Investigating insect neuronal plasticity under genetic and chemical stress. This project aims to study receptors that translate chemical signals into electrical signals in animal brains. These receptors are targeted by insecticides used to control the major pests that afflict agriculture and domestic pets. The project aims to establish the functions of nicotinic acetylcholine receptors in several behaviours and in insecticide responsiveness in the model insect, Drosophila melanogaster, using mut ....Investigating insect neuronal plasticity under genetic and chemical stress. This project aims to study receptors that translate chemical signals into electrical signals in animal brains. These receptors are targeted by insecticides used to control the major pests that afflict agriculture and domestic pets. The project aims to establish the functions of nicotinic acetylcholine receptors in several behaviours and in insecticide responsiveness in the model insect, Drosophila melanogaster, using mutations that knock out the function of receptor subunits. Prior research has pointed to plasticity in the expression and transport of these receptors in response to genetic and environmental change. This project aims to identify the underlying mechanisms that provide the insect with resilience, to provide better options for pest control.Read moreRead less
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
Global genetic regulation of carbon metabolism in filamentous fungi. Fungi are of great importance in medicine, agriculture and industry. They are used extensively for food, antibiotic and chemical production and, increasingly, for generating cheap substrates for bioethanol. However many are serious pathogens of plants and humans. Understanding how fungi control their metabolism is of fundamental importance for their more effective use or control. This project takes advantage of a fungus that is ....Global genetic regulation of carbon metabolism in filamentous fungi. Fungi are of great importance in medicine, agriculture and industry. They are used extensively for food, antibiotic and chemical production and, increasingly, for generating cheap substrates for bioethanol. However many are serious pathogens of plants and humans. Understanding how fungi control their metabolism is of fundamental importance for their more effective use or control. This project takes advantage of a fungus that is easily studied in the laboratory by advanced genetic techniques to identify the ways in which genes are turned on and off in response to changes in the nutrients available. By comparing DNA sequences the results are readily applied to fungi of economic importance.Read moreRead less
REGULATION OF RYANODINE RECEPTOR CALCIUM CHANNELS BY THE CALCIUM BINDING PROTEIN CALSEQUESTRIN. The project is to examine the functional interaction between two proteins in skeletal muscle that are essential for Ca2+ regulation and hence contraction, respiration and movement in all vertebrate species. One protein, the ryanodine receptor, releases calcium from stores inside the muscle cell. The other protein, calsequestrin, binds and sequesters calcium ions. We have recently discovered that th ....REGULATION OF RYANODINE RECEPTOR CALCIUM CHANNELS BY THE CALCIUM BINDING PROTEIN CALSEQUESTRIN. The project is to examine the functional interaction between two proteins in skeletal muscle that are essential for Ca2+ regulation and hence contraction, respiration and movement in all vertebrate species. One protein, the ryanodine receptor, releases calcium from stores inside the muscle cell. The other protein, calsequestrin, binds and sequesters calcium ions. We have recently discovered that the proteins also bind to each other and that calsequestrin regulates Ca2+ release from the stores through the ryanodine receptor ion channel. This regulation is likely to be important in conserving store calcium during stress or fatigue.Read moreRead less
A novel approach to fighting fungal infections: targeted disruption of hydrophobin monolayers. Fungal infestations of important crops such as cotton cause large economic losses to Australian agriculture while in the medical sector, fungal infections are responsible for high levels of mortality in immunocompromised patients. Our research will provide a new approach to fighting fungal infections by targeting the hydrophobin proteins, which form a robust coating on fungal aerial structures, such as ....A novel approach to fighting fungal infections: targeted disruption of hydrophobin monolayers. Fungal infestations of important crops such as cotton cause large economic losses to Australian agriculture while in the medical sector, fungal infections are responsible for high levels of mortality in immunocompromised patients. Our research will provide a new approach to fighting fungal infections by targeting the hydrophobin proteins, which form a robust coating on fungal aerial structures, such as spores. This layer is critical for fungal growth and reproduction and confers water resistance and tolerance to harsh conditions. Our work seeks to develop reagents that can specifically block regions on the protein that are responsible for forming this coating.
