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
Dissection of nodule and lateral root development in the model legume Lotus japonicus. We propose to isolate and decipher the function of plant genes involved in nodule development, with the view to extend and compare this knowledge to lateral root formation. While nodulation and lateral root formation are distinct processes, they appear to share anatomical and biochemical features. Working hypothesis is that nodule formation borrowed functions from lateral root development. Our approach impleme ....Dissection of nodule and lateral root development in the model legume Lotus japonicus. We propose to isolate and decipher the function of plant genes involved in nodule development, with the view to extend and compare this knowledge to lateral root formation. While nodulation and lateral root formation are distinct processes, they appear to share anatomical and biochemical features. Working hypothesis is that nodule formation borrowed functions from lateral root development. Our approach implements T-DNA and transposon insertional mutagenesis in the model legume Lotus japonicus. The success of this project will contribute significantly to the studies of plant-microbe interaction and plant morphogenesis.Read moreRead less
In vitro expression and crystallization of proteins from the thermohalophile, Halothermothrix orenii. The project proposal is to develop enabling state-of-the-art protein technologies for biotechnology. We will for the first time develop a rapid and high throughput technique for the expression, purification and crystallisation of proteins from the extreme thermohalophile, Halothermothrix orenii. This important break through in protein technology will assist in determining structure and function ....In vitro expression and crystallization of proteins from the thermohalophile, Halothermothrix orenii. The project proposal is to develop enabling state-of-the-art protein technologies for biotechnology. We will for the first time develop a rapid and high throughput technique for the expression, purification and crystallisation of proteins from the extreme thermohalophile, Halothermothrix orenii. This important break through in protein technology will assist in determining structure and function relationships of thermohalophilic proteins. It is expected that such an understanding together with comparative bioinformatics will assist researchers to develop "designer proteins" with improved functions for different uses in biotechnology. It is also expected that this technology will be amenable for use with other thermohalophilic microbes.Read moreRead less
Inhibition of pro-inflammatory cytokine secretion- A new route to therapeutics of chronic inflammatory disease. Chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, affect millions of people leading to considerable suffering, economic loss and premature death. Anti-TNF treatments have recently shown success in the treatment of rheumatoid arthritis, inflammatory bowel disease and other conditions, however, a substantial number of patients (~50%) do not re ....Inhibition of pro-inflammatory cytokine secretion- A new route to therapeutics of chronic inflammatory disease. Chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, affect millions of people leading to considerable suffering, economic loss and premature death. Anti-TNF treatments have recently shown success in the treatment of rheumatoid arthritis, inflammatory bowel disease and other conditions, however, a substantial number of patients (~50%) do not respond to the current TNF treatments. Improved anti-TNF strategies would provide enhanced health outcomes and welcome relief to many Australians. In addition, the economic benefit of the TNF market is very substantial. Therefore the potential impact of this research is very high both for health care and economical potential.Read moreRead less
A New Window into Transgene Silencing in Plants: mechanisms of copy-number independent, 5' sequence dependent, post-transcriptional silencing in a complex polyploid. Silencing of introduced genes is a major problem limiting plant molecular improvement. Sugarcane, a complex polyploid, shows the most efficient transgene silencing ever observed in plants. Silencing operates on the RNA, depends on the upstream sequence of the gene, and is independent of copy number. Other plant species develop endop ....A New Window into Transgene Silencing in Plants: mechanisms of copy-number independent, 5' sequence dependent, post-transcriptional silencing in a complex polyploid. Silencing of introduced genes is a major problem limiting plant molecular improvement. Sugarcane, a complex polyploid, shows the most efficient transgene silencing ever observed in plants. Silencing operates on the RNA, depends on the upstream sequence of the gene, and is independent of copy number. Other plant species develop endopolyploidy with age, and show unpredictable or patchy silencing. We speculate that differential silencing is a natural control mechanism in the exploitation of polyploidy in plants. The sugarcane system provides an exceptional opportunity to identify the sequences that trigger and protect from silencing, and to develop approaches to avoid the problem.Read moreRead less
Unravelling the sub-nuclear complexity of the brain. Understanding the function of the brain is a major frontier of scientific research. The ability to increase knowledge of brain function is reliant upon the development of novel methods. This application will develop a novel approach for understanding the function of particular nerve cells. One outcome will be demonstration of the applicability of a novel method of benefit to all brain researchers. Another outcome will be increased understandin ....Unravelling the sub-nuclear complexity of the brain. Understanding the function of the brain is a major frontier of scientific research. The ability to increase knowledge of brain function is reliant upon the development of novel methods. This application will develop a novel approach for understanding the function of particular nerve cells. One outcome will be demonstration of the applicability of a novel method of benefit to all brain researchers. Another outcome will be increased understanding of one brain region that is known to contribute to the development of cardiovascular disease. It is expected that increased knowledge of brain function will lead to novel theories of brain disease and therapeutic strategies.Read moreRead less
