3'UTR switching in eukaryotic cells. The project aims to uncover conserved features fundamental to the mechanism and function of post-transcriptional gene-expression control. RNA systems interface the executive functions of DNA and the worker functions of proteins. mRNA often dictates the level, timing and location of protein synthesis. This project will use RNA-sequencing and bespoke bioinformatics to probe global RNA-dynamics. Mixing yeast-genetics with RNA-technologies, it focuses on 3’ untra ....3'UTR switching in eukaryotic cells. The project aims to uncover conserved features fundamental to the mechanism and function of post-transcriptional gene-expression control. RNA systems interface the executive functions of DNA and the worker functions of proteins. mRNA often dictates the level, timing and location of protein synthesis. This project will use RNA-sequencing and bespoke bioinformatics to probe global RNA-dynamics. Mixing yeast-genetics with RNA-technologies, it focuses on 3’ untranslated region (UTR) dynamics in eukaryotic cell biology. This project expects to significantly advance the understanding of eukaryotic gene function and gene regulation, critical in an age of personalised genomic medicine.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140101728
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
The regulation and evolution of posttranscriptional gene networks. The ability of cells to regulate gene expression is key for organism development, adaptation to new environments and evolutionary changes that shape the diversity of life on Earth. This project studies the RNA binding proteins called PUFs which are central for gene expression in diverse organisms. Using cutting-edge new generation systems biology approaches, this project will study how PUF proteins regulate genes to enable metabo ....The regulation and evolution of posttranscriptional gene networks. The ability of cells to regulate gene expression is key for organism development, adaptation to new environments and evolutionary changes that shape the diversity of life on Earth. This project studies the RNA binding proteins called PUFs which are central for gene expression in diverse organisms. Using cutting-edge new generation systems biology approaches, this project will study how PUF proteins regulate genes to enable metabolic adaptation, differentiation of cell types and the evolution of new gene expression outputs in distinct biological species. The outcomes will include new insights into the regulation and evolution of posttranscriptional gene networks. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100114
Funder
Australian Research Council
Funding Amount
$560,000.00
Summary
High Throughput Cell Genomics Centre. High throughput cell genomics centre: This project will establish a high throughput cell genomics centre comprising a Fluidigm C1™ Single-Cell AutoPrep and BioMark™ HD system providing researchers with the most innovative approach to single cell and small population analyses. The instruments will enable the unique capability to conduct single cell transcriptome analysis and high throughput gene expression, SNP genotyping and copy number variation analysis as ....High Throughput Cell Genomics Centre. High throughput cell genomics centre: This project will establish a high throughput cell genomics centre comprising a Fluidigm C1™ Single-Cell AutoPrep and BioMark™ HD system providing researchers with the most innovative approach to single cell and small population analyses. The instruments will enable the unique capability to conduct single cell transcriptome analysis and high throughput gene expression, SNP genotyping and copy number variation analysis as well as validation of next generation sequencing data. The information generated is crucial to advancing knowledge in important research fields including infection and immunity, regenerative medicine, immune responses, biomarker discovery, drug discovery, biotechnology and agriculture.Read moreRead less
Noncoding RNAs As Prognostic Markers And Therapeutic Targets In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$550,283.00
Summary
Normal human development involves a symphony of genetic changes that control the growth and differentiation of different types of cells during embryogenesis. For many years it has been assumed that most genetic information is transacted by proteins, and that the remaining 98% of the human genome that does not encode proteins was (apart from a limited amount of associated regulatory elements) largely non-functional evolutionary junk. However, this may not be the case. Recent results from our labo ....Normal human development involves a symphony of genetic changes that control the growth and differentiation of different types of cells during embryogenesis. For many years it has been assumed that most genetic information is transacted by proteins, and that the remaining 98% of the human genome that does not encode proteins was (apart from a limited amount of associated regulatory elements) largely non-functional evolutionary junk. However, this may not be the case. Recent results from our laboratory and others have shown that most of our genome and that of other mammals is actually expressed as noncoding RNA, which appears to be developmentally regulated. These RNAs (of which there appear to be tens of thousands, well outnumbering the protein-coding mRNAs) have been referred to as the hidden layer or dark matter of our genome, as they have barely been studied, but appear to play a central role in both normal and abnormal development in humans. There is now increasing evidence that many noncoding RNAs, including small regulatory RNAs called microRNAs, are perturbed in cancer and that these perturbations may be directly involved in, and be an accurate indicator of, cancer state and the direction of cancer progression. If this is true we need to understand the expression and functions of these RNAs in order to develop better diagnostics and perhaps powerful new therapeutics for cancer, based on RNA technology and generic delivery systems. This project will explore the patterns of noncoding RNA expression in normal breast development and in breast cancer, to identify those RNAs that direct or accompany the differentiation of these tissues, and to test the effects of interfering with their expression on these processes. These foundation studies lie at the leading edge of a new understanding of human genetics and cancer, and will provide a platform for future applications in medicine that utilize this information and understanding.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100116
Funder
Australian Research Council
Funding Amount
$415,737.00
Summary
Cell types and cell states revealed by single-cell regulatory networks. This project aims to use single-cell gene regulation networks to predict cell types. Computational approaches are needed to recapitulate how the over 37 trillion cells program the shared genome sequence in a human body to create astoundingly diverse forms and functions. This project integrates millions of high-resolution single-cell gene expression profiles with large-scale population regulatory data to systematically recons ....Cell types and cell states revealed by single-cell regulatory networks. This project aims to use single-cell gene regulation networks to predict cell types. Computational approaches are needed to recapitulate how the over 37 trillion cells program the shared genome sequence in a human body to create astoundingly diverse forms and functions. This project integrates millions of high-resolution single-cell gene expression profiles with large-scale population regulatory data to systematically reconstruct gene regulatory networks. These networks are the molecular basis for understanding human cells. This projects outcomes intend to include the first reference single-cell regulatory database and novel methods and software to predict individual cells. This project will contribute to advancing Australia's capabilities in single-cell, precision medicine, and big biological data analysis leading to significant scientific, societal and commercial benefits.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
Transcriptional regulation by microRNAs. This project aims to better understand microRNAs, which are of central importance to how genes are regulated. Despite recent data indicating microRNAs may also play more extensive and diverse roles as nuclear regulators of gene transcription, research has been restricted to their well known mechanism of action in the cytoplasm where they post transcriptionally silence genes. This project will investigate the potential for microRNAs to regulate transcripti ....Transcriptional regulation by microRNAs. This project aims to better understand microRNAs, which are of central importance to how genes are regulated. Despite recent data indicating microRNAs may also play more extensive and diverse roles as nuclear regulators of gene transcription, research has been restricted to their well known mechanism of action in the cytoplasm where they post transcriptionally silence genes. This project will investigate the potential for microRNAs to regulate transcription on a genome-wide scale and will thereby reveal the full extent of mechanisms by which these important genetic switches control gene expression networks the characteristics of cells. This is of fundamental significance to our understanding of gene regulation.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
Understanding protein-nucleic-acid interaction networks in cold-adapted archaea. The aim of this project is to learn how microorganisms can function effectively in naturally cold environments. Results will determine how important cellular processes occur when microorganisms grow in the cold, and hence why they are able to maintain a natural balance in ecosystems such as Antarctica.
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