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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
Defensive behaviours elicited by predator odours. Rats display a powerful anxiety responses when confronted with the odours of predators such as cats. This response may occur even though rats have never encountered an actual predator before. This project aims to investigate the nature of this anxiety and the nature of the stimuli that produce it. The outcomes should be a better understanding of the neural basis and pharmacology of anxiety states and the identification of novel chemicals that hav ....Defensive behaviours elicited by predator odours. Rats display a powerful anxiety responses when confronted with the odours of predators such as cats. This response may occur even though rats have never encountered an actual predator before. This project aims to investigate the nature of this anxiety and the nature of the stimuli that produce it. The outcomes should be a better understanding of the neural basis and pharmacology of anxiety states and the identification of novel chemicals that have powerful rodent repellent properties. Such chemicals may be of great use in domestic and agricultural contexts where rodents are pests.Read moreRead less
Asymmetric Synthesis and Biological Evaluation of Bioactive Alkaloids and their Analogues. We propose to develop innovative methods for preparing bioactive natural products and their analogues with potential applications as new and safer therapeutic drugs and agricultural chemicals. This project would make important scientific contributions to the advancement of the fundamentals of synthetic organic chemistry and contribute to Australia's development as a knowledge-based economy. The methodolo ....Asymmetric Synthesis and Biological Evaluation of Bioactive Alkaloids and their Analogues. We propose to develop innovative methods for preparing bioactive natural products and their analogues with potential applications as new and safer therapeutic drugs and agricultural chemicals. This project would make important scientific contributions to the advancement of the fundamentals of synthetic organic chemistry and contribute to Australia's development as a knowledge-based economy. The methodology and products developed may have potential pharmaceutical and agricultural applications from which the country could benefit from in the future. This project would help developed skilled people that may develop innovative outcomes in the future, especially in the developing pharmaceutical and biotechnology industries in Australia.Read moreRead less
Stereoselective Synthesis of Bioactive Alkaloids for Structure Elucidation and Drug Discovery. It is proposed to develop innovative methods for preparing bioactive natural products and their analogues with potential applications as new and safer therapeutic drugs and agricultural chemicals. This project would make important scientific contributions to the advancement of the fundamentals of synthetic organic chemistry and contribute to Australia's development as a knowledge-based economy. The m ....Stereoselective Synthesis of Bioactive Alkaloids for Structure Elucidation and Drug Discovery. It is proposed to develop innovative methods for preparing bioactive natural products and their analogues with potential applications as new and safer therapeutic drugs and agricultural chemicals. This project would make important scientific contributions to the advancement of the fundamentals of synthetic organic chemistry and contribute to Australia's development as a knowledge-based economy. The methodology and products developed are likely to have potential pharmaceutical and agricultural applications from which the country could benefit in the future. This project will train skilled people who may develop innovative outcomes in the future, especially in the developing pharmaceutical and biotechnology industries in Australia.Read moreRead less
Large Scale Production of Stemona Alkaloids for Agricultural Applications and New Drug Discovery. The Stemona alkaloids form a large group of natural products that have significant potential as agricultural and pharmaceutical drugs. Extracts of these natural products have many applications in traditional medicine and as insecticides in Asia. We propose to develop innovative methods for the large scale production and synthesis of these bioactive alkaloids. The methodology and products developed ....Large Scale Production of Stemona Alkaloids for Agricultural Applications and New Drug Discovery. The Stemona alkaloids form a large group of natural products that have significant potential as agricultural and pharmaceutical drugs. Extracts of these natural products have many applications in traditional medicine and as insecticides in Asia. We propose to develop innovative methods for the large scale production and synthesis of these bioactive alkaloids. The methodology and products developed may have potential pharmaceutical and agricultural applications from which the country could benefit in the future. This project would help develop skilled people who may produce innovative outcomes in the future, especially in the developing pharmaceutical and biotechnology industries in Australia.Read moreRead less