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
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
Dynamic evolution of mutation rates: causes and impacts on genomic analysis. This project aims to illuminate the role of variation in mutation rate in driving evolutionary change. Mutation rate is a core parameter in evolutionary analyses in essential applications including epidemiology, conservation and medicine, yet remains a “black box” given arbitrary universal values. This project will take a whole-of-biodiversity approach to understanding the forces shaping mutation rate, impact on evoluti ....Dynamic evolution of mutation rates: causes and impacts on genomic analysis. This project aims to illuminate the role of variation in mutation rate in driving evolutionary change. Mutation rate is a core parameter in evolutionary analyses in essential applications including epidemiology, conservation and medicine, yet remains a “black box” given arbitrary universal values. This project will take a whole-of-biodiversity approach to understanding the forces shaping mutation rate, impact on evolution of biodiversity and effect on accuracy and precision of phylogenetic analyses. Using Australian case studies, the expected outcome of this project will be a greater understanding variation in mutation rate between species, providing significant benefits in developing more sophisticated and reliable phylogenetic analyses.Read moreRead less
Earth's Dynamic Topography Through Space and Time. A key component of Earth’s topography remains enigmatic. This so-called dynamic topography is transient, varying in response to convection within Earth’s mantle. This project aims to use a data-driven computational approach to: (i) reconstruct the evolution of dynamic topography over the recent geological history of our planet (Cenozoic Era, 0-66 million years ago); and (ii) uncover the mechanisms controlling its spatial and temporal evolution. ....Earth's Dynamic Topography Through Space and Time. A key component of Earth’s topography remains enigmatic. This so-called dynamic topography is transient, varying in response to convection within Earth’s mantle. This project aims to use a data-driven computational approach to: (i) reconstruct the evolution of dynamic topography over the recent geological history of our planet (Cenozoic Era, 0-66 million years ago); and (ii) uncover the mechanisms controlling its spatial and temporal evolution. This transformational new understanding will connect the evolution of our planet's surface environments to its deep interior, revealing the impact of dynamic topography on sea level change, flooding, river networks, groundwater systems, habitat development and the distribution of economic resources. Read moreRead less
Evolution and mechanisms of interactions in biofilm communities. This project aims to study the long-term experimental evolution of a mixed species bacterial biofilm community. This project expects to gain understanding of the genetic and physiological basis of community evolution. Expected outcomes of this project will be an understanding of how synthetic communities evolve. This will significantly benefit the use of synthetic communities relevant to fields such as antibiotic design, biotechnol ....Evolution and mechanisms of interactions in biofilm communities. This project aims to study the long-term experimental evolution of a mixed species bacterial biofilm community. This project expects to gain understanding of the genetic and physiological basis of community evolution. Expected outcomes of this project will be an understanding of how synthetic communities evolve. This will significantly benefit the use of synthetic communities relevant to fields such as antibiotic design, biotechnology, bioremediation, and synthetic biology where evolution can be inhibited or exploited, respectively.Read moreRead less
How are visual gene pathways lost and restored during reptile evolution? This project aims to investigate how complex traits are lost during evolution, and once lost if they can be regained. The project will use the diverse visual systems of snakes and lizards to shed light on the process of gene loss in degenerative lineages, and discover the mechanisms that compensate for gene losses in taxa with secondarily evolved visual capabilities- providing a case of evolutionary re-innovation in complex ....How are visual gene pathways lost and restored during reptile evolution? This project aims to investigate how complex traits are lost during evolution, and once lost if they can be regained. The project will use the diverse visual systems of snakes and lizards to shed light on the process of gene loss in degenerative lineages, and discover the mechanisms that compensate for gene losses in taxa with secondarily evolved visual capabilities- providing a case of evolutionary re-innovation in complex traits.Read moreRead less
RNA-binding proteins rewire transcriptomes in immune cell differentiation. This project aims to combine advanced computational and experimental techniques to investigate a new layer of gene regulation by novel RNA binding proteins (RBP) which control messenger RNA length in immune cells. This project expects to demonstrate that these RBPs have a profound effect on immune cell differentiation and response to infection. Expected outcomes include the discovery of new RBPs regulating immunity, with ....RNA-binding proteins rewire transcriptomes in immune cell differentiation. This project aims to combine advanced computational and experimental techniques to investigate a new layer of gene regulation by novel RNA binding proteins (RBP) which control messenger RNA length in immune cells. This project expects to demonstrate that these RBPs have a profound effect on immune cell differentiation and response to infection. Expected outcomes include the discovery of new RBPs regulating immunity, with mechanism and function determined by novel CRISPR editing of a transgenic mouse model. The significant benefit will be a more complete understanding of RNA mechanisms of immune response, which will be critical in informing future advances in the rapidly developing areas of RNA-based biotechnologies and synthetic immunology.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
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