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Statistical Methods for Next Generation Genome-Wide Association Studies. This project aims to develop cutting-edge statistical methods to analyse large genomic datasets and identify genetic variants associated with inter-individual differences in various human traits. Knowledge of trait-associated DNA variants is instrumental in understanding how natural selection has shaped human traits. By integrating genomic data from diverse and underrepresented populations, this project further expects to c ....Statistical Methods for Next Generation Genome-Wide Association Studies. This project aims to develop cutting-edge statistical methods to analyse large genomic datasets and identify genetic variants associated with inter-individual differences in various human traits. Knowledge of trait-associated DNA variants is instrumental in understanding how natural selection has shaped human traits. By integrating genomic data from diverse and underrepresented populations, this project further expects to contribute to the equitable use of genomic technologies in humans, regardless of geographical origins. Expected outcomes of this research include novel analysis methods and software tools, which should broadly and significantly benefit gene discovery in other species, including those of agricultural relevance.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
Discovery Early Career Researcher Award - Grant ID: DE230100271
Funder
Australian Research Council
Funding Amount
$463,618.00
Summary
Coordinating gene expression and cell size: the role of feedback regulation. This project aims to reveal how human cells coordinate the kinetics of messenger RNA (mRNA) transcript production, processing and degradation at the single-cell level. It expects to generate significant new biological knowledge of gene regulation by combining innovative interdisciplinary research methodologies in genetics, single-molecule imaging, mathematical modelling and quantitative cell biology. Expected outcomes i ....Coordinating gene expression and cell size: the role of feedback regulation. This project aims to reveal how human cells coordinate the kinetics of messenger RNA (mRNA) transcript production, processing and degradation at the single-cell level. It expects to generate significant new biological knowledge of gene regulation by combining innovative interdisciplinary research methodologies in genetics, single-molecule imaging, mathematical modelling and quantitative cell biology. Expected outcomes include enhanced training of researchers and to build Australia’s capability in the rapidly expanding fields of RNA biology and high-throughput microscopy. This should provide significant benefits for a myriad of applications including health, agriculture and veterinary sciences.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
Histone H3.3-dependent transcriptional control and B cell differentiation. This project aims to investigate the fundamental way cells assemble transcriptional machinery to turn on genes and retain transcriptional memory. This project expects to generate new knowledge in the areas of both chromatin biology and immunology, using interdisciplinary approaches. Expected outcomes of this project include an enhanced capacity, through institutional and international collaborations, to determine whether ....Histone H3.3-dependent transcriptional control and B cell differentiation. This project aims to investigate the fundamental way cells assemble transcriptional machinery to turn on genes and retain transcriptional memory. This project expects to generate new knowledge in the areas of both chromatin biology and immunology, using interdisciplinary approaches. Expected outcomes of this project include an enhanced capacity, through institutional and international collaborations, to determine whether the rapid transcription and function characteristic of immune memory in response to stimuli is due to histone H3 variant and its associated nuclear bodies. This should provide significant benefits, such as understanding epigenetic mechanisms that underlie transcription initiation and maintenance across many species.Read moreRead less
Investigations into the antibacterial mechanism of action of cannabidiol. Cannabidiol (CBD) comes from a set of naturally occurring compounds, with a range of applications in mainstream culture. We have recently reported that CBD has excellent antimicrobial properties, with the ability to kill bacteria. This project aims to understand how CBD works by examining CBD-bacterial interactions at a genetic and molecular level. By understanding how CBD acts on and within bacterial cells, we can create ....Investigations into the antibacterial mechanism of action of cannabidiol. Cannabidiol (CBD) comes from a set of naturally occurring compounds, with a range of applications in mainstream culture. We have recently reported that CBD has excellent antimicrobial properties, with the ability to kill bacteria. This project aims to understand how CBD works by examining CBD-bacterial interactions at a genetic and molecular level. By understanding how CBD acts on and within bacterial cells, we can create fundamental new knowledge that could lead to the design of improved analogs of CBD to that can treat bacterial infections. As a much-needed completely new antibiotic class, this will lead to significant benefits, supporting Australia's National Strategy to combat the challenges posed by antimicrobial resistance.Read moreRead less
