Functional analysis of Bacillus thuringiensis crystal toxins. Pore-forming toxins, such as anthrax, hemolysin, cholera and diphtheria toxins, are among the most virulent microbial toxins, posing a threat to humans and lifestock. We are using a novel functional approach to test possible lectin and antimicrobial peptide functions of a typical and economically important pore-forming toxin, the crystal endotoxin from Bacillus thuringiensis, to examine why toxicity of the lectin-containing toxin is ....Functional analysis of Bacillus thuringiensis crystal toxins. Pore-forming toxins, such as anthrax, hemolysin, cholera and diphtheria toxins, are among the most virulent microbial toxins, posing a threat to humans and lifestock. We are using a novel functional approach to test possible lectin and antimicrobial peptide functions of a typical and economically important pore-forming toxin, the crystal endotoxin from Bacillus thuringiensis, to examine why toxicity of the lectin-containing toxin is restricted to invertebrates only, while the amphipathic peptide alone is also toxic to many vertebrate cells. The outcome of these experiments has important implications for the sustainable use of biopesticides and for the prevention and containment of infectious diseases.Read moreRead less
Theoretical and computational approaches to accurately predict the structures of a unique family of circular and knotted proteins. The primary outcome will be a fundamental new knowledge on cyclotide structures and a new protein engineering method to design stabilised proteins. Because cyclotides have significantly higher stabilities than conventional proteins, they have a range of pharmaceutical and agricultural applications. Both fields of use have the potential for very great economic and soc ....Theoretical and computational approaches to accurately predict the structures of a unique family of circular and knotted proteins. The primary outcome will be a fundamental new knowledge on cyclotide structures and a new protein engineering method to design stabilised proteins. Because cyclotides have significantly higher stabilities than conventional proteins, they have a range of pharmaceutical and agricultural applications. Both fields of use have the potential for very great economic and social benefits for Australia. From a pharmaceutical perspective our computing development will greatly facilitate the design of stabilised peptide-based drugs using the cyclotide framework. Such drugs have potential sales of several billion dollars per annum and the royalty returns from successful commercialisation of IP can be substantial.Read moreRead less
Structural studies of plant disease resistance proteins. Plant cells have evolved a gene-for-gene disease resistance mechanism, involving an interaction of a plant-derived receptor with a specific pathogen-derived molecule. Currently, plant breeders are restricted to the resistance genes available in particular crop species or sexually compatible relatives. In the last few years, several plant disease resistance genes have been identified, providing a foundation for studying the molecular basis ....Structural studies of plant disease resistance proteins. Plant cells have evolved a gene-for-gene disease resistance mechanism, involving an interaction of a plant-derived receptor with a specific pathogen-derived molecule. Currently, plant breeders are restricted to the resistance genes available in particular crop species or sexually compatible relatives. In the last few years, several plant disease resistance genes have been identified, providing a foundation for studying the molecular basis of the resistance process. We propose to obtain three-dimensional structural information on representative R proteins and their ligand complexes. This will form the basis for modifying existing resistance genes to confer resistance to new diseases, resulting in large economic benefits.Read moreRead less
Suction pipette measurements of mammalian rod photoreceptor recovery following intense bleaching exposures. The aim of this project is to discover the events and processes that prevent retinal photoreceptors from recovering instantaneously following the cessation of exposure to extremely bright illumination. Recordings will be made from single rod photoreceptors cells isolated from the mammalian retina. The work will uncover the relative roles of the 'photoproducts' created when rhodopsin abso ....Suction pipette measurements of mammalian rod photoreceptor recovery following intense bleaching exposures. The aim of this project is to discover the events and processes that prevent retinal photoreceptors from recovering instantaneously following the cessation of exposure to extremely bright illumination. Recordings will be made from single rod photoreceptors cells isolated from the mammalian retina. The work will uncover the relative roles of the 'photoproducts' created when rhodopsin absorbs light: e.g. intermediates such as metarhodopsin and opsin. The molecular knowledge obtained will help us to understand why it is that the visual system recovers so slowly after the eye has experienced very intense light.Read moreRead less
The first stage of vision: transduction and adaptation in retinal photoreceptors. The project aims to provide a detailed understanding of the molecular steps involved in the first stage of vision - the conversion of light into a neural signal in the rod and cone photoreceptors of the retina. The significance of this is that it will explain the initial events that enable us to see, and will help explain the deficits that occur when the process fails. The outcome will be a comprehensive understand ....The first stage of vision: transduction and adaptation in retinal photoreceptors. The project aims to provide a detailed understanding of the molecular steps involved in the first stage of vision - the conversion of light into a neural signal in the rod and cone photoreceptors of the retina. The significance of this is that it will explain the initial events that enable us to see, and will help explain the deficits that occur when the process fails. The outcome will be a comprehensive understanding of how our photoreceptors respond with extreme sensitivity, yet great rapidity, and over an enormous range of light intensities, thus endowing us with our remarkable sense of vision.Read moreRead less
