This is a study of the biological system of epigenetics. Every cell in our body has the same genetics, or library of information contained in the form of DNA sequence. Epigenetics is the system that controls how this DNA is used in a particular situation, or what books are opened and read. During embryonic development, cells know what they want to become, e.g., a muscle cell, and, once they take on an identity, remember that they are when they duplicate themselves during growth. Epigenetics does ....This is a study of the biological system of epigenetics. Every cell in our body has the same genetics, or library of information contained in the form of DNA sequence. Epigenetics is the system that controls how this DNA is used in a particular situation, or what books are opened and read. During embryonic development, cells know what they want to become, e.g., a muscle cell, and, once they take on an identity, remember that they are when they duplicate themselves during growth. Epigenetics does not achieve this through changing genetics the library always stays intact. Rather, it acts by using proteins or chemicals to make DNA functional in one way, or another. Genomic imprinting is a special type of epigenetics. While an embryo has received identical genetic information from each of its parents, the epigenetic information received from each parent was not entirely the same. Some genes which behave differently according to what parent they came from. For example, a gene that makes a growth factor protein is active only if received from the father. If received from the mother, it is inactive, and makes no protein. Genes behaving in this way are known as imprinted genes. We are trying to discover what epigenetic mechanisms are behind this behaviour of imprinted genes. One way we are approaching this problem is to study germ cells the cells giving rise to eggs and sperm. These cells are unusual in that their imprinted genes behave in the same way regardless of whether they were received from the mother or father, i.e., like any other gene. If we can understand why this is the case, we will be better able to understand why imprinted genes behave the way they do in the rest of the cells of the body. Broadly, the mechanisms we uncover should further our understanding of germ cell development, gene expression, and disease. Perturbations in the epigenetic profile are likely causes of human disease, including cancer.Read moreRead less
Integrated genetic regulation of photomorphogenesis in Pisum. This project will use a molecular genetic approach in garden pea to investigate the roles of photoreceptors that mediate developmental responses to light. It will define gene families encoding phytochrome, cryptochrome and phototropin photoreceptors, characterise photoreceptor gene expression, and identify mutants with impaired response to light. The mutants will be used in molecular, physiological and biochemical studies to examine h ....Integrated genetic regulation of photomorphogenesis in Pisum. This project will use a molecular genetic approach in garden pea to investigate the roles of photoreceptors that mediate developmental responses to light. It will define gene families encoding phytochrome, cryptochrome and phototropin photoreceptors, characterise photoreceptor gene expression, and identify mutants with impaired response to light. The mutants will be used in molecular, physiological and biochemical studies to examine how photoreceptors control and co-ordinate development throughout the plant via effects on plant hormone synthesis and response. Results from the project will be of practical importance in manipulating key aspects of plant growth to better suit particular environmental and agronomic objectives.Read moreRead less
Physiological and molecular controls of plant transpiration efficiency: investigating the role of the ERECTA gene. Water is the single most limiting factor in agriculture and the world's supply of fresh water is diminishing, the greatest fraction of total water use being by agriculture. Progress in water-use efficiency will have social value, and this program should help us to achieve it. Our progress in this area is already one of the most successful of 'bottom-up' approaches - in the sense of ....Physiological and molecular controls of plant transpiration efficiency: investigating the role of the ERECTA gene. Water is the single most limiting factor in agriculture and the world's supply of fresh water is diminishing, the greatest fraction of total water use being by agriculture. Progress in water-use efficiency will have social value, and this program should help us to achieve it. Our progress in this area is already one of the most successful of 'bottom-up' approaches - in the sense of transferring knowledge from biochemistry and biophysics to breeding and agronomy, as CSIRO now has a successful wheat breeding program based on this earlier work of ours. Now that we have discovered a gene that controls water-use efficiency at the leaf level, we wish to see how the gene works, and how it affects mineral nutrition of leaves.Read moreRead less
Neurogenesis in bilateral larval and radial adult body plans: identification of echinoderm homologues of the chordate central nervous system. The modern synthesis of embryology and gene expression studies, as undertaken in this project with sea stars, is a major way forward to achieve advances in our understanding of animal evolution and generate new insights into the mystery that surrounds the origin of our own phylum, the Chordata. This project utilises life history diversity in species that a ....Neurogenesis in bilateral larval and radial adult body plans: identification of echinoderm homologues of the chordate central nervous system. The modern synthesis of embryology and gene expression studies, as undertaken in this project with sea stars, is a major way forward to achieve advances in our understanding of animal evolution and generate new insights into the mystery that surrounds the origin of our own phylum, the Chordata. This project utilises life history diversity in species that are unique Australian fauna. Extreme life history diversity as seen in these sea stars is unparalleled on a global scale and provides an important resource to generate new discoveries on the processes underlying evolution in the sea and enhance our understanding of marine systems. 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
Function of a new splicing factor, RBM4. New genomic knowledge is revolutionizing our world. However our understanding of the basic mechanisms of RNA maturation, especially regulation of splicing lags significantly behind our understanding of related genomic processes. This project is a genetic approach to help elucidate the function of new splicing factors and characterize the way in which specific RNA sequences are recognized. It should promote the better understanding of regulatory events inv ....Function of a new splicing factor, RBM4. New genomic knowledge is revolutionizing our world. However our understanding of the basic mechanisms of RNA maturation, especially regulation of splicing lags significantly behind our understanding of related genomic processes. This project is a genetic approach to help elucidate the function of new splicing factors and characterize the way in which specific RNA sequences are recognized. It should promote the better understanding of regulatory events involved in controlling gene expression during development and differentiation. Results from this project will also provide new insights into the 'multifunctionality' of cellular proteins and will illustrate the importance of RNA studies in molecular medicine.Read moreRead less
microRNA are non-coding RNAs with fundamental functions in biology and emerging roles in disease. Hundreds of microRNA have been found and they control gene expression by destroying RNA or controlling their translation into cellular proteins. We will characterise their mechanisms of action and the cellular factors that are involved. Understanding the way microRNA work is a key question in gene regulation research and will aid the development of therapeutic strategies invovling small RNA.
Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific kno ....Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific knockout techniques to study key cohesin regulators in Drosophila. These studies will provide us with novel insights into how multicellular organisms regulate the structure and stability of their chromosomes.Read moreRead less
The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu pr ....The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu proteins of two proteins in the BMP pathway. Verification of a post-transcriptional regulatory mechanism for cell fate determination would be a major discovery, and may prompt investigation of how to harness the neuron-inducing function of the Hu proteins to address the therapeutic need for new neurons in neurologic diseases.Read moreRead less
Oxidative Damage and Cell Ageing. This research will benefit Australia by providing a fundamental understanding of how cells age. This will have immediate international impact at the scientific level and will inform strategies to reduce the rate of ageing and alleviation of age-related disorders. In the longer term the research may provide commercial and social outcomes by identifying antioxidant systems that will provide a genuine benefit in reducing ageing.