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
Nuclear and chromatin architecture in the replication stress response. DNA replication is an essential biological activity required for the transmittance of genomic material across cell divisions. If errors occur during DNA replication, this results in dangerous outcomes including mutation, genome instability, and cell death. Cells cope with challenges to DNA replication through a process called the replication stress response. This fellowship explores a newly discovered pathway in the replicati ....Nuclear and chromatin architecture in the replication stress response. DNA replication is an essential biological activity required for the transmittance of genomic material across cell divisions. If errors occur during DNA replication, this results in dangerous outcomes including mutation, genome instability, and cell death. Cells cope with challenges to DNA replication through a process called the replication stress response. This fellowship explores a newly discovered pathway in the replication stress response where changes to the architecture of a cell nucleus, and movement of the genomic material inside, promotes repair of genomic damage that occurs during replication. The result of this project will be an understanding of fundamental biological processes that protect human genomes.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
How do cells survive nutrient stress? Insight into mechanisms. This project studies cell survival under nutrient stress in eukaryotes. Building on extensive preliminary data that identifies novel TOR (Target of Rapamycin) Complex 2 (TORC2) control points it expects to generate new knowledge of critical and conserved features of stress control of macroautophagy that ensures cell survival. It uses interdisciplinary and innovative approaches to validate and characterize nutrient-stress dependent si ....How do cells survive nutrient stress? Insight into mechanisms. This project studies cell survival under nutrient stress in eukaryotes. Building on extensive preliminary data that identifies novel TOR (Target of Rapamycin) Complex 2 (TORC2) control points it expects to generate new knowledge of critical and conserved features of stress control of macroautophagy that ensures cell survival. It uses interdisciplinary and innovative approaches to validate and characterize nutrient-stress dependent signaling. Expected outcomes include novel insights into environmental control of cell proliferation and forging cross institutional collaborations. This knowledge benefits basic and applied biology and is relevant to industries/projects utilizing living cells as nutrient supports cell survival and proliferation.Read moreRead less
Dissecting cell cycle regulation using programmable gene editing technology. This program aims to harness the unprecedented power of CRISPR-Cas13 gene-editing technology to develop high-throughput tools to explore the role of RNA regulation in cell cycle control. This project expects to generate new knowledge about cell division and RNA biology by utilizing this new technology and applying interdisciplinary approaches. Expected outcomes of this proposal include new research tools capable of broa ....Dissecting cell cycle regulation using programmable gene editing technology. This program aims to harness the unprecedented power of CRISPR-Cas13 gene-editing technology to develop high-throughput tools to explore the role of RNA regulation in cell cycle control. This project expects to generate new knowledge about cell division and RNA biology by utilizing this new technology and applying interdisciplinary approaches. Expected outcomes of this proposal include new research tools capable of broadly addressing biological questions across multiple disciplines (e.g. from health to food production). This project intends to provide significant benefits, such as enhanced biological knowledge, multidisciplinary training opportunities and will build Australia’s capability in this rapidly expanding field.Read moreRead less
Understanding platinum dissolution in biomedical stimulating electrodes. Platinum is the main material used in electrodes for neurostimulators like the cochlear implant. Platinum electrodes can experience dissolution during implantation, which can impact on their function. The mechanisms governing this dissolution process are complex and still not fully understood. This research aims to understand the chemical, electrical and biological factors that impact on platinum dissolution in electrodes. ....Understanding platinum dissolution in biomedical stimulating electrodes. Platinum is the main material used in electrodes for neurostimulators like the cochlear implant. Platinum electrodes can experience dissolution during implantation, which can impact on their function. The mechanisms governing this dissolution process are complex and still not fully understood. This research aims to understand the chemical, electrical and biological factors that impact on platinum dissolution in electrodes. It will also develop new 3D models to simulate conditions in the human body for more rapid testing of electrodes. The new knowledge generated will improve the accuracy of predictions of platinum dissolution, develop new approaches for minimising dissolution, and contribute to reducing need for animal experimentation.Read moreRead less
Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cel ....Migration-Dependent Signalling in Macrophages . The project aims to investigate a mechanism of communication used by immune cells to guide each other towards sites of damage. The project will characterise newly revealed cell signalling membrane trails left behind by migrating cells, utilising biochemistry, innovative imaging and microscopy and a transparent zebrafish model to view cell migration through living tissues. Expected outcomes include new fundamental knowledge in the area of immune cell migration with relevance to the basic biology of inflammation, repair and regeneration and new innovations for cell imaging. Significant benefits are expected to arise from this new knowledge and from advanced skills training and improved national capabilities in bio-imaging and analysis.Read moreRead less
Transcriptional and translational regulation of the neuronal protein tau. The microtubule-associated protein tau is important for brain development and performance. To perform these functions, tau levels and its variants are tightly controlled in brain cells. However, the factors that regulate tau remain largely unknown. This project will employ latest gene technologies to identify the molecular regulators of tau, for each step of the process from DNA to the protein. The outcome of this study wi ....Transcriptional and translational regulation of the neuronal protein tau. The microtubule-associated protein tau is important for brain development and performance. To perform these functions, tau levels and its variants are tightly controlled in brain cells. However, the factors that regulate tau remain largely unknown. This project will employ latest gene technologies to identify the molecular regulators of tau, for each step of the process from DNA to the protein. The outcome of this study will significantly advance our understanding of gene regulation and mechanisms for controlling protein levels and contribute to a deeper understanding of brain function during development and aging.Read moreRead less