The role of epigenetics in the early gestational programming of adult phenotype by ethanol. The concept of foetal programming is changing the way we think about the aetiology of complex disease in adults. Our studies would emphasise that adverse events during pregnancy can have long-term health implications, with concomitant social and economic consequences. In America, the prevalence of foetal alcohol syndrome is comparable with rates for Down syndrome. The Aboriginal community in Australia ....The role of epigenetics in the early gestational programming of adult phenotype by ethanol. The concept of foetal programming is changing the way we think about the aetiology of complex disease in adults. Our studies would emphasise that adverse events during pregnancy can have long-term health implications, with concomitant social and economic consequences. In America, the prevalence of foetal alcohol syndrome is comparable with rates for Down syndrome. The Aboriginal community in Australia has been identified as a high-risk group. The knowledge gained from this project could aid in the development of screening strategies to predict the likelihood of disease developing later in life, providing an opportunity for presymptomatic healthcare.Read moreRead less
Does developmental noise have an epigenetic basis? One's ultimate phenotype is the result of a combination of genotype and environment, and includes a poorly understood component termed ?developmental noise?. The molecular basis of developmental noise remains unknown, but it appears to be established in early development and to be retained for the life of the organism. We propose that the molecular basis of developmental noise is the epigenetic state of the genome. The stochastic nature of th ....Does developmental noise have an epigenetic basis? One's ultimate phenotype is the result of a combination of genotype and environment, and includes a poorly understood component termed ?developmental noise?. The molecular basis of developmental noise remains unknown, but it appears to be established in early development and to be retained for the life of the organism. We propose that the molecular basis of developmental noise is the epigenetic state of the genome. The stochastic nature of the establishment of epigenetic state, combined with its heritability during mitosis, provides all the essential components for developmental noise. If our hypothesis proves correct, our work will have a major impact on the understanding of one of the most basic concepts in genetics.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100130
Funder
Australian Research Council
Funding Amount
$850,000.00
Summary
Systems biology: New generation DNA sequencing to functional analysis. The technique of DNA sequencing (or 'reading' the lines of the four repeating letters that make up the genetic code) illustrates how technological developments have become the main drivers in exploring the roles of genetic factors across a spectrum of research activities. Funding provided through this ARC grant will allow the purchase of the latest DNA sequencing platform, the Illumina Solexa, as well as equipment that will b ....Systems biology: New generation DNA sequencing to functional analysis. The technique of DNA sequencing (or 'reading' the lines of the four repeating letters that make up the genetic code) illustrates how technological developments have become the main drivers in exploring the roles of genetic factors across a spectrum of research activities. Funding provided through this ARC grant will allow the purchase of the latest DNA sequencing platform, the Illumina Solexa, as well as equipment that will be used to understand the biological function of the DNA sequencing results that are obtained. The equipment will allow Australian researchers to compete on an equal footing with the international leaders in understanding the roles played by genes in plants, microorganisms, animals and humans.Read moreRead less
Deciphering the cellular functions of caveolae that govern lymphatic vascular development. Lymphatic vessels play crucial roles in tissue fluid homeostasis, immunity, and fatty acid transport. Despite our recent understanding of genetic pathways that modulate lymphatic cell fate specification, how cellular changes mediate morphogenesis of the lymphatic tree remains to be elucidated. This study will combine cell biology and developmental genetics approaches using mouse and zebrafish transgenic li ....Deciphering the cellular functions of caveolae that govern lymphatic vascular development. Lymphatic vessels play crucial roles in tissue fluid homeostasis, immunity, and fatty acid transport. Despite our recent understanding of genetic pathways that modulate lymphatic cell fate specification, how cellular changes mediate morphogenesis of the lymphatic tree remains to be elucidated. This study will combine cell biology and developmental genetics approaches using mouse and zebrafish transgenic lines that label lymphatic endothelial cells to investigate the role of caveolae proteins in the construction of the lymphatic vascular network. This project aims to improve our fundamental understanding of the processes that govern vascular system assembly and will broaden basic knowledge of organ morphogenesis. Read moreRead less
cell-cell adhesive force in vascular development. This project aims to utilize groundbreaking new approaches to visualize cell-cell adhesive forces in vascular development. Vascular system development is one of the earliest events in the vertebrate embryo. It has long been established that one major contributor to the formation of new vessels is physical force, which can be generated through blood flow or cell-cell interactions during tissue morphogenesis. The project plan utilizes live imaging ....cell-cell adhesive force in vascular development. This project aims to utilize groundbreaking new approaches to visualize cell-cell adhesive forces in vascular development. Vascular system development is one of the earliest events in the vertebrate embryo. It has long been established that one major contributor to the formation of new vessels is physical force, which can be generated through blood flow or cell-cell interactions during tissue morphogenesis. The project plan utilizes live imaging in zebrafish and a new generation of biosensors to gain a vastly deeper understanding of how force controls vessel formation.Read moreRead less
