How do stem cells get specified during embryonic muscle development? This project aims to investigate the mechanisms by which muscle stem cells first form in the embryo. This project expects to generate new knowledge on the mechanism that patterns cell types in the embryonic myotome. Expected outcomes of this project include uncovering the developmental mechanisms of cell type specification in the myotome with specific reference to the generation of stem cells. This should provide significant be ....How do stem cells get specified during embryonic muscle development? This project aims to investigate the mechanisms by which muscle stem cells first form in the embryo. This project expects to generate new knowledge on the mechanism that patterns cell types in the embryonic myotome. Expected outcomes of this project include uncovering the developmental mechanisms of cell type specification in the myotome with specific reference to the generation of stem cells. This should provide significant benefits as it will inform how long lived tissue resident stem cells can be made in the first instance, knowledge that is critical for making stem cells on demand outside the animal and manipulating stem cells in living tissue.Read moreRead less
The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehe ....The impact of Hyaluronic Acid on growth factor signalling and angiogenesis. Blood vessel development is controlled by growth factor signalling. Vessels are attracted by and migrate along growth factor gradients, and this is controlled by the extracellular matrix (ECM). From the zebrafish model, we have identified a novel gene that modulates the ECM, impacting growth factor signalling and vessel development. The project will explore by what mechanism this gene impacts signalling. It will comprehensively define where in the embryo it is required and investigate what cofactors it interacts with to perform its function. Using genetic zebrafish and mouse models as well as cell culture models we will investigate the fundamental biology of this gene.Read moreRead less
Characterising a new regulator of the Hedgehog pathway . The Hedgehog pathway is crucial for embryonic development, and disruption causes multi-organ morphogenesis defects. The CI team has uncovered a new gene required for Hedgehog signalling in mouse, zebrafish, and Drosophila. Preliminary data hints at mechanism for this novel gene and shows it may in fact be a member of a new superfamily. The project will examine gene function and identify interacting protein partners, using the zebrafish, Dr ....Characterising a new regulator of the Hedgehog pathway . The Hedgehog pathway is crucial for embryonic development, and disruption causes multi-organ morphogenesis defects. The CI team has uncovered a new gene required for Hedgehog signalling in mouse, zebrafish, and Drosophila. Preliminary data hints at mechanism for this novel gene and shows it may in fact be a member of a new superfamily. The project will examine gene function and identify interacting protein partners, using the zebrafish, Drosophila, and cell-based models. Findings will provide basic knowledge about this mysterious gene and uncover how it modulates an essential pathway in embryonic development. This research is expected to impact knowledge generation, health, and well-being.Read moreRead less
How is the blood cell population size controlled? Macrophage-like cells are an ancient animal blood cell lineage critically important for development, immunity, and homeostasis. This fellowship seeks to reveal the genes and control mechanisms used by animals to achieve an optimally-sized army of these cells - to contain threats for survival upon infection, heal following acute stress exposures, or for development, ongoing maintenance, and repair of wear and tear. By marrying the genetic tractabi ....How is the blood cell population size controlled? Macrophage-like cells are an ancient animal blood cell lineage critically important for development, immunity, and homeostasis. This fellowship seeks to reveal the genes and control mechanisms used by animals to achieve an optimally-sized army of these cells - to contain threats for survival upon infection, heal following acute stress exposures, or for development, ongoing maintenance, and repair of wear and tear. By marrying the genetic tractability of the model organism Drosophila and its simple, yet conserved blood cell system, this project will yield new insights into the mechanisms that govern the animal blood cell population. This will benefit our fundamental understanding of how animals maximise their health throughout life.Read moreRead less
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
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
Investigating Hippo-regulated transcription at single molecule resolution. Signalling pathways operate throughout life to relay signals from the extracellular world to the cellular nucleus, to control transcription and elicit a response. This project aims to understand how the Hippo growth control pathway regulates transcription. Using a combination of biology, biophysics and computational biology, this project aims to quantify behaviour of the Hippo pathway transcription factors at sub-micron r ....Investigating Hippo-regulated transcription at single molecule resolution. Signalling pathways operate throughout life to relay signals from the extracellular world to the cellular nucleus, to control transcription and elicit a response. This project aims to understand how the Hippo growth control pathway regulates transcription. Using a combination of biology, biophysics and computational biology, this project aims to quantify behaviour of the Hippo pathway transcription factors at sub-micron resolution, and how Hippo signalling modulates their behaviour, interaction with the genome and function. We anticipate our discoveries will stimulate new research, e.g. testing of how other signaling pathways regulate transcription. Intended benefits are creation of jobs and new knowledge on fundamental principles of life.Read moreRead less
Understanding how the heart becomes more efficient. The body demands that the heart function at utmost efficiency. Trabeculae – folds within the heart lumen – maximise blood flow, contribute to chamber development and form the electrical conduction network of the heart. Problems with trabeculae formation cause cardiomyopathy and arrhythmia and yet we do not understand its basic development. The project will investigate the earliest stages of when this tissue develops its identity and examine the ....Understanding how the heart becomes more efficient. The body demands that the heart function at utmost efficiency. Trabeculae – folds within the heart lumen – maximise blood flow, contribute to chamber development and form the electrical conduction network of the heart. Problems with trabeculae formation cause cardiomyopathy and arrhythmia and yet we do not understand its basic development. The project will investigate the earliest stages of when this tissue develops its identity and examine the signalling, genetic, cellular and extracellular cues required to instruct trabeculae to form in the heart. Findings from this research will revise our understanding of when and how trabeculae form and provide key information about how to grow and repair this important tissue.Read moreRead less
Regulatory roles of the RNA helicase DDX5 in male germline stem cells. This project aims to investigate the role of the RNA helicase DDX5 in regulating gene expression programs of male germline stem cells by utilising novel mouse models, stem cell culture and genome-wide analysis approaches. This project expects to generate new knowledge in the area of germline maintenance and adult stem cells using innovative in vivo and in vitro experimental systems. Expected outcomes of this project will incl ....Regulatory roles of the RNA helicase DDX5 in male germline stem cells. This project aims to investigate the role of the RNA helicase DDX5 in regulating gene expression programs of male germline stem cells by utilising novel mouse models, stem cell culture and genome-wide analysis approaches. This project expects to generate new knowledge in the area of germline maintenance and adult stem cells using innovative in vivo and in vitro experimental systems. Expected outcomes of this project will include gain of substantial insight into molecular mechanisms underlying germline stem cell function and gene regulation within the male germline. This should provide significant benefits, including advancement of reproductive science and development of systems applicable for animal germline preservation and manipulation.Read moreRead less
Shaping the vertebrate brain: defining the cellular and genetic drivers . This project aims to uncover specific cellular and genetic mechanisms that control growth and shape of the brain. How brain shape and size changes during evolution of vertebrates is enigmatic but important to know for better understanding of behaviour and function of intact and diseased brain. The project aims to assemble team of national and international experts to build international capacity and unique genetics model t ....Shaping the vertebrate brain: defining the cellular and genetic drivers . This project aims to uncover specific cellular and genetic mechanisms that control growth and shape of the brain. How brain shape and size changes during evolution of vertebrates is enigmatic but important to know for better understanding of behaviour and function of intact and diseased brain. The project aims to assemble team of national and international experts to build international capacity and unique genetics model to generate new knowledge of the cellular and genetic components that drive evolution of different brain parts and shapes the vertebrate brain. In doing so the project aims to provide research training, excellence and knowledge that in future may benefit health and the society. Read moreRead less