Organization, function and evolution of marsupial Y chromosomes. The Y chromosome of humans and other mammals contains only a few genes, most specialized for male sex and reproduction. How the Y chromosome evolved to be so peculiar has been debated for 90 years. It began as an ordinary chromosome, but has degraded until there is almost nothing left, and it is likely to disappear in about 13 million years. Molecular characterization of the Y chromosomes of distantly related mammals could serve to ....Organization, function and evolution of marsupial Y chromosomes. The Y chromosome of humans and other mammals contains only a few genes, most specialized for male sex and reproduction. How the Y chromosome evolved to be so peculiar has been debated for 90 years. It began as an ordinary chromosome, but has degraded until there is almost nothing left, and it is likely to disappear in about 13 million years. Molecular characterization of the Y chromosomes of distantly related mammals could serve to 're-run the evolutionary tape', but the Y chromosome has been left out of whole genome sequencing because it is hard to do efficiently. We developed a novel technique to isolate DNA sequences and genes on the Y chromosome in three species of marsupials, which are especially valuable because they are so different from human and mouse.Read moreRead less
Sex in Dragons: Probing the genotype-phenotype interaction in sex determination. Reptiles have two modes of sex determination: genetic (GSD) and temperature dependent (TSD). We will determine if there is an underlying mechanism of sex determination common to TSD and GSD reptiles by comparing the genomes of two sister species of dragon lizard that differ in their mode of sex determination. This study will provide new insights to the mechanism of sex determination in vertebrates and will test the ....Sex in Dragons: Probing the genotype-phenotype interaction in sex determination. Reptiles have two modes of sex determination: genetic (GSD) and temperature dependent (TSD). We will determine if there is an underlying mechanism of sex determination common to TSD and GSD reptiles by comparing the genomes of two sister species of dragon lizard that differ in their mode of sex determination. This study will provide new insights to the mechanism of sex determination in vertebrates and will test the proposition that sex determination results from the interaction between environmental influences and an underlying genetic component.Read moreRead less
Rnomics - The Role of Introns and Other Noncoding RNAs in the Evolution and Development of Complex Organisms. Approximately 98% of the transcriptional output of the human genome is noncoding RNA. The aims of the project are to (a) provide direct evidence that introns contain functional information and are part of an RNA-based regulatory network, (b) identify large numbers of new noncoding RNAs and substantiate the conclusion that noncoding RNAs genes are common in eukaryotic genomes, and (c) pr ....Rnomics - The Role of Introns and Other Noncoding RNAs in the Evolution and Development of Complex Organisms. Approximately 98% of the transcriptional output of the human genome is noncoding RNA. The aims of the project are to (a) provide direct evidence that introns contain functional information and are part of an RNA-based regulatory network, (b) identify large numbers of new noncoding RNAs and substantiate the conclusion that noncoding RNAs genes are common in eukaryotic genomes, and (c) provide supporting evidence that the higher eukaryotes have evolved a second tier of gene expression based on RNA. The project has the capacity to transform our understanding of genetic programming in the higher organisms, with considerable scientific and practical implications.Read moreRead less
Solving the Mysteries of Monotreme Chromosomes. The peculiar chromosomes of Australia's platypus and echidna have been debated for more than 30 years. Classical cytology cannot resolve the puzzling sex chromosome system, or to sort out the bizarre translocation chain (unique in vertebrates) and deduce how it segregates to make viable zyotes. I will microdissect individual chromosomes, and use DNA ?paints? from them (and gene probes isolated by them) to detect homologies between unpaired chromoso ....Solving the Mysteries of Monotreme Chromosomes. The peculiar chromosomes of Australia's platypus and echidna have been debated for more than 30 years. Classical cytology cannot resolve the puzzling sex chromosome system, or to sort out the bizarre translocation chain (unique in vertebrates) and deduce how it segregates to make viable zyotes. I will microdissect individual chromosomes, and use DNA ?paints? from them (and gene probes isolated by them) to detect homologies between unpaired chromosomes at mitosis, meiosis and in sperm. I will use immunohistochemistry to clarify chromosome pairing and recombination at meiosis. This will answer some important general questions about chromosome behaviour and sex chromosome evolution.
