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
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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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
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
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
Heat regulation by the fibre types in muscle. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the fibre types that make up skeletal muscles regulate heat generation against other muscle function, to maintain core body temperature and the normal movement and posture of the mammal. Project outcomes include defining, for the first time, how heat generation in the muscles o ....Heat regulation by the fibre types in muscle. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the fibre types that make up skeletal muscles regulate heat generation against other muscle function, to maintain core body temperature and the normal movement and posture of the mammal. Project outcomes include defining, for the first time, how heat generation in the muscles of the body is regulated. This should provide critical knowledge of mammalian evolution and ways to manipulate metabolism, which may provide ways to assist with achieving a desired meat quality and yield in beef and other commercially important animals.Read moreRead less
Regulated muscle-based thermogenesis for body temperature regulation. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the skeletal muscles that are closer to the body core contribute the majority of heat, how the muscles of the limbs have their heat generation curtailed as necessary, and how this is coordinated by the body in response to ambient temperature. Project out ....Regulated muscle-based thermogenesis for body temperature regulation. Mammals maintain a constant core body temperature by generating heat in resting muscles in response to changes in the environmental temperatures. This project aims to show how the skeletal muscles that are closer to the body core contribute the majority of heat, how the muscles of the limbs have their heat generation curtailed as necessary, and how this is coordinated by the body in response to ambient temperature. Project outcomes include defining, for the first time, how heat generation in the muscles of the body is regulated. This should provide critical knowledge of mammalian evolution and ways to manipulate metabolism, which may provide ways to assist the production of meat by managing hypothermia and hyperthermia risk in agriculture.Read moreRead less
Mechanism and function of cell asymmetry during cell death. This project aims to investigate how dying cells rearrange their cellular contents to aid their removal.
More than 200 billions cells die daily in the human body. It is critical that dying cells are rapidly cleared as their buildup can interfere with normal tissue functions. This project will use a suite of contemporary molecular/cell biological approaches to study a newly identified process that occurs during cell death. Expected outc ....Mechanism and function of cell asymmetry during cell death. This project aims to investigate how dying cells rearrange their cellular contents to aid their removal.
More than 200 billions cells die daily in the human body. It is critical that dying cells are rapidly cleared as their buildup can interfere with normal tissue functions. This project will use a suite of contemporary molecular/cell biological approaches to study a newly identified process that occurs during cell death. Expected outcomes include a paradigm-shift in understanding the process of cell clearance.
This project is expected to generate fundamental new knowledge of the mechanisms by which dying cells are efficiently removed from tissues. This should provide significant benefits to the cell death and general cell biology fields.Read moreRead less
Mechanisms by which Beclin1 regulates intestinal homeostasis. This project aims to investigate if Beclin1, a protein which has an important and well-accepted role in promoting cell survival through the program of autophagy, has an alternate job mediating trafficking within a cell. Using novel mouse models and innovative techniques, the project aims to demonstrate the physiological importance of this alternate role for Beclin1. Expected outcomes include enhancing Australia's international researc ....Mechanisms by which Beclin1 regulates intestinal homeostasis. This project aims to investigate if Beclin1, a protein which has an important and well-accepted role in promoting cell survival through the program of autophagy, has an alternate job mediating trafficking within a cell. Using novel mouse models and innovative techniques, the project aims to demonstrate the physiological importance of this alternate role for Beclin1. Expected outcomes include enhancing Australia's international research standing, and providing research training for young scientists. Benefits include generation of new knowledge and a rethink of the basis for normal development and diseases where Beclin1 has been implicated.Read moreRead less