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
Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important recepto ....Central Muscarinic Receptors as Novel Drug Targets for Parkinson's Disease and Schizophrenia. Psychiatric and neurodegenerative disorders such as schizophrenia and Parkinson's disease are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate dopamine neuron activity by acting on acetylcholine receptors located on dopamine neurons. We aim to determine how these important receptors regulate dopamine neuron activity using genetically modified mice deficient in acetylcholine receptors, together with newly developed physiological methods and new acetylcholine receptor drugs. These studies will foster the design of novel acetylcholine receptor drugs as effective pharmaceutical treatments of neurological and psychiatric disorders related to brain dopamine dysfunction.Read moreRead less
Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly de ....Muscarinic Receptor Regulation of Dopamine Reward Pathways in the Brain. Human disorders such as schizophrenia and drug addiction are linked to alterations in the activity of neurons in the brain containing the chemical dopamine. Other types of brain neurons containing the chemical acetylcholine regulate the activity of dopamine neurons by acting on acetylcholine receptors located on dopamine neurons. We aim to examine how dopamine neuron activity is regulated by these receptors using newly developed physiological methods together with a new acetylcholine receptor drug. We also aim to assess the suitability of mice genetically modified to be deficient in acetylcholine receptors as animal models of dopamine dysfunction related to schizophrenia and drug addiction.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100130
Funder
Australian Research Council
Funding Amount
$850,000.00
Summary
Systems biology: New generation DNA sequencing to functional analysis. The technique of DNA sequencing (or 'reading' the lines of the four repeating letters that make up the genetic code) illustrates how technological developments have become the main drivers in exploring the roles of genetic factors across a spectrum of research activities. Funding provided through this ARC grant will allow the purchase of the latest DNA sequencing platform, the Illumina Solexa, as well as equipment that will b ....Systems biology: New generation DNA sequencing to functional analysis. The technique of DNA sequencing (or 'reading' the lines of the four repeating letters that make up the genetic code) illustrates how technological developments have become the main drivers in exploring the roles of genetic factors across a spectrum of research activities. Funding provided through this ARC grant will allow the purchase of the latest DNA sequencing platform, the Illumina Solexa, as well as equipment that will be used to understand the biological function of the DNA sequencing results that are obtained. The equipment will allow Australian researchers to compete on an equal footing with the international leaders in understanding the roles played by genes in plants, microorganisms, animals and humans.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
Protein methylation: a fundamental regulator of the interactome. Proteins are the functional molecules of the cell. They interact with each other to form small 'protein machines' that are part of large, complicated networks. This study will examine how the cell makes tiny changes to proteins, through the addition of one carbon and two hydrogen atoms, and how this is important in the regulation of protein interactions. The proteins of baker's yeast, a common model organism, will be studied here. ....Protein methylation: a fundamental regulator of the interactome. Proteins are the functional molecules of the cell. They interact with each other to form small 'protein machines' that are part of large, complicated networks. This study will examine how the cell makes tiny changes to proteins, through the addition of one carbon and two hydrogen atoms, and how this is important in the regulation of protein interactions. The proteins of baker's yeast, a common model organism, will be studied here. However, the findings will be directly relevant to understanding the function of many proteins in plants, animals and man.
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The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the rece ....The Immunoregulatory Role of the Endogenous Cannabinoid Anandamide. Anandamides are naturally occurring fatty acids that act at the cannabinoid receptor expressed in the brain and periphery. A new proposal by our research group challenges traditional models of the disease process by suggesting that the anandamide system is an important imunoregulatory system that can be targeted by invading pathogens. We propose that disruption to the anandamide system, by bacteria or viruses acting at the receptor to block immunological responses, contributes to chronic illness states. At this point we have good evidence that anandamides are immunoregulators, however, we have very little knowledge of their precise physiological role. The aim of this research is to begin to characterise the immunoregulatory role of the anandamide system. This project will provide a comprehensive understanding of this endogenous control system, the immunological properties of which have not previously been described. The outcome of this research may lead to the identification of new avenues for the development of pharmaceutical interventions that can target this system.Read moreRead less