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
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
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
A community based social identity approach to loneliness. Loneliness across Australia is a deep concern. Social prescribing is a novel community-based approach to managing loneliness, however it is unclear when and in what circumstances it is effective. This project aims to test a social identity approach to loneliness, incorporating longitudinal, cross-sectional, and experimental methods to understand how best to engage isolated people in group programs. The expected benefits of this project ar ....A community based social identity approach to loneliness. Loneliness across Australia is a deep concern. Social prescribing is a novel community-based approach to managing loneliness, however it is unclear when and in what circumstances it is effective. This project aims to test a social identity approach to loneliness, incorporating longitudinal, cross-sectional, and experimental methods to understand how best to engage isolated people in group programs. The expected benefits of this project are to produce a validated social prescribing model that can be implemented in multiple settings across Australia in order to reduce loneliness, strengthen communities, and guide more appropriate uses of health services.Read moreRead less
Improving Indigenous health and wellbeing over the family life course. Improving Indigenous health and wellbeing over the family life course. This project aims to reduce Indigenous health inequalities, a major social and economic problem, by improving the policy relevant evidence base on the determinants of Indigenous health and wellbeing. This project will compare the impact of the family life course on the health and wellbeing of Indigenous and non-Indigenous mothers and children. It will use ....Improving Indigenous health and wellbeing over the family life course. Improving Indigenous health and wellbeing over the family life course. This project aims to reduce Indigenous health inequalities, a major social and economic problem, by improving the policy relevant evidence base on the determinants of Indigenous health and wellbeing. This project will compare the impact of the family life course on the health and wellbeing of Indigenous and non-Indigenous mothers and children. It will use survey data that follows them over time to: 1) identify family structures that enhance or harm health and wellbeing, and; 2) track changes in health and wellbeing before, during and after family transitions (i.e. births, relationship changes). Anticipated results are better targeted policy interventions to reduce Indigenous health inequalities.Read moreRead less
Confronting everyday harms: preventing abuse of people with disability. The findings of the Disability Royal Commission necessitate new approaches to prevent violence, abuse, neglect and exploitation. Framed by recognition theory, this project proposes empirical research with young people with cognitive disability, using a new concept of ‘everyday harms’ in their paid relationships. The results will inform early responses to poor quality interactions in disability support. The strategic alliance ....Confronting everyday harms: preventing abuse of people with disability. The findings of the Disability Royal Commission necessitate new approaches to prevent violence, abuse, neglect and exploitation. Framed by recognition theory, this project proposes empirical research with young people with cognitive disability, using a new concept of ‘everyday harms’ in their paid relationships. The results will inform early responses to poor quality interactions in disability support. The strategic alliances with the government, industry and community partners will develop a practice framework to prevent everyday harms and the escalation to abuse, and to promote safety and wellbeing. The research has policy benefits for capacity-building in the sector to act on the rights and voices of people with disability. 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