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.
A new paradigm of gene regulation - implications in embryogenesis and disease. The proposed analysis of a new paradigm of gene regulation will provide a new key to understanding genome function and inform some of the most compelling biological issues of our time such as stem cell biology, tissue and organ regeneration and genetic programming. The insights and technologies developed in this program will be widely applicable in biotechnological and pharmacogenomic research in Australia and worldwi ....A new paradigm of gene regulation - implications in embryogenesis and disease. The proposed analysis of a new paradigm of gene regulation will provide a new key to understanding genome function and inform some of the most compelling biological issues of our time such as stem cell biology, tissue and organ regeneration and genetic programming. The insights and technologies developed in this program will be widely applicable in biotechnological and pharmacogenomic research in Australia and worldwide, and assert Australia's leadership in this area of research.Read moreRead less
Lungfish Paired Fins and the Origin of Limbs as an Evolutionary Novelty. This project will utilise a uniquely Australian animal, the lungfish, to address a hitherto unresolved problem of considerable scientific significance - how a fish fin evolved into a tetrapod (four-legged animal) limb. The Australian lungfish is the most primitive of the four surviving genera of lobe-finned fish and is recognised as the closest living ancestor to the tetrapods. It is listed as 'vulnerable' in its native ha ....Lungfish Paired Fins and the Origin of Limbs as an Evolutionary Novelty. This project will utilise a uniquely Australian animal, the lungfish, to address a hitherto unresolved problem of considerable scientific significance - how a fish fin evolved into a tetrapod (four-legged animal) limb. The Australian lungfish is the most primitive of the four surviving genera of lobe-finned fish and is recognised as the closest living ancestor to the tetrapods. It is listed as 'vulnerable' in its native habitat. Macquarie University, however, has the only captive breeding population of lungfish in the world. We are thus uniquely placed to address critically important questions concerning the evolution of fish into tetrapods. Read moreRead less
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
Understanding the control of male germ-line development by the germline-restrictive silencing factor in plants. The world population is currently increasing at an unprecedented rate, with a concomitant requirement to double the food production from the same amount of arable land. To ensure global political and social stability, equitably increasing sustainable food production without compromising environmental integrity remains a major challenge. This proposal investigates the molecular mechanis ....Understanding the control of male germ-line development by the germline-restrictive silencing factor in plants. The world population is currently increasing at an unprecedented rate, with a concomitant requirement to double the food production from the same amount of arable land. To ensure global political and social stability, equitably increasing sustainable food production without compromising environmental integrity remains a major challenge. This proposal investigates the molecular mechanisms underlying male germ line initiation and development in plants. Switching off male gamete development in some crop plants will create male sterile lines, which, when crossed with genetically distinct lines, will have the potential to produce hybrids that yield 20-30 percent more crop without additional inputs. Read moreRead less
Epigenetic programming of plant sperm cells. Most of the grains and seeds that form the world's food supply are the result of the successful functioning of sperm and egg cells during fertilisation. This proposal aims to investigate the nature of sperm cell genome programming in plants and unravel molecular processes that give these cells their unique identity. This innovative and challenging research will also provide an excellent opportunity for training the next generation of scientists. The o ....Epigenetic programming of plant sperm cells. Most of the grains and seeds that form the world's food supply are the result of the successful functioning of sperm and egg cells during fertilisation. This proposal aims to investigate the nature of sperm cell genome programming in plants and unravel molecular processes that give these cells their unique identity. This innovative and challenging research will also provide an excellent opportunity for training the next generation of scientists. The outcomes of this proposal will enhance Australia's international lead in this field and will pave the way toward the development of new approaches for sustaining and enhancing crop productivity under changing environmental conditions. Read moreRead less
Using integrated frontier and smart technologies to identify new drug targets for parasites causing major diseases in humans and animals. The national/community benefits are (1) enhanced focus on animal and human health biotechnology through the development of anti-parasite compounds and/or vaccines; (2) improved and sustainable control of important parasites with decreased risk of induction of drug resistance; (3) increased profitability of agricultural animal production; (4) consolidation of a ....Using integrated frontier and smart technologies to identify new drug targets for parasites causing major diseases in humans and animals. The national/community benefits are (1) enhanced focus on animal and human health biotechnology through the development of anti-parasite compounds and/or vaccines; (2) improved and sustainable control of important parasites with decreased risk of induction of drug resistance; (3) increased profitability of agricultural animal production; (4) consolidation of a technology platform for further applications in genomics and post-genomics of pathogens of global significance and construction of a pipeline for the validation of drug targets; (5) capturing the benefits from fundamental research and strengthening links between fundamental and applied research; (6) increasing the quality and quantity of scientifically skilled people in biotechnology.Read moreRead less
Automated, smart genomic data integration for the exploration of developmentally regulated molecules in parasites of major socioeconomic importance. The national/community benefits are (1) enhanced focus on animal and human health biotechnology through the development of safe anti-parasite compounds/vaccines; (2) improved and sustainable control of key parasites with decreased risk of induction of drug resistance; (3) increased profitability of agricultural animal production; (4) consolidation o ....Automated, smart genomic data integration for the exploration of developmentally regulated molecules in parasites of major socioeconomic importance. The national/community benefits are (1) enhanced focus on animal and human health biotechnology through the development of safe anti-parasite compounds/vaccines; (2) improved and sustainable control of key parasites with decreased risk of induction of drug resistance; (3) increased profitability of agricultural animal production; (4) consolidation of a technology platform for further applications in genomics and post-genomics of pathogens of global significance and construction of a pipeline for the validation of drug targets; (5) capturing the benefits from fundamental research and strengthening links between fundamental and applied research; (6) increasing the quality and quantity of scientifically skilled people in biotechnology.Read moreRead less