Charting the human epi-transcriptome. This project aims to use Oxford nanopore technologies and phage display technologies, to obtain quantitative, single-nucleotide resolution maps for any RNA modification of choice. This will allow systematic mapping of RNA modifications for which we currently lack transcriptome-wide maps, as well as investigate the roles, regulation and impact of RNA modifications in proper cellular functioning and cell differentiation. The project will provide significant be ....Charting the human epi-transcriptome. This project aims to use Oxford nanopore technologies and phage display technologies, to obtain quantitative, single-nucleotide resolution maps for any RNA modification of choice. This will allow systematic mapping of RNA modifications for which we currently lack transcriptome-wide maps, as well as investigate the roles, regulation and impact of RNA modifications in proper cellular functioning and cell differentiation. The project will provide significant benefits, such as to the economy by offering a cost-effective alternative to sequencing methods currently used to map DNA and RNA modifications.Read moreRead less
Using population resequencing data to investigate the evolutionary role and functional impact of inversion polymorphisms. The project will use population re-sequencing data to generate high resolution haplotype maps of inversion polymorphisms in multiple human populations comprising more than 5,000 individuals. These maps will be used to impute inversion polymorphsisms in genotyped samples of more than 100,000 individuals, facilitated by development of novel algorithms for mapping inversion poly ....Using population resequencing data to investigate the evolutionary role and functional impact of inversion polymorphisms. The project will use population re-sequencing data to generate high resolution haplotype maps of inversion polymorphisms in multiple human populations comprising more than 5,000 individuals. These maps will be used to impute inversion polymorphsisms in genotyped samples of more than 100,000 individuals, facilitated by development of novel algorithms for mapping inversion polymorphism from population sequence data. Finally, the project will use this map to assess the functional impact and evolutionary role of inversions, by assessing their effect on quantitative traits and assessing measures of selection and population differentiation. Read moreRead less
Turning back the clock on brain cell aging. This proposal aims to determine the role of fundamental epigenetic mechanisms in the process of aging and whether modulation of the epi-genome underpins an improvement in cognitive function. It combines the fields of epigenetics, neurosciences and mathematics to delineate the dynamics of DNA methylation and histone modification marking on the transcriptome during normal, healthy aging. The outcomes will provide significant new knowledge of the variable ....Turning back the clock on brain cell aging. This proposal aims to determine the role of fundamental epigenetic mechanisms in the process of aging and whether modulation of the epi-genome underpins an improvement in cognitive function. It combines the fields of epigenetics, neurosciences and mathematics to delineate the dynamics of DNA methylation and histone modification marking on the transcriptome during normal, healthy aging. The outcomes will provide significant new knowledge of the variable cognitive decline that occurs in healthy aging and why some populations age less successfully than others do. Better understanding of the impact of environmental change on the biology of aging has potential community benefits.Read moreRead less
How and why cells decorate their genetic messages. This project aims to investigate a new layer of genomic control mediated not by DNA but instead by chemical modifications found on the cell's working copies of genetic information called messenger RNA. The investigations will use cutting-edge RNA sequencing technology and the fruit fly model organism to uncover the scope and mechanisms by which such modifications enact their roles at the molecular level and within the body plan of an animal. Exp ....How and why cells decorate their genetic messages. This project aims to investigate a new layer of genomic control mediated not by DNA but instead by chemical modifications found on the cell's working copies of genetic information called messenger RNA. The investigations will use cutting-edge RNA sequencing technology and the fruit fly model organism to uncover the scope and mechanisms by which such modifications enact their roles at the molecular level and within the body plan of an animal. Expected outcomes include novel molecular tools and models that will assist in understanding and manipulating the function of genomes. Such knowledge should provide benefits in developing innovative biotechnology applications of use in human health, agriculture and managing the environment.
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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100143
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
Flexible architecture high-performance computing facility for the intersect consortium of New South Wales. This new supercomputing facility is an important addition to the nation's research infrastructure and will enable world-leading, New South Wales researchers to continue their ground breaking work in increasingly competitive environments. Much of the research to be undertaken at the facility lies in areas of national priority, including frontier technologies and environmental sustainability.
