Function and regulation of the Schlafen gene family: novel regulators of blood cell proliferation and function. The immediate outcomes of the proposed research will be in fundamental knowledge and understanding of important cellular and biological processes in which the Schlafen genes are involved. In particular, Schlafen genes are likely to play a role in inflammatory responses and in blood cell growth. These process clearly have relevance to a range of major human (and animal) diseases includ ....Function and regulation of the Schlafen gene family: novel regulators of blood cell proliferation and function. The immediate outcomes of the proposed research will be in fundamental knowledge and understanding of important cellular and biological processes in which the Schlafen genes are involved. In particular, Schlafen genes are likely to play a role in inflammatory responses and in blood cell growth. These process clearly have relevance to a range of major human (and animal) diseases including infectious disease, auto-immune disease and leukaemia, and thus a long-term outcome may be improved treatments for such disease. Read moreRead less
The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of ....The molecular basis of macropinocytosis in mammalian cells: the composition of endosome proteins and their function. Individual cells communicate with their immediate environment by the process of macropinocytosis, a process that involves the exchange of materials between the extracellular space and a specialised region of the cell termed endosomes. It is an important process in mammalian cells being essential to the correct functioning of many tissues. This project will advance understanding of macropinocytosis at a molecular level. The project is relevant to understanding the functioning of normal cells and the means by which some pathogens can enter cells and also understanding processes involved in tumour progression and metastasis.Read moreRead less
Actin cytoskeleton regulation by E-cadherin and Src. This project examines a fundamental, novel mechanism of how cells work together in tissues. It will provide important new knowledge about how tissues become organized in health, and how organization might be disturbed in disease. It will build Australia's skill base in cutting-edge scientific research, and promote knowledge directed to the research priority area of Promoting and Maintaining Good Health.
How the Y Chromosome makes a male: Molecular genetic analysis of key sex-determining genes. Sex reversal and intersex syndromes are among the most common and highly stigmatized disorders affecting newborn babies. Our research will reveal how the Y chromosome regulates normal male development, identify the steps that go wrong in many male babies, and suggest ways to diagnose and deal with these conditions. It will also pave the way for biotechnological applications in the areas of stem cell techn ....How the Y Chromosome makes a male: Molecular genetic analysis of key sex-determining genes. Sex reversal and intersex syndromes are among the most common and highly stigmatized disorders affecting newborn babies. Our research will reveal how the Y chromosome regulates normal male development, identify the steps that go wrong in many male babies, and suggest ways to diagnose and deal with these conditions. It will also pave the way for biotechnological applications in the areas of stem cell technology, pest management, wildlife conservation and animal breeding.Read moreRead less
MOLECULAR GENETICS OF MAMMALIAN SEXUAL DEVELOPMENT: Molecular roles of SRY and SOX9. The development of sexual characteristics is critical to the survival of almost all animal species. This project seeks to clarify how male and female embryos develop differently, focusing on the Y-chromosome maleness gene Sry, and a closely related and equally important gene Sox9. We will study how these genes are switched on in developing gonads and how they interact with other genes to bring about testis forma ....MOLECULAR GENETICS OF MAMMALIAN SEXUAL DEVELOPMENT: Molecular roles of SRY and SOX9. The development of sexual characteristics is critical to the survival of almost all animal species. This project seeks to clarify how male and female embryos develop differently, focusing on the Y-chromosome maleness gene Sry, and a closely related and equally important gene Sox9. We will study how these genes are switched on in developing gonads and how they interact with other genes to bring about testis formation in male embryos. In this way we will discover new genes and mechanisms that are important for sexual identity and also other aspects of embryo development.Read moreRead less
Structure and function of novel macrophage proteins using high throughput crystallography. We will combine the cutting edge technologies of microarray analysis and high throughput crystallography in an innovative approach to study the structure and function of important and uncharacterised macrophage proteins. Our strategy for targeting novel macrophage proteins will maximise the success rate of structure determination, while at the same time focusing our efforts on proteins that are important i ....Structure and function of novel macrophage proteins using high throughput crystallography. We will combine the cutting edge technologies of microarray analysis and high throughput crystallography in an innovative approach to study the structure and function of important and uncharacterised macrophage proteins. Our strategy for targeting novel macrophage proteins will maximise the success rate of structure determination, while at the same time focusing our efforts on proteins that are important in macrophage biology. Structures of the novel proteins will underpin functional analysis at a molecular level and could represent a basis for inhibitor design should the proteins ultimately be shown to be therapeutic targets.Read moreRead less
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
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
A shared genetic basis for development of the nervous system and glands. Fruit flies possess strikingly similar versions of the genes that promote normal human development. The list of systems with genetic parallels between humans and fruit flies includes the respiratory and circulatory systems; cardiovascular development and disease; sleep; learning and memory; brain development and disease; taste, sight, smell and hearing. This project could add at least some human glands, the mucous-secreting ....A shared genetic basis for development of the nervous system and glands. Fruit flies possess strikingly similar versions of the genes that promote normal human development. The list of systems with genetic parallels between humans and fruit flies includes the respiratory and circulatory systems; cardiovascular development and disease; sleep; learning and memory; brain development and disease; taste, sight, smell and hearing. This project could add at least some human glands, the mucous-secreting goblet cells, to this list, providing a potentially useful model for studying human diseases associated with gland dysfunction. Read moreRead less
ARC/NHMRC Research Network in Genes and Environment in Development. Interactions between the early environment and the genetic regulatory program of the developing organism have major consequences for the lifetime health of individuals. The primary objective of the Network in Genes and Environment in Development is to harness the resources of leading researchers from the currently distinct disciplines of developmental biology and developmental physiology to define key developmental regulatory ne ....ARC/NHMRC Research Network in Genes and Environment in Development. Interactions between the early environment and the genetic regulatory program of the developing organism have major consequences for the lifetime health of individuals. The primary objective of the Network in Genes and Environment in Development is to harness the resources of leading researchers from the currently distinct disciplines of developmental biology and developmental physiology to define key developmental regulatory networks and to address how environmental factors impinge on these regulatory networks. The formation of this National Research Network is unique, timely and strategic. It will generate new insights into the mechanisms by which events in early life determine the risk of adverse outcomes in perinatal and adult life.Read moreRead less