Discovery of pathways to embryogenesis in pathogenic flatworm parasites using microdissection and transcriptomic technologies. The cost to Australia of flatworm parasites to animal production and human health is substantial (hundreds of millions of dollars per year). This research will give new insights into how flatworms reproduce and equip their progeny for survival, providing impetus for new vaccine or drug therapies to be developed. As these pathogens are more significant in Australia's ne ....Discovery of pathways to embryogenesis in pathogenic flatworm parasites using microdissection and transcriptomic technologies. The cost to Australia of flatworm parasites to animal production and human health is substantial (hundreds of millions of dollars per year). This research will give new insights into how flatworms reproduce and equip their progeny for survival, providing impetus for new vaccine or drug therapies to be developed. As these pathogens are more significant in Australia's near neighbours, this project will strengthen Australia's international leadership in this field. Our study will provide, for the first time for any helminth parasite, a freely available genetic database that profiles the gene expression repertoire of individual parasite tissues, a development likely to enhance the international effort in controlling these harmful diseases.Read moreRead less
Insect host/vector genetic responses to rhabdovirus infection. Rhabdoviruses cause important diseases in humans, animals and plants. These viruses are transmitted by insect vectors in which they persist and propagate, an intimate and specific association. Insect-rhabdovirus interactions will be studied at the molecular level using a planthopper-maize rhabdovirus model. Insect genes specifically induced by rhabdovirus infection as well as the viral genes themselves will be identified and characte ....Insect host/vector genetic responses to rhabdovirus infection. Rhabdoviruses cause important diseases in humans, animals and plants. These viruses are transmitted by insect vectors in which they persist and propagate, an intimate and specific association. Insect-rhabdovirus interactions will be studied at the molecular level using a planthopper-maize rhabdovirus model. Insect genes specifically induced by rhabdovirus infection as well as the viral genes themselves will be identified and characterized using genomics and bioinformatics tools. We will extend the same approaches to a comparative analysis of these planthopper genes with other insect-rhabdovirus systems under investigation in our institutes. Identification of viral genes expressed in insects, the insect genes that respond to virus infection, and interpretation of the roles of these genes in insects, may indicate new opportunities to control serious plant and animal diseases through control of virus transmission.Read moreRead less
Beyond the gene: Linking herbivore behaviour to plant defense gene expression. This collaborative project investigates insect herbivore avoidance of plant defence mechanisms. Our project is novel because it integrates changes in the plant at a number of different levels and links them to insect foraging behaviour. Researchers assume that insects respond to plant defences by changing their foraging behaviour. This has not been tested directly. We use the genetically well characterised plant Arabi ....Beyond the gene: Linking herbivore behaviour to plant defense gene expression. This collaborative project investigates insect herbivore avoidance of plant defence mechanisms. Our project is novel because it integrates changes in the plant at a number of different levels and links them to insect foraging behaviour. Researchers assume that insects respond to plant defences by changing their foraging behaviour. This has not been tested directly. We use the genetically well characterised plant Arabidopsis and the world-wide pest Helicoverpa (heliothis) as a model system. Damage caused to crops by insect herbivores is a direct function of behaviour. Understanding this behaviour will lead to improved pest management and reduced economic losses.Read moreRead less
Why do only some exotics become invasive? Combining ecological and genomic approaches to address alternative hypotheses in a recent Australian weed. This project will specifically test alternative hypotheses about how weeds become invasive. As invasive weeds affect both agricultural and native ecosystems equally, research on understanding the mechanisms of weed invasion is critical. Outcomes will benefit Australia by allowing better prioritisation of management against exotic plants already i ....Why do only some exotics become invasive? Combining ecological and genomic approaches to address alternative hypotheses in a recent Australian weed. This project will specifically test alternative hypotheses about how weeds become invasive. As invasive weeds affect both agricultural and native ecosystems equally, research on understanding the mechanisms of weed invasion is critical. Outcomes will benefit Australia by allowing better prioritisation of management against exotic plants already in the country by providing predictive tools to estimate likelihood of spread. For formal Pest Risk Analysis by regulators (eg Biosecurity Australia), our project will provide genomic tools by which the potential weediness of a regulated plant can be assessed through genetic screening, and forms part of an international effort to identify 'weedy genes'. Read moreRead less
