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
Gene Transcription In Activated T Cells: A Model Of Chromatin Remodeling.
Funder
National Health and Medical Research Council
Funding Amount
$477,500.00
Summary
Cells of the immune system respond to invasion of the body by infectious or other damaging agents by switching on the production of a large array of proteins that are critical for an orchestrated immune response. Some of these proteins, referred to as cytokines, are secreted by the cells and act as intercellular messengers to affect the function of other cells need for an immune response. Switching on the production of these cytokines requires the genes that produce them to interpret the complex ....Cells of the immune system respond to invasion of the body by infectious or other damaging agents by switching on the production of a large array of proteins that are critical for an orchestrated immune response. Some of these proteins, referred to as cytokines, are secreted by the cells and act as intercellular messengers to affect the function of other cells need for an immune response. Switching on the production of these cytokines requires the genes that produce them to interpret the complex signaling pattern to which the cell has been exposed. These complex signaling patterns are interpreted in the nucleus by molecular switches that lie beside the genes in the DNA. The incorrect production of these proteins is involved in immune diseases such as autoimmunity, allergy and leukemia. Genes are housed in the nucleus of the cell, packaged into a structure known as chromatin. When the gene is not producing protein it is tightly packaged in chromatin but when it is activated to produce protein this packaging is altered to allow the gene to see the signals being received by the cell and produce protein. We have identified a protein within the nucleus that is critical in allowing certain cytokine genes to see the signals being received in the nucleus. By investigating the role of this protein (called c-Rel) in chromatin reorganization in immune cells, we hope to better define the steps required for appropriate gene activation in an immune response. This knowledge, in turn, will lead to the identification of novel therapeutic targets to control immune responsesRead moreRead less
Functional Validation Of FoxP3 Target Genes In Human Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$545,341.00
Summary
Using DNA based technologies we have focused on rare white blood cells known as regulatory T cells. These cells are policeman of the immune system and are responsible for maintaining balanced immune reactions, and preventing attack against harmless substances. These cells prevent autoimmune disease in healthy individuals, and only by first understanding how they work normally can we investigate and correct the defects in autoimmune diseases such as type 1 diabetes.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0347607
Funder
Australian Research Council
Funding Amount
$306,000.00
Summary
FishWorks - collaborative infrastructure for zebrafish research. Zebrafish have emerged as a powerful and cost-effective animal model for studying development, biology, and disease. FishWorks represents a large-scale co-operative initiative to develop state-of-the-art zebrafish housing, manipulation, genomics and screening infrastructure in Australia. This will both support and further enhance a core group of high quality researchers to engage in cutting-edge research in areas of acknowledged ex ....FishWorks - collaborative infrastructure for zebrafish research. Zebrafish have emerged as a powerful and cost-effective animal model for studying development, biology, and disease. FishWorks represents a large-scale co-operative initiative to develop state-of-the-art zebrafish housing, manipulation, genomics and screening infrastructure in Australia. This will both support and further enhance a core group of high quality researchers to engage in cutting-edge research in areas of acknowledged expertise as well as priority within their respective institutions. In addition, it will facilitate wide-ranging collaborative arrangements to further develop and exploit this research area.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561030
Funder
Australian Research Council
Funding Amount
$441,100.00
Summary
Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiative ....Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiatives in developmental and cellular biology. This large-scale, high-resolution expression profiling infrastructure is required to maintain international competitiveness and will dramatically improve our gene discovery, functional assessment and understanding of vertebrate development.Read moreRead less
Molecular Basis Of Transgenerational Epigenetic Inheritance In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$477,965.00
Summary
While it has long been recognised that it is not just DNA, but chromosomes, that are passed from the gametes to the embryo, the non-DNA component was thought to carry no information with respect to the offspring's ultimate phenotype. However, there is now evidence that the non-DNA component, the epigenetic component, can play a role in the inheritance of phenotype in mammals. This study will attempt to determine the molecular nature of this phenomenon.
Structure and function of a new class of multi-zinc finger (MZF) transcriptional regulators. An understanding of how genes are switched on and off during the development and lifetime of an organism is central to developing the ability to fight many diseases in a rational way. This project will advance our knowledge in this area at a fundamental molecular level by examining the mechanisms through which a specific set of proteins controls gene expression.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775778
Funder
Australian Research Council
Funding Amount
$196,000.00
Summary
A microarray platform for gene expression analysis and genotyping in biological systems. This technology has substantial benefits for basic science and biotechnology. The ability to rapidly study changes in gene expression in living organisms will benefit agriculture, animal and biomedical science and biotechnology. The Affymetrix platform creates opportunities for new avenues of research, such as studying epigenetic (DNA and protein modifications) mechanisms in development, ageing and disease. ....A microarray platform for gene expression analysis and genotyping in biological systems. This technology has substantial benefits for basic science and biotechnology. The ability to rapidly study changes in gene expression in living organisms will benefit agriculture, animal and biomedical science and biotechnology. The Affymetrix platform creates opportunities for new avenues of research, such as studying epigenetic (DNA and protein modifications) mechanisms in development, ageing and disease. The project falls within the designated national research priority areas of 'promoting and maintaining good health" and the priority goals of "a healthy start to life", "aging well", "aging productively" and "preventative health care."Read moreRead less
The sulfate anion transporter gene, Sat1: physiology, regulation and developmental expression. Sulfate is an essential nutrient for cell growth and survival. The kidneys and liver help regulate sulfate levels in the body, by yet unknown mechanisms. Recently, we cloned a gene, Sat1, expressed in mouse liver and kidneys, which may be responsible for body sulfate maintenance. In this study, we will determine the physiological importance of Sat1 in cell growth/survival and in controlling body sulfa ....The sulfate anion transporter gene, Sat1: physiology, regulation and developmental expression. Sulfate is an essential nutrient for cell growth and survival. The kidneys and liver help regulate sulfate levels in the body, by yet unknown mechanisms. Recently, we cloned a gene, Sat1, expressed in mouse liver and kidneys, which may be responsible for body sulfate maintenance. In this study, we will determine the physiological importance of Sat1 in cell growth/survival and in controlling body sulfate levels. We will generate and characterise a Sat1 lacking mouse, study its expression during development and its effects on other genes. We will elucidate how body sulfate levels are maintained and its importance in cell growth/development.Read moreRead less