Retrotransposon Regulation Of The Human Innate Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$231,937.00
Summary
Complete sequencing of the human genome has revealed the positions of approximately 20,000 genes. In addition, nearly 50% of the human genome is comprised of repetitive sequences previously thought of as junk DNA. Numerous studies are now finding that this DNA actually has a variety of important functions, particularly in the control of gene activity. This project will examine the relationships between gene expression and nearby repetitive sequences during the innate immune response in humans.
The Role Of Ikaros In Establishing Regulatory Networks For Lymphocyte Development
Funder
National Health and Medical Research Council
Funding Amount
$345,809.00
Summary
Ikaros is a protein that regulates gene expression during development of lymphocytes from blood stem cells. Ikaros has a profound importance in normal and malignant lymphocyte development, but we still do not know how it controls these processes. The aim of my study is to identify genes regulated by Ikaros and the molecular mechanisms of their regulation. This study will contribute to understanding of the regulatory network controlling the development and function of lymphocytes.
This project concerns the basic biology of white blood cells called macrophages. Macrophages are required for the immediate defence against infection, as well as wound repair and normal turnover of tissues, but they can also produce toxic products that cause illness, especially in inflammatory diseases and cancer. We are attempting to use the availability of mouse genome information to produce a complete picture of the way that macrophages respond to a challenge from a potential disease-causing ....This project concerns the basic biology of white blood cells called macrophages. Macrophages are required for the immediate defence against infection, as well as wound repair and normal turnover of tissues, but they can also produce toxic products that cause illness, especially in inflammatory diseases and cancer. We are attempting to use the availability of mouse genome information to produce a complete picture of the way that macrophages respond to a challenge from a potential disease-causing microorganism, and the influence of genetic differences between individuals.Read moreRead less
Transcriptional Regulation Of The C-fms (CSF-1R) Gene In Macrophages.
Funder
National Health and Medical Research Council
Funding Amount
$422,310.00
Summary
This project concerns the basic biology of large white blood cells called macrophages. Macrophages are required for the immediate defence against infection, wound repair and normal turnover of tissues, but they can also produce toxic products that cause illness, especially in inflammatory diseases and cancer. We are studying a gene that is normally only produced in macrophages, but appears abnormally in many cancer cells. Our aim is understand at a molecular level exactly how the gene is control ....This project concerns the basic biology of large white blood cells called macrophages. Macrophages are required for the immediate defence against infection, wound repair and normal turnover of tissues, but they can also produce toxic products that cause illness, especially in inflammatory diseases and cancer. We are studying a gene that is normally only produced in macrophages, but appears abnormally in many cancer cells. Our aim is understand at a molecular level exactly how the gene is controlled, and why it appears in tumours.Read moreRead less
The Interferon Inducible Transcription Factor IFI 16.
Funder
National Health and Medical Research Council
Funding Amount
$151,208.00
Summary
Interferons (IFNs) play an important role in human biology by regulating cell growth and differentiation, immune function and inhibiting viral replication. These vital functions of type I (alpha and beta) and type II (gamma) IFN are triggered upon binding of IFN to their cognate cell surface receptors. This initiates a series of intracellular signalling cascades resulting in the activation of key transcription factors which induce the expression of specific cellular target genes. The protein pro ....Interferons (IFNs) play an important role in human biology by regulating cell growth and differentiation, immune function and inhibiting viral replication. These vital functions of type I (alpha and beta) and type II (gamma) IFN are triggered upon binding of IFN to their cognate cell surface receptors. This initiates a series of intracellular signalling cascades resulting in the activation of key transcription factors which induce the expression of specific cellular target genes. The protein products of these genes in turn directly or indirectly mediate the necessary biological response to maintain cellular homeostasis. While there are hundreds of cellular genes that are induced following IFN stimulation, the molecular and biological functions of the protein products of many of these genes are often not known. IFI 16 is one such IFN-induced gene that belongs to a family of related genes found in human and mouse. Little is known about what role IFI 16 may play in an IFN response and how it may function to mediate its effect. The proposed study is aimed at understanding how IFI 16 is upregulated following treatment of cells with IFN, identifying which cellular genes may be directly regulated by IFI 16 and how this happens, and whether IFI 16 plays a role in the development of specific blood cells.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
The Role Of The Microphthalmia Transcription Factor Family In Macrophage Differentiation.
Funder
National Health and Medical Research Council
Funding Amount
$367,193.00
Summary
Macrophages are large white blood cells that are also found in all the tissues of the body. They are a major part of the front line defence against infection and malignancy, but they also cause much of the pathology of many diseases particularly those in which there is chronic inflammation. Macrophages, like all the cells of the blood, are produced from the bone marrow. In the process of macrophage production a suite of genes must be switched on so that the mature macrophage can carry out its fu ....Macrophages are large white blood cells that are also found in all the tissues of the body. They are a major part of the front line defence against infection and malignancy, but they also cause much of the pathology of many diseases particularly those in which there is chronic inflammation. Macrophages, like all the cells of the blood, are produced from the bone marrow. In the process of macrophage production a suite of genes must be switched on so that the mature macrophage can carry out its functions. This project aims to understand the process of selective gene expression in macrophages. It is based upon the identification of four members of a gene family, called the microphthalmia gene family, as candidate master genes that control the overall process of macrophage production. We seek to understand how the products of genes interact.Read moreRead less