Functional and regulatory analysis of n-acetylcholine receptors, key targets of insecticides. Agriculture is one of Australia's mainstay industries and a major user of insecticides. However, current insecticides suffer a number of significant deficiencies, including collateral damage in the environment and insect resistance. One of the major targets for insecticides are a class of neuronal receptors, found in organisms ranging from worms to man. Our work will provide a detailed biological unders ....Functional and regulatory analysis of n-acetylcholine receptors, key targets of insecticides. Agriculture is one of Australia's mainstay industries and a major user of insecticides. However, current insecticides suffer a number of significant deficiencies, including collateral damage in the environment and insect resistance. One of the major targets for insecticides are a class of neuronal receptors, found in organisms ranging from worms to man. Our work will provide a detailed biological understanding of these receptors leading to better ways of developing new insecticides. Similar receptors in humans are the target for nicotine and associated with neurological disorders such as schizophrenia and autism. Thus our work will also increase our understanding of important human receptors associated with disease.Read moreRead less
The transcriptional co-repressor C-terminal Binding Protein (CtBP) in metabolic control. This project will provide insights into the genes that regulate the storage of fat. We will learn about basic biology but will also discover mechanisms that may be used to influence fat storage in human health. We will also consolidate Australia's expertise in the use of the genetic model organism, the worm C. elegans, and validate the findings in mammalian systems. Finally, the process of training young sci ....The transcriptional co-repressor C-terminal Binding Protein (CtBP) in metabolic control. This project will provide insights into the genes that regulate the storage of fat. We will learn about basic biology but will also discover mechanisms that may be used to influence fat storage in human health. We will also consolidate Australia's expertise in the use of the genetic model organism, the worm C. elegans, and validate the findings in mammalian systems. Finally, the process of training young scientists in these modern systems, will also equip future researchers to make additional contributions to Australia's research output.Read moreRead less
RNA splicing: factors and mechanisms. Most primary gene transcripts must have their noncoding intronic sequences spliced out before the mRNA can be translated. Moreover, alternative splicing enables cells to generate a far more proteins than there are genes in the nucleus. Based on our proven success with ZNF265 we will isolate novel RNA interactors and their partners, colocalize these in intranuclear compartments, and elucidate their effect on pre-mRNA splicing. This will provide timely spin-of ....RNA splicing: factors and mechanisms. Most primary gene transcripts must have their noncoding intronic sequences spliced out before the mRNA can be translated. Moreover, alternative splicing enables cells to generate a far more proteins than there are genes in the nucleus. Based on our proven success with ZNF265 we will isolate novel RNA interactors and their partners, colocalize these in intranuclear compartments, and elucidate their effect on pre-mRNA splicing. This will provide timely spin-offs to the Human genome Project and EST sequence information, where the finding of only approx. 30,000 genes in our genome highlights the important role of alternative splicing in generating the large proteome repertoire of cells. This will bring considerable benefits to science, society, and the biotech industry.Read moreRead less
Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and ....Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and to fungal pathogens. Since the fungal genes that form the basis of this project are conserved in higher eukaryotes including humans, the knowledge will be transferable to these systems. A further benefit that cannot be overstated is the research education and training opportunities provided.
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A new mechanism of gene regulation. This project will advance our knowledge of how genes are switched on and off, by focusing on a very common class of gene regulatory proteins known as zinc finger proteins. The results of this study will improve our understanding of the fundamental molecular events that underpin gene regulation and how we might control it in fields such as biotechnology and gene therapy.
New mechanisms of DNA recognition by zinc-finger domains. The work described in this proposal carries long-term benefits to the health of Australians. Many debilitating diseases, including many varieties of cancer, arise as a result of a breakdown in the normal regulation of gene transcription. It is only once we have a thorough understanding of transcriptional regulation in normal organisms that we will be in a position to devise effective therapies to deal with the disorders that result from a ....New mechanisms of DNA recognition by zinc-finger domains. The work described in this proposal carries long-term benefits to the health of Australians. Many debilitating diseases, including many varieties of cancer, arise as a result of a breakdown in the normal regulation of gene transcription. It is only once we have a thorough understanding of transcriptional regulation in normal organisms that we will be in a position to devise effective therapies to deal with the disorders that result from aberrant gene expression. Our proposed research program also provides the opportunity to train younger scientists in state-of-the-art molecular and structural biology, thus representing a significant national benefit. Read moreRead less