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
Australian Laureate Fellowships - Grant ID: FL170100008
Funder
Australian Research Council
Funding Amount
$3,248,822.00
Summary
Genes, reproduction and inheritance in a microbe. The project aims to particularly explore sexual gene inheritance in Plasmodium, a representative of a large group of human and animal parasites. Plasmodium must have a sexual exchange of genes in the mosquito for the transfer of disease to a new host. This project will investigate the fate and behaviour of Plasmodium genes during reproduction; the differing chromosome states resulting from sexual genetic processes and the asymmetrical inheritance ....Genes, reproduction and inheritance in a microbe. The project aims to particularly explore sexual gene inheritance in Plasmodium, a representative of a large group of human and animal parasites. Plasmodium must have a sexual exchange of genes in the mosquito for the transfer of disease to a new host. This project will investigate the fate and behaviour of Plasmodium genes during reproduction; the differing chromosome states resulting from sexual genetic processes and the asymmetrical inheritance of some Plasmodium genes. The project is expected to advance Australia’s ability to understand the reproduction and survival of these parasites in their mosquito vector and develop cutting-edge genetic tools that will advance the microbial genetics discipline globally. This may ultimately lead to biotechnology and biomedical outcomes.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
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
Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of ....Visualising genetic mosaicism during development. Genetic diversity is the variation in DNA sequence among individuals. We now know that there are also differences in the DNA sequences of cells within the same individual, known as genetic mosaicism. The aims of this proposal are 1) to develop a system to visualise genetic mosaicism 2) arising during embryonic development and 3) in the brain, driven by mobile DNA activity. The expected outcome of this proposal is an unprecedented understanding of the scope and consequences of mobile DNA-driven mosaicism. This work will have significant impacts in developmental genetics and neurogenetics, and has the benefit of introducing an innovative experimental system with the potential to spark international scientific collaboration and recognition.Read moreRead less
Signalling pathways for sexual differentiation of apicomplexan parasites. This project aims to study the sexual development of apicomplexan parasites, which cause major diseases in humans, livestock and wildlife, including malaria. Only sexually differentiated cells can survive in the mosquito vector and hence this development is essential for the parasite's life-cycle. This project will employ a new approach that separates female from male parasites, thus enabling new information to be gleaned ....Signalling pathways for sexual differentiation of apicomplexan parasites. This project aims to study the sexual development of apicomplexan parasites, which cause major diseases in humans, livestock and wildlife, including malaria. Only sexually differentiated cells can survive in the mosquito vector and hence this development is essential for the parasite's life-cycle. This project will employ a new approach that separates female from male parasites, thus enabling new information to be gleaned about the development of these parasites. The expected outcomes are an understanding of the mechanisms of sexual differentiation and a functional characterisation of novel sex-specific molecules. This will provide significant benefits, such as pivotal prerequisites for new approaches to parasite intervention.Read moreRead less
Mobile DNA activity in the mammalian primordial germline. Early in pregnancy, a handful of cells in the embryo become primordial germ cells (PGCs). These PGCs will eventually give rise to sperm or egg cells, representing a critical inter-generational genetic link. Mobile DNA sequences target PGCs to create new heritable genetic changes. This proposal aims to analyse the activity, regulation, and consequences of mobile DNA activity in PGCs. This project expects to generate significant knowledge a ....Mobile DNA activity in the mammalian primordial germline. Early in pregnancy, a handful of cells in the embryo become primordial germ cells (PGCs). These PGCs will eventually give rise to sperm or egg cells, representing a critical inter-generational genetic link. Mobile DNA sequences target PGCs to create new heritable genetic changes. This proposal aims to analyse the activity, regulation, and consequences of mobile DNA activity in PGCs. This project expects to generate significant knowledge about the origins of mammalian genetic diversity. Expected outcomes include enhanced national and international collaborations across disciplines and new experimental systems. The expected benefit is an enhanced understanding of the mutational processes underlying genetic diversity and disease in mammals.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