Cytorefractometry - a new technique for refractive index tomography of living cells. An ultrahigh-resolution bifocal optical coherence refractometry is proposed, and will result to micron-scale-resolution refractive index tomography of living cells, termed cytorefractometry. This technique represents an extension from bifocal optical coherence refractometry that has recently shown a remarkable promise for direct, several-frames-per-second, motion-artifact-free determination of refractive index ....Cytorefractometry - a new technique for refractive index tomography of living cells. An ultrahigh-resolution bifocal optical coherence refractometry is proposed, and will result to micron-scale-resolution refractive index tomography of living cells, termed cytorefractometry. This technique represents an extension from bifocal optical coherence refractometry that has recently shown a remarkable promise for direct, several-frames-per-second, motion-artifact-free determination of refractive index in turbid media, including biological tissue in vivo. We propose to apply our novel technique to study tissue calcification, a serious problem in cardiology, by making use of the refractive index contrast mechanism. Calcification of smooth muscle cells and aorta subdermal implant models will be studied aiming for prevention of calcification-associated pathologies.Read moreRead less
From genes to organ function: understanding how heterogeneity in tissue modulates cellular behaviour in the heart. New computational and software engineering approaches are developed to model the electrophysiological variability of the heart and the mechanisms inducing arrhythmias. A significant outcome is a set of practical tools vital to cardiac research that provide medical specialists the ability to test hypotheses on low-cost powerful computing hardware.
Left-right patterning of the heart. This project aims to investigate how the heart responds to left-right (LR) signals, which tissue is dominant in this response; determine tissue intrinsic factors at play, and determine whether we can manipulate this. Expected outcomes include fundamental information about how organs are patterned.
Determination of Conductivity Values for Anisotropic Tissue. Well established mathematical models governing the electrical potential in biological tissue can be combined with measurements of the electric potential on the surface of the tissue to provide insight into subsurface tissue damage. However, before such observations can be convincingly accepted, reliable values for the tissue conductivity must be obtained. The aim of this project is to develop mathematical techniques to calculate the co ....Determination of Conductivity Values for Anisotropic Tissue. Well established mathematical models governing the electrical potential in biological tissue can be combined with measurements of the electric potential on the surface of the tissue to provide insight into subsurface tissue damage. However, before such observations can be convincingly accepted, reliable values for the tissue conductivity must be obtained. The aim of this project is to develop mathematical techniques to calculate the conductivity values so that one can apply the equations to solve problems of potential distribution and proceed to accurately simulate electrical potential distributions in damaged tissue. More accurate and reliable conductivity values will allow a better understanding of the way electric current moves through the heart which, in turn, will result in more efficient defibrillators and better diagnosis of abnormal function.Read moreRead less
Unravelling the sub-nuclear complexity of the brain. Understanding the function of the brain is a major frontier of scientific research. The ability to increase knowledge of brain function is reliant upon the development of novel methods. This application will develop a novel approach for understanding the function of particular nerve cells. One outcome will be demonstration of the applicability of a novel method of benefit to all brain researchers. Another outcome will be increased understandin ....Unravelling the sub-nuclear complexity of the brain. Understanding the function of the brain is a major frontier of scientific research. The ability to increase knowledge of brain function is reliant upon the development of novel methods. This application will develop a novel approach for understanding the function of particular nerve cells. One outcome will be demonstration of the applicability of a novel method of benefit to all brain researchers. Another outcome will be increased understanding of one brain region that is known to contribute to the development of cardiovascular disease. It is expected that increased knowledge of brain function will lead to novel theories of brain disease and therapeutic strategies.Read moreRead less
The molecular control of lymphatic vascular differentiation. This project aims to improve our understanding of how a new vascular system forms and the molecules that control this process. Lymphatic vasculature plays roles in fluid drainage, inflammation, obesity, metastasis and tissue repair, yet we cannot readily promote or inhibit lymphatic vessel formation. This project aims to build new knowledge that is expected to improve our ability to generate lymphatic vessels for stem cell application ....The molecular control of lymphatic vascular differentiation. This project aims to improve our understanding of how a new vascular system forms and the molecules that control this process. Lymphatic vasculature plays roles in fluid drainage, inflammation, obesity, metastasis and tissue repair, yet we cannot readily promote or inhibit lymphatic vessel formation. This project aims to build new knowledge that is expected to improve our ability to generate lymphatic vessels for stem cell applications, tissue engineering, tissue repair and regeneration. This project will use zebrafish embryos, new genomic datasets and novel tools to uncover the genetic control of this process, and should have implications in stem cell biology, tissue engineering, repair and regeneration.Read moreRead less
The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. Thi ....The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. This knowledge will help us understand the process of development in mammals, including birth defects in humans.Read moreRead less
Real-time cardiac magnetic resonance imaging: a compressed-sensing framework incorporating sensor design and multidimensional signal reconstruction. Conventional Magnetic Resonance Imaging (MRI) technology is fundamentally constrained by slow scan speeds. Taking a new approach to cardiac imaging - which integrates MRI hardware design with a novel dynamic imaging method based on compressed sensing - this project enables faster and more accurate dynamic imaging for the diagnosis of heart disease.
Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that ....Understanding the differentiation of the endocardium. The project aims to understand the genetic regulation of endocardial development. The heart is essential for survival, its beat the indicator of life. The endocardium, the heart’s inner lining, is required for signalling during heart development and is a major component of the valves, septa and trabeculae. Despite its indispensable role, little is known about how it forms or develops. This project integrates two complementary approaches that have identified the earliest marker of endocardial differentiation and devised the method to make endocardium from stem cells. Knowledge from this work will inform future research into growing and regenerating damaged tissue.Read moreRead less
Mathematical Modelling of the Mechanobiology of Arterial Plaque Growth. Plaque growth is a chronic inflammatory response induced by the interactions between endothelial cells, lipids, monocytes/macrophages, smooth muscle cells and platelets in the arteries. It involves many different biological processes, such as lipid deposition, inflammation and angiogenesis, and their interactions with the microcirculation. To understand the underlying mechanobiology, we propose to develop a mathematical mode ....Mathematical Modelling of the Mechanobiology of Arterial Plaque Growth. Plaque growth is a chronic inflammatory response induced by the interactions between endothelial cells, lipids, monocytes/macrophages, smooth muscle cells and platelets in the arteries. It involves many different biological processes, such as lipid deposition, inflammation and angiogenesis, and their interactions with the microcirculation. To understand the underlying mechanobiology, we propose to develop a mathematical model to interpret plaque growth by integrating these dynamic biological processes. It will offer a systematic rational understanding of plaque growth. New models will be provided to better interpret biological data and contribute to our knowledge in quantifying complex biological mechanisms during growth and development.Read moreRead less