A Structural And Functional Basis For The Regulation Of Gene Expression By Nuclear Retention Of RNA
Funder
National Health and Medical Research Council
Funding Amount
$504,097.00
Summary
The nuclear retention mechanism is a novel way used by cells to control which genes are made into proteins - a fundamental process for all diseases, particularly cancers. This project will employ cutting edge structural and proteomic techniques to determine the molecular details underpinning nuclear retention. These insights will be important for the development of new tissue-restricted gene therapy applications and drugs targeting the cancers that rely on this mechanism.
A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a ....A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a role in the development of diabetes in humans. In plants, sugars affect many processes including growth, flowering, photosynthesis, nitrogen metabolism, starch synthesis, pigmentation and response to pathogens.Read moreRead less
Discovery of pathways to embryogenesis in pathogenic flatworm parasites using microdissection and transcriptomic technologies. The cost to Australia of flatworm parasites to animal production and human health is substantial (hundreds of millions of dollars per year). This research will give new insights into how flatworms reproduce and equip their progeny for survival, providing impetus for new vaccine or drug therapies to be developed. As these pathogens are more significant in Australia's ne ....Discovery of pathways to embryogenesis in pathogenic flatworm parasites using microdissection and transcriptomic technologies. The cost to Australia of flatworm parasites to animal production and human health is substantial (hundreds of millions of dollars per year). This research will give new insights into how flatworms reproduce and equip their progeny for survival, providing impetus for new vaccine or drug therapies to be developed. As these pathogens are more significant in Australia's near neighbours, this project will strengthen Australia's international leadership in this field. Our study will provide, for the first time for any helminth parasite, a freely available genetic database that profiles the gene expression repertoire of individual parasite tissues, a development likely to enhance the international effort in controlling these harmful diseases.Read moreRead less
Insect host/vector genetic responses to rhabdovirus infection. Rhabdoviruses cause important diseases in humans, animals and plants. These viruses are transmitted by insect vectors in which they persist and propagate, an intimate and specific association. Insect-rhabdovirus interactions will be studied at the molecular level using a planthopper-maize rhabdovirus model. Insect genes specifically induced by rhabdovirus infection as well as the viral genes themselves will be identified and characte ....Insect host/vector genetic responses to rhabdovirus infection. Rhabdoviruses cause important diseases in humans, animals and plants. These viruses are transmitted by insect vectors in which they persist and propagate, an intimate and specific association. Insect-rhabdovirus interactions will be studied at the molecular level using a planthopper-maize rhabdovirus model. Insect genes specifically induced by rhabdovirus infection as well as the viral genes themselves will be identified and characterized using genomics and bioinformatics tools. We will extend the same approaches to a comparative analysis of these planthopper genes with other insect-rhabdovirus systems under investigation in our institutes. Identification of viral genes expressed in insects, the insect genes that respond to virus infection, and interpretation of the roles of these genes in insects, may indicate new opportunities to control serious plant and animal diseases through control of virus transmission.Read moreRead less
I am a molecular biologist determining the mechanisms of eukaryotic mRNA translation and its regulation by RNA-binding proteins and noncoding RNA. In collaborative work I extend these basic science objectives into the medical research areas of cardiology
STUDIES OF NF-E4, A NOVEL FETAL/ERYTHROID SPECIFIC FACTOR INVOLVED IN FETAL GLOBIN GENE REGULATION
Funder
National Health and Medical Research Council
Funding Amount
$753,810.00
Summary
Sickle cell anemia and thalassemia are the commonest genetic disorders worldwide. Those affected suffer devastating clinical sequelae and mortality in the first twenty years of life remains high. A cure for these diseases is dependent on the replacement of the affected or absent hemoglobin protein chains with normally functioning hemoglobins. This is evident in rare patients who co-inherit a natural mutation which elevates fetal hemoglobin (HbF), as these patients have a dramatically ameliorated ....Sickle cell anemia and thalassemia are the commonest genetic disorders worldwide. Those affected suffer devastating clinical sequelae and mortality in the first twenty years of life remains high. A cure for these diseases is dependent on the replacement of the affected or absent hemoglobin protein chains with normally functioning hemoglobins. This is evident in rare patients who co-inherit a natural mutation which elevates fetal hemoglobin (HbF), as these patients have a dramatically ameliorated clinical course. Therefore, treatment strategies which could reactivate fetal globin gene expression after birth should be explored for these diseases. To achieve this goal we must further our understanding of the normal mechanisms of developmental regulation of globin gene expression. To this end we have recently identified a novel gene which is critical for fetal globin expression. The studies we propose here will further define the function of this gene and assess its potential for gene therapy for sickle cell disease and thalassemia.Read moreRead less
Regulation of the EphA3 receptor tyrosine kinase in vertebrate development. The Eph/ephrin system has a critical role in normal embryonic development. Amongst vertebrates, the EphA3 gene is one of the most highly conserved genes in this system with critical roles in development of the visual system and in other developmental processes. Understanding how this gene is regulated will help us to understand the critical role of EphA3 in the basic biology of humans and other animals. This knowledge ma ....Regulation of the EphA3 receptor tyrosine kinase in vertebrate development. The Eph/ephrin system has a critical role in normal embryonic development. Amongst vertebrates, the EphA3 gene is one of the most highly conserved genes in this system with critical roles in development of the visual system and in other developmental processes. Understanding how this gene is regulated will help us to understand the critical role of EphA3 in the basic biology of humans and other animals. This knowledge may also shed light on the basis of congenital abnormalities and other pathological processes and possibly help us to understand how to prevent or treat these conditions.Read moreRead less
Beyond the gene: Linking herbivore behaviour to plant defense gene expression. This collaborative project investigates insect herbivore avoidance of plant defence mechanisms. Our project is novel because it integrates changes in the plant at a number of different levels and links them to insect foraging behaviour. Researchers assume that insects respond to plant defences by changing their foraging behaviour. This has not been tested directly. We use the genetically well characterised plant Arabi ....Beyond the gene: Linking herbivore behaviour to plant defense gene expression. This collaborative project investigates insect herbivore avoidance of plant defence mechanisms. Our project is novel because it integrates changes in the plant at a number of different levels and links them to insect foraging behaviour. Researchers assume that insects respond to plant defences by changing their foraging behaviour. This has not been tested directly. We use the genetically well characterised plant Arabidopsis and the world-wide pest Helicoverpa (heliothis) as a model system. Damage caused to crops by insect herbivores is a direct function of behaviour. Understanding this behaviour will lead to improved pest management and reduced economic losses.Read moreRead less
Osteoporosis is a pathological loss of bone that affects many Australians. It occurs because of an excessive release of calcium from bone that is caused by the overactivity of the cells that break down bone, osteoclasts. We have studied two genes that are involved in the way these cells work and by a close examination of the the way they are regulated we hope to understand how osteoclasts are derived and how their activity is controlled. In particular we will look at two newly dicovered osteocla ....Osteoporosis is a pathological loss of bone that affects many Australians. It occurs because of an excessive release of calcium from bone that is caused by the overactivity of the cells that break down bone, osteoclasts. We have studied two genes that are involved in the way these cells work and by a close examination of the the way they are regulated we hope to understand how osteoclasts are derived and how their activity is controlled. In particular we will look at two newly dicovered osteoclast regulators called PPAR-gamma and PPAR-delta. These offer the opportunity for the development in the future of new, alternative drugs for the treatment of osteoporosis.Read moreRead less