How do transcription factors control cell fate transitions? The aim of this project is to determine how transcription factors control cellular identity, which is relevant to many biological processes including embryogenesis, cellular reprogramming and differentiation. Innovative genomic tools will be combined with various in vitro cellular conversion systems to generate fundamental mechanistic insight into how transcription factors mediate these identity changes. The knowledge gained from this w ....How do transcription factors control cell fate transitions? The aim of this project is to determine how transcription factors control cellular identity, which is relevant to many biological processes including embryogenesis, cellular reprogramming and differentiation. Innovative genomic tools will be combined with various in vitro cellular conversion systems to generate fundamental mechanistic insight into how transcription factors mediate these identity changes. The knowledge gained from this work will allow us to answer standing fundamental questions in regards to cell fate control and the biochemistry of transcription factors, which in turn will aid in the development of novel gene regulation technologies applicable to a myriad of fields and industries.Read moreRead less
Unveiling the epigenome dynamics through the pluripotency continuum. This project aims to utilise stem cells and genomics based technologies, in combination with new computational algorithms to dissect the fundamental molecular events that drive the first steps during development. The project is expected to unveil the basic mechanisms underpinning how genes driving the developmental master plan are controlled in cells that have the capacity to give rise to the whole organism and placenta. The kn ....Unveiling the epigenome dynamics through the pluripotency continuum. This project aims to utilise stem cells and genomics based technologies, in combination with new computational algorithms to dissect the fundamental molecular events that drive the first steps during development. The project is expected to unveil the basic mechanisms underpinning how genes driving the developmental master plan are controlled in cells that have the capacity to give rise to the whole organism and placenta. The knowledge gained from this work will inform and guide future novel approaches, such as in assisted reproductive technologies or regenerative medicine.Read moreRead less
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
Imaging mammalian organogenesis with adaptive optics. Optical and computational barriers to analysing cell movement have limited our understanding of mammalian organogenesis. We have built a super-resolution spinning disk confocal microscope with adaptive optics and developed machine learning-based image processing and cell segmentation workflows to overcome these long-standing barriers. We propose to combine these cutting-edge live imaging and analysis approaches to characterise the role of cel ....Imaging mammalian organogenesis with adaptive optics. Optical and computational barriers to analysing cell movement have limited our understanding of mammalian organogenesis. We have built a super-resolution spinning disk confocal microscope with adaptive optics and developed machine learning-based image processing and cell segmentation workflows to overcome these long-standing barriers. We propose to combine these cutting-edge live imaging and analysis approaches to characterise the role of cell movement in mammalian organ formation and develop advanced cell segmentation and tracking methods for use in the scientific community. We anticipate this project will generate fundamental insights into how cells interact to build complex organs.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
Molecular definition of cellular states in the vascular endothelium. The endothelium is the main cell type forming blood vessels and spans across multiple cell states from stem/progenitor to a variety of terminally differentiated cells. How each of these cell states are defined at the molecular level is not known preventing the optimal formation and integration of blood vessels in bioengineered tissues. Using innovative single cell gene expression and chromatin accessibility studies combined wit ....Molecular definition of cellular states in the vascular endothelium. The endothelium is the main cell type forming blood vessels and spans across multiple cell states from stem/progenitor to a variety of terminally differentiated cells. How each of these cell states are defined at the molecular level is not known preventing the optimal formation and integration of blood vessels in bioengineered tissues. Using innovative single cell gene expression and chromatin accessibility studies combined with innovative analysis, we propose to define and validate each cell state at the molecular level.
This new knowledge would greatly enhance our ability to control the transition between cell states leading to a more widespread use of endothelial cells in bioengineering of tissues globally for many applications.
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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
Understanding how the heart becomes more efficient. The body demands that the heart function at utmost efficiency. Trabeculae – folds within the heart lumen – maximise blood flow, contribute to chamber development and form the electrical conduction network of the heart. Problems with trabeculae formation cause cardiomyopathy and arrhythmia and yet we do not understand its basic development. The project will investigate the earliest stages of when this tissue develops its identity and examine the ....Understanding how the heart becomes more efficient. The body demands that the heart function at utmost efficiency. Trabeculae – folds within the heart lumen – maximise blood flow, contribute to chamber development and form the electrical conduction network of the heart. Problems with trabeculae formation cause cardiomyopathy and arrhythmia and yet we do not understand its basic development. The project will investigate the earliest stages of when this tissue develops its identity and examine the signalling, genetic, cellular and extracellular cues required to instruct trabeculae to form in the heart. Findings from this research will revise our understanding of when and how trabeculae form and provide key information about how to grow and repair this important tissue.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