In Vivo And In Vitro Studies Of The Human -308 TNF Promoter Polymorphism.
Funder
National Health and Medical Research Council
Funding Amount
$232,131.00
Summary
The identification of genetic variation in region of the DNA that controls expression of the inflammatory cytokine Tumour Necrosis Factor (TNF) and its association with a number of autoimmune and inflammatory diseases, has led to speculation that this genetic difference may play a role in predisposing some people to these diseases. We have isolated an activity, TPF1, that may regulate expression through interaction with this DNA control region. During the tenure of this grant we intend to clarif ....The identification of genetic variation in region of the DNA that controls expression of the inflammatory cytokine Tumour Necrosis Factor (TNF) and its association with a number of autoimmune and inflammatory diseases, has led to speculation that this genetic difference may play a role in predisposing some people to these diseases. We have isolated an activity, TPF1, that may regulate expression through interaction with this DNA control region. During the tenure of this grant we intend to clarify some of these questions, we will generate genetically modified mice that have either of the two genetic forms of the human TNF promoter. These mice will be compared in two models of associated disease, murine Lupus and cerebral malaria. We will also characterise the interactions of TPF1 with other components of the TNF control region. An understanding of the role of TPF1 in controlling TNF expression and an appreciation of the cell types that are able to express the phenotype, will allow the development of more subtle, cell specific strategies to modulate the activity of TNF without completely abolishing expression and may lead to better preventative and therapeutic strategies.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453920
Funder
Australian Research Council
Funding Amount
$108,680.00
Summary
Molecular diagnostics based on real-time polymerase chain reactions for emerging tropical infectious diseases aimed at protecting Australia from invasive diseases. The project aims to use the technique of real-time polymerase chain reaction to rapidly detect and quantify the organisms associated with emerging and re-emerging infectious diseases of man and animals. It will also be used to determine related gene expression.
The equipment will be used to support a wide range of projects that req ....Molecular diagnostics based on real-time polymerase chain reactions for emerging tropical infectious diseases aimed at protecting Australia from invasive diseases. The project aims to use the technique of real-time polymerase chain reaction to rapidly detect and quantify the organisms associated with emerging and re-emerging infectious diseases of man and animals. It will also be used to determine related gene expression.
The equipment will be used to support a wide range of projects that require the detection of specific RNA or DNA and it will allow the rapid, cost effective and efficient processing of either RNA or DNA from large numbers of samples. Minor variations in organisms will be detected using this equipment.
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The sponge genome project and the evolution of multicellularity: using comparative genomics and developmental biology to reconstruct the first animals. Recently the entire genome from a living fossil - a sponge from the Great Barrier Reef - was sequenced (jointly supported by the ARC and US Department of Energy). As this genome is assembled and analysed, many of the fundamental biological processes that underlie the construction and evolution of all animals, including humans, will be revealed. ....The sponge genome project and the evolution of multicellularity: using comparative genomics and developmental biology to reconstruct the first animals. Recently the entire genome from a living fossil - a sponge from the Great Barrier Reef - was sequenced (jointly supported by the ARC and US Department of Energy). As this genome is assembled and analysed, many of the fundamental biological processes that underlie the construction and evolution of all animals, including humans, will be revealed. In addition, sponge genomics will fuel innovations in medicine and biotechnology. Specifically, sponges are renowned for their capacity to synthesise bioactive compounds used in drug development, and high-grade silica used for semi-conductor construction. This project will identify the gene networks controlling these biosynthetic processes.Read moreRead less
Variation in larval gene expression in a marine invertebrate: implications for population divergence via differential settlement response. Evolutionary and ecological functional genomics is an emerging field that integrates gene profiling technologies with experimental and field approaches of ecology and evolution. I take this approach to address a key problem in marine invertebrate biology: how do larvae respond to their environment and how does variation in this response influence the distribu ....Variation in larval gene expression in a marine invertebrate: implications for population divergence via differential settlement response. Evolutionary and ecological functional genomics is an emerging field that integrates gene profiling technologies with experimental and field approaches of ecology and evolution. I take this approach to address a key problem in marine invertebrate biology: how do larvae respond to their environment and how does variation in this response influence the distribution and evolution of a species? I will use a marine gastropod (abalone) model, for which there exists substantial development and population genetic data, and established aquaculture methodologies. Outcomes of this study will enhance knowledge of the stock structure of this and other commercial fisheries, as well as aquaculture efficiency.Read moreRead less
