The control of chromosome division during female meiosis. Mammalian eggs are stored life-long and finally mature in the hours before ovulation. This project examines how the chromosomes in the egg are separated properly so as to produce a mature egg capable of being fertilized by a sperm. Often in eggs chromosome division is imprecisely executed, and this project will help us understand why this occurs.
Understanding Mitotic Telomere Deprotection. This project aims to study telomeres, the DNA and protein structures that protect chromosome ends. During cell division, cells under stress intentionally uncap their telomeres. This project expects to generate new knowledge that challenges the conventional notion of telomeres as static elements, showing instead that telomeres can be dynamic signalling hubs. Expected outcomes of this project include an understanding of the genetic, proteomic, and signa ....Understanding Mitotic Telomere Deprotection. This project aims to study telomeres, the DNA and protein structures that protect chromosome ends. During cell division, cells under stress intentionally uncap their telomeres. This project expects to generate new knowledge that challenges the conventional notion of telomeres as static elements, showing instead that telomeres can be dynamic signalling hubs. Expected outcomes of this project include an understanding of the genetic, proteomic, and signalling pathways involved in this novel phenomenon. This should provide significant benefits to our fundamental understanding of biological processes that protect human genomes and provide a valuable dataset for research on telomere biology, DNA repair, and genome stability.Read moreRead less
Controlling cell polarity and asymmetric cell division in space and time. This project seeks to increase our understanding of how cells divide. Asymmetric cell division is a specialised form of cell division essential for the development of all organisms. The two meiotic divisions of the oocyte are extreme examples of asymmetric cell division that allow a reduction in chromosome content while retaining cytoplasmic vestments necessary for development. Successful asymmetric cell division requires ....Controlling cell polarity and asymmetric cell division in space and time. This project seeks to increase our understanding of how cells divide. Asymmetric cell division is a specialised form of cell division essential for the development of all organisms. The two meiotic divisions of the oocyte are extreme examples of asymmetric cell division that allow a reduction in chromosome content while retaining cytoplasmic vestments necessary for development. Successful asymmetric cell division requires the integration of cell cycle events with cell polarity. Understanding how this is achieved would improve our understanding of how to generate a healthy embryo in women, endangered species and in animals of commercial importance.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
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
cell-cell adhesive force in vascular development. This project aims to utilize groundbreaking new approaches to visualize cell-cell adhesive forces in vascular development. Vascular system development is one of the earliest events in the vertebrate embryo. It has long been established that one major contributor to the formation of new vessels is physical force, which can be generated through blood flow or cell-cell interactions during tissue morphogenesis. The project plan utilizes live imaging ....cell-cell adhesive force in vascular development. This project aims to utilize groundbreaking new approaches to visualize cell-cell adhesive forces in vascular development. Vascular system development is one of the earliest events in the vertebrate embryo. It has long been established that one major contributor to the formation of new vessels is physical force, which can be generated through blood flow or cell-cell interactions during tissue morphogenesis. The project plan utilizes live imaging in zebrafish and a new generation of biosensors to gain a vastly deeper understanding of how force controls vessel formation.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
Studying early human kidney development using stem cells. This project aims to improve our understanding of cell types, lineage relationships, cell-cell interactions and morphogenetic processes in human kidney development. Investigators have developed a method to produce multicellular kidney organoids from human pluripotent stem cells (hPSC). This project will use gene-edited reporter hPSC lines and high-res imaging to study the lineage relationships and morphogenetic mechanisms of these human k ....Studying early human kidney development using stem cells. This project aims to improve our understanding of cell types, lineage relationships, cell-cell interactions and morphogenetic processes in human kidney development. Investigators have developed a method to produce multicellular kidney organoids from human pluripotent stem cells (hPSC). This project will use gene-edited reporter hPSC lines and high-res imaging to study the lineage relationships and morphogenetic mechanisms of these human kidney organoids. This project aims to validate the origin of nephrons in kidney organoids, study the origin of the renal stroma versus the nephron progenitor, and monitor nephron patterning and segmentation at a clonal level. This will improve our knowledge of human kidney development in a human model.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
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