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
From genotype to phenotype - systems biology bridging the gap. This project is basic research at the forefront of international science and deals with a fundamental question of modern biology: 'How do genes determine the makeup of an organism?' The main outcome will be a deeper understanding of the internal working mechanisms of a higher organism. The project combines some of the most advanced systems technologies - genomics, proteomics, metabonomics, fluxomics and computational biology in a nov ....From genotype to phenotype - systems biology bridging the gap. This project is basic research at the forefront of international science and deals with a fundamental question of modern biology: 'How do genes determine the makeup of an organism?' The main outcome will be a deeper understanding of the internal working mechanisms of a higher organism. The project combines some of the most advanced systems technologies - genomics, proteomics, metabonomics, fluxomics and computational biology in a novel and unique way. This combination is in itself a major advancement of scientific methods that will accelerate discovery in the field of systems biology. In this respect, the project is a premier example of the priority goal Breakthrough Science and of the national research priority Frontier Technologies.Read moreRead less
Monolayer crystallization of membrane proteins. Membrane proteins comprise 25-40% of all proteins and conduct a myriad of finely tuned reactions in every cell. Despite their importance and diversity only ~40 membrane protein structures have been solved, due to the difficulty of producing high quality 2D and 3D crystals. We propose to develop and use the new monolayer crystallization technique, which employs a lipid monolayer as a crystallization template for 2D crystal production. A number of ....Monolayer crystallization of membrane proteins. Membrane proteins comprise 25-40% of all proteins and conduct a myriad of finely tuned reactions in every cell. Despite their importance and diversity only ~40 membrane protein structures have been solved, due to the difficulty of producing high quality 2D and 3D crystals. We propose to develop and use the new monolayer crystallization technique, which employs a lipid monolayer as a crystallization template for 2D crystal production. A number of important membrane proteins are available for these structural studies including ABC transporters, Caveolin-3 and the NS1 protein of Dengue virus, all of which are difficult to crystallize using conventional techniques.Read moreRead less
Novel approaches for structural and functional analysis of the protein complex COG, a tether that controls intra-Golgi trafficking. Production and engineering of proteins are key methodologies of the life sciences in general and biotechnology in particular. Our ability to produce and analyse protein-based components of the cell determines the expense and speed of discovery, as well as the creation of new vaccines, drugs, and diagnostic methods. The current project aims to develop new approaches ....Novel approaches for structural and functional analysis of the protein complex COG, a tether that controls intra-Golgi trafficking. Production and engineering of proteins are key methodologies of the life sciences in general and biotechnology in particular. Our ability to produce and analyse protein-based components of the cell determines the expense and speed of discovery, as well as the creation of new vaccines, drugs, and diagnostic methods. The current project aims to develop new approaches for protein production and to apply them to the analysis of the basic mechanisms of cell self-maintenance.Read moreRead less
NmlR-dependent thiol-based redox systems and their role in global stress responses in bacteria. All cells sense changes to their environment and respond by altering their metabolism. A major environmental change is oxidative stress which damages cells. Cells have the ability to sense oxidative stress and alter metabolic processes to defend against the damage that it elicits. This proposal will characterize a novel oxidative stress defense system that is found in a number of bacterial pathogens t ....NmlR-dependent thiol-based redox systems and their role in global stress responses in bacteria. All cells sense changes to their environment and respond by altering their metabolism. A major environmental change is oxidative stress which damages cells. Cells have the ability to sense oxidative stress and alter metabolic processes to defend against the damage that it elicits. This proposal will characterize a novel oxidative stress defense system that is found in a number of bacterial pathogens that need to defend themselves against attack by the host. The project may identify new ways to manage these bacterial pathogens. It may also provide an insight into oxidative stress defense processes that are linked to pathologies in humans.Read moreRead less
