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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
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.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
Microbiome Regulation of the Host Mitochondrial Genome. This project aims to describe newly discovered processes by which bacteria that reside in the gut of an animal influences host mitochondria, the powerhouses of the cell. Using advanced genetic and molecular methodologies, this project aims to generate new knowledge on improving mitochondrial function as well as advance our understanding of the emerging field of microbiome research. Expected outcomes include a novel and universal technology ....Microbiome Regulation of the Host Mitochondrial Genome. This project aims to describe newly discovered processes by which bacteria that reside in the gut of an animal influences host mitochondria, the powerhouses of the cell. Using advanced genetic and molecular methodologies, this project aims to generate new knowledge on improving mitochondrial function as well as advance our understanding of the emerging field of microbiome research. Expected outcomes include a novel and universal technology platform in which to engineer small molecules and probiotics to improve mitochondrial health and enhance fitness in a range of animals. This should provide significant benefits, through both scientifically relevant outcomes and economic benefits through technological advancements.Read moreRead less
Statistical Methods for Next Generation Genome-Wide Association Studies. This project aims to develop cutting-edge statistical methods to analyse large genomic datasets and identify genetic variants associated with inter-individual differences in various human traits. Knowledge of trait-associated DNA variants is instrumental in understanding how natural selection has shaped human traits. By integrating genomic data from diverse and underrepresented populations, this project further expects to c ....Statistical Methods for Next Generation Genome-Wide Association Studies. This project aims to develop cutting-edge statistical methods to analyse large genomic datasets and identify genetic variants associated with inter-individual differences in various human traits. Knowledge of trait-associated DNA variants is instrumental in understanding how natural selection has shaped human traits. By integrating genomic data from diverse and underrepresented populations, this project further expects to contribute to the equitable use of genomic technologies in humans, regardless of geographical origins. Expected outcomes of this research include novel analysis methods and software tools, which should broadly and significantly benefit gene discovery in other species, including those of agricultural relevance.Read moreRead less
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
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