Discovery Early Career Researcher Award - Grant ID: DE230101315
Funder
Australian Research Council
Funding Amount
$461,154.00
Summary
The dynamic interplay between the matrix and cell fate in developing heart. Malformations in the developing heart can lead to catastrophic defects and embryonic loss. The valves play a critical role in blood flow regulation and are made of a stratified matrix that is laid down early in development. This project aims to determine how the cellular fate of the early valve cells establish the layered matrix and in turn how the matrix can influence cell fate by utilising a multi-omics approach to ide ....The dynamic interplay between the matrix and cell fate in developing heart. Malformations in the developing heart can lead to catastrophic defects and embryonic loss. The valves play a critical role in blood flow regulation and are made of a stratified matrix that is laid down early in development. This project aims to determine how the cellular fate of the early valve cells establish the layered matrix and in turn how the matrix can influence cell fate by utilising a multi-omics approach to identify unique cell populations and integrate transcriptional and protein changes during matrix disruption. This project expects to generate fundamental knowledge on how matrix structure can influence cell fate in the valves and will advance Australia's knowledge base and research capabilities in developmental biology.Read moreRead less
Unravelling the contributions of Denisovan DNA to the peoples of Oceania. This project aims to investigate the impact gene flow from Denisovans, an archaic hominin species, has had on individuals from Papua New Guinea and eastern Indonesia. These people owe up to 5% of their genomes to these mysterious ancestors, but the repercussions of this finding remain poorly understood. In order to identify the biological contributions these fragments of DNA make to the individuals who carry them, this pro ....Unravelling the contributions of Denisovan DNA to the peoples of Oceania. This project aims to investigate the impact gene flow from Denisovans, an archaic hominin species, has had on individuals from Papua New Guinea and eastern Indonesia. These people owe up to 5% of their genomes to these mysterious ancestors, but the repercussions of this finding remain poorly understood. In order to identify the biological contributions these fragments of DNA make to the individuals who carry them, this project aims to combine anthropological genetics with cutting-edge functional genomics in a pioneer multidisciplinary approach. Ultimately, this project may transform our understanding of both the population and evolutionary pressures that have acted upon these groups in the past 50,000 years.Read moreRead less
Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations ....Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations of super resolution microscopy to visualise in 3 dimensions how changes in chromatin modifications impact genome spatial organisation within the nucleus, and how this then links to cellular differentiation. This will provide a picture of how spatial organisation within the nucleus supports general cell differentiation.
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Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this ....Identification of Biological pathways regulated by circular RNAs. Circular RNAs (circRNAs) are a, recently discovered molecule. circRNAs are highly abundant and expressed in a tissue and disease specific manner. Yet, currently the understanding of how circRNAs regulate biological processes is very poor. This project aims to use pooled shRNA libraries to screen a large panel of cell lines and systematically identify cellular activities that are regulated by circRNAs. The expected outcome of this study will be a catalogue of functionally active circRNAs. Over the past decades, the wealth of knowledge on the function of linear mRNAs has had a significant impact on medicine and agriculture. Similarly understanding how circRNAs regulate cellular activities may have an analogous impact on humans.Read moreRead less
Investigating a new way in which diet impacts animal biology. This project aims to investigate the importance of a new way in which diet can alter animal biology. High fat or high sugar diets increase the binding of products of metabolism to chromosomes, which can completely alter the way that DNA is packaged and read. This project will use cell culture, rodent and fly models to identify the regions of the genome that are most affected by the new process. The project will also determine whether ....Investigating a new way in which diet impacts animal biology. This project aims to investigate the importance of a new way in which diet can alter animal biology. High fat or high sugar diets increase the binding of products of metabolism to chromosomes, which can completely alter the way that DNA is packaged and read. This project will use cell culture, rodent and fly models to identify the regions of the genome that are most affected by the new process. The project will also determine whether the cell is harmed, or in fact harnesses the process to control development or metabolism. This project has implications for our understanding of the ways in which genes interact with the environment especially in times of change.Read moreRead less
