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
Faecal Microbiota Transplantation And Other Novel Therapeutic Microbial Manipulation Strategies In Inflammatory Bowel Disease
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
There is growing interest in the role of microbial-based strategies including faecal microbiota transplantation (FMT) for the treatment of inflammatory bowel disease. This project will develop such strategies into valid treatment options through a combination of clinical & basic science work including (1) characterising viral & fungal factors of importance, (2) evaluation of novel orally-delivered formulations of FMT, and (3) development of better defined, more reproducible microbial treatments.
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
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
Digging deeper to improve yield stability. This project aims to provide innovative breeding solutions that harness the ‘hidden’ part of the plant, roots, to support the development of more productive crops in the face of climate variability. The project expects to generate new insights into the biology and genetics of root development in barley, a model cereal crop, by applying cutting-edge genome editing, phenotyping and genomics technologies. Anticipated outcomes include novel methodologies to ....Digging deeper to improve yield stability. This project aims to provide innovative breeding solutions that harness the ‘hidden’ part of the plant, roots, to support the development of more productive crops in the face of climate variability. The project expects to generate new insights into the biology and genetics of root development in barley, a model cereal crop, by applying cutting-edge genome editing, phenotyping and genomics technologies. Anticipated outcomes include novel methodologies to accelerate breeding for diverse production environments, with direct applications in barley, and other major cereals including wheat and oats. This should provide significant economic and social benefits to the Australian grains industry through yield stability amidst climate variability.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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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
Exploring The Occurrence And Potential Associated Risk Factors For Pilchard Orthomyxovirus (POMV) In Tasmanian Farmed Atlantic Salmon
Funder
Fisheries Research and Development Corporation
Funding Amount
$209,295.62
Summary
Following basic epidemiology principles, no infectious disease occurs ‘randomly’ and its occurrence follow logical and predictable patterns. The presence of an infectious agent is unlikely sufficient to explain these patterns and most aquatic diseases result from the complex interaction between the agent, the host and its environment. Therefore, the targeted outcome for a POMV control plan is threefold: 1. Decrease transmission between infected and susceptible fish groups – this requires ide ....Following basic epidemiology principles, no infectious disease occurs ‘randomly’ and its occurrence follow logical and predictable patterns. The presence of an infectious agent is unlikely sufficient to explain these patterns and most aquatic diseases result from the complex interaction between the agent, the host and its environment. Therefore, the targeted outcome for a POMV control plan is threefold: 1. Decrease transmission between infected and susceptible fish groups – this requires identifying risk factors associated with the introduction, spread, and maintenance of the pathogen within the industry; 2. Decrease the number of susceptible fish – this mainly requires identifying risk factors associated with the susceptibility of the host (e.g. husbandry-related stress) and the development of a safe and effective prophylaxis; 3. Decrease the amount of virus in the environment - this requires detecting infected fish cage(s) early to implement timely control strategies. Diagnostic capacity to confirmed POMV outbreak has been developed and is currently used in routine by the industry. A vaccine against POMV is currently under development at the Tasmanian Aquatic Animal Health and Vaccines Centre of Excellence and will be available in the future. However, little is known about risk factors specific to POMV and about its full economic impact. We define as a ‘risk factor’ any attribute of the agent, the host or its environment that increases the risk and intensity of a disease outbreak. Most of the environmental risk factors (including farming practices) facilitate the introduction, transmission, or maintenance of the pathogen; while the host risk factors affect the susceptibility of the host and its capacity to become diseased. Like the closely related ISAv, the magnitude and occurrence of POMV outbreaks appeared to be highly variable. This supports the existence of additional factors other than the POMV infection that contribute to the intensity of an outbreak. It is anticipated that by identifying and intervening on some of the manageable risk factors, the frequency and the severity of POMV outbreaks can be reduced. Objectives: 1. Describe the occurrence of POMV outbreaks in the Tasmanian salmon industry 2. Quantify the direct financial impact of POMV mortality to the Tasmanian salmon industry 3. Identify potential management, environmental and stock risk factors directly or indirectly increasing the risk and intensity of a POMV outbreaks Read moreRead less
How do cells survive nutrient stress? Insight into mechanisms. This project studies cell survival under nutrient stress in eukaryotes. Building on extensive preliminary data that identifies novel TOR (Target of Rapamycin) Complex 2 (TORC2) control points it expects to generate new knowledge of critical and conserved features of stress control of macroautophagy that ensures cell survival. It uses interdisciplinary and innovative approaches to validate and characterize nutrient-stress dependent si ....How do cells survive nutrient stress? Insight into mechanisms. This project studies cell survival under nutrient stress in eukaryotes. Building on extensive preliminary data that identifies novel TOR (Target of Rapamycin) Complex 2 (TORC2) control points it expects to generate new knowledge of critical and conserved features of stress control of macroautophagy that ensures cell survival. It uses interdisciplinary and innovative approaches to validate and characterize nutrient-stress dependent signaling. Expected outcomes include novel insights into environmental control of cell proliferation and forging cross institutional collaborations. This knowledge benefits basic and applied biology and is relevant to industries/projects utilizing living cells as nutrient supports cell survival and proliferation.Read moreRead less