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
Microarrays are a new technology for measuring the relative expression levels of thousands of genes simultaneously. They allow medical researchers to take a genome-wide look at which genes are active in a particular tissue type in an organism at a particular time. Many biomedical and biological research groups in Australia have recently untaken microarray experiments for the first time or are planning microarray experiments in the near future. Microarray experiments produce massive amounts of in ....Microarrays are a new technology for measuring the relative expression levels of thousands of genes simultaneously. They allow medical researchers to take a genome-wide look at which genes are active in a particular tissue type in an organism at a particular time. Many biomedical and biological research groups in Australia have recently untaken microarray experiments for the first time or are planning microarray experiments in the near future. Microarray experiments produce massive amounts of information and the study of how to extract this information is still in a fledgling state. This project will solve a number of fundamental problems in microarray data analysis. The emphasis is not on special methods of down-stream analysis but on basic issues which are common to all microarray experiments. The project will determine how tissue samples from different organisms should be combined in complex experiments. It will develop methods for evaluating the quality of results from microarray experiments. It will make microarray analysis less sensitive to production artifacts. It will make novel use of serial analysis of gene expression (SAGE), a more accurate but more expensive and less available technology, to calibrate the results of microarray experiments. The results will be applied during the lifetime of the project to a number of experiments at the Walter and Eliza Hall Institute and the University of Melbourne on blood cell development, cell growth and proliferation, resistance to malaria and leishmaniasis parasites, and Down syndrome.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
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
Oxidative Damage and Cell Ageing. This research will benefit Australia by providing a fundamental understanding of how cells age. This will have immediate international impact at the scientific level and will inform strategies to reduce the rate of ageing and alleviation of age-related disorders. In the longer term the research may provide commercial and social outcomes by identifying antioxidant systems that will provide a genuine benefit in reducing ageing.