Matching Between Codon Usage And TRNA Abundance Determines The Expression Of Targeting Genes In Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$358,500.00
Summary
This proposal is about optimal production of protein drugs (biopharmaceuticals), using genetic engineering in the laboratory and gene therapy in patients. It will explore the science behind a novel observation that the optimal way to use the genetic code to encode proteins for production varies from cell to cell in the lab, and from tissue to tissue in patients. If successful, a simple test can be used to decide the optimal genetic code for a specific application.
Functional Characterisation Of Regulators Of Human Globin Gene Switching
Funder
National Health and Medical Research Council
Funding Amount
$232,131.00
Summary
Red blood cells produce haemoglobin, a tetramer of two alpha globin chains and two beta-globin chains. Haemoglobin reversibly interacts with oxygen in such a way that it efficiently shuttles oxygen between the lungs and the rest of the body. Integrity of the hemoglobin molecule, and red cells which carry it, is essential for life of all organisms with blood. The alpha-globin and beta-globin chains that make up haemoglobin are prodcued by red cell precursors in the bone marrow according to the ge ....Red blood cells produce haemoglobin, a tetramer of two alpha globin chains and two beta-globin chains. Haemoglobin reversibly interacts with oxygen in such a way that it efficiently shuttles oxygen between the lungs and the rest of the body. Integrity of the hemoglobin molecule, and red cells which carry it, is essential for life of all organisms with blood. The alpha-globin and beta-globin chains that make up haemoglobin are prodcued by red cell precursors in the bone marrow according to the genetic blueprint (genes) that are inherited. Genetic disorders resulting from defects in the beta-globin gene are the most common inherited disorders of man. Children who fail to make beta-globin have a disease known as beta-thalassaemia. They are transfusion dependent from ~ 6 months of age and need intensive chelation therapy (infusions) to avoid the serious consequnces of iron overload. The average life expectancy in Western cultures is ~ 30 years. There is no cure. In third world countries where a reliable blood supply is unavailable, death occurs earlier. Patients are aften infected with blood born viruses such as hepatitis B, hepatitis C and the AIDS virus, HIV. Sickle cell anaemia is also a very common disease. It is due to a single DNA base mutation at in the beta-globin gene that results in production of normal amounts of a defective beta-globin molecule (HbS). In low oxygen, HbS molecules polymerize in red cells and irreversibly damage them. These red cells get trapped in small blood capillaries throughout the circulation causing small infarcts which results in severe pain and organ damage. The life expectancy is <2 years in the thrid world and ~20-30 years in the west. The irony of these two diseases is that there is a perfectly normal fetal globin gene that has been silenced during fetal life. This grant aims to understand the mechanism of the switch from fetal to adult globin gene usage so it can be reversed in adults with b-thalassemia and sickle cell diseaseRead moreRead less
Identification Of Critical Regulatory Elements In The BRCA1 Gene
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the molecular defects that contribute to disease initiation and progression. Over the last twenty years significant progress has been made in this regard, however there still remain a considerable number of unanswered questions. For example, it is not yet clear precisely what contribution each of the ....Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the molecular defects that contribute to disease initiation and progression. Over the last twenty years significant progress has been made in this regard, however there still remain a considerable number of unanswered questions. For example, it is not yet clear precisely what contribution each of these genes makes. This is largely due to limitations in current mutation detection strategies and an incomplete understanding of all of the genetic elements for which disruption can lead to loss of gene function. This propsal aims to identify all of the genetic elements critical for the expression of an important breast cancer gene called BRCA1. Furthermore, it aims to determine the status of these elements in breast cancer patients, thus expanding our knowledge of the actual contribution disruption of this gene makes to this disease.Read moreRead less
The sponge genome project and the evolution of multicellularity: using comparative genomics and developmental biology to reconstruct the first animals. Recently the entire genome from a living fossil - a sponge from the Great Barrier Reef - was sequenced (jointly supported by the ARC and US Department of Energy). As this genome is assembled and analysed, many of the fundamental biological processes that underlie the construction and evolution of all animals, including humans, will be revealed. ....The sponge genome project and the evolution of multicellularity: using comparative genomics and developmental biology to reconstruct the first animals. Recently the entire genome from a living fossil - a sponge from the Great Barrier Reef - was sequenced (jointly supported by the ARC and US Department of Energy). As this genome is assembled and analysed, many of the fundamental biological processes that underlie the construction and evolution of all animals, including humans, will be revealed. In addition, sponge genomics will fuel innovations in medicine and biotechnology. Specifically, sponges are renowned for their capacity to synthesise bioactive compounds used in drug development, and high-grade silica used for semi-conductor construction. This project will identify the gene networks controlling these biosynthetic processes.Read moreRead less
Variation in larval gene expression in a marine invertebrate: implications for population divergence via differential settlement response. Evolutionary and ecological functional genomics is an emerging field that integrates gene profiling technologies with experimental and field approaches of ecology and evolution. I take this approach to address a key problem in marine invertebrate biology: how do larvae respond to their environment and how does variation in this response influence the distribu ....Variation in larval gene expression in a marine invertebrate: implications for population divergence via differential settlement response. Evolutionary and ecological functional genomics is an emerging field that integrates gene profiling technologies with experimental and field approaches of ecology and evolution. I take this approach to address a key problem in marine invertebrate biology: how do larvae respond to their environment and how does variation in this response influence the distribution and evolution of a species? I will use a marine gastropod (abalone) model, for which there exists substantial development and population genetic data, and established aquaculture methodologies. Outcomes of this study will enhance knowledge of the stock structure of this and other commercial fisheries, as well as aquaculture efficiency.Read moreRead less
Microbial genomics of the southern ocean: monitoring environmental health. This program will derive an integrated understanding of microbial ecology which is essential for determining ways of preserving the health of the World's ecosystems. Through the development of a unique microbial genomics program, Australia will remain a world leader in Antarctic biology, strengthening Australia's reputation in technologically innovative scientific programs of global significance, training local scientists ....Microbial genomics of the southern ocean: monitoring environmental health. This program will derive an integrated understanding of microbial ecology which is essential for determining ways of preserving the health of the World's ecosystems. Through the development of a unique microbial genomics program, Australia will remain a world leader in Antarctic biology, strengthening Australia's reputation in technologically innovative scientific programs of global significance, training local scientists in cutting edge genomic biology and fostering the interests of the international community in sciences ranging from microbial ecology to climate change.Read moreRead less
The transcriptome, genome and metagenome of Acropora millepora: a model system for studying coral health and disease. Corals have an iconic significance for Australia, which has the best-preserved reef system in the world. The Great Barrier Reef is worth more than $6 billion per year to the Australian economy, and provides employment for 68000 people. The research will provide insights into the molecular bases of stress and disease in corals and the internal mechanisms by which corals attempt to ....The transcriptome, genome and metagenome of Acropora millepora: a model system for studying coral health and disease. Corals have an iconic significance for Australia, which has the best-preserved reef system in the world. The Great Barrier Reef is worth more than $6 billion per year to the Australian economy, and provides employment for 68000 people. The research will provide insights into the molecular bases of stress and disease in corals and the internal mechanisms by which corals attempt to combat them. The results will allow the design of strategies for better reef management, resulting in economic, environmental and social benefits for Australia.Read moreRead less