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How novel ribosomal RNA gene repeat variants drive cellular function. The hundreds of ribosomal RNA gene repeat copies are a remarkable part of our genomes, as they encode the machinery responsible for all cellular protein synthesis and shape the structure of the nucleus. However, due to their high degree of sequence similarity, they still have not been assembled into the human genome reference. This project will resolve this impasse and furthermore uncover the functional impacts of a newly iden ....How novel ribosomal RNA gene repeat variants drive cellular function. The hundreds of ribosomal RNA gene repeat copies are a remarkable part of our genomes, as they encode the machinery responsible for all cellular protein synthesis and shape the structure of the nucleus. However, due to their high degree of sequence similarity, they still have not been assembled into the human genome reference. This project will resolve this impasse and furthermore uncover the functional impacts of a newly identified molecular diversity in the ribosomal RNA gene repeats. Outcomes include new paradigms for how the ribosomal RNA gene repeats drive protein synthesis and genome structure, and a blueprint to develop novel genomics applications for human health, biotechnology, and agriculture.Read moreRead less
Differentiation of effector and tissue regulatory T cells . Regulatory T cells (Tregs) populate almost every organ of the body and play a central role in preventing inflammation and maintaining health. To exercise these functions, Tregs undergo a developmental program, the details of which are poorly known. This project will utilize newly developed biological tools and state-of-the-art technology to uncover the molecular mechanisms that govern Treg development and function. The project will gene ....Differentiation of effector and tissue regulatory T cells . Regulatory T cells (Tregs) populate almost every organ of the body and play a central role in preventing inflammation and maintaining health. To exercise these functions, Tregs undergo a developmental program, the details of which are poorly known. This project will utilize newly developed biological tools and state-of-the-art technology to uncover the molecular mechanisms that govern Treg development and function. The project will generate basic scientific knowledge and new intellectual property that will afford new opportunities for research and development. The outcomes of this project will help to devise strategies to treat diseases such as autoimmunity, cancer and metabolic syndrome, and will thus benefit veterinary and human health.Read moreRead less
Australian Heritage: constructing the first Aboriginal reference genome. This project aims to use DNA sequencing technologies to generate the first complete and accurate Aboriginal genomes, along with maps of genomic variation around Australia. It will combine a range of advanced analytical methods to integrate past and present indigenous genetic diversity from human populations around the world into a new pan-human reference genome. This project will lead to a step change in our understanding o ....Australian Heritage: constructing the first Aboriginal reference genome. This project aims to use DNA sequencing technologies to generate the first complete and accurate Aboriginal genomes, along with maps of genomic variation around Australia. It will combine a range of advanced analytical methods to integrate past and present indigenous genetic diversity from human populations around the world into a new pan-human reference genome. This project will lead to a step change in our understanding of global human genomic variants and provide a range of new targets relevant to medical biology, while significantly improving our knowledge of human genetic history and its consequences in the modern day.Read moreRead less
Demographic and evolutionary inferences from large, whole-genome datasets. A new data structure for genome-wide datasets has allowed great improvements in the efficiency of genomic data storage and in population genomics simulations, which are crucial to developing and testing mathematical models of population history and species evolution. We will take these advances in new directions, using efficient data structures to dramatically improve inferences about: the demographic histories of popul .... Demographic and evolutionary inferences from large, whole-genome datasets. A new data structure for genome-wide datasets has allowed great improvements in the efficiency of genomic data storage and in population genomics simulations, which are crucial to developing and testing mathematical models of population history and species evolution. We will take these advances in new directions, using efficient data structures to dramatically improve inferences about: the demographic histories of populations, rates of genome change, and phylogenetic networks, and we will develop the first inference methods for the multispecies coalescent with recombination. Outcomes will include advances in understanding the evolutionary histories of humans and other species, including pathogens of importance for global health.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL180100072
Funder
Australian Research Council
Funding Amount
$3,460,832.00
Summary
Causes and consequence of human trait variation. This project aims to exploit the availability of Big Data from the genomics revolution to understand the relationship between the genome, the environment and complex human traits. New statistical methods and user-friendly software tools will be developed and applied to datasets on millions of individuals to generate new knowledge on human life history variation and healthy ageing. This project will position Australia to benefit from rapid advances ....Causes and consequence of human trait variation. This project aims to exploit the availability of Big Data from the genomics revolution to understand the relationship between the genome, the environment and complex human traits. New statistical methods and user-friendly software tools will be developed and applied to datasets on millions of individuals to generate new knowledge on human life history variation and healthy ageing. This project will position Australia to benefit from rapid advances in genomic technologies, to build and sustain critical capacity in statistical genetics, and better understand the causes and consequence of individual differences in human traits from genetic and environmental factors across the entire human lifespan.Read moreRead less
