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
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
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.
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
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 Analysis Of The P160 Myb-binding Protein - A Regulator Of Multiple Transcription Factors?
Funder
National Health and Medical Research Council
Funding Amount
$376,697.00
Summary
The c-myb gene is a key molecular regulator of normal blood cell production, but alterations to this gene can also lead to leukaemia. The protein (Myb) encode by the c-myb gene acts as a transcription factor, ie, it controls the activity of other genes. There is good evidence that interactions with other proteins can regulate the activity of Myb. Our laboratory has identified what we believe is one such protein - p160 - that binds to a part of Myb that reduces its activity, and thus that is like ....The c-myb gene is a key molecular regulator of normal blood cell production, but alterations to this gene can also lead to leukaemia. The protein (Myb) encode by the c-myb gene acts as a transcription factor, ie, it controls the activity of other genes. There is good evidence that interactions with other proteins can regulate the activity of Myb. Our laboratory has identified what we believe is one such protein - p160 - that binds to a part of Myb that reduces its activity, and thus that is likely to be responsible for regulating Myb. However, it has recently become apparent that p160 interacts with a number of other transcription factors in addition Myb. The primary aim of this project is to elucidate precisely how p160 interacts with Myb and what the consequences of this interaction are. A range of experimental approaches, which range from in vitro to genetic studies, will be employed to do this. We will test a specific role of p160 suggested by our preliminary studies - that of a transporter of transcription factors between the nucleus and the cytoplasm of the cell. Because of the wide range of transcription factors that p160 interacts with, its effects on the function of the cell are likely to be profound. For this same reason, it is difficult to specifically predict the possible medical-health implications of this work However, what we know to date is consistent with a role for p160 as a tumour suppressor gene. Moreover, parts of this project aim to generate genetic information and tools which will help in determining whether p160 does play such a role and generally, in identifying any other associations of p160 with particular diseases.Read moreRead less