Innovative Approaches to Membrane Protein Crystallography & Drug Discovery. Membrane proteins make up around 30% of the predicted products from our human genome, are critical for life, and represent the targets of biological agents like hormones and toxins as well as most drugs. Yet these proteins have persistently defied our best efforts to study them: we know very little about what they do or what they look like. This project is aimed at cracking the problem of membrane proteins, while at the ....Innovative Approaches to Membrane Protein Crystallography & Drug Discovery. Membrane proteins make up around 30% of the predicted products from our human genome, are critical for life, and represent the targets of biological agents like hormones and toxins as well as most drugs. Yet these proteins have persistently defied our best efforts to study them: we know very little about what they do or what they look like. This project is aimed at cracking the problem of membrane proteins, while at the same time developing screening methods that can be used to design drugs against them. The long-term benefits to the community will include fundamental new knowledge and the development of new technologies and pharmaceuticals.Read moreRead less
Subunit stoichiometry and arrangement in the glycine receptor. Glycine receptors are important for nervous system function. These receptors comprise a mixture of 5 alpha and beta subunits arranged around a central ion-conducting pore. The subunit stoichiometry (i.e., numbers of alpha and beta subunits) and arrangement (i.e., subunit order) are unknown. The first aim of this project is to define these parameters using tethered subunits. The second aim is to use the tethered subunits to probe th ....Subunit stoichiometry and arrangement in the glycine receptor. Glycine receptors are important for nervous system function. These receptors comprise a mixture of 5 alpha and beta subunits arranged around a central ion-conducting pore. The subunit stoichiometry (i.e., numbers of alpha and beta subunits) and arrangement (i.e., subunit order) are unknown. The first aim of this project is to define these parameters using tethered subunits. The second aim is to use the tethered subunits to probe the structure and function of glycine and zinc binding sites at an unprecedented level of resolution. The results will provide crucial new information concerning glycine receptor structure and function.Read moreRead less
Development of a novel high yield cell-free protein expression system. Recombinant proteins are used as vaccines, drugs, and research tools, as well as food and detergent additives, comprising a A$100 billion international market. Their production requires laborious, expensive, and time-consuming construction of transgenic organisms or cells. Alternatively, recombinant proteins can be produced in extracts prepared from cells or organisms. The aim of this proposal is to develop a new technology t ....Development of a novel high yield cell-free protein expression system. Recombinant proteins are used as vaccines, drugs, and research tools, as well as food and detergent additives, comprising a A$100 billion international market. Their production requires laborious, expensive, and time-consuming construction of transgenic organisms or cells. Alternatively, recombinant proteins can be produced in extracts prepared from cells or organisms. The aim of this proposal is to develop a new technology that will make cell-free production of recombinant proteins rapid, cheap, and scalable. This will advance Australia’s intellectual leadership in the area of biotechnology and will bring numerous economic benefits by accelerating pharmaceutical development. Read moreRead less
Evolution of halophytes: a phyloinformatic approach to understanding and exploiting the traits underlying salt-tolerance in plants. Salinity is an increasing burden on the Australian economy & environment, with >2 million ha of salt-affected land, at an annual cost to agriculture over $187 million. One solution is to exploit naturally salt-tolerant plants to increase productive agricultural land and restore salt-affected environments. To do this, we must increase basic knowledge of the diversity ....Evolution of halophytes: a phyloinformatic approach to understanding and exploiting the traits underlying salt-tolerance in plants. Salinity is an increasing burden on the Australian economy & environment, with >2 million ha of salt-affected land, at an annual cost to agriculture over $187 million. One solution is to exploit naturally salt-tolerant plants to increase productive agricultural land and restore salt-affected environments. To do this, we must increase basic knowledge of the diversity & distribution of salt-tolerance. This project is the first to use DNA sequences from thousands of species to understand the evolution of salt-tolerance in order to provide the foundation for the development of new crop varieties, selection of species that can be developed for bioremediation, and identification of traits that will be profitable targets for breeding programs. Read moreRead less
Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will ....Assessing the physiological roles of ubiquitination in regulating neuronal ion channels, receptors and transporters. Significant alterations in the activity neuronal transporters and receptors occur during tissue injury and regeneration as well as in many neurodegenerative disease states. Modulation of the pathways that control these transporters is an emerging therapeutic target, however, the molecular basis of these control mechanisms remain poorly understood. The outcome of this project will be a thorough characterisation of a novel regulatory paradigm in neurons that is likely to be crucial for neuronal development and regeneration, and will potentially provide novel therapeutic targets for various neuronal diseases.Read moreRead less