Molecular neurobiology of the GABAB receptor: Studies of heteromeric receptor function and signalling. The G protein-coupled receptor (GPCR) for the inhibitory transmitter gamma- aminobutyric acid (GABA) is a unique heterodimer. Molecular analyses will be undertaken to provide insights into its signalling mechanisms and functional regulation. Investigations employing point mutant and chimeric receptors will analyse how ligand binding to the extracellular domain of the GABA-BR1 subunit triggers ....Molecular neurobiology of the GABAB receptor: Studies of heteromeric receptor function and signalling. The G protein-coupled receptor (GPCR) for the inhibitory transmitter gamma- aminobutyric acid (GABA) is a unique heterodimer. Molecular analyses will be undertaken to provide insights into its signalling mechanisms and functional regulation. Investigations employing point mutant and chimeric receptors will analyse how ligand binding to the extracellular domain of the GABA-BR1 subunit triggers G protein-coupling to the intracellular portion of the GABA-BR2 subunit. Focus will be on different modes of GPCR signalling, including constitutive activity and roles for membrane and cytosolic regulatory proteins. Targeted studies of GABAB receptor subunits will provide new information on the mechanistic regulation of GPCR signalling.Read moreRead less
Alpha-Conotoxins: Selective Probes For Nicotinic Receptor Subtype Structure And Function. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a ....Alpha-Conotoxins: Selective Probes For Nicotinic Receptor Subtype Structure And Function. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a greater understanding of how the nervous system functions. This knowledge will help in the design of new drugs to treat a variety of diseases and disorders. Essentially we will use a chemical armoury developed by the cone snail to design state-of-the-art mini-protein drugs.Read moreRead less
New modulators of voltage-gated sodium channel subtypes from Australian Tarantula venoms. The venoms of Australian tarantula spiders provide a unique and untapped source of bioactive molecules. From a large stock of venom, and in collaboration with Australian pharmaceutical company Xenome, we will develop a comprehensive library of venom components suitable for drug screening. Potential national benefits from this work include a huge reduction in the healthcare bill deriving from a new treatmen ....New modulators of voltage-gated sodium channel subtypes from Australian Tarantula venoms. The venoms of Australian tarantula spiders provide a unique and untapped source of bioactive molecules. From a large stock of venom, and in collaboration with Australian pharmaceutical company Xenome, we will develop a comprehensive library of venom components suitable for drug screening. Potential national benefits from this work include a huge reduction in the healthcare bill deriving from a new treatment for pain, as well as substantial royalty returns from drugs sales. Discoveries from the program are also likely to lead to an enhancement in Australia's reputation in the neurosciences and to the development of new diagnostic research tools. The major community benefit will be a reduction in the suffering of chronic pain patients.Read moreRead less
Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a gr ....Defining mechanisms of action of novel alpha-conotoxins at nicotinic receptor-channels. Marine snails from the waters off the Australian coast produce an amazing variety of mini-proteins in their venoms called conotoxins that they use to capture prey. These conotoxins bind very specifically to receptors in our body associated with the transmission of nerve signals. We will use natural and synthetically modified conotoxins to selectively block particular types of neuronal 'receptors' to gain a greater understanding of how the nervous system functions. This knowledge will help in the design of new drugs to treat a variety of diseases and disorders. Essentially we will use a chemical armoury developed by the cone snail to design state-of-the-art mini-protein drugs.Read moreRead less
Immobilised Lipid Chromatography for Membrane Protein Isolation and Analysis. Current techniques for membrane protein are inadequate for the emerging proteomic challenge, in which approximately 40% of proteins are predicted to be membrane associated. The aim of this proposal is to develop a new approach to purify membrane proteins using our recently-developed immobilised membrane chromatography materials. The present proposal will provide a new high-resolution separation technique that allows is ....Immobilised Lipid Chromatography for Membrane Protein Isolation and Analysis. Current techniques for membrane protein are inadequate for the emerging proteomic challenge, in which approximately 40% of proteins are predicted to be membrane associated. The aim of this proposal is to develop a new approach to purify membrane proteins using our recently-developed immobilised membrane chromatography materials. The present proposal will provide a new high-resolution separation technique that allows isolation and on-line mass analysis of complex mixtures of membrane proteins for subsequent proteomic analysis, high-throughput screening or structural studies and could form the basis for further development of new commercial tools for membrane protein analysis.Read moreRead less
