Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less
Tissue Engineering of Human Heart Valve Grown In Vitro. Tissue engineering (TE) of heart valves is a new approach to cultivate a functional heart valve from human autologous cells. This innovative study aims to develop the technology to transplant cells onto a 3D biocompatible valve scaffold that is capable of mimicking native valve. The work proposed is a ground breaking study that will encompass development of a new biomaterial, manufacture of scaffolds using the Fused Deposition Modelling ra ....Tissue Engineering of Human Heart Valve Grown In Vitro. Tissue engineering (TE) of heart valves is a new approach to cultivate a functional heart valve from human autologous cells. This innovative study aims to develop the technology to transplant cells onto a 3D biocompatible valve scaffold that is capable of mimicking native valve. The work proposed is a ground breaking study that will encompass development of a new biomaterial, manufacture of scaffolds using the Fused Deposition Modelling rapid prototyping process, hemodynamic optimisation and in vitro cell culture. This will advance our knowledge in cellular and scaffold technologies and may ultimately lead to the development of a TE heart valve.Read moreRead less
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
Rapid Development of Biocompatible Stent Grafts for Aortic Aneurysms. Weakening of the aorta may cause an aneurysm. The present technique of its treatment involves replacing the weakened portion of the aorta with a synthetic graft. Failure of this treatment often occurs due to non-compatibility of the stent graft with natural aorta. One possible reason for this is a mismatch between elastic natural aorta and the non-elastic artificial graft. The core component of our project is the selection and ....Rapid Development of Biocompatible Stent Grafts for Aortic Aneurysms. Weakening of the aorta may cause an aneurysm. The present technique of its treatment involves replacing the weakened portion of the aorta with a synthetic graft. Failure of this treatment often occurs due to non-compatibility of the stent graft with natural aorta. One possible reason for this is a mismatch between elastic natural aorta and the non-elastic artificial graft. The core component of our project is the selection and development of a suitable biomaterial and optimization of the stent design based on hemodynamics flow analysis and its fabrication with the Fused Deposition Modelling (FDM) process.Read moreRead less
Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in ....Novel sources of nitric oxide (NO) in cells: Implications for an endocrine role for NO. Communication between cells is essential for coordinating and controlling a healthy body. A key regulator and cell-communicating molecule is the gas, nitric oxide. Although nitric oxide is a simple substance we still do not fully understand all aspects of its cellular functions. It is assumed that nitric oxide is synthesised in the body and, after release, is rapidly metabolized and eliminated. Reductions in the levels of nitric oxide in the body are associated with several diseases states and states of dysfunction including cardiovascular disease, diabetes and also impotence. Professor Triggle's study seeks to characterize how tissues may store nitric oxide, thus prolonging the life of nitric oxide, and how such stores are released. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100066
Funder
Australian Research Council
Funding Amount
$443,311.00
Summary
Electrophysiology facility for cell phenotyping and drug discovery. This project aims to establish a high-throughput, automated patch clamp facility to enable research at the forefront of cell phenotyping and drug discovery. Ion channels are membrane proteins that underlie cell function and are therefore important drug targets. The patch clamp technique is the most powerful tool available to functionally characterise cells and study the function of ion channels. The significant advance provided ....Electrophysiology facility for cell phenotyping and drug discovery. This project aims to establish a high-throughput, automated patch clamp facility to enable research at the forefront of cell phenotyping and drug discovery. Ion channels are membrane proteins that underlie cell function and are therefore important drug targets. The patch clamp technique is the most powerful tool available to functionally characterise cells and study the function of ion channels. The significant advance provided by the high-throughput, automated patch clamp system is that it allows up to 384 cells to be recorded simultaneously. This project expects to enhance capacity to automate and standardise the quality of recordings, substantially increase the rate of data production, and enable greater access to patch clamp technology.Read moreRead less
Transduction of neuronal signals by brain macroglial cells: implications for neuronal function. Study of mechanisms regulating brain cell (neuron and glial) communication is essential for understanding of normal brain function and transformations that occur in neurodegenerative states and age-related disorders. Mechanisms underlying neuron-glia communication are not well understood. By combining cell physiology, digital imaging technologies, and genetically designed and delivered molecules we w ....Transduction of neuronal signals by brain macroglial cells: implications for neuronal function. Study of mechanisms regulating brain cell (neuron and glial) communication is essential for understanding of normal brain function and transformations that occur in neurodegenerative states and age-related disorders. Mechanisms underlying neuron-glia communication are not well understood. By combining cell physiology, digital imaging technologies, and genetically designed and delivered molecules we will enhance our understanding of this brain cell communication and critical roles played by intracellular calcium. This will enhance international competitiveness of Australian biological research and provide novel insight of glial function in neurodegeneration and potential for specific therapeutic intervention in disease.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
Do depolarizing currents in the endothelium evoke contraction of vascular smooth muscle? Establishment of our concept involving a novel constricting influence in blood vessels will have two major benefits. First, it will keep Australian research at the leading edge in blood vessel research and thus maintain a very high international profile for Australian science. Second, our concept represents a whole new field of therapeutic potential for treating a range of vascular diseases involving excess ....Do depolarizing currents in the endothelium evoke contraction of vascular smooth muscle? Establishment of our concept involving a novel constricting influence in blood vessels will have two major benefits. First, it will keep Australian research at the leading edge in blood vessel research and thus maintain a very high international profile for Australian science. Second, our concept represents a whole new field of therapeutic potential for treating a range of vascular diseases involving excessive constriction of blood vessels. The development and manufacture of drugs in Australia would contribute to the national economy, and their consumption could improve the quality of life for those suffering from vascular diseases amenable to treatment by such drugs, likely to include pre-eclampsia, diabetes, hypertension.
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Regulating calcium handling in skeletal muscle - implications for muscle contraction, injury and repair, ageing and development. Understanding the mechanisms regulating calcium in skeletal muscle has important relevance for studying muscle growth and development, injury and repair, and for identifying therapeutic targets and potential therapies for ageing-related disorders, reconstructive surgery, sporting and workplace injuries, and muscle diseases. Combining cell physiology, fluorescence micro ....Regulating calcium handling in skeletal muscle - implications for muscle contraction, injury and repair, ageing and development. Understanding the mechanisms regulating calcium in skeletal muscle has important relevance for studying muscle growth and development, injury and repair, and for identifying therapeutic targets and potential therapies for ageing-related disorders, reconstructive surgery, sporting and workplace injuries, and muscle diseases. Combining cell physiology, fluorescence microscopy and digital imaging technologies for studying multicellular tissues such as skeletal muscle will enhance the international competitiveness of Australian biological research. The research will optimise development of gene delivery systems that may find eventual application for muscle wasting disorders and conditions where muscle weakness compromises quality of life.Read moreRead less