Controlling the first step of differentiation of embryonic cells. This project aims to improve understanding of how diverse cell types are generated for building the body plan of the embryo. The first step of embryonic cell lineage differentiation takes place at early gastrulation when the multipotent embryonic cells acquire the attributes of specific tissue lineages. This project intends to elucidate how inductive signals and gene function are integrated to drive the lineage choice of the naïve ....Controlling the first step of differentiation of embryonic cells. This project aims to improve understanding of how diverse cell types are generated for building the body plan of the embryo. The first step of embryonic cell lineage differentiation takes place at early gastrulation when the multipotent embryonic cells acquire the attributes of specific tissue lineages. This project intends to elucidate how inductive signals and gene function are integrated to drive the lineage choice of the naïve cells, by tracking the impact of the activity of signalling pathways and gene regulation on cell differentiation. This may deliver insights into the temporal hierarchy and functional attributes of the molecular switches that control stem cell differentiation. Expected outcomes may have applications in tissue engineering.Read moreRead less
A molecular paradigm of organ formation during embryonic development: the role of RhoGTPase. How do cells in the embryo acquire the correct shape and structure to form tissues and organs? This project will reveal the genes and proteins required for the formation of the early gut and associated organs and will enhance our understanding of how organs are constructed from the building blocks in the embryo.
Capturing tissue-specific progenitors from embryos and stem cells. This project aims to delineate the precursor cells in the embryo that give rise specifically to major cell types in the body. The project will use genetic analysis to elucidate the critical genetic activity that underpins the genesis of these precursor cells and to track the trajectory and the scope of cell differentiation. The embryological knowledge will provide insights into the fundamentals of developmental process for gener ....Capturing tissue-specific progenitors from embryos and stem cells. This project aims to delineate the precursor cells in the embryo that give rise specifically to major cell types in the body. The project will use genetic analysis to elucidate the critical genetic activity that underpins the genesis of these precursor cells and to track the trajectory and the scope of cell differentiation. The embryological knowledge will provide insights into the fundamentals of developmental process for generating cellular diversity and enable identifying unique precursors and the evaluation of the efficacy of deriving the biological relevant cell types from the stem cells. This project expects to have a significant impact on the translation to cell production methodology for tissue engineering and bioreactor technology.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
Gamete-specific knockout of Fizzy-Related to examine its meiotic role in oocytes and sperm. Fizzy-Related is a gene that appears to be essential in making an ovulated egg, and it may also have an important role to play in making sperm. A mouse knockout will be generated to examine exactly how it functions; because it affects the egg number remaining in the ovary and egg quality Fizzy-Related may be eventually an important therapeutic target.
Discovery Early Career Researcher Award - Grant ID: DE120101242
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Regulation of germ cell number and quality by Fizzy-related protein. Females have a limited supply of eggs in their ovaries and it appears that the Fizzy-related gene (FZR1) is important in making sure this full complement is gained. By using novel mouse knockouts of the FZR1 gene, the project will determine how this protein functions at the earliest stages of egg development.
Discovery Early Career Researcher Award - Grant ID: DE220100006
Funder
Australian Research Council
Funding Amount
$383,872.00
Summary
Determining the regulation of ovary development with single cell sequencing. This project will greatly advance our understanding of ovary development and mammalian reproduction. I will investigate the process of ovarian primordial follicle activation including its genetic regulation, the importance of supportive granulosa cells and the biological significance of regulatory factors. This will be achieved through the comprehensive investigation of a single cell transcriptomic dataset of ovarian de ....Determining the regulation of ovary development with single cell sequencing. This project will greatly advance our understanding of ovary development and mammalian reproduction. I will investigate the process of ovarian primordial follicle activation including its genetic regulation, the importance of supportive granulosa cells and the biological significance of regulatory factors. This will be achieved through the comprehensive investigation of a single cell transcriptomic dataset of ovarian development (Aim 1) in conjunction with functional studies (Aim 2). The outcomes of which will hold significant benefit to animal reproduction through new strategies to improve livestock productivity and control invasive pest species. These outcomes are of economic and environmental and benefit nationally.Read moreRead less
Molecular function of the ribonucleic acid binding protein RBM47 in embryonic and mature endoderm cells. This project aims to test the hypothesis that a novel ribonucleic acid (RNA) binding protein, called RBM47, regulates the processing of the RNA transcripts of genes. This project will reveal the identity and the function of these genes that are essential for controlling the growth of the embryo and the organism after birth.
Control of developmental switches by importin 5. Aims: This project will study a key molecular switch called IPO5, a protein that is required for cells and organs to form and function normally, and it will reveal how it works.
Significance: These experiments will provide the first complete description of how this molecular switch controls the behaviour of a cell across its lifespan. IPO5 is highly conserved, so these studies will be relevant to a wide range of animals.
Expected Outcomes: This k ....Control of developmental switches by importin 5. Aims: This project will study a key molecular switch called IPO5, a protein that is required for cells and organs to form and function normally, and it will reveal how it works.
Significance: These experiments will provide the first complete description of how this molecular switch controls the behaviour of a cell across its lifespan. IPO5 is highly conserved, so these studies will be relevant to a wide range of animals.
Expected Outcomes: This knowledge will reveal how IPO5 controls formation of sperm by revealing what other proteins it binds to and how this affects cell signaling and responses to the environment.
Benefits: This will provide information about potential interventions to control fertility or to repair abnormal cells.
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Sprouting Angiogenesis and its Role in Development of Chamber Myocardium. The project aims to investigate how heart chambers form by testing the hypothesis that morphogenesis of the muscular walls of the heart is regulated during development by a Notch signalling-dependent process akin to angiogenic sprouting in other vascular beds. The project outcomes may have implications for diagnosis of congenital heart disease and for the fields of cardiac tissue engineering and regeneration. The project p ....Sprouting Angiogenesis and its Role in Development of Chamber Myocardium. The project aims to investigate how heart chambers form by testing the hypothesis that morphogenesis of the muscular walls of the heart is regulated during development by a Notch signalling-dependent process akin to angiogenic sprouting in other vascular beds. The project outcomes may have implications for diagnosis of congenital heart disease and for the fields of cardiac tissue engineering and regeneration. The project plans to elucidate cellular and molecular pathways underlying heart chamber development in mice using contemporary genetic methods, molecular embryology and imaging. Benefits may include a new framework for understanding heart development and disease, and the future application of this knowledge to translational cardiology.Read moreRead less