Discovery Early Career Researcher Award - Grant ID: DE150101117
Funder
Australian Research Council
Funding Amount
$327,000.00
Summary
The functional impact of new genes acquired through retrotransposition. Novel copies of genes often arise through retrotransposition of processed messenger RNAs. Many thousands of gene copies have arisen over evolutionary time and some of these have retained functionality while diverging from the parental gene leading to new paralogs under different regulatory regimes. Through analysis of whole-genome sequence data, we are now able to identify very recent gene copies that are not present in the ....The functional impact of new genes acquired through retrotransposition. Novel copies of genes often arise through retrotransposition of processed messenger RNAs. Many thousands of gene copies have arisen over evolutionary time and some of these have retained functionality while diverging from the parental gene leading to new paralogs under different regulatory regimes. Through analysis of whole-genome sequence data, we are now able to identify very recent gene copies that are not present in the reference genomes for various species, giving us the opportunity to explore the effects of new copies on the regulation of the original gene and the surrounding genomic environment into which the new copy is inserted. This project aims to address these important open questions through computational and biochemical approaches.Read moreRead less
Evolution and functional impact of gene silencing by hairpin derived RNAs. This project aims to study RNA-mediated gene silencing in genome evolution. RNA interference (RNAi) has been widely used as an experimental tool since its Nobel Prize-winning discovery in 1998, but little is known about endogenous RNAi or its evolution. This project uses bioinformatics, high-throughput sequencing and molecular approaches to study hpRNAs, a class of small interfering RNAs, their adaptive evolution across f ....Evolution and functional impact of gene silencing by hairpin derived RNAs. This project aims to study RNA-mediated gene silencing in genome evolution. RNA interference (RNAi) has been widely used as an experimental tool since its Nobel Prize-winning discovery in 1998, but little is known about endogenous RNAi or its evolution. This project uses bioinformatics, high-throughput sequencing and molecular approaches to study hpRNAs, a class of small interfering RNAs, their adaptive evolution across fly species and vertebrates, and their functional effect on testis morphogenesis and distortion of female/male sex-ratio. The project also studies splicing-dependent small RNAs and miRNA-target interaction. This research could have applications from animal development to human pathology.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100883
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Palaeo-population genomics: studying adaptation using ancient human DNA. This project aims to apply state-of-the-art population and quantitative genetic techniques to a powerful new database of ancient human genomes - spanning from hunter gatherers and early farmers through to the Middle Ages. This will be used to build the first detailed portrait of human genetic adaptation through time. This record will capture the major socio-cultural transitions in human history, and reveal the genetic and e ....Palaeo-population genomics: studying adaptation using ancient human DNA. This project aims to apply state-of-the-art population and quantitative genetic techniques to a powerful new database of ancient human genomes - spanning from hunter gatherers and early farmers through to the Middle Ages. This will be used to build the first detailed portrait of human genetic adaptation through time. This record will capture the major socio-cultural transitions in human history, and reveal the genetic and environmental drivers that have shaped modern human genetic diversity and pathology.Read moreRead less
Genome-wide discovery of translation control mechanisms. This project aims to reveal currently unknown molecular details of protein synthesis, a step of gene expression that is central to all of life. To achieve this, innovative methods based on next-generation sequencing will be deployed in the yeast model organism. Yeasts are of importance as pathogens as well as in the food and biotechnology industry sector. Thus, new knowledge generated in this project will help solve problems of invasive pa ....Genome-wide discovery of translation control mechanisms. This project aims to reveal currently unknown molecular details of protein synthesis, a step of gene expression that is central to all of life. To achieve this, innovative methods based on next-generation sequencing will be deployed in the yeast model organism. Yeasts are of importance as pathogens as well as in the food and biotechnology industry sector. Thus, new knowledge generated in this project will help solve problems of invasive pathogenic behaviour and biomass production.Read moreRead less
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