Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins ....Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins of high biochemical or biomedical importance, and the approach will be applied to established drug targets.Read moreRead less
Molecular structure and function of the glycine receptor. This proposal will employ a cutting edge approach to reveal fundamental new insights into the ways that ligand-gated ion channels, and proteins in general, work. The new knowledge and technology developed here will broaden and strengthen Australia's research expertise across a number of basic scientific disciplines. The results will also have relevance to human health. Glycine receptors have an essential role in brain function and are ....Molecular structure and function of the glycine receptor. This proposal will employ a cutting edge approach to reveal fundamental new insights into the ways that ligand-gated ion channels, and proteins in general, work. The new knowledge and technology developed here will broaden and strengthen Australia's research expertise across a number of basic scientific disciplines. The results will also have relevance to human health. Glycine receptors have an essential role in brain function and are targets for anaesthetics and drugs of abuse. GlyRs are also important in modulating pain sensation by the brain. New insights into how natural agonists and drugs affect ion channel structure and function may lead to novel therapeutic opportunities and improved drug structure predictions.Read moreRead less
Structure of the essential Commander protein trafficking complex. This project aims to provide a fundamental understanding of the structure and function of Commander, a large protein complex that controls export and recycling of internalised receptors. Commander is highly conserved throughout evolution and is essential for maintaining the homeostasis of hundreds of transmembrane receptors required for cell function and survival, regulating processes as diverse as lipid metabolism and cell adhesi ....Structure of the essential Commander protein trafficking complex. This project aims to provide a fundamental understanding of the structure and function of Commander, a large protein complex that controls export and recycling of internalised receptors. Commander is highly conserved throughout evolution and is essential for maintaining the homeostasis of hundreds of transmembrane receptors required for cell function and survival, regulating processes as diverse as lipid metabolism and cell adhesion. Despite advances in the understanding of Commander function, little is known about how Commander is assembled and interacts with other essential proteins. This project will use multidisciplinary cellular and structural biology approaches to reveal the architecture of Commander at an atomic level.Read moreRead less
Lipid droplet membrane tethers at atomic resolution. Eukaryotic cells are distinguished by the presence of membrane-bound compartments called organelles. This project will use structural biology to determine how essential proteins called sorting nexins (SNXs) regulate membrane interactions required for lipid droplet formation. These interactions are essential for life, controlling protein and lipid homeostasis needed for cell survival. The major outcome of this proposal will be a fundamental und ....Lipid droplet membrane tethers at atomic resolution. Eukaryotic cells are distinguished by the presence of membrane-bound compartments called organelles. This project will use structural biology to determine how essential proteins called sorting nexins (SNXs) regulate membrane interactions required for lipid droplet formation. These interactions are essential for life, controlling protein and lipid homeostasis needed for cell survival. The major outcome of this proposal will be a fundamental understanding of how SNXs control this process, and the work will significantly strengthen our international collaboration in this emerging area. The knowledge has potential future translation in the treatment of neurodegenerative disorders where dysregulation of these proteins is known to cause disease.Read moreRead less
The functional architecture of a unique family of lipid droplet proteins. Eukaryotic cells are distinguished by the presence of membrane-bound compartments called organelles. This project will use structural biology to determine how essential proteins called sorting nexins (SNXs) regulate membrane interactions required for lipid droplet formation. These interactions are essential for life, controlling protein and lipid homeostasis needed for cell survival. The major outcome of this proposal will ....The functional architecture of a unique family of lipid droplet proteins. Eukaryotic cells are distinguished by the presence of membrane-bound compartments called organelles. This project will use structural biology to determine how essential proteins called sorting nexins (SNXs) regulate membrane interactions required for lipid droplet formation. These interactions are essential for life, controlling protein and lipid homeostasis needed for cell survival. The major outcome of this proposal will be a fundamental understanding of how SNXs control this process, and the work will significantly strengthen our international collaboration in this emerging area. The knowledge has potential future translation in the treatment of neurodegenerative disorders where dysregulation of these proteins is known to cause disease. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240101233
Funder
Australian Research Council
Funding Amount
$447,237.00
Summary
Developing the toolbox of compounds that target acid-sensing proteins. This project aims to examine the interaction between acid-sensing proteins and their modulatory compounds. Animals, including humans, must sense changes in environmental acidity to successfully interact with the surrounding world. Expected outcomes of the project include a better understanding of which regions of these proteins detect acidity, and to develop new compounds that modulate the proteins’ function. This would advan ....Developing the toolbox of compounds that target acid-sensing proteins. This project aims to examine the interaction between acid-sensing proteins and their modulatory compounds. Animals, including humans, must sense changes in environmental acidity to successfully interact with the surrounding world. Expected outcomes of the project include a better understanding of which regions of these proteins detect acidity, and to develop new compounds that modulate the proteins’ function. This would advance our fundamental knowledge in the physiological process of acid sensing. This expects to provide significant benefits, by aiding the potential development of agrochemicals and pain-relieving medications that regulate acid-sensing protein function, resulting in economic benefit to Australia via these new products.
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Discovery Early Career Researcher Award - Grant ID: DE240100793
Funder
Australian Research Council
Funding Amount
$463,180.00
Summary
Unraveling a new cytokine working model in immune cell exhaustion. This project will investigate a novel paradigm of how a key messenger protein can be sensed by fundamental immune cells, preventing their ‘exhaustion’. Immune cell exhaustion is a fundamental mechanism to maintain the internal homeostasis of vertebrates. However, it is often hijacked by pathogens to dampen the defensive capacity of the immune system. And this specific messenger protein is the only known soluble factor that can d ....Unraveling a new cytokine working model in immune cell exhaustion. This project will investigate a novel paradigm of how a key messenger protein can be sensed by fundamental immune cells, preventing their ‘exhaustion’. Immune cell exhaustion is a fundamental mechanism to maintain the internal homeostasis of vertebrates. However, it is often hijacked by pathogens to dampen the defensive capacity of the immune system. And this specific messenger protein is the only known soluble factor that can deliver ‘anti-exhaustion’ signals to immune cells. This study will advance basic knowledge in biochemistry and immunology by combining interdisciplinary and cutting-edge approaches. The expected outcomes include the developing new scientific theories and identifying novel molecular basis of biological processes. Read moreRead less
Membrane proteins in innate immunity. The application of smarter and faster methods for understanding membrane proteins, targets of most drugs, is vital to a knowledge-based economy and a healthy society. The long-term benefits will include fundamental new knowledge on immunity, and implementation of new approaches that streamline costs and efforts of challenging, high-impact research.
Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanis ....Structure and function of human zinc transporter membrane proteins. The aim of this project is to create fundamental new knowledge on how important mammalian membrane proteins operate. Membrane proteins are key drug targets and are significantly under-represented in structural databases. The project plans to combine innovative membrane protein screening technology with gene expression, structural biology, biophysics and cell biology. The project outcomes may elucidate specific molecular mechanisms underpinning the essential biological process of zinc homeostasis.Read moreRead less