Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek ....Investigation of a Phagocytic Synapse in the Uptake of Apoptotic Cells. Rapid clearance of cells that die by apoptosis is crucial for embryonic development, tissue turnover, and after inflammatory events. Specialised phagocytes engulf the apoptotic cell corpses in a way that minimises inflammation and prevents autoimmunity. Genetic studies have identified the key evolutionary receptors involved, but the molecular basis of this phagocytosis is still poorly understood. We have developed, and seek to establish, an integrated model that incorporates new findings to explain how the distinctive functions of specialised receptors can be orchestrated to achieve this function. A successful outcome to the project will provide new knowledge of value to human health.Read moreRead less
Lipid raft and cyotoskeleton organization: How membrane domains give cells direction. For a large number of cells in our body it is imperative that they are able to orientate themselves relative to their environment, sense direction and translate incoming signals. To do so it is hypothesised that lipids on the cell surface are redistributed to form specialized domains. An asymmetric distribution of membrane domains can provide cells with a front and rear end and can further concentrate and co-or ....Lipid raft and cyotoskeleton organization: How membrane domains give cells direction. For a large number of cells in our body it is imperative that they are able to orientate themselves relative to their environment, sense direction and translate incoming signals. To do so it is hypothesised that lipids on the cell surface are redistributed to form specialized domains. An asymmetric distribution of membrane domains can provide cells with a front and rear end and can further concentrate and co-ordinate signalling molecules to a specific site. The project will determine the role of lipid domain in stabilizing cell shape and their remodelling during cell migration, the digestion of foreign particles and the formation of cell-cell contacts.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882295
Funder
Australian Research Council
Funding Amount
$225,000.00
Summary
X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic re ....X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic research and collaborations with industry, which will enhance Australia's profile and commercialisation of research. The facility will enhance the usage of the Australian synchrotron, producing flagship projects on the edge of technical possibilities.Read moreRead less
Phloem unloading of sucrose: cloning, functional characterisation and regulation of novel membrane transporters. Sucrose is the principal form in which plant biomass, produced in photosynthetic leaves, is transported to non-photosynthetic organs for growth and storage. Sucrose transport proteins play pivotal roles in facilitating sucrose transport around plants. Hence activities of sucrose transporters directly impact on plant growth rates and crop yields. Our aim is to isolate hitherto unkno ....Phloem unloading of sucrose: cloning, functional characterisation and regulation of novel membrane transporters. Sucrose is the principal form in which plant biomass, produced in photosynthetic leaves, is transported to non-photosynthetic organs for growth and storage. Sucrose transport proteins play pivotal roles in facilitating sucrose transport around plants. Hence activities of sucrose transporters directly impact on plant growth rates and crop yields. Our aim is to isolate hitherto unknown membrane proteins that move sucrose at high rates between cells and discover their transport properties. Expected outcomes are to better understand mechanisms and regulation of sucrose transport and hence provide novel opportunities to enhance crop yield. The project will foster a productive international collaboration.Read moreRead less
In situ measurements of the electrostatic properties inside photosynthetic reaction centres: correlation with the energy conversion function of the protein. The photochemical reaction centre is a key protein complex involved in energy conversion. It converts solar energy into chemical energy as a transmembrane charge separation. Coupling of electron and proton transfer is catalysed at the level of a ubiquinone cofactor. In order to understand how the redox properties of this cofactor are fine tu ....In situ measurements of the electrostatic properties inside photosynthetic reaction centres: correlation with the energy conversion function of the protein. The photochemical reaction centre is a key protein complex involved in energy conversion. It converts solar energy into chemical energy as a transmembrane charge separation. Coupling of electron and proton transfer is catalysed at the level of a ubiquinone cofactor. In order to understand how the redox properties of this cofactor are fine tuned by the protein environment, we plan to probe the ubiquinone site using a voltage-sensitive fluorescent dye. This exciting multidisciplinary project will contribute to the understanding of how protein matrices influence and govern the midpoint redox potential of their cofactors and the environments of theirRead moreRead less
