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
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
Novel vaccines and serotyping scheme for Haemophilus parasuis. Glasser's disease, caused by the bacterium Haemophilus parasuis, is a significant problem in Australian and overseas pig industries. Current approaches to the management of Glassers disease utilise antibacterials and also vaccines. However, antibacterials are of limited effectiveness in juvenile pigs (weaners) that are difficult to medicate other than by injection, and current vaccines are only protective against the serotypes incl ....Novel vaccines and serotyping scheme for Haemophilus parasuis. Glasser's disease, caused by the bacterium Haemophilus parasuis, is a significant problem in Australian and overseas pig industries. Current approaches to the management of Glassers disease utilise antibacterials and also vaccines. However, antibacterials are of limited effectiveness in juvenile pigs (weaners) that are difficult to medicate other than by injection, and current vaccines are only protective against the serotypes included in the vaccine. We propose to examine the immune response to natural infection and identify potential vaccine candidates which will then be tested in vaccine trials. The APAI will focus on developing a DNA-based typing scheme for H. parasuis.Read moreRead less
Cell-free immune reactions and suppression. Insects pests and insect vectors of diseases are managed by toxic substances, but insects have a cunning ability to persist. How pesticide-tolerant insect pests recognise and inactivate chemical and biological toxins is poorly understood. While vertebrates with a closed circulatory system use coagulation reactions mainly for wound-healing, invertebrates employ cell-free aggregation reactions for the sequestration and inactivation of potentially damagin ....Cell-free immune reactions and suppression. Insects pests and insect vectors of diseases are managed by toxic substances, but insects have a cunning ability to persist. How pesticide-tolerant insect pests recognise and inactivate chemical and biological toxins is poorly understood. While vertebrates with a closed circulatory system use coagulation reactions mainly for wound-healing, invertebrates employ cell-free aggregation reactions for the sequestration and inactivation of potentially damaging objects and substances. We use insect plasma to dissect recognition and inactivation of damaging objects and substances with the aim to understand tolerance and its inhibition to design novel strategies in delaying tolerance to pesticides in insect pests.Read moreRead less
Disruption of Sex Pheromone Biosynthesis: A Novel Control Method for Pestiferous Fruit Flies by. Fruit flies from the genus Bactrocera are economically important worldwide. B. tryoni, (Queensland fruit fly) is the most damaging horticultural pest in Australia and B. oleae (olive fly) is a major European pest. These flies use chemicals of similar but distinct structure for communication and particularly for finding mates. This research will examine the pathways and enzymes these flies use to sy ....Disruption of Sex Pheromone Biosynthesis: A Novel Control Method for Pestiferous Fruit Flies by. Fruit flies from the genus Bactrocera are economically important worldwide. B. tryoni, (Queensland fruit fly) is the most damaging horticultural pest in Australia and B. oleae (olive fly) is a major European pest. These flies use chemicals of similar but distinct structure for communication and particularly for finding mates. This research will examine the pathways and enzymes these flies use to synthesise sex pheromones. We propose that understanding the chemical and biochemical steps employed by the flies will allow us to design inhibitors to prevent pheromone production and thus provide a novel, species specific method for controlling fruit flies.Read moreRead less
Development of new herbicides targeting enzymes involved in the biosynthesis of branched-chain amino acids. Modern agriculture is heavily reliant on the use of herbicides. An inevitable consequence of herbicide usage is that resistant weeds will develop. Therefore, there is a continuing need to develop new herbicides to kill these resistant species. Herbicides interact with vulnerable molecular targets in plants, such as photosynthesis or the biosynthesis of certain amino acids. This project wil ....Development of new herbicides targeting enzymes involved in the biosynthesis of branched-chain amino acids. Modern agriculture is heavily reliant on the use of herbicides. An inevitable consequence of herbicide usage is that resistant weeds will develop. Therefore, there is a continuing need to develop new herbicides to kill these resistant species. Herbicides interact with vulnerable molecular targets in plants, such as photosynthesis or the biosynthesis of certain amino acids. This project will attempt to develop new herbicides that act upon two molecular targets that are not exploited by herbicides that are used currently. We will design, synthesize and test a variety of new compounds as potential environmentally-benign herbicides.Read moreRead less
Design and evaluation of new environmentally-benign herbicides that inhibit branched-chain amino acid biosynthesis. Herbicides interfere with processes that occur in plants, such as photosynthesis or the biosynthesis of certain amino acids. In this project we will focus on branched-chain amino acid biosynthesis, designing and evaluating inhibitors of the first two enzymes in this process. Based on their three dimensional structures we will develop an understanding of the molecular features that ....Design and evaluation of new environmentally-benign herbicides that inhibit branched-chain amino acid biosynthesis. Herbicides interfere with processes that occur in plants, such as photosynthesis or the biosynthesis of certain amino acids. In this project we will focus on branched-chain amino acid biosynthesis, designing and evaluating inhibitors of the first two enzymes in this process. Based on their three dimensional structures we will develop an understanding of the molecular features that contribute to a potent inhibitor and those that are required for it to be effective upon plants. Using this information we will design and synthesis new compounds as potential environmentally-benign herbicides.Read moreRead less