Defining the Molecular Targets of Evolution. With significant advances in next-generation sequencing technologies we now have the genomes of hundreds vertebrate species, but understanding how the differences and similarities within these genomes control species diversity is largely unknown. The similarity in skull shape between the thylacine and dogs coupled with their deep ancestry, having last shared a common ancestor over 160 million years ago, provides an unprecedented opportunity to examine ....Defining the Molecular Targets of Evolution. With significant advances in next-generation sequencing technologies we now have the genomes of hundreds vertebrate species, but understanding how the differences and similarities within these genomes control species diversity is largely unknown. The similarity in skull shape between the thylacine and dogs coupled with their deep ancestry, having last shared a common ancestor over 160 million years ago, provides an unprecedented opportunity to examine how evolution works at the DNA level. This proposal will determine if animals that develop identical skull shapes, also show identical changes in their DNA. The findings will define new developmental genes and explain how selection, adaptation and evolution works at the DNA level. Read moreRead less
Genetic networks regulating gene silencing by intronic repeat expansions . Changes in the copy number of DNA repeats are associated with phenotypic variations in several species. Expansions of DNA repeats underlie several human genetic diseases, including Friedreich’s ataxia. The molecular mechanisms that mediate these genetic abnormalities are currently unclear. This project aims to identify the novel genetic pathways and mechanisms mediating these genetic disorders. Using a plant model in an .... Genetic networks regulating gene silencing by intronic repeat expansions . Changes in the copy number of DNA repeats are associated with phenotypic variations in several species. Expansions of DNA repeats underlie several human genetic diseases, including Friedreich’s ataxia. The molecular mechanisms that mediate these genetic abnormalities are currently unclear. This project aims to identify the novel genetic pathways and mechanisms mediating these genetic disorders. Using a plant model in an innovative way this project will discover novel genes, uncover fundamental molecular mechanisms and reveal the genetic networks that govern gene silencing caused by triplet repeat expansions. This project, in addition to revealing fundamental biological mechanisms, will also have implications for human disease.
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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
Investigating a novel factor impacting stem cell development. This project aims to investigate how stem cells are controlled during animal development, by exploring how a specific protein, essential for embryonic development, controls cell fate decisions during the early stages of life. This project expects to generate new knowledge in stem cell biology, embryonic development, and general mechanisms controlling cell fates, using innovative approaches in gene editing and high-throughput imaging. ....Investigating a novel factor impacting stem cell development. This project aims to investigate how stem cells are controlled during animal development, by exploring how a specific protein, essential for embryonic development, controls cell fate decisions during the early stages of life. This project expects to generate new knowledge in stem cell biology, embryonic development, and general mechanisms controlling cell fates, using innovative approaches in gene editing and high-throughput imaging. Expected outcomes of this project include enhanced capacity for fundamental stem cell biology in Australia. This should provide significant benefits, such as training of young Australian researchers in frontier technologies, and new knowledge in fundamental aspects of life, including embryonic development.Read moreRead less
Predicting adaptation and range expansion under climate change. This project investigates the repeatability and thereby the predictability of adaptation to climate change by leveraging 1000 genomes sampled over 150 years and multiple climatic gradients in the rapidly adapting, globally invasive, and highly allergenic ragweed. We expect to deepen our understanding of the genetic basis of adaptation and decipher the circumstances under which adaptive genetic change is repeatable, by integrating a ....Predicting adaptation and range expansion under climate change. This project investigates the repeatability and thereby the predictability of adaptation to climate change by leveraging 1000 genomes sampled over 150 years and multiple climatic gradients in the rapidly adapting, globally invasive, and highly allergenic ragweed. We expect to deepen our understanding of the genetic basis of adaptation and decipher the circumstances under which adaptive genetic change is repeatable, by integrating a novel evolutionary model with genomic data. We will develop the capacity to predict species’ distributions and trait evolution under climate change using a powerful empirical dataset. This will provide us with the capacity to anticipate and manage the effects of climate change on noxious and threatened species.Read moreRead less