How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understandi ....How does timing affect mammalian brain development and evolution? This project aims to generate fundamental knowledge on the origin of diversity in mammalian brain circuits by studying development of marsupials and rodents. The expected outcome is to elucidate how differences in the timing, rate and sequence of development of gene expression, cell differentiation and circuit formation can relate to the origin of key evolutionary innovations in the mammalian brain. The significance of understanding the dynamics of developmental systems that shape complex brain traits includes establishing new developmental paradigms in evolutionary theory, generating new tools to investigate and manipulate brain gene expression in vivo, and the potential discovery of the causes of neurodevelopmental dysfunction.Read moreRead less
Dynamic DNA structure states and memory formation. Activity-induced gene expression is central to neural plasticity, learning, and memory; however, the underlying mechanisms of these processes in the brain have yet to be fully resolved. The aim of this proposal is to obtain a deeper understanding of the functional relationship between genes and brain function. By elucidating the full repertoire of epigenetic mechanisms in the brain during learning and the formation of memory, it is hoped that t .... Dynamic DNA structure states and memory formation. Activity-induced gene expression is central to neural plasticity, learning, and memory; however, the underlying mechanisms of these processes in the brain have yet to be fully resolved. The aim of this proposal is to obtain a deeper understanding of the functional relationship between genes and brain function. By elucidating the full repertoire of epigenetic mechanisms in the brain during learning and the formation of memory, it is hoped that the true nature of brain adaptation across the lifespan will be revealed. Findings which may then provide new opportunities to strengthen, maintain and optimise cognitive function.Read moreRead less
Identification of causal variants for complex traits. The aim of this project is to identify causal variants for complex traits in cattle and humans. Although most important traits in agriculture, medicine and evolution are complex traits, very few of the genetic variants affecting these traits are known and this undermines our understanding of how genetic variants affect a trait and practical uses of this knowledge. Huge datasets of individuals with genome sequence and phenotypes and new statis ....Identification of causal variants for complex traits. The aim of this project is to identify causal variants for complex traits in cattle and humans. Although most important traits in agriculture, medicine and evolution are complex traits, very few of the genetic variants affecting these traits are known and this undermines our understanding of how genetic variants affect a trait and practical uses of this knowledge. Huge datasets of individuals with genome sequence and phenotypes and new statistical methods provide the opportunity to close this gap. The outcome will be identification of many genomic variants causing variation in complex traits. This will benefit scientific understanding of complex traits and the ability to predict traits for individuals from their genome sequence.Read moreRead less
Defining novel neuroepigenetic pathways that influence learning and memory. This project aims to better understand the functional relationship between epigenetic mechanisms and regulatory RNAs in the brain and how they influence learning and the formation of memory. Activity-induced gene expression is central to neural plasticity, learning, and memory. However, efforts to elucidate the underlying mechanisms in the brain have not been fully resolved. By elucidating the full repertoire of epigenet ....Defining novel neuroepigenetic pathways that influence learning and memory. This project aims to better understand the functional relationship between epigenetic mechanisms and regulatory RNAs in the brain and how they influence learning and the formation of memory. Activity-induced gene expression is central to neural plasticity, learning, and memory. However, efforts to elucidate the underlying mechanisms in the brain have not been fully resolved. By elucidating the full repertoire of epigenetic mechanisms in the brain during learning and memory formation, the findings of the project will be broadly applicable and create new opportunities for understanding the true nature of brain adaptation.Read moreRead less
Investigations into the antibacterial mechanism of action of cannabidiol. Cannabidiol (CBD) comes from a set of naturally occurring compounds, with a range of applications in mainstream culture. We have recently reported that CBD has excellent antimicrobial properties, with the ability to kill bacteria. This project aims to understand how CBD works by examining CBD-bacterial interactions at a genetic and molecular level. By understanding how CBD acts on and within bacterial cells, we can create ....Investigations into the antibacterial mechanism of action of cannabidiol. Cannabidiol (CBD) comes from a set of naturally occurring compounds, with a range of applications in mainstream culture. We have recently reported that CBD has excellent antimicrobial properties, with the ability to kill bacteria. This project aims to understand how CBD works by examining CBD-bacterial interactions at a genetic and molecular level. By understanding how CBD acts on and within bacterial cells, we can create fundamental new knowledge that could lead to the design of improved analogs of CBD to that can treat bacterial infections. As a much-needed completely new antibiotic class, this will lead to significant benefits, supporting Australia's National Strategy to combat the challenges posed by antimicrobial resistance.Read moreRead less
Molecular definition of cellular states in the vascular endothelium. The endothelium is the main cell type forming blood vessels and spans across multiple cell states from stem/progenitor to a variety of terminally differentiated cells. How each of these cell states are defined at the molecular level is not known preventing the optimal formation and integration of blood vessels in bioengineered tissues. Using innovative single cell gene expression and chromatin accessibility studies combined wit ....Molecular definition of cellular states in the vascular endothelium. The endothelium is the main cell type forming blood vessels and spans across multiple cell states from stem/progenitor to a variety of terminally differentiated cells. How each of these cell states are defined at the molecular level is not known preventing the optimal formation and integration of blood vessels in bioengineered tissues. Using innovative single cell gene expression and chromatin accessibility studies combined with innovative analysis, we propose to define and validate each cell state at the molecular level.
