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
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
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
Proteomic analysis of subcellular changes during apoptosis. This project aims to use a novel proteomic approach to examine mechanisms of apoptosis at the level of the plasma membrane, mitochondrion, nucleus and cytosol, screening protein extracts of cell organelles by the new technique of SELDI-TOF mass spectrometry in which proteins are adsorbed onto activated chips. This will provide protein mass profiles characteristic of various stages of apoptosis, and will allow identification of proteins ....Proteomic analysis of subcellular changes during apoptosis. This project aims to use a novel proteomic approach to examine mechanisms of apoptosis at the level of the plasma membrane, mitochondrion, nucleus and cytosol, screening protein extracts of cell organelles by the new technique of SELDI-TOF mass spectrometry in which proteins are adsorbed onto activated chips. This will provide protein mass profiles characteristic of various stages of apoptosis, and will allow identification of proteins of interest by conventional proteomic methods. The establishment of SELDI-MS as a viable tool for cell proteomics would open new opportunities to understand a broad range of cellular functions at the level of protein expression.Read moreRead less
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
Genome wide screening for gene products that regulate the celluar dynamics of lipid droplets. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also provide novel ta ....Genome wide screening for gene products that regulate the celluar dynamics of lipid droplets. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also provide novel targets and strategies for treating obesity. The proposed study will also benefit Australian agriculture by providing strategies to improve oil production from plant seeds. 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
A molecular structure-function investigation of major membrane channels involved in olfactory transduction. Olfactory receptor neurons are extraordinarily-sensitive sensors for detecting minute concentrations of odorant molecules. This project aims to extend our previous studies of these specialised mammalian olfactory cells by using state-of-the art technologies: electrophysiology (patch-clamp) and molecular biology (site-directed-mutagenesis), to investigate how the molecular structure of the ....A molecular structure-function investigation of major membrane channels involved in olfactory transduction. Olfactory receptor neurons are extraordinarily-sensitive sensors for detecting minute concentrations of odorant molecules. This project aims to extend our previous studies of these specialised mammalian olfactory cells by using state-of-the art technologies: electrophysiology (patch-clamp) and molecular biology (site-directed-mutagenesis), to investigate how the molecular structure of their ion channels (selective protein pores) and receptors contribute to the odorant-induced generation of electrical activity, which mediates our sense of smell (olfaction). The project has specific relevance for understanding olfaction, as well as relevance for other sensory systems and other ion channels.Read moreRead less
Cholesterol-dependent control of plasma membrane lipid rafts. Lipid rafts are recently discovered micro-domains in the plasma membrane that are highly enriched in cholesterol, giving these domains a unique lipid structure. Because of their distinct structure specific proteins partition into these domains so that lipid rafts act as message transduction centres in a variety of cell functions. It is hypothesised that cholesterol is the link between the distinct biophysical parameters of lipid rafts ....Cholesterol-dependent control of plasma membrane lipid rafts. Lipid rafts are recently discovered micro-domains in the plasma membrane that are highly enriched in cholesterol, giving these domains a unique lipid structure. Because of their distinct structure specific proteins partition into these domains so that lipid rafts act as message transduction centres in a variety of cell functions. It is hypothesised that cholesterol is the link between the distinct biophysical parameters of lipid rafts and their function. The aim of this proposal is to understand how cellular cholesterol levels contribute to raft structure and function, thus elevating cholesterol to a regulatory element for lipid raft and their function.Read moreRead less