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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
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
Discovery Early Career Researcher Award - Grant ID: DE230100036
Funder
Australian Research Council
Funding Amount
$465,803.00
Summary
Tracing the epigenetic life-history of cells. Each cell of the human body contains identical genetic information that is activated in different ways to form varied cell types. This research aims to develop novel single-cell genomic technologies to explain the origins of different cell types. This project expects to discover the molecular mechanisms through which specialised cell types are formed, which has been difficult to decipher using existing methods. My novel approach will elucidate how a ....Tracing the epigenetic life-history of cells. Each cell of the human body contains identical genetic information that is activated in different ways to form varied cell types. This research aims to develop novel single-cell genomic technologies to explain the origins of different cell types. This project expects to discover the molecular mechanisms through which specialised cell types are formed, which has been difficult to decipher using existing methods. My novel approach will elucidate how a small population of seemingly homogenous cells can give rise to a myriad of types of cells. Tracing the life histories of cells across time should lead to broad applications including in developmental biology, neuroscience and immunology.Read moreRead less
Foundations of a good egg: correctly transitioning from mitosis to meiosis. Production of viable offspring is essential to the survival of any species. In all sexually reproducing species, this requires a unique cell type, the germ cell. Germ cells undergo a special type of cell division, called meiosis, so that they can eventually produce gametes (sperm in males and eggs in females). This project aims to discover how germ cells halt the standard form of cell division, called mitosis, and initia ....Foundations of a good egg: correctly transitioning from mitosis to meiosis. Production of viable offspring is essential to the survival of any species. In all sexually reproducing species, this requires a unique cell type, the germ cell. Germ cells undergo a special type of cell division, called meiosis, so that they can eventually produce gametes (sperm in males and eggs in females). This project aims to discover how germ cells halt the standard form of cell division, called mitosis, and initiate meiotic division instead. It is important to understand all the fundamental processes that occur during normal germ cell development so that, in the future, we can use this knowledge to support agricultural advances, rescue endangered species and solve human problems such as infertility and genetic disease.Read moreRead less
Mid-Career Industry Fellowships - Grant ID: IM230100042
Funder
Australian Research Council
Funding Amount
$980,358.00
Summary
Unlocking the full reproductive potential for hybrid wheat breeding. Globally, wheat is cultivated as an inbred self-fertile crop with yield gains stagnating over the last decades. This contrasts with unabated yield gains and yield stability achieved for rice and corn through hybrid breeding and cross-pollination. Wheat hybrids hold potential for a 10-22% yield boost, but commercial deployment is restricted due to high seed production costs, a result of wheat’s floral architecture and poor outcr ....Unlocking the full reproductive potential for hybrid wheat breeding. Globally, wheat is cultivated as an inbred self-fertile crop with yield gains stagnating over the last decades. This contrasts with unabated yield gains and yield stability achieved for rice and corn through hybrid breeding and cross-pollination. Wheat hybrids hold potential for a 10-22% yield boost, but commercial deployment is restricted due to high seed production costs, a result of wheat’s floral architecture and poor outcrossing characteristics. This project aims to reduce costs by improving wheat’s female receptivity to airborne pollen, a major bottleneck to commercial realization of hybrids globally. Higher and more stable yields from wheat hybrids will ensure food security in the face of climate uncertainty and growing population.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