Biological Role of Contraction-Induced Heat Shock Protein Expression. It is well known that mammalian skeletal muscle increases its expression of a group of highly conserved proteins, the heat shock proteins (HSP) in response to repeated contraction. However, the biological role of this expression is unclear. The aim of this project is to determine the biological role of contraction-induced HSP expression. We expect to show that HSP synthesis in response to exercise has three major roles; 1) to ....Biological Role of Contraction-Induced Heat Shock Protein Expression. It is well known that mammalian skeletal muscle increases its expression of a group of highly conserved proteins, the heat shock proteins (HSP) in response to repeated contraction. However, the biological role of this expression is unclear. The aim of this project is to determine the biological role of contraction-induced HSP expression. We expect to show that HSP synthesis in response to exercise has three major roles; 1) to act to repair damaged proteins in recovery from muscle injury 2) to act as a "molecular motor" to translocate proteins from one region of a muscle cell to another and 3) to be released into the circulation in order to act as a central signal to activate immune cells. Such a project will be significant because it will allow for a fundamental understanding as to why these proteins are produced in response to exercise. We expect to enhance our understanding of fundamental cell biology.Read moreRead less
Understanding and predicting small molecule binding to G protein-coupled receptors (GPCRs). The discovery of new treatments for serious diseases is a time consuming and expensive process. Our work involves developing and testing new computational modelling approaches with experimental validation for the understanding and prediction of how current and new drugs interact with their targets, and these methods can be extended for improved understanding of how other proteins work. Our approaches have ....Understanding and predicting small molecule binding to G protein-coupled receptors (GPCRs). The discovery of new treatments for serious diseases is a time consuming and expensive process. Our work involves developing and testing new computational modelling approaches with experimental validation for the understanding and prediction of how current and new drugs interact with their targets, and these methods can be extended for improved understanding of how other proteins work. Our approaches have the potential to increase the speed, reduce the cost and lead to the discovery of new treatments for serious crippling diseases such as anxiety, depression, diabetes, and obesity. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561224
Funder
Australian Research Council
Funding Amount
$267,767.00
Summary
14CHRONOS (Chronologies from High-ResolutiON Organic Separations): a centre for radiocarbon dating of specific compounds for the environmental and archaeological sciences. Accurate timekeeping is central to the environmental and archaeological sciences. Radiocarbon dating is the leading geochronological technique for events of the past 50,000 years, but the issue for sample contamination remains a major source of concern. Avoidance of contaminants can be achieved through the identification of sp ....14CHRONOS (Chronologies from High-ResolutiON Organic Separations): a centre for radiocarbon dating of specific compounds for the environmental and archaeological sciences. Accurate timekeeping is central to the environmental and archaeological sciences. Radiocarbon dating is the leading geochronological technique for events of the past 50,000 years, but the issue for sample contamination remains a major source of concern. Avoidance of contaminants can be achieved through the identification of specific biomolecular compounds that unambiguously formed part of the original sample, and the isolation of these biomolecules for radiocarbon dating using accelerator mass spectrometry. Here we request funds to establish Australia's first compound-specific radiocarbon dating facility, to obtain ages of high accuracy for key studies of climate and landscape change, evolutionary biology and archaeology.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882682
Funder
Australian Research Council
Funding Amount
$100,000.00
Summary
The Australasian Pollen and Spore Atlas. The results generated in this project will enhance Australian research capabilities across multiple disciplines by providing access to key knowledge of pollen and spores in our region. A unified approach to the archiving, presentation and accessibility to existing and evolving databases will provide a considerably improved context for identification and knowledge pooling of any given pollen or spore type. This will create a nexus for novel interactions be ....The Australasian Pollen and Spore Atlas. The results generated in this project will enhance Australian research capabilities across multiple disciplines by providing access to key knowledge of pollen and spores in our region. A unified approach to the archiving, presentation and accessibility to existing and evolving databases will provide a considerably improved context for identification and knowledge pooling of any given pollen or spore type. This will create a nexus for novel interactions between researchers and end users of these data from within and beyond Australia's borders.Read moreRead less
Reconstructing landscapes for biodiversity: From predictive modelling to future scenarios. Many landscapes around the world have been effectively denuded of natural vegetation, causing precipitous declines in native biodiversity. Mitigation of such effects in the near/medium-term future requires substantial ecological advice. We will employ our skills developed in modelling distributions of species across landscapes based on terrain, soils and climate to assess alternative landscape-reconstructi ....Reconstructing landscapes for biodiversity: From predictive modelling to future scenarios. Many landscapes around the world have been effectively denuded of natural vegetation, causing precipitous declines in native biodiversity. Mitigation of such effects in the near/medium-term future requires substantial ecological advice. We will employ our skills developed in modelling distributions of species across landscapes based on terrain, soils and climate to assess alternative landscape-reconstruction scenarios. This links use of existing data sets for initial modelling, a validation phase for testing model reliability and for refining models, and a subsequent GIS-based modelling phase in which alternative options for reconstructing landscapes are evaluated for their effectiveness in sustaining landscape-scale native biodiversity.Read moreRead less