New models for the role of chromatin in controlling inducible gene expression. This proposal aims to test novel models of how packaging of DNA in the nucleus plays a fundamental role in gene expression. Understanding these concepts is important in the context of successful gene therapy where major hurdles need to be overcome. This work also has implications for somatic cell therapy since it is important to understand how genes are expressed in order to successfully reprogram cells. Both of these ....New models for the role of chromatin in controlling inducible gene expression. This proposal aims to test novel models of how packaging of DNA in the nucleus plays a fundamental role in gene expression. Understanding these concepts is important in the context of successful gene therapy where major hurdles need to be overcome. This work also has implications for somatic cell therapy since it is important to understand how genes are expressed in order to successfully reprogram cells. Both of these areas are important to the Biotechnology industry. Answering questions about higher order chromatin structure in gene transcription will provide cutting edge, innovative knowledge that will have international significance. Read moreRead less
Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. Inte ....Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. International attention has already resulted in genome characterization of Australian icons (wallaby, Tasmanian devil and platypus), more research on these, and other Australian animals, will further highlight the importance of Australian fauna and impact positively on our scientific profile.Read moreRead less
Origin and evolution of genes on the human X chromosome. Two groups of functionally related genes are found on the human X chromosome in disproportionately high numbers. I will test whether an uneven distribution of genes is common in mammalian genomes, or whether the human X is special. I will test hypotheses of how the gene groups arose on the human X by comparing their location and expression patterns in other mammals, and other vertebrates. It will then be clear whether the ancestral autosom ....Origin and evolution of genes on the human X chromosome. Two groups of functionally related genes are found on the human X chromosome in disproportionately high numbers. I will test whether an uneven distribution of genes is common in mammalian genomes, or whether the human X is special. I will test hypotheses of how the gene groups arose on the human X by comparing their location and expression patterns in other mammals, and other vertebrates. It will then be clear whether the ancestral autosome was ?chosen?, whether it ?selfishly? accumulated these genes, or whether the function of genes changed in response to selective pressures.Read moreRead less
Small is beautiful: Did gene-rich regions of mammal chromosomes evolve from microchromosomes? Most birds and reptile genomes feature many tiny microchromosomes. These are not junk, as previously thought, but contain most of the genes. Mammals lack microchromosomes, but contain gene-rich regions with similar attributes. We suggest that microchromosomes originated by genome duplication, and evolved into the gene-rich regions of mammalian chromosomes. We will test this hypothesis by comparing seque ....Small is beautiful: Did gene-rich regions of mammal chromosomes evolve from microchromosomes? Most birds and reptile genomes feature many tiny microchromosomes. These are not junk, as previously thought, but contain most of the genes. Mammals lack microchromosomes, but contain gene-rich regions with similar attributes. We suggest that microchromosomes originated by genome duplication, and evolved into the gene-rich regions of mammalian chromosomes. We will test this hypothesis by comparing sequences and genes in microchromosomes of birds, reptiles and monotremes. This will clarify the origin and evolution of the ?microgenome?, establish its suitability as a model for vertebrate genome organisation, and demonstrate whether microchromosomes are the ancestors of the gene-rich regions of mammalian chromosomes.Read moreRead less
Origin and Evolution of Mammalian Dosage Compensation. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional comparative genomics in Australia, with the research priority of 'Frontier Technologies for Building and Transforming Australian Industries' and priority goals in 'Breakthrough Science and Frontier Technologies'. This project addresses fundamental questions about the evolution of mammalian X-chromosome inactivation, of importance as a mo ....Origin and Evolution of Mammalian Dosage Compensation. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional comparative genomics in Australia, with the research priority of 'Frontier Technologies for Building and Transforming Australian Industries' and priority goals in 'Breakthrough Science and Frontier Technologies'. This project addresses fundamental questions about the evolution of mammalian X-chromosome inactivation, of importance as a model for epigenetic change, and sex chromosomes, which has engaged some of the greatest genetic minds over nearly a century. Therefore my results will attract wide international interest and impact positively on Australia's scientific profile, and further highlight the importance of Australian mammals.Read moreRead less
