Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultim ....Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultimately inform our capacity to better deploy personalised medicines.Read moreRead less
Metabolite regulation of mitochondrial fission. This project aims to understand how the function and health of mitochondria – the energy producing structures in cells - are controlled by fat molecules. The project expects to integrate cutting edge techniques and instrumentation to generate new knowledge of how fat molecules interact with, and influence, enzymes that control how cells maintain their mitochondria in response to nutrient state. An anticipated goal is to define a fingerprint for enz ....Metabolite regulation of mitochondrial fission. This project aims to understand how the function and health of mitochondria – the energy producing structures in cells - are controlled by fat molecules. The project expects to integrate cutting edge techniques and instrumentation to generate new knowledge of how fat molecules interact with, and influence, enzymes that control how cells maintain their mitochondria in response to nutrient state. An anticipated goal is to define a fingerprint for enzymes regulated by fat molecules that will be of great interest to researchers across many branches of life sciences. Expected outcomes and benefits will be deeper understanding of fat molecules as nutrient signalling metabolites, and how they influence cell metabolism, growth and development.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
How bacteria form resistant aggregates and biofilms. This research aims to use interdisciplinary approaches to advance fundamental knowledge on bacterial aggregates and biofilms. These bacterial clusters are a significant problem as they have extraordinary resistance to disinfectants and antibiotics, and currently no effective methods are available to disrupt them. The expected outcomes of this project are to dissect how autotransporters, the most common group of bacterial cell-surface proteins, ....How bacteria form resistant aggregates and biofilms. This research aims to use interdisciplinary approaches to advance fundamental knowledge on bacterial aggregates and biofilms. These bacterial clusters are a significant problem as they have extraordinary resistance to disinfectants and antibiotics, and currently no effective methods are available to disrupt them. The expected outcomes of this project are to dissect how autotransporters, the most common group of bacterial cell-surface proteins, promote aggregation and biofilm formation, and to develop inhibitors that prevent the formation of these damaging bacterial clusters. Ultimately, this new knowledge will help address the increasing economic and social burden of industrial, environmental and biomedical biofilms.Read moreRead less
Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor ....Molecular mechanisms of novel bacterial copper defense proteins. This project aims to reveal molecular and cellular mechanisms used by bacteria to neutralise the destructive effects of copper. Copper is an essential trace element in living systems. It is toxic to bacteria and so plays a vital role in nutritional immunity. To counteract copper toxicity, bacteria have evolved defense mechanisms. The project will investigate a novel but poorly understood class of bacterial proteins, the suppressor of copper sensitivity proteins, that contribute to this key virulence trait. The expected outcomes will be fundamental new knowledge of metallo-protein diversity, bacterial virulence mechanisms, and membrane protein function with potential impact on health, environment, and biotechnology.Read moreRead less