The Role Of GRHL-3, A Mammalian Homologue Of Drosophila Grainyhead, In Neural Tube Development
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first ....Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first few hours of life. These abnormalities occur frequently (1-1000 live births) and are a direct result of failure of the neural tube to close during embryogenesis. NTDs are influenced by both environmental and genetic factors. The best characterised environmental factor is the dietary supplement folate, which when administered before conception results in a reduction in the incidence of spina bifida. The genetic complexity is evidenced by the array of mouse genetic mutations that give rise to NTDs. One of these mouse mutations, known as Curly tail (ct), has served as the major animal model of human NTDs. This is because the ct mice are resistant to folate administration (like most of the cases of spina bifida currently seen in patients) and because the mice seem to have normal development in virtually all other organ systems. Ironically, the genetic mutation that causes the curly tail phenotype has remained undiscovered for over 50 years. We have now identified the gene mutated in the curly tail mice. This gene is highly conserved in humans suggesting that it will play a similar role in neural tube development in man. The gene, known as GRHL-3, is a descendant of a fly gene critical for development of the nervous system in that organism. The studies we propose here will examine the developmental pathways involved in normal neural tube closure in mice and humans and will impact on our understanding of these devastating congenital malformations.Read moreRead less
Targeting Bone Marrow Lesions To Find Interventions In The Progression Of Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$467,395.00
Summary
It is essential to elucidate the underlying cause(s) of osteoarthritis because our current level of understanding of this condition has failed to produce effective treatments. Lesions in the bone under the cartilage (BMLs), seen using MRI, have strong potential value for the objective monitoring and management of OA. However, because the nature of BMLs is not well understood, the aim of this application is to perform a comprehensive study of BMLs in OA bone.
Epigenetic Regulation Of Male Fetal Germ Cell Development.
Funder
National Health and Medical Research Council
Funding Amount
$562,176.00
Summary
Men’s health has declined over recent decades, but the causes remain unknown. Non-genetic (epigenetic) mechanisms affecting formation and function of the male germ cells (which produce sperm) may play an important role. We will determine the role of a key epigenetic modifier on the formation and function of male germ cells, including germ cell tumours. This study will provide fundamental insights into male germ cell epigenetics, and significantly contribute to understanding men's health.
Identifying The Pathological Mechanism Of PCDH19-Girls Clustering Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$523,988.00
Summary
Changes in the PCDH19 gene are a relatively common cause of epilepsy. To better understand the basis of this disorder, we have developed unique mouse models that mimic the genetic changes and symptoms of this condition. We will perform careful analysis of brain development in these models to determine the primary cause of this condition. These experiments will create greater understanding of how changes in PCDH19 cause epilepsy in girls and facilitate the development of new treatments.
Developing the dunnart as a marsupial model for conservation research. The Australian bushfire crisis of 2020 has taken an enormous toll on our unique wildlife. With no halt in sight to rising global temperatures, more extreme weather events are predicted to increase in frequency and severity. We simply must act now to preserve our unique native mammals in Australia and safeguard against species loss and irreversible declines in genetic diversity. This project will develop methods for the genera ....Developing the dunnart as a marsupial model for conservation research. The Australian bushfire crisis of 2020 has taken an enormous toll on our unique wildlife. With no halt in sight to rising global temperatures, more extreme weather events are predicted to increase in frequency and severity. We simply must act now to preserve our unique native mammals in Australia and safeguard against species loss and irreversible declines in genetic diversity. This project will develop methods for the generation and preservation of stem cells from a range of our most endangered and vulnerable marsupial species. These cells not only allow us to ‘bank’ species and genetic diversity but also provide a route to enabling genetic manipulation, opening up a completely new niche for conservation biology in marsupials.Read moreRead less
The genetic basis of leaf lamina establishment and growth. This study will help reveal how the development of leaves is coordinated by tissue patterning genes and the plant growth hormone auxin. All plants grow in this way, and the findings, made using a model laboratory plant, will be applicable to crop species as well.
The evolution of the alternation of generations in land plants. This project aims to investigate how a genetic system, comprised of a homeodomain protein encoding gene family controlling the haploid to diploid transition, has evolved during land plant evolution.
The project expects to generate new knowledge concerning the evolution of land plants from which our food and fibre are derived.
The intended outcomes include an elucidation of how an ancestral genetic network was elaborated during the e ....The evolution of the alternation of generations in land plants. This project aims to investigate how a genetic system, comprised of a homeodomain protein encoding gene family controlling the haploid to diploid transition, has evolved during land plant evolution.
The project expects to generate new knowledge concerning the evolution of land plants from which our food and fibre are derived.
The intended outcomes include an elucidation of how an ancestral genetic network was elaborated during the evolution of a multicelluar organism, including the retention of ancestral functions and the origins of new functions.
An anticipated benefit is the ability to manipulate the the growth and development of plants based on fundamental principles, which has broad agricultural implications.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140100190
Funder
Australian Research Council
Funding Amount
$388,600.00
Summary
Tracing the Evolutionary History of Plant Developmental Mechanisms. Knowledge of the evolutionary history of genes involved in developmental processes provides a foundation for understanding how genetic networks were established and how their manipulation may influence plant growth and form. Genetic programs that direct growth and development in response to light will be examined functionally in Marchantia, a liverwort. Liverworts hold a key position in plant evolution as the sister group to all ....Tracing the Evolutionary History of Plant Developmental Mechanisms. Knowledge of the evolutionary history of genes involved in developmental processes provides a foundation for understanding how genetic networks were established and how their manipulation may influence plant growth and form. Genetic programs that direct growth and development in response to light will be examined functionally in Marchantia, a liverwort. Liverworts hold a key position in plant evolution as the sister group to all other land plants and possess many attributes reminiscent of the ancestral land plant. This project is expected to reveal some of the ancestral mechanisms for how light regulates plant form via the hormone auxin and could, in the future, aid the precise design of plants for diverse agricultural applications.Read moreRead less
The origin and evolution of the land plant meristem. This project aims to identify the extent of overlap between the genetic determinants of the gametophyte and sporophyte shoot meristems.
The project expects to generate new knowledge of the evolution and development of land plants by applying comparative genomics and new technologies to a novel model genetic system.
Expected outcomes include an elucidation of the genetic basis for one of the key morphological adaptations for life on land.
Th ....The origin and evolution of the land plant meristem. This project aims to identify the extent of overlap between the genetic determinants of the gametophyte and sporophyte shoot meristems.
The project expects to generate new knowledge of the evolution and development of land plants by applying comparative genomics and new technologies to a novel model genetic system.
Expected outcomes include an elucidation of the genetic basis for one of the key morphological adaptations for life on land.
The ability to manipulate the growth and development of plants via the activity of meristems based on fundamental principles has broad agricultural implications.
Read moreRead less
Understanding the evolution of the alternation of generations in the land plant life cycle. This project will investigate the genetic basis and evolution of the land plant life cycle, in which both haploid and diploid phases consist of complex multicellular bodies. The project's findings, which will be made using two model laboratory plants, will be applicable to all plants and will help understand important processes such as pollen and seed production.