Regulating the composition of biomolecular condensates in living cells. Biomolecular condensation is a novel organising principle of living cells, driven by ‘unmixing’ of the cellular contents into compartments. It is observed from plants to animals and is involved in diverse processes from how cells repair DNA to how they perceive signals. This project aims to reveal how human cells control the composition of condensates, which is critical for their function. It expects to uncover new regulator ....Regulating the composition of biomolecular condensates in living cells. Biomolecular condensation is a novel organising principle of living cells, driven by ‘unmixing’ of the cellular contents into compartments. It is observed from plants to animals and is involved in diverse processes from how cells repair DNA to how they perceive signals. This project aims to reveal how human cells control the composition of condensates, which is critical for their function. It expects to uncover new regulatory principles of cellular organisation by combining methods from quantitative cell biology and statistical physics. Expected benefits include building Australia’s capability in the potentially transformational field of biomolecular condensates, which has diverse future biotechnology applications in health and agriculture.Read moreRead less
Molecular definition of cellular states in the vascular endothelium. The endothelium is the main cell type forming blood vessels and spans across multiple cell states from stem/progenitor to a variety of terminally differentiated cells. How each of these cell states are defined at the molecular level is not known preventing the optimal formation and integration of blood vessels in bioengineered tissues. Using innovative single cell gene expression and chromatin accessibility studies combined wit ....Molecular definition of cellular states in the vascular endothelium. The endothelium is the main cell type forming blood vessels and spans across multiple cell states from stem/progenitor to a variety of terminally differentiated cells. How each of these cell states are defined at the molecular level is not known preventing the optimal formation and integration of blood vessels in bioengineered tissues. Using innovative single cell gene expression and chromatin accessibility studies combined with innovative analysis, we propose to define and validate each cell state at the molecular level.
This new knowledge would greatly enhance our ability to control the transition between cell states leading to a more widespread use of endothelial cells in bioengineering of tissues globally for many applications.
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Synthetic genes as reference standards for biology and biomanufacture. Reference standards are needed to improve the measurement of biology and the reliability of biomanufacturing processes. This project aims to engineer synthetic genes capable of acting as reference standards for DNA, RNA and protein. The synthetic genes can be transcribed into mRNA standards, and translated into protein standards, and be further integrated into living cells to measure internal cellular processes.
The outcomes ....Synthetic genes as reference standards for biology and biomanufacture. Reference standards are needed to improve the measurement of biology and the reliability of biomanufacturing processes. This project aims to engineer synthetic genes capable of acting as reference standards for DNA, RNA and protein. The synthetic genes can be transcribed into mRNA standards, and translated into protein standards, and be further integrated into living cells to measure internal cellular processes.
The outcomes include a unified understanding of gene expression and more accurate next-generation sequencing and mass-spectrophotometry technologies. The synthetic genes also allow standardisation and optimisation of biomanufacturing processes that will produce mRNA and biologics products at a higher purity and lower cost.Read moreRead less
Structural and molecular studies of endocrine disruption in Australia fauna. Contamination of waterways with compounds that disrupt hormone (endocrine) function is a major environmental problem and threat to the health and fertility of animals. Specifically, we lack an understanding of how these potent endocrine disrupting compounds function in native species. Using an innovative combination of structural and molecular biology approaches we will elucidate the mechanisms of action of environmenta ....Structural and molecular studies of endocrine disruption in Australia fauna. Contamination of waterways with compounds that disrupt hormone (endocrine) function is a major environmental problem and threat to the health and fertility of animals. Specifically, we lack an understanding of how these potent endocrine disrupting compounds function in native species. Using an innovative combination of structural and molecular biology approaches we will elucidate the mechanisms of action of environmental endocrine disrupting compounds in native aquatic species - model fish and the platypus; and develop novel technologies for their detection. This work will provide an understanding of the environmental threat of these pollutants to our unique wildlife and will guide future waterway management. Read moreRead less