Role of R-loops and double R-loops in genome organisation and transcription. The majority of our genome is converted to an extensive network of non-protein-coding RNA molecules (ncRNAs), but the function of these ncRNAs is unknown. This project aims to identify and determine the mechanism of action of nuclear ncRNA networks with a particular focus on nuclear ncRNAs that form RNA-DNA hybrids with the genomic DNA. These studies have the potential to lead to ground-breaking discoveries in our under ....Role of R-loops and double R-loops in genome organisation and transcription. The majority of our genome is converted to an extensive network of non-protein-coding RNA molecules (ncRNAs), but the function of these ncRNAs is unknown. This project aims to identify and determine the mechanism of action of nuclear ncRNA networks with a particular focus on nuclear ncRNAs that form RNA-DNA hybrids with the genomic DNA. These studies have the potential to lead to ground-breaking discoveries in our understanding of genome organisation and the mechanism of transcription control, and might provide an entirely new tool-box to manipulate genome function. This should provide significant benefits to efforts to develop innovative biotechnology and genome editing technologies in plants and animals.Read moreRead less
RNA surveillance and the initial steps of RNA biogenesis. This project aims to understand the initial steps of RNA biogenesis and how this process is linked to the chromatin environment. Although less than five per cent of our genome encodes proteins, almost the entire genome is transcribed to RNA. A large portion of these transcripts are degraded during the early steps of RNA biogenesis by the RNA surveillance machinery, but the mechanism for the recognition and degradation of these transcripts ....RNA surveillance and the initial steps of RNA biogenesis. This project aims to understand the initial steps of RNA biogenesis and how this process is linked to the chromatin environment. Although less than five per cent of our genome encodes proteins, almost the entire genome is transcribed to RNA. A large portion of these transcripts are degraded during the early steps of RNA biogenesis by the RNA surveillance machinery, but the mechanism for the recognition and degradation of these transcripts is not understood. New evidence suggests that the chromatin environment of the transcribed locus plays an important role in this process. This project will lead to significant benefits in the implementation of emerging RNA-based technologies and in understanding how genome stability is maintained.Read moreRead less
Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between the ....Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between these two important processes and will fill a significant gap in our understanding of how splicing quality control and nuclear RNA surveillance work. The project will also identify sequence features that trigger abortive splicing reactions and will thus help to improve the design of synthetic mRNAs.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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Kingdom switching microbial pathogens: the bioinformatics of mutation in the genomes of viruses and bacteria affecting crops, livestock and people. Some organisms that cause infectious diseases have moved between plants and vertebrates, either recently or repeatedly over evolutionary time. Switching between plants and vertebrates strongly influences the way these microbes mutate and evolve. We will search the genomic sequence databases for information about how the choice of host influences muta ....Kingdom switching microbial pathogens: the bioinformatics of mutation in the genomes of viruses and bacteria affecting crops, livestock and people. Some organisms that cause infectious diseases have moved between plants and vertebrates, either recently or repeatedly over evolutionary time. Switching between plants and vertebrates strongly influences the way these microbes mutate and evolve. We will search the genomic sequence databases for information about how the choice of host influences mutations in viral and bacterial genomes and model the evolutionary processes involved. This project will advance our understanding of the fine structure of microbial genomes and the importance of selection pressures on genes. It will lead to better disease management strategies for humans, and for domestic crops and livestock.Read moreRead less
Chromatin structure and pervasive transcription. This project aims to understand mechanisms that repress pervasive transcription and to identify chromatin characteristics that repress transcription initiation outside the promoter regions. Chromatin characteristics, such as position, occupancy and turnover-rate of nucleosomes, establish an elaborate genomic indexing mechanism, which defines functional units in the genome. Defects in this process increase pervasive transcription, toxic accumulatio ....Chromatin structure and pervasive transcription. This project aims to understand mechanisms that repress pervasive transcription and to identify chromatin characteristics that repress transcription initiation outside the promoter regions. Chromatin characteristics, such as position, occupancy and turnover-rate of nucleosomes, establish an elaborate genomic indexing mechanism, which defines functional units in the genome. Defects in this process increase pervasive transcription, toxic accumulation of non-coding transcripts and genomic instability. This work aims to understand eukaryotic genome organisation and may have long-term therapeutic implications for cancer and ageing-related diseases.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100068
Funder
Australian Research Council
Funding Amount
$240,000.00
Summary
Mass spectrometry platform for high throughput genotyping, epigenetic analysis and validation of genome wide sequencing studies. This facility will provide a platform for Australian researchers to quantitatively measure genetic information in a rapid, accurate and cost-efficient manner. This technology will enhance Australia's ability to perform basic research into the genetic and epigenetic mechanisms of cellular function.
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
Discovery Early Career Researcher Award - Grant ID: DE130101450
Funder
Australian Research Council
Funding Amount
$374,300.00
Summary
The molecular basis of division of labour in the beehive. This study will dissect the genes and gene networks underpinning behaviour using cutting edge molecular and computational techniques. As a model, this project will study the division of labour in a social insect, the honeybee.
The roles and regulators of new plant cells linked to root transport. Plant genomics has moved to the single cell resolution, allowing precise investigations of previously hidden cell types and cell states that respond to environmental stress and that vary among differentially adapted plant populations. Here, we will extend our pioneering efforts that have mapped and discovered novel root cell types, to determine their salt and nutrient stress responses, and to elegantly dissect the underling ca ....The roles and regulators of new plant cells linked to root transport. Plant genomics has moved to the single cell resolution, allowing precise investigations of previously hidden cell types and cell states that respond to environmental stress and that vary among differentially adapted plant populations. Here, we will extend our pioneering efforts that have mapped and discovered novel root cell types, to determine their salt and nutrient stress responses, and to elegantly dissect the underling causal genetic variation. The unique cell markers and regulatory networks will be validated with tissue specific and transgenic tools that can work across a host of plant species to reveal adaptive cellular responses to harsh environmental conditions.Read moreRead less