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
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
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
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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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
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
Discovery Early Career Researcher Award - Grant ID: DE240101286
Funder
Australian Research Council
Funding Amount
$469,707.00
Summary
SARS-CoV-2-induced dead cell fragments drive viral uptake and inflammation. This project will apply advanced cell biology and imaging techniques to investigate how macrophages, which lacks a canonical receptor for viral entry, become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and elicit inflammatory responses. Its insights into a novel pathway of viral entry is expected to advance our understanding of host-pathogen interaction. The project is intended to uncover t ....SARS-CoV-2-induced dead cell fragments drive viral uptake and inflammation. This project will apply advanced cell biology and imaging techniques to investigate how macrophages, which lacks a canonical receptor for viral entry, become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and elicit inflammatory responses. Its insights into a novel pathway of viral entry is expected to advance our understanding of host-pathogen interaction. The project is intended to uncover the role of SARS-CoV-2-induced dead cell fragmentation in promoting viral uptake and inflammation. Its findings should provide significant scientific, health and economic benefits by informing new research directions on infection and innate immunity as well as future therapeutic designs for infection treatment.Read moreRead less
Formation and clearance of endothelial cell-derived exophers. This project aims to investigate how cells that line the blood vessels release cellular wastes and their subsequent removal by immune cells.
It is critical that cellular waste are removed in a timely manner as their accumulation inside the cell can interfere with normal cell functions. The intended outcome of the project is to generate fundamental new knowledge of the mechanisms by which cellular waste are efficiently removed.
Exp ....Formation and clearance of endothelial cell-derived exophers. This project aims to investigate how cells that line the blood vessels release cellular wastes and their subsequent removal by immune cells.
It is critical that cellular waste are removed in a timely manner as their accumulation inside the cell can interfere with normal cell functions. The intended outcome of the project is to generate fundamental new knowledge of the mechanisms by which cellular waste are efficiently removed.
Expected outcomes encompass a paradigm-shift in understanding how cells that line the blood vessels dispose unwanted cellular contents. This should provide significant benefits including understanding how these specialised cells maintain the integrity of blood vessels and communicate with immune cells.Read moreRead less
Tree-mediated methane fluxes: A new frontier in the global carbon cycle. Methane is an extremely potent greenhouse gas. Recent evidence suggests that tree-mediated fluxes may be a significant, but overlooked source of methane to the atmosphere. This project aims to quantify the magnitude and drivers of tree-mediated methane fluxes from Australia’s dominant forest types. Innovatively, we will be using a novel combination of empirical field based measurements, gas tracer experiments, microbial ana ....Tree-mediated methane fluxes: A new frontier in the global carbon cycle. Methane is an extremely potent greenhouse gas. Recent evidence suggests that tree-mediated fluxes may be a significant, but overlooked source of methane to the atmosphere. This project aims to quantify the magnitude and drivers of tree-mediated methane fluxes from Australia’s dominant forest types. Innovatively, we will be using a novel combination of empirical field based measurements, gas tracer experiments, microbial analysis and modelling methods. Expected outcomes are a mechanistic understanding of tree-mediated methane fluxes, helping to constrain regional, national and global methane budgets. The results of this study will help inform publicly funded greenhouse gas abatement strategies, ensuring a maximal return on investment.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