The biology of arbovirus virulence and fitness in arthropod and vertebrate hosts in vivo. In Australia, Ross River virus (RRV) represents significant concern to human health. Between 1992-2005 more than 50,000 notifications of RRV infection have been reported. While not fatal, the disease is responsible for morbidity in the community/individual that can have both social and economic costs. The project has several national benefits. It will help elucidate whether there is any association between ....The biology of arbovirus virulence and fitness in arthropod and vertebrate hosts in vivo. In Australia, Ross River virus (RRV) represents significant concern to human health. Between 1992-2005 more than 50,000 notifications of RRV infection have been reported. While not fatal, the disease is responsible for morbidity in the community/individual that can have both social and economic costs. The project has several national benefits. It will help elucidate whether there is any association between RRV strain and increased risk of RRV transmission and/or occurrence of more severe cases of human disease. It will help develop technologies that can lead towards the identification of viral markers, which could provide new avenues in the design of novel antiviral strategies.
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Characterisation of interacting genes that condition avirulence and resistance between Phytophthora pathogens and soybean. Plant pathogens from the genus Phytophthora cause severe crop losses in Australia and worldwide. Resistance in host plants is frequently overcome by mutation of avirulence genes in the pathogen to create virulent new races. We will clone and characterise genes from Phytophthora sojae that control virulence and avirulence, and isolate soybean genes whose products interact w ....Characterisation of interacting genes that condition avirulence and resistance between Phytophthora pathogens and soybean. Plant pathogens from the genus Phytophthora cause severe crop losses in Australia and worldwide. Resistance in host plants is frequently overcome by mutation of avirulence genes in the pathogen to create virulent new races. We will clone and characterise genes from Phytophthora sojae that control virulence and avirulence, and isolate soybean genes whose products interact with the Phytophthora gene products. An understanding of the molecular mechanisms than enable current plant varieties to recognise Phytophthora pathogens leading to resistance or susceptibility will assist the development of novel strategies for durable disease resistance in soybean and other crop plants.Read moreRead less
Plant transformation: exploiting anti-apoptosis genes for very high efficiency transformation. Crop improvement through genetic modification depends on the ability to transform target species. The most desirable method is Agrobacterium mediated transformation. However, plant species and cultivars differ significantly in their ability to be efficiently transformed by Agrobacterium. This is particularly true for the economically important cereals. We have discovered that anti-apoptosis genes, whic ....Plant transformation: exploiting anti-apoptosis genes for very high efficiency transformation. Crop improvement through genetic modification depends on the ability to transform target species. The most desirable method is Agrobacterium mediated transformation. However, plant species and cultivars differ significantly in their ability to be efficiently transformed by Agrobacterium. This is particularly true for the economically important cereals. We have discovered that anti-apoptosis genes, which inhibit programmed cell death, dramatically increase the Agrobacterium transformation efficiency in bananas and sugarcane. We will utilise this information and develop the use of these genes to increase the efficiency of transformation in those crops and cultivars that are difficult to transform using Agrobacterium.Read moreRead less
Towards the development of a novel live vaccine for the control of Glässer's disease (Haemophilus parasuis), a globally significant respiratory disease of swine. Respiratory diseases are common in intensively housed pigs, costing the Australian industry millions of dollars in lost production annually. Glässer's is a highly contagious and often fatal respiratory disease of pigs. Antibiotic therapy is expensive and often results in the emergence of antibiotic resistant organisms. There is also a t ....Towards the development of a novel live vaccine for the control of Glässer's disease (Haemophilus parasuis), a globally significant respiratory disease of swine. Respiratory diseases are common in intensively housed pigs, costing the Australian industry millions of dollars in lost production annually. Glässer's is a highly contagious and often fatal respiratory disease of pigs. Antibiotic therapy is expensive and often results in the emergence of antibiotic resistant organisms. There is also a trend to move away from the use of antibiotics in food production animals. Current vaccines are based on inactivated preparations and do not offer a high level of immune protection. Therefore, there is a great need worldwide for a live vaccine for the effective control of Glässer's disease.Read moreRead less