Progenitor cells within the peritoneal cavity. Implantation of a foreign object into the peritoneal cavity of animals recruits undifferentiated cells of bone marrow origin that encapsulate the free-floating object, then differentiate into myofibroblasts. When large pieces of myofibroblast capsule tissue are subsequently grafted into autologous artery, bladder or vas deferens, they develop the structure and morphology of that organ. We hypothesise that multipotent progenitor cells sequestered t ....Progenitor cells within the peritoneal cavity. Implantation of a foreign object into the peritoneal cavity of animals recruits undifferentiated cells of bone marrow origin that encapsulate the free-floating object, then differentiate into myofibroblasts. When large pieces of myofibroblast capsule tissue are subsequently grafted into autologous artery, bladder or vas deferens, they develop the structure and morphology of that organ. We hypothesise that multipotent progenitor cells sequestered to the peritoneal cavity can be manipulated to differentiate along smooth muscle and other pathways. The proposed project aims to identify the origin of these cells and characterise the transcriptional program that regulates their differentiation.Read moreRead less
Calcium regulation in the skeletal muscle triad and along the fibre. The fundamental role of skeletal muscle is posture and movement. Alterations in the normal way calcium regulates skeletal muscle function in fatigue, age and disease states causes loss of normal function. Preventing or controlling these changes is a key therapeutic aim. However, we currently lack full understanding of key mechanisms of calcium regulation in healthy skeletal muscle. This project will define key aspects of cal ....Calcium regulation in the skeletal muscle triad and along the fibre. The fundamental role of skeletal muscle is posture and movement. Alterations in the normal way calcium regulates skeletal muscle function in fatigue, age and disease states causes loss of normal function. Preventing or controlling these changes is a key therapeutic aim. However, we currently lack full understanding of key mechanisms of calcium regulation in healthy skeletal muscle. This project will define key aspects of calcium regulation that could be crucial to developing targets for improving function of skeletal muscle under stressed states.Read moreRead less
High Resolution EM Tomography of Specialised Plasma Membrane Domains. This project will provide National benefits in two major areas. Firstly, these studies will greatly increase our understanding of the cellular structures which are crucial to the functioning of cells in the body. Understanding the structure of the components of animal cells in three dimensions will provide long-term benefits in the quest to understand how a cell works in health and what goes wrong in disease. Secondly, this pr ....High Resolution EM Tomography of Specialised Plasma Membrane Domains. This project will provide National benefits in two major areas. Firstly, these studies will greatly increase our understanding of the cellular structures which are crucial to the functioning of cells in the body. Understanding the structure of the components of animal cells in three dimensions will provide long-term benefits in the quest to understand how a cell works in health and what goes wrong in disease. Secondly, this project will allow us to develop the new method of electron microscope tomography and apply it to a crucial question in biology. This will be a vital technique for Australian investigators in the coming years and this project will allow scientists and students to be trained in these state-of-the-art techniques.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
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