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
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
Structural analysis of membrane proteins using template-mediated crystallization. A new frontier technology will be developed in the form of a systematic crystallization pipeline for membrane proteins. This high throughput monolayer template technology is particularly suited for the structure determination of proteins that are otherwise difficult to crystallize and has clear commercial potential. Membrane protein structures are themselves of value to the biotechnology and pharmaceutical industry ....Structural analysis of membrane proteins using template-mediated crystallization. A new frontier technology will be developed in the form of a systematic crystallization pipeline for membrane proteins. This high throughput monolayer template technology is particularly suited for the structure determination of proteins that are otherwise difficult to crystallize and has clear commercial potential. Membrane protein structures are themselves of value to the biotechnology and pharmaceutical industry for targeted drug design, which could realise benefits in the form of novel medical treatments and reduced side effects. The monolayer template technology will also extend the capabilities of the National Cryo-EM facility, the infrastructure of which, is open for all Australian researchers. Read moreRead less
Disulfide catalysis and protein folding in bacterial virulence. The molecular mechanisms that underpin disulfide bond formation have had a major impact on our understanding of protein folding and function. This project will make a major contribution to fundamental areas of disulfide catalysis pathways in bacterial pathogens and thus help maintain a strong international profile for Australian research in this field. The work will lead to training of research scientists and students in techniques ....Disulfide catalysis and protein folding in bacterial virulence. The molecular mechanisms that underpin disulfide bond formation have had a major impact on our understanding of protein folding and function. This project will make a major contribution to fundamental areas of disulfide catalysis pathways in bacterial pathogens and thus help maintain a strong international profile for Australian research in this field. The work will lead to training of research scientists and students in techniques that include molecular genetics, protein biochemistry and structural biology. Our findings may impact future directions for vaccine research on pathogens that cause life threatening infections in humans and therefore lead to improved health and reduced health care expenditure.Read moreRead less
Origins of Parasitism in the Psocodea (Insecta). The Psocodea has 2 groups: the lice and the psocopterans (the psocids and their kin). The lice are parasites whereas the psocopterans are free-living. The Psocodea are a unique model-system that will allow us to discover the processes that preadapt arthropods for parasitism and the processes that facilitate "explosive" radiations of arthropods once they become parasites. We will infer evolutionary trees for these insects from 3 genes. Then we ....Origins of Parasitism in the Psocodea (Insecta). The Psocodea has 2 groups: the lice and the psocopterans (the psocids and their kin). The lice are parasites whereas the psocopterans are free-living. The Psocodea are a unique model-system that will allow us to discover the processes that preadapt arthropods for parasitism and the processes that facilitate "explosive" radiations of arthropods once they become parasites. We will infer evolutionary trees for these insects from 3 genes. Then we will use these trees to track the evolution of feeding, attachment, senses and reproduction through evolutionary time. Our work should provide unprecedented insight into the evolution of parasitism in the arthropods.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561169
Funder
Australian Research Council
Funding Amount
$188,000.00
Summary
Facility for multidimensional fractionation of complex biological mixtures. Acquisition of multidimensional fractionation equipment will allow researchers to separate proteins from complex mixtures, and to compare whole protein profiles of multiple samples. This will permit correlation of specific protein changes associated with infection or disease, a major focus of post-genomic programs of research. The equipment will also provide identification of the key differentiating proteins using mini ....Facility for multidimensional fractionation of complex biological mixtures. Acquisition of multidimensional fractionation equipment will allow researchers to separate proteins from complex mixtures, and to compare whole protein profiles of multiple samples. This will permit correlation of specific protein changes associated with infection or disease, a major focus of post-genomic programs of research. The equipment will also provide identification of the key differentiating proteins using minimal material. Numerous world-class projects and researchers will be able to move more rapidly and reliably from crude cell extracts to identifiable markers, and maintain their competitive positions the recognition of key targets in drug design, disease diagnosis and vaccine development.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL0992138
Funder
Australian Research Council
Funding Amount
$3,100,000.00
Summary
Towards antibacterials without resistance. Innovative automation technologies will be used to create and investigate a revolutionary new approach to disable pathogenic superbugs, bacteria resistant to multiple antibiotics. The chemicals created and proteins evaluated in this research program will advance fundamental knowledge about the molecular weapons that bacteria produce to cause disease; deliver social and economic benefits to Australia through the development of potential new antibacterial ....Towards antibacterials without resistance. Innovative automation technologies will be used to create and investigate a revolutionary new approach to disable pathogenic superbugs, bacteria resistant to multiple antibiotics. The chemicals created and proteins evaluated in this research program will advance fundamental knowledge about the molecular weapons that bacteria produce to cause disease; deliver social and economic benefits to Australia through the development of potential new antibacterial treatments; contribute to Australia's continued international leading role in drug discovery research; enhance international links and attract industry investment in Australia; and provide a stimulating research training environment to inspire and motivate the next generation of scientists.Read moreRead less
Insect age: an ecological genomics approach to understanding host-parasite interactions. The importance of insect age (or the age structure of a population of insects) in understanding relationships between insects and their abiotic and biotic environment has been stressed in many theoretical studies but seldom directly tested. This is because few tools exist that can accurately measure the age of a wild-caught insect with any accuracy. In this proposal we plan to use a genomics approach to deve ....Insect age: an ecological genomics approach to understanding host-parasite interactions. The importance of insect age (or the age structure of a population of insects) in understanding relationships between insects and their abiotic and biotic environment has been stressed in many theoretical studies but seldom directly tested. This is because few tools exist that can accurately measure the age of a wild-caught insect with any accuracy. In this proposal we plan to use a genomics approach to develop tools that can be used to efficiently determine the age of an insect and then apply these tools to better understand the relationship between insect age and the ability of an insect to transmit pathogens to humans, livestock or plants. These tools will also have future applicability in developing new approaches to control insect transmitted disease as well as provide methodology to determine the effectiveness of current control programs that seek to kill pest insect populations of agricultural or public health significance.Read moreRead less
Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host ....Red Cell Polymorphisms and Malaria. Certain red blood cell disorders have been associated with innate protection against malaria infection. However many early studies were inconclusive. We intend to carry out a comprehensive study to investigate the effect of red blood cell differences on the invasion and/or growth of Plasmodium falciparum in vitro using improved techniques. Identification of red cell components involved in interaction with P.falciparum would give a better understanding of host parasite interactions which may in turn suggest novel approaches or pathways to persue. This may eventually lead to the development of novel therapeutics.
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Novel control strategies for mosquitoes threatening Australia. Increased global transport and human mobility have led to the spread and establishment of potential disease vectors and pathogens of public health importance in many parts of the world from which these were absent or had been eradicated. Aversion of this risk can be more effective when applying area-wide rather than focal (e.g. insecticide) control efforts. We will further the development of genetic and biological control tactics. We ....Novel control strategies for mosquitoes threatening Australia. Increased global transport and human mobility have led to the spread and establishment of potential disease vectors and pathogens of public health importance in many parts of the world from which these were absent or had been eradicated. Aversion of this risk can be more effective when applying area-wide rather than focal (e.g. insecticide) control efforts. We will further the development of genetic and biological control tactics. We aim to reduce the risks posed by two important dengue-vectoring mosquitoes: the yellow fever and the Asian tiger mosquito. This will lead to environmentally friendly and sustainable mosquito control and protect the Australian population and its regional neighbours against the threats of mosquito-borne disease.Read moreRead less