I am a cell-molecular biologist studying the role and regulation of the plasminogen activating (fibrinolytic) system in health and disease. My recent studies have defined a novel role for tissue-type plasminogen activator in the central nervous system and
Heterogeneous Nuclear Ribonucleoprotein A2-dependent MRNA Trafficking In The Cytoplasm Of Cells.
Funder
National Health and Medical Research Council
Funding Amount
$346,650.00
Summary
Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes of DNA is transferred to an intermediate molecule, mRNA, in a process called transcription. The genetic information in the mRNA is subsequently used to make the protein encoded by the original gene. The switching on and off of DNA appears to be most frequently controlled at the transcription step but recently it has become apparent that there are many ....Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes of DNA is transferred to an intermediate molecule, mRNA, in a process called transcription. The genetic information in the mRNA is subsequently used to make the protein encoded by the original gene. The switching on and off of DNA appears to be most frequently controlled at the transcription step but recently it has become apparent that there are many post-transcriptional events that govern how efficiently the genetic information is ultimately converted to protein molecules. The RNA molecules may be confined to a small region of the cell, resulting in the localization of the protein produced from it; the RNA may be rapidly degraded or stabilized; and the efficiency of production of the protein from its RNA precursor may be modulated by other molecules. It had previously been shown that the mRNA encoding a protein that is an essential structural component of central nervous system myelin is selectively transported to the regions in the cell where the myelin is made. We have identified the molecule that recognises this RNA as a protein called hnRNP A2 and shown how it selects the RNA molecules that have to be transported from the myriad of RNA moleclues in the cell at any given time. hnRNP A2 was previously thought to be confined to the nuclei of cells, but we have shown that it is also present outside the nucleus and is involved in RNA transport in a variety of cell types. hnRNP A2 appears to be directly involved in rheumatoid arthritis, lung cancer and other cancers. It has been proposed as a diagnostic test for cancer as elevated intracellular levels and circulating antibodies against this protein appear before the cancerous cells are visible under the microscope. The major aim of the proposed project is to explore the molecular mechanism by which hnRNP A2 transports RNA molecules in cells.Read moreRead less
Heterogeneous Nuclear Ribonucleoprotein Role In Alternative RNA Splicing And Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes of DNA is transferred to an intermediate molecule, mRNA, in a process called transcription. The genetic information in the mRNA is subsequently used, in the process called translation, to make the protein encoded by the original gene. The switching on and off of DNA appears to be most frequently controlled at the transcription step but recently it has ....Control of the use of DNA, gene expression, is vital to all living organisms, especially in development and disease. The information in the genes of DNA is transferred to an intermediate molecule, mRNA, in a process called transcription. The genetic information in the mRNA is subsequently used, in the process called translation, to make the protein encoded by the original gene. The switching on and off of DNA appears to be most frequently controlled at the transcription step but recently it has become apparent that there are many post-transcriptional events that govern how efficiently the genetic information is ultimately converted to protein molecules. An important step is the cutting out of parts (introns) of the RNA molecule that is copied from DNA, and splicing of the retained sections (exons). During this process the RNA may also lose one or more of its exons. As a result of this variable retention of exons a single gene may produce many isoforms of the protein it encodes. By this mechanism the roughly 30,000 genes in the human genome can give rise to potentially hundreds of thousands of proteins. RNA splicing connects to cancer in two ways. First, changes in the concentrations of the proteins that control splicing may change the isoforms, resulting in changes that lead to uncontrolled cell proliferation. Secondly, DNA mutations that affect the splicing process can also vary the ratios of the isoforms produced from a gene: if this occurs in a protein that is involved in the growth of cells this too may lead to cancer. In this project we will study the molecular mechanism of this alternative splicing, and particularly a group of proteins that generally favour the excision of some exons, with a focus on cancer cells. Recent publications have highlighted the potential for the therapeutic use of drugs that target the splicing apparatus: it is anticipated that studies of alternative splicing will underpin development of new therapeutic agents.Read moreRead less