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
Molecular And Cellular Studies Of The Copper-transporting ATPases Affected In Menkes And Wilson Diseases
Funder
National Health and Medical Research Council
Funding Amount
$558,300.00
Summary
Copper is an element that is essential for life but is highly toxic in excess. Because of this, the regulation of copper uptake, distribution in the body and excretion of excess is a very tightly regulated process. Until recently little was known about the molecular basis of this process. Two genetic disorders that show these two aspects of copper are Menkes disease (deficiency) and Wilson disease (toxicity). Both diseases are caused by mutations in similar copper pumping proteins. Our research ....Copper is an element that is essential for life but is highly toxic in excess. Because of this, the regulation of copper uptake, distribution in the body and excretion of excess is a very tightly regulated process. Until recently little was known about the molecular basis of this process. Two genetic disorders that show these two aspects of copper are Menkes disease (deficiency) and Wilson disease (toxicity). Both diseases are caused by mutations in similar copper pumping proteins. Our research is trying to establish the molecular mechanisms used in the body to control copper metabolism. We made a major breakthrough in 1993 with the isolation of the gene affected in Menkes disease, and we continue to be one of the leading groups in the world in studying the molecular mechanisms that handle copper, and the importance of these mechanisms in health and disease. Research into the biology of copper has become much more important following the recent discoveries of the involvement of the metal in such important neurodegenerative conditions such as Alzheimer's, Mad Cow, and Parkinson's diseases. Health effects from the lack of copper may be widespread also, copper deficiency is suspected to contribute to some common diseases, such as cardiovascular problems and osteoporosis. Our research is providing information about copper transport mechanisms that are necessary for the understanding of, and may lead to better treatment and diagnosis of common and important diseases. In this grant we propose to continue our studies into the molecular signals that control the copper pumps, that make the regulation of copper metabolism possible. We also will use various test systems for studying the effect of mutations on the activity of these proteins and relate these effects to the type of disease produced in patients.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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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
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
Characterisation of the novel mitochondrial protein (CABC1/ADCK3) and its role in protecting against oxidative stress. This is the first detailed characterisation and mechanistic study on a protein that protects against oxidative stress and neurodegeneration. Demonstrating the basis for this oxidative stress and its possible contribution to the cellular phenotype will be of benefit in understanding the disease process and ultimately designing approaches to minimise oxidative stress. An investiga ....Characterisation of the novel mitochondrial protein (CABC1/ADCK3) and its role in protecting against oxidative stress. This is the first detailed characterisation and mechanistic study on a protein that protects against oxidative stress and neurodegeneration. Demonstrating the basis for this oxidative stress and its possible contribution to the cellular phenotype will be of benefit in understanding the disease process and ultimately designing approaches to minimise oxidative stress. An investigation of this protein presents an opportunity for the investigator to work at the forefront in this field adding to Australia's scientific leadership in the area. It also represents an ideal project for post-graduate training and is a collaboration between groups in Brisbane and Melbourne. Read moreRead less