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
Deciphering genome function in animal development. The normal development of an embryo depends on complex and finely tuned gene regulatory mechanisms. In this Fellowship, I will use sophisticated new technologies to discover which of our 30,000 genes is important for embryonic development, reveal the roles of these genes, and identify the control mechanisms that can go awry to cause birth defects. Our research will suggest new ways to diagnose and deal with these conditions, and will be applicab ....Deciphering genome function in animal development. The normal development of an embryo depends on complex and finely tuned gene regulatory mechanisms. In this Fellowship, I will use sophisticated new technologies to discover which of our 30,000 genes is important for embryonic development, reveal the roles of these genes, and identify the control mechanisms that can go awry to cause birth defects. Our research will suggest new ways to diagnose and deal with these conditions, and will be applicable to stem cell technologies, tissue regeneration, cancer biology, conservation, pest management and livestock breeding, thus delivering significant economic and social benefits to Australia. Read moreRead less
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561030
Funder
Australian Research Council
Funding Amount
$441,100.00
Summary
Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiative ....Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiatives in developmental and cellular biology. This large-scale, high-resolution expression profiling infrastructure is required to maintain international competitiveness and will dramatically improve our gene discovery, functional assessment and understanding of vertebrate development.Read moreRead less
The structure and patterning of branching morphogenesis in the developing kidney. This project aims to understand a fundamental developmental process known as branching morphogenesis, which drives the formation of many organs including the kidney, lungs and glands. Understanding this process will be of key importance in understand how our organs form.
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 Centre of Excellence in Biotechnology and Development. The Centre will create a multidisciplinary research team focusing on the molecular mechanisms that drive the specification and differentiation of male germ cells. This research will improve our fundamental understanding of how complex regulatory networks control the expression of a complex phenotype, the spermatozoon. It will also create a platform of knowledge from which we can stimulate the growth of the Australian Biotechnology indust ....ARC Centre of Excellence in Biotechnology and Development. The Centre will create a multidisciplinary research team focusing on the molecular mechanisms that drive the specification and differentiation of male germ cells. This research will improve our fundamental understanding of how complex regulatory networks control the expression of a complex phenotype, the spermatozoon. It will also create a platform of knowledge from which we can stimulate the growth of the Australian Biotechnology industry, the protection of the Australian Environment and the well-being of the Australian people. Key issues for this Centre include testicular cancer, male infertility, contraception, pest animal control, environmental impacts on human health and gene pharming.Read moreRead less
Morphological development of the kidney – a paradigm for organogenesis. This project aims to shed new light on how the kidney develops, how normal adult function is established and how congenital kidney malformations occur. It aims to investigate a mathematical pattern that has been discovered in the program of branching morphogenesis which dictates kidney development. By combining cutting-edge genetic approaches, morphological analysis and mathematical modelling, this project plans to explore h ....Morphological development of the kidney – a paradigm for organogenesis. This project aims to shed new light on how the kidney develops, how normal adult function is established and how congenital kidney malformations occur. It aims to investigate a mathematical pattern that has been discovered in the program of branching morphogenesis which dictates kidney development. By combining cutting-edge genetic approaches, morphological analysis and mathematical modelling, this project plans to explore how this pattern is established, how it dictates kidney development and whether it constitutes an ancient mechanism central to organ formation. Project outcomes may improve understanding of fundamental developmental processes and developmental disease and variation. Project findings may also be important for understanding the development of other organ systems.Read moreRead less
Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will im ....Molecular genetic analyses of trinucleotide repeat expansions. Several neuronal diseases like Huntington's disease, Frederick's ataxia and fragile X syndrome are caused by expansion of trinucleotide repeat sequences in the deoxyribonucleic acid (DNA). These diseases show progressive severity in subsequent generations. Here we use a simple plant model with a very similar DNA mutation to study the genetic basis of repeat expansions over several generations across populations. This proposal will improve our mechanistic understanding of genetic diseases in populations. In addition, this proposal is expected to lead to identification of potential targets and technologies that would be of interest to Australian industry.Read moreRead less