as providing the knowledge base needed to improve our abilities to manipulate cell death both in basic research and commercial applications of cell death.Read moreRead less
Mapping and defining inter-organ cross talk during exercise. This project aims to examine precisely how organs communicate and interact. These interactions are particularly important during exercise, when continued movement demands intricate organ communication, and have major ramifications for the whole organism as it ages. Precisely how this communication takes place is unclear, but we now know that the movement of cargo with extracellular vesicles (EVs) plays an integral role in organ to orga ....Mapping and defining inter-organ cross talk during exercise. This project aims to examine precisely how organs communicate and interact. These interactions are particularly important during exercise, when continued movement demands intricate organ communication, and have major ramifications for the whole organism as it ages. Precisely how this communication takes place is unclear, but we now know that the movement of cargo with extracellular vesicles (EVs) plays an integral role in organ to organ communication. This project expects to build upon unprecedented recent developments we have made in the biology of inter-organ communication via EVs. The expected outcomes will have broad impact across life science and biotechnology.Read moreRead less
Imaging the foundation of the nervous system. This Project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, the Project expects to reveal the complex interplay of molecular, cellular and mechanical processes that direct neural tissue formation and cell fate specification. Outcomes from the Project include knowle ....Imaging the foundation of the nervous system. This Project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, the Project expects to reveal the complex interplay of molecular, cellular and mechanical processes that direct neural tissue formation and cell fate specification. Outcomes from the Project include knowledge of previously intractable developmental processes, training of future scientists and development of international collaborations. This should provide enhanced imaging capacity, a higher quality scientific workforce and position Australia at the forefront of developmental biology.
Read moreRead less
Determining how the soluble dietary fibre beta-glucan is made in cereals. This Project aims to define the molecular mechanisms that control the processes involved in the biosynthesis and regulation of mixed linkage glucan, a major soluble dietary fibre in the cell walls of cereal grains. Plant cell walls determine the quality of most plant-based products used in modern human societies, yet the regulatory mechanisms responsible for their modulation are not well understood. Key distinguishing feat ....Determining how the soluble dietary fibre beta-glucan is made in cereals. This Project aims to define the molecular mechanisms that control the processes involved in the biosynthesis and regulation of mixed linkage glucan, a major soluble dietary fibre in the cell walls of cereal grains. Plant cell walls determine the quality of most plant-based products used in modern human societies, yet the regulatory mechanisms responsible for their modulation are not well understood. Key distinguishing features of the Project will be the international, integrative, and multidisciplinary approach towards addressing this major challenge in plant biology and the potential of the fundamental scientific discoveries to benefit end-users in the food, feed and beverage industries.Read moreRead less
Molecular networks underlying mitochondrial biogenesis in humans. Mitochondria are essential for life, and we propose a highly-innovative approach (employing multiple, cutting-edge ‘omic’ technologies and bioinformatics) to advance the fundamental understanding of how mitochondria respond and adapt to exercise in humans. The project outcomes should include significant new knowledge and advanced expertise that can be used by others to facilitate additional research outcomes. The project anticipa ....Molecular networks underlying mitochondrial biogenesis in humans. Mitochondria are essential for life, and we propose a highly-innovative approach (employing multiple, cutting-edge ‘omic’ technologies and bioinformatics) to advance the fundamental understanding of how mitochondria respond and adapt to exercise in humans. The project outcomes should include significant new knowledge and advanced expertise that can be used by others to facilitate additional research outcomes. The project anticipates the contribution of innovative tools for molecular biology research, benefiting therapeutic and biotechnology applications. This project will support advanced training of young researchers in frontier technologies, which will expand Australian research capabilities and help produce a higher quality workforce.Read moreRead less
Revealing the mechanobiology of neural tube formation. This project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, we expect to reveal the complex interplay between cells and their environment that generates mechanical forces to direct neural tissue formation. Outcomes include knowledge of previously intractab ....Revealing the mechanobiology of neural tube formation. This project aims to understand the formation of the neural tube; a fundamental tissue structure that generates the brain and the spinal cord. Using interdisciplinary approaches and exploiting recent advances in transgenic and imaging technologies, we expect to reveal the complex interplay between cells and their environment that generates mechanical forces to direct neural tissue formation. Outcomes include knowledge of previously intractable developmental processes, training of future scientists and development of international collaborations. This should provide enhanced imaging capacity, a higher quality scientific workforce and position Australia at the forefront of cell and developmental biology.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
Nuclear and chromatin architecture in the replication stress response. DNA replication is an essential biological activity required for the transmittance of genomic material across cell divisions. If errors occur during DNA replication, this results in dangerous outcomes including mutation, genome instability, and cell death. Cells cope with challenges to DNA replication through a process called the replication stress response. This fellowship explores a newly discovered pathway in the replicati ....Nuclear and chromatin architecture in the replication stress response. DNA replication is an essential biological activity required for the transmittance of genomic material across cell divisions. If errors occur during DNA replication, this results in dangerous outcomes including mutation, genome instability, and cell death. Cells cope with challenges to DNA replication through a process called the replication stress response. This fellowship explores a newly discovered pathway in the replication stress response where changes to the architecture of a cell nucleus, and movement of the genomic material inside, promotes repair of genomic damage that occurs during replication. The result of this project will be an understanding of fundamental biological processes that protect human genomes.Read moreRead less