Functional imaging of colour pathways in the living eye. In order to repair or regenerate a diseased eye, we require knowledge of the normal pattern or nerve cell connections, and knowing how biology solves the problem of colour vision can be used to improve the design of artificial vision systems. The adaptive optics machine we will build in this project can be used to image nerve cells, fine blood vessels, and nerve fibre bundles in the normal and diseased eye. This will improve Australia's re ....Functional imaging of colour pathways in the living eye. In order to repair or regenerate a diseased eye, we require knowledge of the normal pattern or nerve cell connections, and knowing how biology solves the problem of colour vision can be used to improve the design of artificial vision systems. The adaptive optics machine we will build in this project can be used to image nerve cells, fine blood vessels, and nerve fibre bundles in the normal and diseased eye. This will improve Australia's research and development capacity in this new area of medical diagnostics. Our machine will be made available to other Australian laboratories and will improve the national capacity for making further scientific discoveries about how the visual system works.Read moreRead less
Molecular basis of the interaction between plant disease resistance proteins and pathogen avirulence proteins. Management of crop diseases involves the integrated use of resistant cultivars and the application of chemical pesticides. Many diseases, however, including rust, continue to pose an economically significant threat to agricultural productivity in Australia. The research outlined in this proposal aims to understand the mechanisms, at a molecular and structural level, that enable resistan ....Molecular basis of the interaction between plant disease resistance proteins and pathogen avirulence proteins. Management of crop diseases involves the integrated use of resistant cultivars and the application of chemical pesticides. Many diseases, however, including rust, continue to pose an economically significant threat to agricultural productivity in Australia. The research outlined in this proposal aims to understand the mechanisms, at a molecular and structural level, that enable resistant plants to detect and respond to pathogen attack. The outcomes of this currently unavailable fundamental understanding will enable new, durable and more effective resistance genes to be engineered. Therefore, the work has significant economic and environmental implications for agricultural crop plant productivity in this country.Read moreRead less
Mechanisms and management of inducible tolerance to synthetic insecticides and Bacillus thuringiensis (Bt)-formulations in Australian populations of diamondback moth. Insects have a cunning ability to respond to damaging environments by evolving genetic resistance or mobilising metabolic tolerance mechanisms. Recent observations of inducible tolerance to synthetic and biopesticides, which can be transmitted to offspring by a maternal effect has the potential to cause ecological and economic prob ....Mechanisms and management of inducible tolerance to synthetic insecticides and Bacillus thuringiensis (Bt)-formulations in Australian populations of diamondback moth. Insects have a cunning ability to respond to damaging environments by evolving genetic resistance or mobilising metabolic tolerance mechanisms. Recent observations of inducible tolerance to synthetic and biopesticides, which can be transmitted to offspring by a maternal effect has the potential to cause ecological and economic problems in agricultural production. We will use field-collected Diamondback moth (DBM), a major insect pest in canola and brassica vegetable crops, to investigate the genetic implications of inducible tolerance for the integrated management of DBM and for the design of new resistance management strategies.Read moreRead less
Understanding and Modelling Insect Motion Vision. The interdisciplinary project proposed will offer a stimulating environment for research/training into computational neuroscience, an attractive area for aspiring scientists. We have already demonstrated the feasibility of transferring physiology into applications, and expect this project to deliver functional motion vision models and devices. Our proposed work will have an impact beyond the advancement of neuro-physiology as knowledge gained is ....Understanding and Modelling Insect Motion Vision. The interdisciplinary project proposed will offer a stimulating environment for research/training into computational neuroscience, an attractive area for aspiring scientists. We have already demonstrated the feasibility of transferring physiology into applications, and expect this project to deliver functional motion vision models and devices. Our proposed work will have an impact beyond the advancement of neuro-physiology as knowledge gained is applicable in a range of areas, with applications in miniature unmanned vehicles and collision avoidance detectors in defence and civilian roles. Our project could also assist in the development of artificial intelligence and as a basis for designing implantable artificial eyes.Read moreRead less
Relationship of the functional architecture of the mammalian brain to its microcircuitry. The project seeks to understand a very fundamental issue in neuroscience: how the connectivity and architecture of the cortex are related to the functions of neurones in that area? This will be investigated by imaging the surface of the visual cortex of anaesthetised cats and monkeys as special visual patterns are shown to the eye/s. The overall picture gained of the active and inactive cortical areas will ....Relationship of the functional architecture of the mammalian brain to its microcircuitry. The project seeks to understand a very fundamental issue in neuroscience: how the connectivity and architecture of the cortex are related to the functions of neurones in that area? This will be investigated by imaging the surface of the visual cortex of anaesthetised cats and monkeys as special visual patterns are shown to the eye/s. The overall picture gained of the active and inactive cortical areas will be related to the properties of neurones in those areas and to those of individual input and output fibres. An optical imaging equipment will be acquired in 2004 using a recently awarded LIEF grant to the CI.Read moreRead less