Transcriptional regulation of erythropoiesis. The major expected outcome from this proposal will be development of a pipeline for the study of how transcription factors work at a genome level. There will be national benefit in the areas of Frontier Technologies, and Promoting and Maintaining Good Health. There will be specific outcomes with respect to development of tests for human blood diseases, future design of drugs to target the aberrant activities of transcription factors in genetic and de ....Transcriptional regulation of erythropoiesis. The major expected outcome from this proposal will be development of a pipeline for the study of how transcription factors work at a genome level. There will be national benefit in the areas of Frontier Technologies, and Promoting and Maintaining Good Health. There will be specific outcomes with respect to development of tests for human blood diseases, future design of drugs to target the aberrant activities of transcription factors in genetic and degenerative diseases. Also, a strong bridge will be built upon the previous collaborations of the research teams in Brisbane and Pennsylvania, which will facilitate advanced teaching and training of Australian PhD and post-doctoral scientists.Read moreRead less
Characterisation of the oxygen-sensing asparaginyl hydroxylase, FIH-1, and hydroxylase-specific antagonists. This research will provide fundamental information on how cells and whole organisms can sense and respond accordingly to oxygen deficiency. This information is fundamental for our understanding of embryo development and adult life in different environments, and central to the diagnosis and treatment of diseases such as stroke, cardiovascular disease, and cancer. This research will contrib ....Characterisation of the oxygen-sensing asparaginyl hydroxylase, FIH-1, and hydroxylase-specific antagonists. This research will provide fundamental information on how cells and whole organisms can sense and respond accordingly to oxygen deficiency. This information is fundamental for our understanding of embryo development and adult life in different environments, and central to the diagnosis and treatment of diseases such as stroke, cardiovascular disease, and cancer. This research will contribute to our basic knowledge of these processes, provide invaluable information about the specific genes and proteins involved, and provide direct information about the therapeutic potential of specific drugs or inhibitors designed to target this oxygen response in human disease.Read moreRead less
An RNA interference based genetic screen for novel epigenetic modifiers involved in mammalian X inactivation. All the information required to form an adult human is contained in the DNA of the fertilized egg. Development is achieved by a complex orchestration of genes being switched on and off, controlled by proteins called epigenetic modifiers. Sometimes this goes awry, leading to disease. Despite their vital role, only around ten percent of the potential epigenetic modifiers have been characte ....An RNA interference based genetic screen for novel epigenetic modifiers involved in mammalian X inactivation. All the information required to form an adult human is contained in the DNA of the fertilized egg. Development is achieved by a complex orchestration of genes being switched on and off, controlled by proteins called epigenetic modifiers. Sometimes this goes awry, leading to disease. Despite their vital role, only around ten percent of the potential epigenetic modifiers have been characterized in humans, making it impossible to interpret how they work together, or when they fail. We will develop a novel screen-based technology to find hundreds more true epigenetic modifiers. This technology will aid us and other Australian scientists to understand the role of epigenetics in normal development and disease, ultimately leading to better public health.Read moreRead less
Tissue specific regulation of gene expression. Despite the polarized public debate concerning the use of stem cells for tissue regeneration, fundamental questions relating to the identity and hierarchy of these cells remain unanswered. The benefit to Australia will be scientific in terms of providing an understanding of how stem and progenitor cells integrate transcriptional control systems during differentiation and the networks that are involved. This is fundamental to the future isolation a ....Tissue specific regulation of gene expression. Despite the polarized public debate concerning the use of stem cells for tissue regeneration, fundamental questions relating to the identity and hierarchy of these cells remain unanswered. The benefit to Australia will be scientific in terms of providing an understanding of how stem and progenitor cells integrate transcriptional control systems during differentiation and the networks that are involved. This is fundamental to the future isolation and manipulation of these stem cell types to benefit the community. The work will also provide postgraduate students with training in state of the art genomic techniques and in the interface between bioinformatics and experimental science. Read moreRead less
Regulation Of Tissue-type Plasminogen Activator Gene Expression In Endothelial Cells And In Transgenic Mice
Funder
National Health and Medical Research Council
Funding Amount
$244,009.00
Summary
Tissue-type plasminogen activator (t-PA) is an enzyme which plays an important role in the removal of blood clots from the circulation. One of the major sites of production of t-PA are endothelial cells which line the blood vessel wall. The rate of t-PA production is greatly influenced by factors released from other cells. One of these factors is tumour necrosis factor (TNF). The t-PA gene is switched off in endothelial cells exposed to TNF. One of the aims of this project is to understand how t ....Tissue-type plasminogen activator (t-PA) is an enzyme which plays an important role in the removal of blood clots from the circulation. One of the major sites of production of t-PA are endothelial cells which line the blood vessel wall. The rate of t-PA production is greatly influenced by factors released from other cells. One of these factors is tumour necrosis factor (TNF). The t-PA gene is switched off in endothelial cells exposed to TNF. One of the aims of this project is to understand how the t-PA gene is suppressed by TNF in human endothelial cells and in transgenic mice. The transgenic mice we have available express the regulatory region of the t-PA gene (called the gene promoter) connected to a reporter gene called LacZ. We will use these animals to visualise the expression pattern of LacZ expression under normal conditions and in mice treated with TNF. The results of these experiments will provide new information as to how the t-PA gene is controlled in cells and in the body.Read moreRead less
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.
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