Metabolic control of gene expression networks and microbiome interactions. The proposal aims to advance our understanding of how metabolism (and resulting metabolites) regulate the expression of genes, and investigate how these processes dictate the interaction of microbiota with the immune system. The project is expected to generate transformative knowledge of gene regulation, a fundamental process for cellular function, and decipher how the microbiome yeast Candida albicans interacts with immu ....Metabolic control of gene expression networks and microbiome interactions. The proposal aims to advance our understanding of how metabolism (and resulting metabolites) regulate the expression of genes, and investigate how these processes dictate the interaction of microbiota with the immune system. The project is expected to generate transformative knowledge of gene regulation, a fundamental process for cellular function, and decipher how the microbiome yeast Candida albicans interacts with immune cells and bacteria. By utilising a powerful combination of molecular and systems biology with molecular genetics and imaging, the project outcomes should foster interdisciplinary collaborations and build capacity for fundamental and applied research to benefit academia and industry, locally and globally.Read moreRead less
The transcriptome dynamics that refine eukaryotic gene expression. This project aims to understand the fundamental mechanisms of gene expression control, by exploring how cells respond to acute perturbation with changes to RNA expression and processing. Unlike the static information encoded within the genome, the information encoded in its intermediary RNA, is transient, plastic and responsive to environmental and developmental cues. This project will use new technologies encompassing RNA-bioche ....The transcriptome dynamics that refine eukaryotic gene expression. This project aims to understand the fundamental mechanisms of gene expression control, by exploring how cells respond to acute perturbation with changes to RNA expression and processing. Unlike the static information encoded within the genome, the information encoded in its intermediary RNA, is transient, plastic and responsive to environmental and developmental cues. This project will use new technologies encompassing RNA-biochemistry, Next Generation Sequencing, and bioinformatics to answer long-standing questions in RNA processing. The project expects to significantly enhance our understanding of the mechanisms underpinning gene-expression control, benefitting Australia by positioning it as a world leader in the field of RNA Biology.Read moreRead less
Uncovering microRNA decay regulation in mammalian cells. MicroRNAs (miRNAs) constitute a novel mechanism used by cells to regulate gene expression, however, very little is known about the mechanisms affecting miRNA accumulation. Characterisation of the kinetics of miRNA turnover is of paramount importance to establish the reliability of miRNAs as novel biomarkers. This project aims to characterise miRNA stability in mammalian cells, investigate mechanisms of turnover and establish their importan ....Uncovering microRNA decay regulation in mammalian cells. MicroRNAs (miRNAs) constitute a novel mechanism used by cells to regulate gene expression, however, very little is known about the mechanisms affecting miRNA accumulation. Characterisation of the kinetics of miRNA turnover is of paramount importance to establish the reliability of miRNAs as novel biomarkers. This project aims to characterise miRNA stability in mammalian cells, investigate mechanisms of turnover and establish their importance on the regulatory function of miRNAs. Such information is critical in the future development of targeted therapeutics.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150100652
Funder
Australian Research Council
Funding Amount
$345,000.00
Summary
Regulation of organ size and stem cell hierarchy in the developing kidney. Transient stem/progenitor cell populations play essential roles in establishing organ systems. The balance between self-renewal and differentiation in the nephron progenitor population plays a major, but poorly understood, role in regulating kidney development. Factors produced by undifferentiated progenitors promote organ expansion, whereas differentiation of these cells builds functional capacity. What is not clear is h ....Regulation of organ size and stem cell hierarchy in the developing kidney. Transient stem/progenitor cell populations play essential roles in establishing organ systems. The balance between self-renewal and differentiation in the nephron progenitor population plays a major, but poorly understood, role in regulating kidney development. Factors produced by undifferentiated progenitors promote organ expansion, whereas differentiation of these cells builds functional capacity. What is not clear is how the balance between self-renewal and differentiation is regulated in these cells, nor how the control of this fate decision impacts on optimal organ development. This project aims to dissect the molecular identity, regulation, and influence of this stem cell population on kidney development.Read moreRead less
Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisa ....Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisation or decay to control development. RNA-driven processes program morphogenesis and differentiation of spermatids, but via mechanisms only poorly understood. Uncovering the function of extensive cytoplasmic polyadenylation, which is essential for murine fertility, may fuel the next wave of RNA biotech applications. Read moreRead less
