A Genomic analysis of macrophage differentiation: Epigenetic factors that determine transcriptional choices in a lineage dependant manner. Our genetic information is fundamental to who we are, how we develop, & how we age. This project will build the research capacity of Australia's genome sciences, providing an analytical framework to describe & study the many products expressed from any single gene and to assess the function of genetic variation & test genome regulatory events. An immediate ou ....A Genomic analysis of macrophage differentiation: Epigenetic factors that determine transcriptional choices in a lineage dependant manner. Our genetic information is fundamental to who we are, how we develop, & how we age. This project will build the research capacity of Australia's genome sciences, providing an analytical framework to describe & study the many products expressed from any single gene and to assess the function of genetic variation & test genome regulatory events. An immediate outcome is a better understanding of the regulation of our immune system. This approach will fuel the discovery of new signalling molecules & their effects on a population of cells, & likewise provides a novel approach to study the dysregulation of cell signalling pathways.Read moreRead less
A new statistical framework to understand the biological basis of Ankylosing Spondylitis and other complex diseases. Ankylosing Spondylitis (AS) is a highly heritable and common inflammatory arthritis which causes stiffness and progressive fusion of the spine, decreased quality of life and reduced lifespan. There is no known cure for the condition. This project aims to identify genes and biological pathways involved in AS pathogenesis using a new statistical framework that will be applied to tho ....A new statistical framework to understand the biological basis of Ankylosing Spondylitis and other complex diseases. Ankylosing Spondylitis (AS) is a highly heritable and common inflammatory arthritis which causes stiffness and progressive fusion of the spine, decreased quality of life and reduced lifespan. There is no known cure for the condition. This project aims to identify genes and biological pathways involved in AS pathogenesis using a new statistical framework that will be applied to thousands of individuals with the disease. This project will improve understanding of the underlying mechanisms involved in AS pathophysiology, inform development of new drug treatments for the condition, and create a powerful new statistical approach that can be used to identify biological pathways which are important in the pathogenesis of other complex diseases.Read moreRead less
How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, ....How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, this project expects to provide insights into non-coding regulatory element reprogramming and control of immune cell function and memory with implications for understanding general cellular differentiation.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
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