Beyond pineal melatonin: sensing the seasons without the eye. The project will identify the causal connection between seasonal breeding in animals and a recently recognised brain biochemical pathway by applying experimental treatments mimicking seasonal environmental changes in a mutant and wild-type nematode worm model. Through experimentation we will identify useful biological targets that might be manipulated to enhance control of seasonal breeding in managed animals. With better control of r ....Beyond pineal melatonin: sensing the seasons without the eye. The project will identify the causal connection between seasonal breeding in animals and a recently recognised brain biochemical pathway by applying experimental treatments mimicking seasonal environmental changes in a mutant and wild-type nematode worm model. Through experimentation we will identify useful biological targets that might be manipulated to enhance control of seasonal breeding in managed animals. With better control of reproductive output in animals, farmers and managers can increase and/or decrease reproductive output as needed in managed species including livestock and vertebrate pests. This will enhance the use of precious land resources and minimize ecological damage from overbreeding.Read moreRead less
Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this ....Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this study will be a catalogue of functionally active circRNAs. Over the past decades, the wealth of knowledge on the function of linear mRNAs has had a significant impact on medicine and agriculture. Similarly understanding how circRNAs regulate cellular activities may have an analogous impact on humans.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220101210
Funder
Australian Research Council
Funding Amount
$451,634.00
Summary
Deciphering molecular genetic mechanisms underlying chromatin interactions. This project aims to generate the high confidence map of enhancer-promoter links in 61 tissues and cells through robust integration of novel machine learning tools with genomic and epigenomic datasets. Understanding which key elements in the genome may be important to fine-tune gene expression is essential for understanding biological pathways. The expected outcomes include i) New tools to robustly identify true chromati ....Deciphering molecular genetic mechanisms underlying chromatin interactions. This project aims to generate the high confidence map of enhancer-promoter links in 61 tissues and cells through robust integration of novel machine learning tools with genomic and epigenomic datasets. Understanding which key elements in the genome may be important to fine-tune gene expression is essential for understanding biological pathways. The expected outcomes include i) New tools to robustly identify true chromatin pairs; ii) Comperehensive maps of regulatory interactomes in 61 tissues & cells, which will provide a roadmap for interpreting & prioritising noncoding variants.
This should provide significant benefit to Australia's capacity for cutting-edge genomics research through fundamental understanding of gene regulation mechanism.Read moreRead less
Targeting the genome and epigenome of the exercising skeletal muscle. This project aims is to discover epigenetic and genetic biomarkers that predict fitness changes, following exercise intervention. Individuals are remarkably variable in their responses to exercise interventions, and a large portion of these responses is attributed to genetics, and epigenetics (the effect of the environment on the expression of genes). Using controlled exercise training as a model, this project expects to disco ....Targeting the genome and epigenome of the exercising skeletal muscle. This project aims is to discover epigenetic and genetic biomarkers that predict fitness changes, following exercise intervention. Individuals are remarkably variable in their responses to exercise interventions, and a large portion of these responses is attributed to genetics, and epigenetics (the effect of the environment on the expression of genes). Using controlled exercise training as a model, this project expects to discover epigenetic and genomic markers in skeletal muscle predictive of exercise adaptations. This will contribute to the development and future delivery of targeted and personalised exercise programs for the general population. This has important implications for improving health in the Australian population.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190101069
Funder
Australian Research Council
Funding Amount
$390,000.00
Summary
Adaptation and diversification of the first peoples of Sahul. This project aims to further advance work on the genetic history of Indigenous Australians and Papuans that has revealed that Aboriginal Australians have inhabited a variety of diverse and challenging environments for approximately 50,000 years. Using novel techniques for extraction of human DNA from soil and the use of cutting-edge graph-based methods, hundreds of Indigenous Australian and Papuan genomes will be analysed. This projec ....Adaptation and diversification of the first peoples of Sahul. This project aims to further advance work on the genetic history of Indigenous Australians and Papuans that has revealed that Aboriginal Australians have inhabited a variety of diverse and challenging environments for approximately 50,000 years. Using novel techniques for extraction of human DNA from soil and the use of cutting-edge graph-based methods, hundreds of Indigenous Australian and Papuan genomes will be analysed. This project expects to generate new knowledge by filling in the gaps in the Australian genetic record via ancient human DNA from sediments. Expected outcomes from this project are producing a detailed picture of genomic adaptation in Indigenous Australians and Papuans and creating a comprehensive genetic history of the First Peoples of Sahul.Read moreRead less