Molecular microscopy: protein and membrane dynamics in resting and activated T cells. The aim of this research, to understand the molecular organization and dynamics of the plasma membrane that underlie the signal transduction events, is at the very heart of understanding cell communication. T cell recognition and activation initiates an adaptive immune response to invading pathogens and structurally altered proteins that can be found in cancers. By providing functional insights into the molecul ....Molecular microscopy: protein and membrane dynamics in resting and activated T cells. The aim of this research, to understand the molecular organization and dynamics of the plasma membrane that underlie the signal transduction events, is at the very heart of understanding cell communication. T cell recognition and activation initiates an adaptive immune response to invading pathogens and structurally altered proteins that can be found in cancers. By providing functional insights into the molecular mechanism of T cell activation, we will not only provide fundamental knowledge of receptor signalling but also specific details of T cell receptort triggering that may lead to the development of new therapeutic strategies to control T cell activation.Read moreRead less
Symbiosomes and symbiosome membranes of corals and other cnidaria. Reef building corals and many other marine animals depend on symbiotic algae. Very little is known about the ways in which these organisms achieve effective communication with their endosymbionts, yet this is vital for understanding coral bleaching, a major present-day problem. In corals and their relatives, algae are housed in membrane-bounded vesicles, symbiosomes, which mediate the signal regulation that maintains an ongoin ....Symbiosomes and symbiosome membranes of corals and other cnidaria. Reef building corals and many other marine animals depend on symbiotic algae. Very little is known about the ways in which these organisms achieve effective communication with their endosymbionts, yet this is vital for understanding coral bleaching, a major present-day problem. In corals and their relatives, algae are housed in membrane-bounded vesicles, symbiosomes, which mediate the signal regulation that maintains an ongoing and healthy association at the cellular level. Unlike some terrestrial symbioses, little is known about the structure and function of the coral symbiosome. This study sets out to investigate this membrane at the cellular and molecular level.Read moreRead less
Streamlining the dynamin epilepsy drug pipeline. Epilepsy affects up to one percent of Australia's population, yet one in three fail to respond to current medications. Our results will greatly impact on development of future epilepsy therapy. Identification of a new target for epileptic will allow better drug design to improve the potency of our lead drugs. This holds hope that new generation drugs will be more effective. The drugs are predicted to have fewer complications and side-effects. Th ....Streamlining the dynamin epilepsy drug pipeline. Epilepsy affects up to one percent of Australia's population, yet one in three fail to respond to current medications. Our results will greatly impact on development of future epilepsy therapy. Identification of a new target for epileptic will allow better drug design to improve the potency of our lead drugs. This holds hope that new generation drugs will be more effective. The drugs are predicted to have fewer complications and side-effects. The outcome has the potential to vastly improve prospects for up to 200,000 Australians. Intellectual property (IP) retained in Australia will generate future biotechnology industry. The novel chemical biological approaches will facilitate training of future generations of Australian scientists.Read moreRead less
Symbiosomes and symbiosome membranes of corals and other cnidaria. Reef building corals and many other marine animals depend on symbiotic algae. Very little is known about the ways in which these organisms achieve effective communication with their endosymbionts, yet this is vital for understanding coral bleaching, a major present-day problem. In corals and their relatives, algae are housed in membrane-bounded vesicles, symbiosomes, which mediate the signal regulation that maintains an ongoin ....Symbiosomes and symbiosome membranes of corals and other cnidaria. Reef building corals and many other marine animals depend on symbiotic algae. Very little is known about the ways in which these organisms achieve effective communication with their endosymbionts, yet this is vital for understanding coral bleaching, a major present-day problem. In corals and their relatives, algae are housed in membrane-bounded vesicles, symbiosomes, which mediate the signal regulation that maintains an ongoing and healthy association at the cellular level. Unlike some terrestrial symbioses, little is known about the structure and function of the coral symbiosome. This study sets out to investigate this membrane at the cellular and molecular level.Read moreRead less
Mechanism of glutamate transport from experimental and simulation studies. Glutamate transporters play key roles in shaping the electrical signaling in the brain. Under conditions of stress or after a stroke, glutamate transporter function is impaired, which can lead to excessive levels of glutamate, cell death and impaired brain function. The project will help to decipher the operation of glutamate transporters at a molecular level and provide greater understanding of how glutamate levels are c ....Mechanism of glutamate transport from experimental and simulation studies. Glutamate transporters play key roles in shaping the electrical signaling in the brain. Under conditions of stress or after a stroke, glutamate transporter function is impaired, which can lead to excessive levels of glutamate, cell death and impaired brain function. The project will help to decipher the operation of glutamate transporters at a molecular level and provide greater understanding of how glutamate levels are controlled, which is vital for developing better treatments for neurological disorders such as stroke. The project will also provide research training in experimental/computational molecular biology, which is a rapidly growing field underpinning the biotechnological and pharmaceutical industries. Read moreRead less