The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehe ....The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehensively define where in the embryo it is required and investigate what cofactors it interacts with to perform its function. Using genetic zebrafish and mouse models as well as cell culture models we will investigate the fundamental biology of this gene.Read moreRead less
Regulation of mammalian differentiation by methylation of histones and transcription factors. The objective of this proposal is to examine the functional role of arginine and lysine methylation during skeletal muscle differentiation. Differentiation, i.e the acquisition of a specific phenotype, is the biological end point of the ?Genome-Phenome? transition. Specifically, the proposal will seek to understand the role of protein methylation in the control of tissue specific gene expression and ce ....Regulation of mammalian differentiation by methylation of histones and transcription factors. The objective of this proposal is to examine the functional role of arginine and lysine methylation during skeletal muscle differentiation. Differentiation, i.e the acquisition of a specific phenotype, is the biological end point of the ?Genome-Phenome? transition. Specifically, the proposal will seek to understand the role of protein methylation in the control of tissue specific gene expression and cell signaling during differentiation. Key areas of study in the ARC priority area of Genome-Phenome research. We will test the hypothesis that the activity/function of the hierarchical myogenic transcription factors and cofactors that control skeletal myogenesis is influenced by protein methylation.Read moreRead less
Foundations of a good egg: correctly transitioning from mitosis to meiosis. Production of viable offspring is essential to the survival of any species. In all sexually reproducing species, this requires a unique cell type, the germ cell. Germ cells undergo a special type of cell division, called meiosis, so that they can eventually produce gametes (sperm in males and eggs in females). This project aims to discover how germ cells halt the standard form of cell division, called mitosis, and initia ....Foundations of a good egg: correctly transitioning from mitosis to meiosis. Production of viable offspring is essential to the survival of any species. In all sexually reproducing species, this requires a unique cell type, the germ cell. Germ cells undergo a special type of cell division, called meiosis, so that they can eventually produce gametes (sperm in males and eggs in females). This project aims to discover how germ cells halt the standard form of cell division, called mitosis, and initiate meiotic division instead. It is important to understand all the fundamental processes that occur during normal germ cell development so that, in the future, we can use this knowledge to support agricultural advances, rescue endangered species and solve human problems such as infertility and genetic disease.Read moreRead less
Inter-kingdom signalling in animal health and disease. This project aims to understand how animals can control their bacterial associates. Animals evolved in a world dominated by bacteria, and intimately associated microbes affect the development, health and disease of all animals – from corals to man. To date, animal-microbe interactions have been studied nearly exclusively in terms of how bacteria affect animals. the researchers have discovered that the coral Acropora can control its associate ....Inter-kingdom signalling in animal health and disease. This project aims to understand how animals can control their bacterial associates. Animals evolved in a world dominated by bacteria, and intimately associated microbes affect the development, health and disease of all animals – from corals to man. To date, animal-microbe interactions have been studied nearly exclusively in terms of how bacteria affect animals. the researchers have discovered that the coral Acropora can control its associated bacteria. Understanding how a simple animal manipulates its microbial associates should have implications for coral disease and resilience and for health and disease across the animal kingdom.Read moreRead less
Mechanisms that control the inheritance of mitochondrial DNA mutations. How do humans and other organisms prevent the accumulation of dangerous mitochondrial genome (mtDNA) mutations across generations? This Project aims to uncover the cellular and molecular pathways that help prevent the inheritance of mtDNA mutations to offspring by employing cutting-edge genetic technologies that the laboratory has recently developed in the germline of an animal model system. This Project will generate new kn ....Mechanisms that control the inheritance of mitochondrial DNA mutations. How do humans and other organisms prevent the accumulation of dangerous mitochondrial genome (mtDNA) mutations across generations? This Project aims to uncover the cellular and molecular pathways that help prevent the inheritance of mtDNA mutations to offspring by employing cutting-edge genetic technologies that the laboratory has recently developed in the germline of an animal model system. This Project will generate new knowledge in the area of mitochondrial genetics and evolution. Expected outcomes include the development of new theories for mtDNA inheritance, which should provide significant benefits for agricultural breeding programs and the interpretation of mtDNA inheritance patterns in the human population.Read moreRead less