The macrophage nucleus - its form and function during migration in vivo. As cells migrate through tissues, they encounter complex, 3-dimensional environments that provide cues to guide them and present obstacles in their path. This project focuses on macrophages, a large immune cell capable of both amoeboid and mesenchymal modes of migration. The nucleus is the largest organelle and its bulk and stiffness must be managed as migrating cells travel through constrictions. The project uses specialis ....The macrophage nucleus - its form and function during migration in vivo. As cells migrate through tissues, they encounter complex, 3-dimensional environments that provide cues to guide them and present obstacles in their path. This project focuses on macrophages, a large immune cell capable of both amoeboid and mesenchymal modes of migration. The nucleus is the largest organelle and its bulk and stiffness must be managed as migrating cells travel through constrictions. The project uses specialised high-end microscopy and genetic methods to examine how the nucleus of migrating zebrafish macrophages deforms, repositions and is restructured during migration in living tissues, and how this influences macrophage locomotion. The goal is to provide fundamental insights into the cell biology of macrophage migration.Read moreRead less
The mathematics of stochastic transport and signalling in cells. The project aims to develop new stochastic mathematical models of the dynamics of protein transport and cell signalling. The mathematics will link macro scale biological observations to micro scale molecular movements to characterise the relative role that different components and processes play. Expected outcomes are robust mathematical analyses of the transient dynamics of closed, finite capacity queueing networks and biological ....The mathematics of stochastic transport and signalling in cells. The project aims to develop new stochastic mathematical models of the dynamics of protein transport and cell signalling. The mathematics will link macro scale biological observations to micro scale molecular movements to characterise the relative role that different components and processes play. Expected outcomes are robust mathematical analyses of the transient dynamics of closed, finite capacity queueing networks and biological insight into the major control mechanisms in cellular insulin signalling. The project should provide significant benefits via the delivery of new mathematical tools and analysis for stochastic networks, impacting our understanding of metabolic transport, and providing interdisciplinary research training.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220100403
Funder
Australian Research Council
Funding Amount
$468,582.00
Summary
Defining how gut bacteria regulate metabolism: a role for gut serotonin. This project aims to understand how serotonin-producing cells in the gut interact with gut bacteria (the microbiome), using a combination of cells in culture and live germ-free and genetically modified mice. This project expects to generate new knowledge regarding cellular interactions that underlie important physiological pathways, such as the control of blood glucose and fat storage. The intended outcomes of this project ....Defining how gut bacteria regulate metabolism: a role for gut serotonin. This project aims to understand how serotonin-producing cells in the gut interact with gut bacteria (the microbiome), using a combination of cells in culture and live germ-free and genetically modified mice. This project expects to generate new knowledge regarding cellular interactions that underlie important physiological pathways, such as the control of blood glucose and fat storage. The intended outcomes of this project are to identify how gut bacteria communicate with serotonin-producing cells to regulate metabolism, and whether diet acts via a gut microbiome-serotonin axis to impact physiology. The expected benefit of this project will be to provide a new understanding of highly complex physiological systems that regulate our health.Read moreRead less
New mathematics for lipids and cells: structured models for atherosclerosis. The project aims to create new mathematical theory for immune cell behaviour which leads to heart attacks and strokes. This includes formulation and analysis of new types of mathematical models for atherosclerotic plaque development, leading to the creation of new mathematical tools to investigate cell fate in plaques and to generate new hypotheses for experimental research. Expected outcomes of this project include po ....New mathematics for lipids and cells: structured models for atherosclerosis. The project aims to create new mathematical theory for immune cell behaviour which leads to heart attacks and strokes. This includes formulation and analysis of new types of mathematical models for atherosclerotic plaque development, leading to the creation of new mathematical tools to investigate cell fate in plaques and to generate new hypotheses for experimental research. Expected outcomes of this project include powerful and reliable mathematical models ready for application, and national and international collaborations with scientists and mathematicians. This should provide significant benefits including increased capacity to use mathematical models in vascular biology and training young researchers in interdisciplinary methods.Read moreRead less
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
Understanding how an old heart gets stiff. Aging is accompanied by a stiffening of the heart and reduced function, which is accelerated by cardiovascular disease and leads to heart failure. How the heart stiffens is poorly understood. A new mechanism is proposed here, involving structural membrane proteins (termed caveolae and cavins) and a signalling molecule (nitric oxide). The current research aims to unravel the interplay between cardiac cells and these proteins/signals to cause stiffness an ....Understanding how an old heart gets stiff. Aging is accompanied by a stiffening of the heart and reduced function, which is accelerated by cardiovascular disease and leads to heart failure. How the heart stiffens is poorly understood. A new mechanism is proposed here, involving structural membrane proteins (termed caveolae and cavins) and a signalling molecule (nitric oxide). The current research aims to unravel the interplay between cardiac cells and these proteins/signals to cause stiffness and to determine whether this process governs normal aging of the heart. This work will advance understanding of how heart function is determined and reveal how the human heart changes with normal aging. Read moreRead less
Space, time and boundary conditions: Mathematics for evolving plaques. This project aims to create new mathematical theory to model the morphology of atherosclerotic plaques, which cause heart attacks and strokes, as plaques grow or regress. The project expects to devise new mathematical tools for formulating novel spatial models for cellular processes inside the plaque. These should give a new window into plaque growth and spatial structures . Expected outcomes include powerful and reliable mat ....Space, time and boundary conditions: Mathematics for evolving plaques. This project aims to create new mathematical theory to model the morphology of atherosclerotic plaques, which cause heart attacks and strokes, as plaques grow or regress. The project expects to devise new mathematical tools for formulating novel spatial models for cellular processes inside the plaque. These should give a new window into plaque growth and spatial structures . Expected outcomes include powerful and reliable mathematical models, new tools to understand plaque evolution, and national and international collaborations with scientists and mathematicians. This should provide significant benefits including increased capacity to use mathematical models in vascular biology and training young researchers in interdisciplinary methods.
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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