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Characterisation Of SRY Macromolecular Complexes To Provide An Enhanced Understanding Of Human Genetic Sex Reversal And Embryonic Sex Determination
Funder
National Health and Medical Research Council
Funding Amount
$237,360.00
Summary
SRY is the most important gene in the determination of human sex. Mutations in the SRY gene that disrupt its ability to interact with other cellular proteins that regulate its function have shown to result in genetic sex reversal. This project will provide a detailed structural profile of the interfaces that are critical for sex determination, provide a molecular basis for XY-genetic sex reversal, and an enhanced understanding of foetal development.
Understanding gonadal development and disease using a unique model system, the avian embryo. This project will provide information on normal and abnormal gonadal development during embryonic life. The study will aid in the diagnosis and management of humans born with disorders of sexual development and will be useful for sex ratio manipulation in the poultry industry.
Genetic regulation of testis development in the chicken embryo. This project aims to shed light on the genetic control of testis development during embryonic life, using the chicken embryo as a model. The results will have implications for sex ratio manipulation in poultry and for our understanding of sexual disorders in humans.
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
Cellular and molecular mechanisms underlying skeletal muscle organisation. In vertebrates, processes as diverse as earing, neural tube closure, skeletal muscle organisation or even cancer rely on the coordinated behaviour of cells regulated by the Planar Cell Polarity (PCP) pathway. The aim of this project is to expand previous analyses on the role of PCP in skeletal muscle formation in the embryo.
Post-translational control of cell fate decision. Deciphering the multi-layered regulation of cell fate decisions is challenging. While progress has been made in understanding the role of transcriptional regulation, the influence of post-translational modification is poorly understood. Neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4)-mediated ubiquitination is absolute necessary for sex determination, a unique model of cell fate decision where gonadal cell precurs ....Post-translational control of cell fate decision. Deciphering the multi-layered regulation of cell fate decisions is challenging. While progress has been made in understanding the role of transcriptional regulation, the influence of post-translational modification is poorly understood. Neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4)-mediated ubiquitination is absolute necessary for sex determination, a unique model of cell fate decision where gonadal cell precursors differentiate either along the male or the female pathway. Thus, this project aims to analyse in detail at which stage NEDD4 action is required and what are the crucial target proteins. This project could provide a deeper understanding of how post-translational modifications influence cell fate decisions during embryogenesis.Read moreRead less
Understanding the evolution of the alternation of generations in the land plant life cycle. This project will investigate the genetic basis and evolution of the land plant life cycle, in which both haploid and diploid phases consist of complex multicellular bodies. The project's findings, which will be made using two model laboratory plants, will be applicable to all plants and will help understand important processes such as pollen and seed production.
Molecular mechanisms that generate muscle cell type diversity. The general aim of this project is to exploit the advantages of the zebrafish system and our access to the embryology of Australian shark species to generate an understanding of the basis for muscle fibre diversity and evolution. While there is some understanding of the fundamental genetic basis of how to make an individual muscle cell from a nascent myoblast there is far less knowledge on how individual muscle cells generate mature ....Molecular mechanisms that generate muscle cell type diversity. The general aim of this project is to exploit the advantages of the zebrafish system and our access to the embryology of Australian shark species to generate an understanding of the basis for muscle fibre diversity and evolution. While there is some understanding of the fundamental genetic basis of how to make an individual muscle cell from a nascent myoblast there is far less knowledge on how individual muscle cells generate mature muscle types and patterns. The intended outcome of this research is to generate understanding of the complex molecular basis of muscle patterning in the simple paradigm of the zebrafish myotome that could be applied across the vertebrate phylogeny.Read moreRead less
Development and evolution of land plant shoots. How do plants grow and develop their wonderful diversity of forms, from cereal crops to eucalypt forests? The project aims to understand basic mechanisms of plant development via comparative studies using the model angiosperm, Arabidopsis, and the liverwort, Marchantia, which possesses a simplified genome. Comparative studies of the genetic basis of the body plan, branching, and hormonal action could unlock their evolutionary elaboration from the s ....Development and evolution of land plant shoots. How do plants grow and develop their wonderful diversity of forms, from cereal crops to eucalypt forests? The project aims to understand basic mechanisms of plant development via comparative studies using the model angiosperm, Arabidopsis, and the liverwort, Marchantia, which possesses a simplified genome. Comparative studies of the genetic basis of the body plan, branching, and hormonal action could unlock their evolutionary elaboration from the simpler liverworts to more complex flowering plants. The project may generate new understanding of the principles of how genes and hormones control the architecture of plant shoot systems, and support the targeted selection of new agricultural plants.Read moreRead less