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Regulatory architecture of the trunk-to-tail transition. This project aims to elucidate gene regulatory mechanisms that control how the head-to-tail axis is laid down during embryonic development. The project capitalises on unique pluripotent stem cell resources and cutting-edge genomic technology developed by the team. This project expects to generate new knowledge in the area of developmental biology and gene regulation that is anticipated to have wider application to the understanding of evol ....Regulatory architecture of the trunk-to-tail transition. This project aims to elucidate gene regulatory mechanisms that control how the head-to-tail axis is laid down during embryonic development. The project capitalises on unique pluripotent stem cell resources and cutting-edge genomic technology developed by the team. This project expects to generate new knowledge in the area of developmental biology and gene regulation that is anticipated to have wider application to the understanding of evolutionary mechanisms and ultimately regenerative medicine.Read moreRead less
Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of ....Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of the scope and consequences of mobile DNA-driven mosaicism. This work will have significant impacts in developmental genetics and neurogenetics, and has the benefit of introducing an innovative experimental system with the potential to spark international scientific collaboration and recognition.Read moreRead less
Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will im ....Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will improve our mechanistic understanding of genetic diseases in populations. In addition, this proposal is expected to lead to identification of potential targets and technologies that would be of interest to Australian industry.Read moreRead less
microRNAs: discovery and analysis in mouse development. MicroRNAs (miRNAs) are a new class of regulatory molecule, recently found to be abundant and strongly conserved in several eukaryotic species, encoded by genes that are transcribed into short stem-loop structures and then processed into ~22nt single-stranded RNAs by the RNAi pathway. We have cloned novel miRNAs, and obtained the first evidence for regulation of a miRNA in a mammal. We propose to continue cloning novel miRNAs by the tried m ....microRNAs: discovery and analysis in mouse development. MicroRNAs (miRNAs) are a new class of regulatory molecule, recently found to be abundant and strongly conserved in several eukaryotic species, encoded by genes that are transcribed into short stem-loop structures and then processed into ~22nt single-stranded RNAs by the RNAi pathway. We have cloned novel miRNAs, and obtained the first evidence for regulation of a miRNA in a mammal. We propose to continue cloning novel miRNAs by the tried method, and to explore bioinformatics-based methods of identification. We will also study the expression of miRNAs in mouse embryos at successive stages, and develop a microarray assay for miRNA expression.Read moreRead less
Gene regulatory networks in heart development. In humans, structural and functional malformations of the heart are very common and are associated with a high economic and emotional burden. In this project, we will study how genetic networks initiate and control heart development at a molecular level. We will establish and employ state-of-the-art technologies and bioinformatics tools to explore the function of cardiac regulatory genes in detail. Our work will contribute both to discover new cardi ....Gene regulatory networks in heart development. In humans, structural and functional malformations of the heart are very common and are associated with a high economic and emotional burden. In this project, we will study how genetic networks initiate and control heart development at a molecular level. We will establish and employ state-of-the-art technologies and bioinformatics tools to explore the function of cardiac regulatory genes in detail. Our work will contribute both to discover new cardiac pathways for a better understanding of heart formation and disease, and to develop advanced techniques that will contribute to strengthen Australian basic and strategic research.Read moreRead less
Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time t ....Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time the cardiac regulatory repertoire in zebrafish and will compare it with that of fly and mouse using cutting-edge bioinformatics pipelines. This work will unravel cardiac-specific regulatory modifications that give rise to evolutionary changes. On a broader scale, it will shed new light on the role of regulatory innovations over gene innovations in the emergence of new traits.Read moreRead less