Early evolution of the endomesoderm gene regulatory network. This project aims to unravel the endomesoderm gene network’s evolutionary history by identifying its conserved components’ target genes in the calcareous sponge Sycon. Little is known about the evolutionary origin of the developmental gene regulatory networks active in the development of all Eumetazoans (animals with nerves and digestive systems). Sponges are key models to study the transition from protists to eumetazoans, and gene exp ....Early evolution of the endomesoderm gene regulatory network. This project aims to unravel the endomesoderm gene network’s evolutionary history by identifying its conserved components’ target genes in the calcareous sponge Sycon. Little is known about the evolutionary origin of the developmental gene regulatory networks active in the development of all Eumetazoans (animals with nerves and digestive systems). Sponges are key models to study the transition from protists to eumetazoans, and gene expression data supports homology between sponge and eumetazoan tissues and body plans. This project could illuminate the evolutionary history of the animal body plan.Read moreRead less
Uncovering an evolutionary advanced mechanism of gene expression control. This project aims to uncover a new mechanism that activates gene expression in mammals, which involves unexpected connections between the core components of chromosomes and essential enzymatic machines required for the expression of genes. This project will generate new knowledge on the poorly understood process of how the extensive genomic information of multicellular organisms is selectively chosen to enable the expressi ....Uncovering an evolutionary advanced mechanism of gene expression control. This project aims to uncover a new mechanism that activates gene expression in mammals, which involves unexpected connections between the core components of chromosomes and essential enzymatic machines required for the expression of genes. This project will generate new knowledge on the poorly understood process of how the extensive genomic information of multicellular organisms is selectively chosen to enable the expression of only the required subset of genes. This will revolutionise our understanding of the mechanisms of gene control thereby shaping the field in the future. Significantly, this will allow new ways to manipulate gene expression that will impact biotechnology by providing new efficient ways to produce proteins or RNA. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100184
Funder
Australian Research Council
Funding Amount
$425,000.00
Summary
Pioneering alpine epigenomics to discover adaptive genetic elements. The genetic code of native plants are yet to be explored for DNA elements that promote resilience to climate change. These elements are now ripe for discovery due to recent advances in epigenomics allowing for rapid identification. This proposal aims to discover heat-associated elements in waxy bluebells, which inhabit Australia’s vulnerable high country. Expected outcomes include new insights on gene regulatory mechanisms in n ....Pioneering alpine epigenomics to discover adaptive genetic elements. The genetic code of native plants are yet to be explored for DNA elements that promote resilience to climate change. These elements are now ripe for discovery due to recent advances in epigenomics allowing for rapid identification. This proposal aims to discover heat-associated elements in waxy bluebells, which inhabit Australia’s vulnerable high country. Expected outcomes include new insights on gene regulatory mechanisms in native plants; the generation of resources for genetic conservation, and catalysing further molecular research into Australian flora. This should provide significant benefits by revealing genome regulation in native plants, thereby improving the ability to predict the impacts of climate change.Read moreRead less
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
Dissecting a RNA-histone variant interaction and its role in splicing. This project aims to define the molecular details of how a chromatin component, histone H2A.B, binds RNA and influences RNA splicing. This is unprecedented for histones, which are typically associated with DNA and transcriptional regulation. Over 90 per cent of human genes may be alternatively spliced. This explains how complex organisms develop from a limited set of genes, but how alternative splicing decisions are made is u ....Dissecting a RNA-histone variant interaction and its role in splicing. This project aims to define the molecular details of how a chromatin component, histone H2A.B, binds RNA and influences RNA splicing. This is unprecedented for histones, which are typically associated with DNA and transcriptional regulation. Over 90 per cent of human genes may be alternatively spliced. This explains how complex organisms develop from a limited set of genes, but how alternative splicing decisions are made is unclear. The intended outcome is to reveal links between chromatin, RNA splicing and gene expression regulation to explain how multicellular organisms have evolved. The translation of this knowledge will ultimately provide long-term economic and health benefits for Australia.Read moreRead less
Understanding how dynamic changes in chromatin composition control genome function. DNA is tightly packaged in eukaryotic cells as chromatin. Important genetic processes, such as transcription, require manipulation of chromatin structure to access the DNA. The cell sets up specialised chromatin structures to regulate these processes. Currently, precise molecular details of these specialised structures are limited. This project will push the envelope of an in vitro model chromatin system and dete ....Understanding how dynamic changes in chromatin composition control genome function. DNA is tightly packaged in eukaryotic cells as chromatin. Important genetic processes, such as transcription, require manipulation of chromatin structure to access the DNA. The cell sets up specialised chromatin structures to regulate these processes. Currently, precise molecular details of these specialised structures are limited. This project will push the envelope of an in vitro model chromatin system and determine the architecture of several chromatin states with unique functional implications inside the cell. This will unravel the molecular instructions that define how our genomes are organised, significantly advancing our knowledge of fundamental eukaryotic genome biology and paving the way for the future development of new tools and therapies.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
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
Tracking factor footprints to reveal the intricacy and control of translation initiation. Messenger ribonucleic acid (RNA) translation is required for all of life and knowledge of how it works is central to modern life sciences. This project will develop novel ways of studying translation, generating entirely new descriptions of its inner workings that may transform knowledge of gene function and its use in medical and biotechnological processes.