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
Understanding telomere privilege in pluripotent stem cells. We recently identified that fundamental mechanisms which protect chromosome ends (i.e. “telomeres”) are not conserved between somatic and embryo-derived stem cells. This discovery is without precedent and challenges the dogmatic expectation that cellular functions promoting genome stability are conserved in stem cells. We term the unexpected protective capacity of pluripotent chromosome ends “telomere privilege”. Here we will uncover th ....Understanding telomere privilege in pluripotent stem cells. We recently identified that fundamental mechanisms which protect chromosome ends (i.e. “telomeres”) are not conserved between somatic and embryo-derived stem cells. This discovery is without precedent and challenges the dogmatic expectation that cellular functions promoting genome stability are conserved in stem cells. We term the unexpected protective capacity of pluripotent chromosome ends “telomere privilege”. Here we will uncover the molecular, genomic, and proteomic regulators or telomere privilege; determine the breath of telomere privilege in stem cell lineages; elucidate the functional significance of telomere privilege; and exploit telomere privilege to study fundamental biology related to telomeres and the DNA damage response.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
Defining how cells relay mechanical signals to changes in cell architecture. Mechanical signals play crucial roles in shaping organs and entire organisms during development, though how these signals are relayed to changes in cell architecture is a major unanswered question. Within vascular networks, mechanical signals including fluid flow, tension and stretch play key roles in vessel patterning, identity and maturation. This application aims to employ cutting-edge technologies to determine how t ....Defining how cells relay mechanical signals to changes in cell architecture. Mechanical signals play crucial roles in shaping organs and entire organisms during development, though how these signals are relayed to changes in cell architecture is a major unanswered question. Within vascular networks, mechanical signals including fluid flow, tension and stretch play key roles in vessel patterning, identity and maturation. This application aims to employ cutting-edge technologies to determine how the atypical cadherin FAT4 relays mechanical signals including flow and tension to the lymphatic endothelial cell skeleton, thereby enabling changes in cell shape important for building lymphatic vessels. This project will increase our understanding of how cells sense touch and may be applied for tissue engineering purposes.
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
Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key ch ....Awaking quiescent neural stem cells. This project aims to generate new knowledge in the area of the evolutionary size of animals and plants, which is determined by intrinsic cell regulation and is constrained by nutrient availability. Brain size is perhaps the most profound example of this. Brain size regulation is underpinned by control of proliferation of neural stem cells (NSCs). Using Drosophila NSCs, the project will examine how nutrients impact on NSC quiescence versus activation, a key characteristic of stem cell control throughout evolution. This will increase our understanding of how energy metabolism and nutrition influence organ size control in multicellular organisms, by determining how organs communicate with each other to convert nutrient signals to action stem cell proliferation.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