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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
Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time t ....Old genes learning new tricks: characterising regulatory changes driving increased heart complexity during vertebrate evolution. The heart has dramatically increased in morphological complexity during vertebrate evolution but the molecular basis driving these major changes remains unknown. Using comparative genomics approaches, this project will explore changes in the regulation of genes involved in heart formation that lead to changes in cardiac structure. It will elucidate for the first time the cardiac regulatory repertoire in zebrafish and will compare it with that of fly and mouse using cutting-edge bioinformatics pipelines. This work will unravel cardiac-specific regulatory modifications that give rise to evolutionary changes. On a broader scale, it will shed new light on the role of regulatory innovations over gene innovations in the emergence of new traits.Read moreRead less
Developing the Dunnart as a Model Species for Marsupial Research. The project aims to develop a marsupial model capable of genome manipulations to take our understanding of marsupial biology to the next level. In doing so, the project would produce the first comprehensive transcriptome data defining early cell lineage specification in a marsupial. Combined with similar data from mouse and human, it would enable us to examine diversity in early mammals. In addition, it would identify cohorts of g ....Developing the Dunnart as a Model Species for Marsupial Research. The project aims to develop a marsupial model capable of genome manipulations to take our understanding of marsupial biology to the next level. In doing so, the project would produce the first comprehensive transcriptome data defining early cell lineage specification in a marsupial. Combined with similar data from mouse and human, it would enable us to examine diversity in early mammals. In addition, it would identify cohorts of genes with fundamental roles in differentiation of the earliest cell lineages: trophoblast, pluriblast and hypoblast. The project may identify maternally localised transcripts with a marsupial-specific role in trophoblast–pluriblast specification, giving new insights into the fundamental pathways maintaining pluripotency in mammals and the evolution of the mammalian genome.Read moreRead less
The developmental and evolutionary origins of vertebrate fins and limbs. This project aims to investigate the origin of paired appendages, a major event in early vertebrate history that changed ecological opportunity and fuelled the radiation of jawed vertebrates. This project expects to generate new knowledge on the mechanism that drove this innovation, which despite over a century of debate, remains one
of the great unknowns of comparative vertebrate evolution. Expected outcomes of this projec ....The developmental and evolutionary origins of vertebrate fins and limbs. This project aims to investigate the origin of paired appendages, a major event in early vertebrate history that changed ecological opportunity and fuelled the radiation of jawed vertebrates. This project expects to generate new knowledge on the mechanism that drove this innovation, which despite over a century of debate, remains one
of the great unknowns of comparative vertebrate evolution. Expected outcomes of this project include uncovering the anatomical changes underpinning the origin of the vertebrate appendicular system. This should provide significant benefits as it will inform our own natural history and provide a paradigm for studying gene network
conservation, phylogenetic modifications, and the acquisition of novel structures.Read moreRead less
Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develo ....Revealing molecular detail of DNA triplexes to underpin antigene technology. Variations from the classic DNA double helix structure are proposed to play key roles in a range of cellular processes, particularly gene regulation. However, the biological function and therapeutic potential of these unusual DNA structures are poorly explored, since the fundamental molecular details which govern their formation and interactions with cellular machinery are not well described. This project aims to develop innovative methods to investigate, and importantly modulate, DNA and RNA triple helix assembly, specificity and molecular interactions. Resulting insights will underpin novel approaches to gene regulation, principally in the context of designing new antibacterial agents to address the antibacterial resistance problem.Read moreRead less
The social and environmental implications of privately regulated food quality standards for agri-food networks in Asia-Pacific. This proposal will contribute to an environmentally sustainable Australia in two ways. First, the research will highlight barriers to the uptake of environmental standards among fruit and vegetable growers as well as potential strategies to encourage certification. Second, the research will assess the extent to which compliance with internationally harmonised standards ....The social and environmental implications of privately regulated food quality standards for agri-food networks in Asia-Pacific. This proposal will contribute to an environmentally sustainable Australia in two ways. First, the research will highlight barriers to the uptake of environmental standards among fruit and vegetable growers as well as potential strategies to encourage certification. Second, the research will assess the extent to which compliance with internationally harmonised standards actually assists or encourages farmers to address local priority environmental issues. Improved understanding of the social and environmental impact of standards will highlight domestic policy and regulatory shifts which may be necessary to maximise positive environmental outcomes.Read moreRead less
Gastrointestinal hormones: linking insulin dysregulation and laminitis. This project aims to identify the earliest pathogenic factors of disease by investigating two key hormones, ghrelin and GLP-2, and whether a specific genetic mutation underlies insulin dysregulation. Using innovative approaches the project will enable the identification of at-risk animals and pinpoint novel treatment strategies. In the long term improved disease treatment and prevention will reduce the suffering associated w ....Gastrointestinal hormones: linking insulin dysregulation and laminitis. This project aims to identify the earliest pathogenic factors of disease by investigating two key hormones, ghrelin and GLP-2, and whether a specific genetic mutation underlies insulin dysregulation. Using innovative approaches the project will enable the identification of at-risk animals and pinpoint novel treatment strategies. In the long term improved disease treatment and prevention will reduce the suffering associated with painful and often lethal co-morbidities.Read moreRead less
Understanding how cells compact and segregate DNA in vertebrates. How a cell compacts and divides its DNA is still a major unanswered question in biology. This project will determine the way in which a cell compacts its DNA nearly ten thousand fold to allow the faithful and accurate segregation to daughter nuclei.
Cellular determinants of retrotransposition. This project aims to understand the processes that control retrotransposition in a genome. Transposable elements make up more than 50% of human genomes. The accumulation of retrotransposons through millions of years of evolution has shaped the genomes of all eukaryotic organisms, including humans. Researchers have elucidated mechanisms the host uses to defend the genome against insertional mutagenesis by retrotransposons, but the cellular machinery an ....Cellular determinants of retrotransposition. This project aims to understand the processes that control retrotransposition in a genome. Transposable elements make up more than 50% of human genomes. The accumulation of retrotransposons through millions of years of evolution has shaped the genomes of all eukaryotic organisms, including humans. Researchers have elucidated mechanisms the host uses to defend the genome against insertional mutagenesis by retrotransposons, but the cellular machinery and genomic environments needed for retrotransposition are undefined. This project aims to use models to uncover the mechanisms that control retrotransposition. This is expected to reveal more about human origins.Read moreRead less
How does an essential histone variant effect changes in gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are not clearly known. It is well established that gene expression patterns are determined in part by the molecular signals transmitted by variation in the proteins that package eukaryotic DNA. Our aim is to understand new aspects of these mechanisms that revolve around how our DNA is packaged. This foundational knowl ....How does an essential histone variant effect changes in gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are not clearly known. It is well established that gene expression patterns are determined in part by the molecular signals transmitted by variation in the proteins that package eukaryotic DNA. Our aim is to understand new aspects of these mechanisms that revolve around how our DNA is packaged. This foundational knowledge will deepen our understanding of gene regulation in all complex organisms and will inform future efforts to rationally modulate gene expression patterns in agriculture, research and other important areas.Read moreRead less