Macrophages are a key component of the immune system; thier functions include killing of pathogens as well as cancerous cells. Macrophage lineage cells are derived from stem cells within the bone marrow and thier differentiation, proliferation and survival is mediated by a particular growth factor termed colony stimulating factor-1 (CSF-1). The understanding of how macrophage lineage cells develop will help us to treat many diseases including certain cancers (such as leukemia), arthritis and inf ....Macrophages are a key component of the immune system; thier functions include killing of pathogens as well as cancerous cells. Macrophage lineage cells are derived from stem cells within the bone marrow and thier differentiation, proliferation and survival is mediated by a particular growth factor termed colony stimulating factor-1 (CSF-1). The understanding of how macrophage lineage cells develop will help us to treat many diseases including certain cancers (such as leukemia), arthritis and inflammation, and disorders of the immune system. The action of CSF-1 is mediated by the CSF-1 receptor (CSF-1R) which, when activated, controls gene regulation. In this proposal we will study CSF-1R activation and identify the genes regulated by CSF-1 with a view to characterize genes critical for macrophage development. These genes may provide potential targets for new pharmacological agents.Read moreRead less
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
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
microRNA are non-coding RNAs with fundamental functions in biology and emerging roles in disease. Hundreds of microRNA have been found and they control gene expression by destroying RNA or controlling their translation into cellular proteins. We will characterise their mechanisms of action and the cellular factors that are involved. Understanding the way microRNA work is a key question in gene regulation research and will aid the development of therapeutic strategies invovling small RNA.
Probing The Cellular Functions Of The Translation Factor P97
Funder
National Health and Medical Research Council
Funding Amount
$370,307.00
Summary
The protein p97 takes part in the synthesis of cellular proteins from messenger RNA, a central step in gene expression. We will characterise p97 function as cells progress through their cycle of growth and division, and during responses to stress. Cellular stress is important in many diseases, such as viral infection, diabetes, heart disease, cancer, or complications during major surgery. Knowledge of p97 function may help us to better understand and treat these diseases.
Identifying Target Molecules Regulated By Nuclear Retention In Cancer And Development
Funder
National Health and Medical Research Council
Funding Amount
$267,173.00
Summary
Human DNA contains approximately 30000 genes; only twice as many as worms and flies, ten times as many as bacteria, and fewer than rice. Humans, however have considerably more complexity than these lower organisms. What are the factors responsible for the additional complexity? In the simplest scenario, one gene is transcribed to produce one message (mRNA), which is the blueprint for producing one protein. We now know that there are numerous mechanisms that potentially allow many different prote ....Human DNA contains approximately 30000 genes; only twice as many as worms and flies, ten times as many as bacteria, and fewer than rice. Humans, however have considerably more complexity than these lower organisms. What are the factors responsible for the additional complexity? In the simplest scenario, one gene is transcribed to produce one message (mRNA), which is the blueprint for producing one protein. We now know that there are numerous mechanisms that potentially allow many different proteins to be made from one gene. Also, it is the decisions about which gene will be made ( expressed ) into protein where and when in development, that is critical for our complexity. The control of gene expression is thus fundamental to all cellular processes and many diseases such as cancer and metabolic disorders are associated with some aspect of aberrant gene expression. The production of mRNA from DNA occurs in the human cell nucleus. The nucleus is not simply a bag of DNA, in fact, many important nuclear factors are organised into sub-nuclear bodies . Recently we discovered a novel sub-nuclear body, the paraspeckle and have been identifying its components and their function. Paraspeckles are involved in a previously undiscovered mechanism of the control of gene expression. Here, certain mRNA molecules are trapped in the nucleus until a signal is received from elsewhere in the cell, which causes the mRNA to be released and protein to be made. This Rapid Release Nuclear Retention mechanism effectively allows the quick production of specific proteins to be made on demand. In this project we propose to use cutting edge molecular and cell biology techniques to identify the special mRNA molecules that are trapped in paraspeckles in cancer cells. This will increase our understanding about the molecular details of this process, ultimately leading to potential uses in gene therapy, and should result in the discovery of important targets for cancer treatment.Read moreRead less
All cells in the blood are the descendants of a single cell type, the stem cell. Stem cells are found in the bone marrow and throughout life have the unique ability to generate more of themselves (termed self-renewal) as well as to produce the functional cell types of the blood, ie. red and white blood cells. This project concentrates on the processes by which these stem cells can achieve these two functions. What are the genes that enable a stem cell to have this self-renewal characteristic and ....All cells in the blood are the descendants of a single cell type, the stem cell. Stem cells are found in the bone marrow and throughout life have the unique ability to generate more of themselves (termed self-renewal) as well as to produce the functional cell types of the blood, ie. red and white blood cells. This project concentrates on the processes by which these stem cells can achieve these two functions. What are the genes that enable a stem cell to have this self-renewal characteristic and conversely what are the genes that are activated when a cell becomes committed to become, for example, a white blood cell ? We have identified a gene, Pax5, which is essential in the process whereby a stem cell commits to become a lymphocyte . Our aim is to understand the function of Pax5 as a model for understanding how the commitment process as a whole works in the blood. These studies, as well as having an underlying fundamental scientific importance, are relevant to the clinical development of a number of stem cell therapies which rely on boosting stem cell production in procedures such as bone marrow transplantation for leukaemia and immune deficiency. In addition a number of characterised human blood malignancies indicate that inappropriate lineage commitment may be a factor in cancer.Read moreRead less
Does a novel class of small RNA molecules control self-incompatibility in solanaceous plants? Self-incompatibility is a simple and genetically defined cell recognition system that prevents inbreeding in many plant species. Flowers of self-incompatible plants can distinguish self pollen from foreign pollen, and allow only foreign pollen to fertilise their egg cells. This proposal will investigate the possibility that the part of the genetic self-incompatibility locus controlling recognition of ....Does a novel class of small RNA molecules control self-incompatibility in solanaceous plants? Self-incompatibility is a simple and genetically defined cell recognition system that prevents inbreeding in many plant species. Flowers of self-incompatible plants can distinguish self pollen from foreign pollen, and allow only foreign pollen to fertilise their egg cells. This proposal will investigate the possibility that the part of the genetic self-incompatibility locus controlling recognition of pollen is a novel type of gene that encodes a small RNA molecule but no protein. Knowledge gained by studying the self-incompatibility genes will help us to understand how plant cells recognise each other, and may allow us to manipulate seed (and hence crop) production.Read moreRead less