Epigenesis and sociality: Unraveling the link between nutrition and the genome - how do genes and environment interact to produce phenotypes? This project has the capacity to transform our understanding of how genes and environment interact to produce whole-organism phenotypes. It will provide novel data on how an entire genome responds to nutrition and how external factors can enforce a differential expression of a common heritable genetic program. The national and community benefits of the pro ....Epigenesis and sociality: Unraveling the link between nutrition and the genome - how do genes and environment interact to produce phenotypes? This project has the capacity to transform our understanding of how genes and environment interact to produce whole-organism phenotypes. It will provide novel data on how an entire genome responds to nutrition and how external factors can enforce a differential expression of a common heritable genetic program. The national and community benefits of the project will be to maintain Australian leadership in epigenetics and advanced genetics of complex self-organizing systems. The findings of this project have the potential to be applicable to explaining regulatory networks underlying diet induced changes in human gene expression.Read moreRead less
Molecular characterization of marsupial genome organization, function and evolution. I will initiate a coherent investigation of the genome of an Australian marsupial (the tammar wallaby), exploiting new resources, new techniques and the hugely increased capacity for large-scale investigations of genomes at the molecular level. I will isolate and characterize large-insert (BAC) clones of the gene-rich region of the Y chromosome, ancient, added and controlling regions of the X chromosome, and aut ....Molecular characterization of marsupial genome organization, function and evolution. I will initiate a coherent investigation of the genome of an Australian marsupial (the tammar wallaby), exploiting new resources, new techniques and the hugely increased capacity for large-scale investigations of genomes at the molecular level. I will isolate and characterize large-insert (BAC) clones of the gene-rich region of the Y chromosome, ancient, added and controlling regions of the X chromosome, and autosomal imprinted regions. Comparisons with the homologous regions of the human and mouse genomes will identify and characterize new mammalian genes and control signals, untangle complex regulatory systems, and discover how mammalian genes, and the mammalian genome, evolved.Read moreRead less
The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Austr ....The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Australians who inherit Hartnup disorder with a better understanding of this disease by enabling individuals and families to make choices that lead to healthy, productive and fulfilling lives.Read moreRead less
Controlling the rate of transcription and translation of Rubisco transgenes effectively in higher-plant plastids. Genetic transformation of the circular genome of the plastids provides a containable means for modifying plant growth by manipulating photosynthesis. Although the transformation mechanism is precise, predicting the level of foreign gene expression is difficult because the amounts of messenger RNA and protein produced by foreign genes in plastids varies widely, even when the protein a ....Controlling the rate of transcription and translation of Rubisco transgenes effectively in higher-plant plastids. Genetic transformation of the circular genome of the plastids provides a containable means for modifying plant growth by manipulating photosynthesis. Although the transformation mechanism is precise, predicting the level of foreign gene expression is difficult because the amounts of messenger RNA and protein produced by foreign genes in plastids varies widely, even when the protein assembles without difficulty. This project will devise strategies for controlling this variability that will facilitate attempts to exploit plastid transformation for transplanting better versions of the photosynthetic CO2-fixing enzyme, Rubisco, into plants to improve their growth efficiency in terms of water, fertiliser and light use.Read moreRead less
Molecular analysis of photosynthetically-linked, active CO2 uptake and CO2 signal transduction by cyanobacteria (blue-green algae). Cyanobacteria (blue-green algae) have evolved a very efficient means of capturing and concentrating CO2 for photosynthetic fixation into sugars, the basic building blocks for cell growth. This process is dependent on the operation of several unique, active uptake systems for CO2 and HCO3-, with their genetic expression regulated by CO2 supply. This proposal will cap ....Molecular analysis of photosynthetically-linked, active CO2 uptake and CO2 signal transduction by cyanobacteria (blue-green algae). Cyanobacteria (blue-green algae) have evolved a very efficient means of capturing and concentrating CO2 for photosynthetic fixation into sugars, the basic building blocks for cell growth. This process is dependent on the operation of several unique, active uptake systems for CO2 and HCO3-, with their genetic expression regulated by CO2 supply. This proposal will capitalize on our progress in describing the functional genetics of this process and aims to elucidate the mechanism of active CO2 uptake and the way that cells sense the ambient CO2 concentration. The information gained is likely to be useful for designing improved crops.Read moreRead less