Spatio-temporal activation of genes in cells and mice. This project aims to develop novel genetic methods and instrumentation for the local, rapid and reversible activation of genes in cells and mice. This project expects to generate highly innovative light- and sound-based technologies that will permit to study living systems on the gene-level with unprecedented precision. Expected outcomes include new research and technology capacity to broadly address fundamental biological questions and to c ....Spatio-temporal activation of genes in cells and mice. This project aims to develop novel genetic methods and instrumentation for the local, rapid and reversible activation of genes in cells and mice. This project expects to generate highly innovative light- and sound-based technologies that will permit to study living systems on the gene-level with unprecedented precision. Expected outcomes include new research and technology capacity to broadly address fundamental biological questions and to create new applied processes. This project intends to provide significant benefits, such as enhanced knowledge generation, multidisciplinary training opportunities and patentable technologies.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100085
Funder
Australian Research Council
Funding Amount
$414,864.00
Summary
Elucidating a novel mechanism for coping with harmful mutations. This project aims to improve our understanding of the complex regulatory mechanisms that increase genetic and phenotypic robustness. Survival of organisms depends on their ability to cope with genetic variation. A novel process of genetic compensation has recently been identified, producing a normal phenotype in a homozygous mutant, that would be expected to have deleterious effects. This project will reveal how compensation is ach ....Elucidating a novel mechanism for coping with harmful mutations. This project aims to improve our understanding of the complex regulatory mechanisms that increase genetic and phenotypic robustness. Survival of organisms depends on their ability to cope with genetic variation. A novel process of genetic compensation has recently been identified, producing a normal phenotype in a homozygous mutant, that would be expected to have deleterious effects. This project will reveal how compensation is achieved by examining the molecular pathways that are activated following genetic mutation. This project is expected to strengthen Australian reputation in evolutionary genetics, and in turn enhance our understanding of how organisms adapt to changing environments.Read moreRead less
Understanding co-activator function in transcriptional regulation. A change in gene expression underpins all cell fate decisions yet there is scant knowledge about how transcription factors (TF), the master regulators of transcription, specifically interact with some, but not all, transcription cofactors to nuance gene expression. Aims: Using innovative molecular technologies we will identify and characterise the shared and unique relationships between TF and cofactors. Significance: This study ....Understanding co-activator function in transcriptional regulation. A change in gene expression underpins all cell fate decisions yet there is scant knowledge about how transcription factors (TF), the master regulators of transcription, specifically interact with some, but not all, transcription cofactors to nuance gene expression. Aims: Using innovative molecular technologies we will identify and characterise the shared and unique relationships between TF and cofactors. Significance: This study is important to every biological process in plants and animals driven by a change in gene expression. Expected Outcomes: This study will increase our biological knowledge in transcription control. Benefit: The knowledge gained has future applications in genomics and broad implications for biotechnology and industry.Read moreRead less
Can we exploit mRNA modifications to control protein expression? Genes are encoded by DNA but are transcribed into a message called RNA before they can be translated into protein. RNA can be chemically modified at a gene-specific level, and this modification has been central to the success of RNA vaccines against COVID-19. Despite the importance of these modifications in cellular life and in biotechnology, the role of the most abundant RNA modifications is unclear. This project will investigate ....Can we exploit mRNA modifications to control protein expression? Genes are encoded by DNA but are transcribed into a message called RNA before they can be translated into protein. RNA can be chemically modified at a gene-specific level, and this modification has been central to the success of RNA vaccines against COVID-19. Despite the importance of these modifications in cellular life and in biotechnology, the role of the most abundant RNA modifications is unclear. This project will investigate how we can exploit RNA modifications to modulate protein expression in a tractable single-celled organism with a small genome, Plasmodium. This information is important because understanding gene regulation is fundamental to all life, and the role of RNA modifications is emerging as integral to biotechnology.Read moreRead less
Genetic variation of single cell transcriptional heterogeneity in HiPSCs. This project aims to investigate whether induced pluripotent stem cells (iPSC) can be used to study the functions of genetic variants associated with human phenotypes and cell fate decisions. The project will utilise technology to produce single cell RNA sequence data for 100,000s of cells. By sequencing individual cells, the genetic control of cellular heterogeneity both within and between cells can be identified, and in ....Genetic variation of single cell transcriptional heterogeneity in HiPSCs. This project aims to investigate whether induced pluripotent stem cells (iPSC) can be used to study the functions of genetic variants associated with human phenotypes and cell fate decisions. The project will utilise technology to produce single cell RNA sequence data for 100,000s of cells. By sequencing individual cells, the genetic control of cellular heterogeneity both within and between cells can be identified, and in doing so, will provide significant benefit by revealing the potential for iPSC to be used for functional translation of human genomics.Read moreRead less