Identification of the basic elements of Plasmodium transcription. This Discovery Project falls under the NRP for safeguarding Australia. Australian troops stationed in malaria endemic areas face the threat of infection and require medical attention upon return.Any research on malaria will expand our knowledge on prevention and treatment. Australia near malariaendemic locations such as Indonesia and Papua New Guinea.These countries do not have the means to support effective basic research into ....Identification of the basic elements of Plasmodium transcription. This Discovery Project falls under the NRP for safeguarding Australia. Australian troops stationed in malaria endemic areas face the threat of infection and require medical attention upon return.Any research on malaria will expand our knowledge on prevention and treatment. Australia near malariaendemic locations such as Indonesia and Papua New Guinea.These countries do not have the means to support effective basic research into the disease and wealthier countries such as Australia have the responsibility to fill this void.Furthermore, the aims of this Discovery Project are unique within the Australian malaria research community and the results fully complement other studies on transcription regulation of antigenic genes. Read moreRead less
Improving vaccine performance through understanding host-pathogen interaction in yersiniosis. This project will significantly contribute to the economic and environmental sustainability of the Australian salmon industry. It will reduce salmon production costs, ensure sufficient supply of fish from hatchery to grow-out and reduce the use of antibiotics. Reduced use of antibiotics will benefit both the environment and human health. As the salmon industry is based in regional and rural areas, th ....Improving vaccine performance through understanding host-pathogen interaction in yersiniosis. This project will significantly contribute to the economic and environmental sustainability of the Australian salmon industry. It will reduce salmon production costs, ensure sufficient supply of fish from hatchery to grow-out and reduce the use of antibiotics. Reduced use of antibiotics will benefit both the environment and human health. As the salmon industry is based in regional and rural areas, this project will support rural and regional communities. This project will further strengthen Australian leadership in aquaculture research through use of molecular methods to address industry issues and will therefore increase the competitiveness of Australian science.Read moreRead less
The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. Thi ....The function of menin in mammalian development. This project aims to determine the role of a ubiquitous transcriptional co-regulator, menin, in mammalian development. Mice that lack menin through targeted deletion of the gene die during embryogenesis, but the cause is unknown, although is likely to be due to the abnormal expression of genes usually regulated by this factor. We will determine which genes are inappropriately expressed and responsible for the accompanying developmental defects. This knowledge will help us understand the process of development in mammals, including birth defects in humans.Read moreRead less
Chromatin barriers in Plasmodium falciparum gene regulation. Malaria is a major world disease that kills around 2 million people annually. The genome of the causative agent has now been completely sequenced, but we still know very little of how and why some genes are activated while their neighbours are turned off. I will study the DNA barriers that separate such genes, and the proteins that interact with these regions to better understand how genetic regulation functions in these parasites. A b ....Chromatin barriers in Plasmodium falciparum gene regulation. Malaria is a major world disease that kills around 2 million people annually. The genome of the causative agent has now been completely sequenced, but we still know very little of how and why some genes are activated while their neighbours are turned off. I will study the DNA barriers that separate such genes, and the proteins that interact with these regions to better understand how genetic regulation functions in these parasites. A better understanding of gene regulation in malaria parasites will help us to better combat the tricks utilised by this and other organisms to elude our immune systems.Read moreRead less
Microbial genomics of the southern ocean: monitoring environmental health. This program will derive an integrated understanding of microbial ecology which is essential for determining ways of preserving the health of the World's ecosystems. Through the development of a unique microbial genomics program, Australia will remain a world leader in Antarctic biology, strengthening Australia's reputation in technologically innovative scientific programs of global significance, training local scientists ....Microbial genomics of the southern ocean: monitoring environmental health. This program will derive an integrated understanding of microbial ecology which is essential for determining ways of preserving the health of the World's ecosystems. Through the development of a unique microbial genomics program, Australia will remain a world leader in Antarctic biology, strengthening Australia's reputation in technologically innovative scientific programs of global significance, training local scientists in cutting edge genomic biology and fostering the interests of the international community in sciences ranging from microbial ecology to climate change.Read moreRead less
Identifying Novel Biosynthetic Pathways in Mycobacteria using DNA Microarray Technology. DNA microarrays are a powerful new bioinformatics-based technology and an ideal tool for characterising complex biosynthetic pathways since the expression of all genes in the bacterial genome can be monitored in a single experiment. In this project we aim to construct and use a DNA microarray to identify novel biosynthetic pathways in mycobacteria. Of particular interest are pathways used to create compone ....Identifying Novel Biosynthetic Pathways in Mycobacteria using DNA Microarray Technology. DNA microarrays are a powerful new bioinformatics-based technology and an ideal tool for characterising complex biosynthetic pathways since the expression of all genes in the bacterial genome can be monitored in a single experiment. In this project we aim to construct and use a DNA microarray to identify novel biosynthetic pathways in mycobacteria. Of particular interest are pathways used to create components of the highly complex and poorly characterised cell wall. Since this structure is unique in the bacterial world, we expect to identify and characterise pathways that are unique to mycobacteria.Read moreRead less