Patient Toxicity Prediction: Identification Of Mucosal Injury Mediators Using Microarray Technology
Funder
National Health and Medical Research Council
Funding Amount
$292,639.00
Summary
There is no effective way to identify all patients that will develop toxic side-effects during the course of their cancer treatment. Current pharmacogenetic testing is too narrow. This project aims to examine whole-genome profiles of patient blood to determine if risk markers of toxicity can be identified prior to beginning treatment. I will do this by comparing oesophageal cancer patients who go on to develop severe toxicity with those who only get mild treatment side-effects.
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
Genomic Characterisation Of Asbestos Related Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$88,099.00
Summary
Lung cancer causes more deaths in Australia than any other cancer. Smoking is the main cause, but people exposed to asbestos are also at risk, and it can be difficult to know whether a case is due to tobacco, asbestos or both. We will study lung cancer genes in people with asbestos exposure to find whether asbestos lung cancer has a specific pattern of abnormal genes (signature). If so, this could help people entitled to compensation, and also point to new treatments for asbestos lung cancer
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.
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 transcriptional co-repressor C-terminal Binding Protein (CtBP) in metabolic control. This project will provide insights into the genes that regulate the storage of fat. We will learn about basic biology but will also discover mechanisms that may be used to influence fat storage in human health. We will also consolidate Australia's expertise in the use of the genetic model organism, the worm C. elegans, and validate the findings in mammalian systems. Finally, the process of training young sci ....The transcriptional co-repressor C-terminal Binding Protein (CtBP) in metabolic control. This project will provide insights into the genes that regulate the storage of fat. We will learn about basic biology but will also discover mechanisms that may be used to influence fat storage in human health. We will also consolidate Australia's expertise in the use of the genetic model organism, the worm C. elegans, and validate the findings in mammalian systems. Finally, the process of training young scientists in these modern systems, will also equip future researchers to make additional contributions to Australia's research output.Read moreRead less
RNA splicing: factors and mechanisms. Most primary gene transcripts must have their noncoding intronic sequences spliced out before the mRNA can be translated. Moreover, alternative splicing enables cells to generate a far more proteins than there are genes in the nucleus. Based on our proven success with ZNF265 we will isolate novel RNA interactors and their partners, colocalize these in intranuclear compartments, and elucidate their effect on pre-mRNA splicing. This will provide timely spin-of ....RNA splicing: factors and mechanisms. Most primary gene transcripts must have their noncoding intronic sequences spliced out before the mRNA can be translated. Moreover, alternative splicing enables cells to generate a far more proteins than there are genes in the nucleus. Based on our proven success with ZNF265 we will isolate novel RNA interactors and their partners, colocalize these in intranuclear compartments, and elucidate their effect on pre-mRNA splicing. This will provide timely spin-offs to the Human genome Project and EST sequence information, where the finding of only approx. 30,000 genes in our genome highlights the important role of alternative splicing in generating the large proteome repertoire of cells. This will bring considerable benefits to science, society, and the biotech industry.Read moreRead less
Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and ....Genetic dissection of a regulatory deubiquitlyation network. The potential impact of this work is widespread, because although it is known that ubiquitlyation has regulatory consequences in multicellular eukaryotes, individual networks have not been completely described in higher eukaryotes. Knowledge gained about fundamental processes in the A. nidulans model system is directly applicable to fungi used in biotechnology in the food, beverage, enzyme and pharmaceutical production industries, and to fungal pathogens. Since the fungal genes that form the basis of this project are conserved in higher eukaryotes including humans, the knowledge will be transferable to these systems. A further benefit that cannot be overstated is the research education and training opportunities provided.
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A new mechanism of gene regulation. This project will advance our knowledge of how genes are switched on and off, by focusing on a very common class of gene regulatory proteins known as zinc finger proteins. The results of this study will improve our understanding of the fundamental molecular events that underpin gene regulation and how we might control it in fields such as biotechnology and gene therapy.