This new knowledge would greatly enhance our ability to control the transition between cell states leading to a more widespread use of endothelial cells in bioengineering of tissues globally for many applications.
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Prediction of phenotype for multiple traits from multi-omic data. This project aims to develop better methods for predicting traits in an individual based on their genome sequence. This method will be tested in agricultural animals and plants and in humans. The prediction formula is derived from a training dataset that has information on the traits and genome sequence of a sample of individuals. The prediction formula can then be applied to predict the trait in individuals where the trait is un ....Prediction of phenotype for multiple traits from multi-omic data. This project aims to develop better methods for predicting traits in an individual based on their genome sequence. This method will be tested in agricultural animals and plants and in humans. The prediction formula is derived from a training dataset that has information on the traits and genome sequence of a sample of individuals. The prediction formula can then be applied to predict the trait in individuals where the trait is unknown. This is useful for selecting the best parents for breeding in agriculture and for predicting the future phenotype of animals, crops and people. The proposed method uses data on very many traits to identify sequence variants that have a function and to predict the traits affected by each variant.Read moreRead less
A macrophage-centric holistic view of postnatal development. The immediate postnatal period in mammals is crucial for survival, long term health and productivity. It is also a time when animals are especially susceptible to infectious disease. This project aims to investigate how cells of the innate immune system called macrophages control somatic growth and development of mature organ function in the early postnatal period. The project aims to build upon investment in new animal models and a no ....A macrophage-centric holistic view of postnatal development. The immediate postnatal period in mammals is crucial for survival, long term health and productivity. It is also a time when animals are especially susceptible to infectious disease. This project aims to investigate how cells of the innate immune system called macrophages control somatic growth and development of mature organ function in the early postnatal period. The project aims to build upon investment in new animal models and a novel discovery to generate significant new knowledge that challenges current concepts of mammalian growth control. The outcomes will enhance Australia's international reputation in the fields of physiology, immunology and developmental biology and may translate to improvements in health in animals and humans. Read moreRead less
How do mammalian germ cells transition from mitosis to meiosis? This project aims to determine how germ cells are regulated in the mammalian embryo. Germ cells go on to form the sperm and eggs and are, therefore, critical for reproduction. In particular, this project expects to generate new knowledge about the process of meiosis, a cellular process that is specific to the germ cells. Expected outcomes will inform efforts to control fertility and infertility in livestock, humans and other mammali ....How do mammalian germ cells transition from mitosis to meiosis? This project aims to determine how germ cells are regulated in the mammalian embryo. Germ cells go on to form the sperm and eggs and are, therefore, critical for reproduction. In particular, this project expects to generate new knowledge about the process of meiosis, a cellular process that is specific to the germ cells. Expected outcomes will inform efforts to control fertility and infertility in livestock, humans and other mammalian animals (e.g. pets and endangered species). They are also likely to inform the discipline of stem cell biology in general.Read moreRead less