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Organising Intracellular Compartments by Formation of Transport Carriers. This project aims to investigate the cellular components which generate carriers that transport material between compartments within the cell. The process of sorting proteins and sending them to the right place is a fundamental mechanism critical to understand how individual proteins function as the move around within cells. The generated knowledge about how cells organise themselves through the movement of proteins betwee ....Organising Intracellular Compartments by Formation of Transport Carriers. This project aims to investigate the cellular components which generate carriers that transport material between compartments within the cell. The process of sorting proteins and sending them to the right place is a fundamental mechanism critical to understand how individual proteins function as the move around within cells. The generated knowledge about how cells organise themselves through the movement of proteins between endosomal intracellular compartments will provide significant benefits by enhancing our capacity to understand this conserved cellular pathway which ensures the integrity of all cellular processes including signalling, communication, homeostasis and development.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL210100107
Funder
Australian Research Council
Funding Amount
$2,960,000.00
Summary
Tracking nanoparticles: from cell culture to in vivo delivery. Understanding how cells function in the ‘real-time’ context of a living organism is a key challenge in the new era of cell biology. Using super-resolution light microscopy and state-of-the-art correlative electron microscopy together with model systems, this Fellowship aims to deliver new understandings of cells in their natural environment. Significantly, the project will elucidate how proteins or nanoparticles pass from the bloodst ....Tracking nanoparticles: from cell culture to in vivo delivery. Understanding how cells function in the ‘real-time’ context of a living organism is a key challenge in the new era of cell biology. Using super-resolution light microscopy and state-of-the-art correlative electron microscopy together with model systems, this Fellowship aims to deliver new understandings of cells in their natural environment. Significantly, the project will elucidate how proteins or nanoparticles pass from the bloodstream into tissues and then into cells, and in doing so deliver much-needed knowledge of protein and particle trafficking in situ. Outcomes and benefits include leading-edge fundamental science into the function of cells, education, outreach and building of Australian capacity in high-demand skill sets.Read moreRead less
Regulation of activity-induced glutamate receptor trafficking in neurons. Neurons communicate via synapses, where chemicals (such as glutamate) are released to transmit neuronal signals. This proposal is aimed at understanding the molecular mechanisms of neuronal communication and adaptive plasticity, which are essential for normal brain function. The proposed research will combine biophysical, biochemical, molecular and cell biological assays to elucidate the role of a calcium binding protein i ....Regulation of activity-induced glutamate receptor trafficking in neurons. Neurons communicate via synapses, where chemicals (such as glutamate) are released to transmit neuronal signals. This proposal is aimed at understanding the molecular mechanisms of neuronal communication and adaptive plasticity, which are essential for normal brain function. The proposed research will combine biophysical, biochemical, molecular and cell biological assays to elucidate the role of a calcium binding protein in controlling glutamate receptor trafficking in neurons. The outcomes will enhance our understanding of how neural plasticity is generated and maintained, knowledge that is critical for our understanding of cellular correlates of information, sensory and motor processing, as well as learning, memory and cognition. Read moreRead less
Unveiling the nanoscale organisation and dynamics of synaptic vesicle pools. This project aims to uncover the role of key molecules in allowing brain cells to actively communicate with each other. Communication between neurons relies on the fusion of synaptic vesicles containing neurotransmitters with the presynaptic plasma membrane. The addition of vesicular membrane is transient as the vesicles quickly reform from the plasma membrane and refill with neurotransmitter ready for subsequent rounds ....Unveiling the nanoscale organisation and dynamics of synaptic vesicle pools. This project aims to uncover the role of key molecules in allowing brain cells to actively communicate with each other. Communication between neurons relies on the fusion of synaptic vesicles containing neurotransmitters with the presynaptic plasma membrane. The addition of vesicular membrane is transient as the vesicles quickly reform from the plasma membrane and refill with neurotransmitter ready for subsequent rounds of fusion. This recycling process ensures that neurons communicate efficiently, however the underpinning mechanism is unknown. This project aims to use a recently developed single synaptic vesicle super-resolution tracking method to establish how Myosin-VI and Synapsin-IIa orchestrate this recycling in central and peripheral neurons. It will explain how neurons manage to preserve their ability to communicate.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
Understanding how cells regulate self eating during starvation and stress. This project aims to investigate how autophagosomes are built during autophagy by using advanced multi-modal imaging and unique gene-edited human cell lines. This project expects to generate new knowledge on how a family of evolutionary conserved proteins regulate autophagosome formation during starvation and stress conditions. Expected outcomes include the development of frontier imaging technologies that can be subseque ....Understanding how cells regulate self eating during starvation and stress. This project aims to investigate how autophagosomes are built during autophagy by using advanced multi-modal imaging and unique gene-edited human cell lines. This project expects to generate new knowledge on how a family of evolutionary conserved proteins regulate autophagosome formation during starvation and stress conditions. Expected outcomes include the development of frontier imaging technologies that can be subsequently utilised for the advancement of any field of cell biology. This should provide significant benefits by placing Australia at the forefront of cell biology technologies and increasing our understanding of how plant and human cells can protect themselves during starvation and stress.
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Characterising the transport and delivery of oligonucleotides . Short RNA and DNA molecules represent a class of macromolecules that have great potential, but to facilitate their trafficking across cellular and membrane barriers into specific sites of action is challenging. This project aims to develop and apply novel imaging approaches to track them in cells and tissues. Expected outcomes include better understanding of the trafficking across cellular and membrane barriers, and improved imaging ....Characterising the transport and delivery of oligonucleotides . Short RNA and DNA molecules represent a class of macromolecules that have great potential, but to facilitate their trafficking across cellular and membrane barriers into specific sites of action is challenging. This project aims to develop and apply novel imaging approaches to track them in cells and tissues. Expected outcomes include better understanding of the trafficking across cellular and membrane barriers, and improved imaging tools that could be used to further study the molecular mechanisms of accumulation, metabolism and trafficking of these molecules. This project should provide new strategies to target these molecules to specific cells and tissues, which have significant social and economic benefits to the Australian community.Read moreRead less
Reprogramming Innate Immunity To Combat Inflammatory And Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$1,788,220.00
Summary
Our immune system protects us from infection, but also drives cancer, autoimmune diseases, inflammatory diseases and many other conditions. Innate immunity, a key component of our immune system, mediates the pathology that is associated with these diseases. This research program aims to define innate immune mechanisms that combat infection and/or drive inflammation-mediated diseases. It also aims to deliver novel anti-infective and anti-inflammatory strategies.