Mobile DNA activity in the mammalian primordial germline. Early in pregnancy, a handful of cells in the embryo become primordial germ cells (PGCs). These PGCs will eventually give rise to sperm or egg cells, representing a critical inter-generational genetic link. Mobile DNA sequences target PGCs to create new heritable genetic changes. This proposal aims to analyse the activity, regulation, and consequences of mobile DNA activity in PGCs. This project expects to generate significant knowledge a ....Mobile DNA activity in the mammalian primordial germline. Early in pregnancy, a handful of cells in the embryo become primordial germ cells (PGCs). These PGCs will eventually give rise to sperm or egg cells, representing a critical inter-generational genetic link. Mobile DNA sequences target PGCs to create new heritable genetic changes. This proposal aims to analyse the activity, regulation, and consequences of mobile DNA activity in PGCs. This project expects to generate significant knowledge about the origins of mammalian genetic diversity. Expected outcomes include enhanced national and international collaborations across disciplines and new experimental systems. The expected benefit is an enhanced understanding of the mutational processes underlying genetic diversity and disease in mammals.Read moreRead less
Foundations of a good egg: correctly transitioning from mitosis to meiosis. Production of viable offspring is essential to the survival of any species. In all sexually reproducing species, this requires a unique cell type, the germ cell. Germ cells undergo a special type of cell division, called meiosis, so that they can eventually produce gametes (sperm in males and eggs in females). This project aims to discover how germ cells halt the standard form of cell division, called mitosis, and initia ....Foundations of a good egg: correctly transitioning from mitosis to meiosis. Production of viable offspring is essential to the survival of any species. In all sexually reproducing species, this requires a unique cell type, the germ cell. Germ cells undergo a special type of cell division, called meiosis, so that they can eventually produce gametes (sperm in males and eggs in females). This project aims to discover how germ cells halt the standard form of cell division, called mitosis, and initiate meiotic division instead. It is important to understand all the fundamental processes that occur during normal germ cell development so that, in the future, we can use this knowledge to support agricultural advances, rescue endangered species and solve human problems such as infertility and genetic disease.Read moreRead less
Mechanisms that control the inheritance of mitochondrial DNA mutations. How do humans and other organisms prevent the accumulation of dangerous mitochondrial genome (mtDNA) mutations across generations? This Project aims to uncover the cellular and molecular pathways that help prevent the inheritance of mtDNA mutations to offspring by employing cutting-edge genetic technologies that the laboratory has recently developed in the germline of an animal model system. This Project will generate new kn ....Mechanisms that control the inheritance of mitochondrial DNA mutations. How do humans and other organisms prevent the accumulation of dangerous mitochondrial genome (mtDNA) mutations across generations? This Project aims to uncover the cellular and molecular pathways that help prevent the inheritance of mtDNA mutations to offspring by employing cutting-edge genetic technologies that the laboratory has recently developed in the germline of an animal model system. This Project will generate new knowledge in the area of mitochondrial genetics and evolution. Expected outcomes include the development of new theories for mtDNA inheritance, which should provide significant benefits for agricultural breeding programs and the interpretation of mtDNA inheritance patterns in the human population.Read moreRead less
Neurobiology Of Childhood Speech Disorders: Improving Detection, Diagnosis And Clinical Care
Funder
National Health and Medical Research Council
Funding Amount
$994,575.00
Summary
One in 20 children have a speech disorder at school entry, with lifelong deficits in psychosocial, academic and employment outcomes. Little is known about the aetiology of speech disorders, preventing targeted care. We combine expertise in speech pathology, gene discovery and brain imaging, to advance knowledge on gene and brain contributions to speech disorder. We will have direct impacts on clinical care including detection, diagnosis and counselling, optimising outcomes for affected children.
Discovering sex determining genes in a reptile with genetic and environmental sex determination. Reptile sex determination is particularly fascinating because it is triggered either by genes on sex chromosomes or by the nest temperature. This project will identify and characterise candidate sex determining genes in a model reptile to understand how genes control sexual differentiation and how they interact with temperature.
Left-right patterning of the heart. This project aims to investigate how the heart responds to left-right (LR) signals, which tissue is dominant in this response; determine tissue intrinsic factors at play, and determine whether we can manipulate this. Expected outcomes include fundamental information about how organs are patterned.
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
The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehe ....The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehensively define where in the embryo it is required and investigate what cofactors it interacts with to perform its function. Using genetic zebrafish and mouse models as well as cell culture models we will investigate the fundamental biology of this gene.Read moreRead less
Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of ....Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of the scope and consequences of mobile DNA-driven mosaicism. This work will have significant impacts in developmental genetics and neurogenetics, and has the benefit of introducing an innovative experimental system with the potential to spark international scientific collaboration and recognition.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