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
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
Using Drosophila to analyse a master regulator of epithelial homeostasis. Aims:
This proposal aims to use genetic and cell biological analysis of the vinegar fly, Drosophila, to identify the function of the grainyhead gene in intestinal regeneration.
Significance:
This gene is conserved in all animal species and appears to be a master regulator of epithelial tissue development but it is unclear how it can both influence stem cell maintenance and production of functional cell types.
Expected out ....Using Drosophila to analyse a master regulator of epithelial homeostasis. Aims:
This proposal aims to use genetic and cell biological analysis of the vinegar fly, Drosophila, to identify the function of the grainyhead gene in intestinal regeneration.
Significance:
This gene is conserved in all animal species and appears to be a master regulator of epithelial tissue development but it is unclear how it can both influence stem cell maintenance and production of functional cell types.
Expected outcomes:
We will identify a new mechanism that governs tissue development, and introduce new imaging and genetic technologies to the Australian research community.
Benefit:
We expect potential economic and commercial interest in development of new gene analysis tools and biotechnological tissue manipulation applications.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
Control of vascular form and fate by a novel pre-mRNA splicing mechanism . Vertebrate vasculature forms elaborate, branched networks essential for life. As developing vessels permeate tissues and organs, dynamic and spatiotemporally regulated cellular signalling determines the fate, patterning and distribution of new vascular networks. This project follows the recent discovery of a mechanism whereby RNA diversification through alternative splicing controls complex signalling patterns in forming ....Control of vascular form and fate by a novel pre-mRNA splicing mechanism . Vertebrate vasculature forms elaborate, branched networks essential for life. As developing vessels permeate tissues and organs, dynamic and spatiotemporally regulated cellular signalling determines the fate, patterning and distribution of new vascular networks. This project follows the recent discovery of a mechanism whereby RNA diversification through alternative splicing controls complex signalling patterns in forming vessels. This project investigates this molecular mechanism in embryo and tissue development. The project will produce fundamental knowledge in RNA diversification, vascular fate, growth and cell signalling. New knowledge generated may lead to new approaches in stem cell biology, tissue engineering and regenerative biology.Read moreRead less
Hippo signalling control of transcription in lymphatic vascular development. Lymphatic vasculature forms complex, branched networks present in almost all vertebrate tissues and organs. Signalling in lymphatic endothelial cells determines the fate, structure and function of these complex and essential networks. This project follows our recent discovery of a major role for the Hippo signalling pathway in lymphatic vascular development. It aims to investigate how Hippo signalling regulates essenti ....Hippo signalling control of transcription in lymphatic vascular development. Lymphatic vasculature forms complex, branched networks present in almost all vertebrate tissues and organs. Signalling in lymphatic endothelial cells determines the fate, structure and function of these complex and essential networks. This project follows our recent discovery of a major role for the Hippo signalling pathway in lymphatic vascular development. It aims to investigate how Hippo signalling regulates essential target genes that drive lymphatic development. The project expects to generate fundamental knowledge in vascular signalling, transcription and the control of vascular network growth and expansion. Outcomes may provide significant benefits in new approaches in stem cell biology, tissue engineering and regenerative biology. Read moreRead less
Regulatory architecture of the trunk-to-tail transition. This project aims to elucidate gene regulatory mechanisms that control how the head-to-tail axis is laid down during embryonic development. The project capitalises on unique pluripotent stem cell resources and cutting-edge genomic technology developed by the team. This project expects to generate new knowledge in the area of developmental biology and gene regulation that is anticipated to have wider application to the understanding of evol ....Regulatory architecture of the trunk-to-tail transition. This project aims to elucidate gene regulatory mechanisms that control how the head-to-tail axis is laid down during embryonic development. The project capitalises on unique pluripotent stem cell resources and cutting-edge genomic technology developed by the team. This project expects to generate new knowledge in the area of developmental biology and gene regulation that is anticipated to have wider application to the understanding of evolutionary mechanisms and ultimately regenerative medicine.Read moreRead less