Understanding How RUVBL1 And RUVBL2 Organise Chromosomes And Their Links To Disease
Funder
National Health and Medical Research Council
Funding Amount
$605,005.00
Summary
Our proposal will provide a deep mechanistic framework to inform both clinicians in diagnosis and management of RUVBL related diseases and also therapeutically, as industry looks to use these proteins as drug targets. The great excitement of RUVBL in translation has outpaced the gathering of vital knowledge underpinning the function; knowledge this proposal will provide for the first time.
The function of small ribonucleic acid derived from the 5´ end of transfer ribonucleic acid (5´tRFs) in the regulation of gene expression and the control of the cell cycle. Small regulatory ribonucleic acid (RNAs) are key regulators of gene expression. The numbers of identified small RNAs are increasing, however the exact functions of many of these RNAs are not known. This project aims to describe the function of a small RNA which may play a role in suppressing uncontrolled cell division.
Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the ....Regulation of cell proliferation and survival by the ubiquitin system. This project aims to investigate how the fundamental processes of cell division and cell death are controlled at the molecular level by protein degradation enzymes (known as ubiquitin ligases), and how these regulate cellular homeostasis. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, this project seeks to delineate the components of signalling pathways implicated in the degradation of proteins implicated in cell division and cell death. Expected outcomes include an increased understanding of how proteins are specifically selected for degradation. Protein degradation pathways operate with remarkable selectivity and this work is expected to illuminate the mechanisms of substrate targeting. The biochemical approaches will provide insight and impact in the areas of cell signaling, organelle biology and cell biology.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
Decoding the spatiotemporal control of DNA replication and repair. DNA replication is the fundamental mechanism of genetic inheritance and essential for all cellular life. This project aims to inform our understanding of how human cells coordinate the DNA replication machinery in time and space to accurately copy the human genome. By applying multiple innovative approaches and employing an interdisciplinary research team, this project is anticipated to generate new knowledge that explains how th ....Decoding the spatiotemporal control of DNA replication and repair. DNA replication is the fundamental mechanism of genetic inheritance and essential for all cellular life. This project aims to inform our understanding of how human cells coordinate the DNA replication machinery in time and space to accurately copy the human genome. By applying multiple innovative approaches and employing an interdisciplinary research team, this project is anticipated to generate new knowledge that explains how the human genome is replicated. This knowledge is expected to generate research publications of high quality and provide economic benefits, such as unlocking new potentially patentable DNA technologies. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100984
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Unravelling the cell biology of a blood vessel. This project aims to understand the molecular mechanisms of vascular regeneration in adult homeostasis. Maintaining a viable circulatory system is essential for organ survival and function. The data generated from this project has the capacity to significantly impact our fundamental understanding of cardiovascular repair and regeneration. This will be of future benefit to many industries including science, bioengineering, healthcare technologies, a ....Unravelling the cell biology of a blood vessel. This project aims to understand the molecular mechanisms of vascular regeneration in adult homeostasis. Maintaining a viable circulatory system is essential for organ survival and function. The data generated from this project has the capacity to significantly impact our fundamental understanding of cardiovascular repair and regeneration. This will be of future benefit to many industries including science, bioengineering, healthcare technologies, and ensuring significant economic outcomes and benefit the Australian community.Read moreRead less
Investigation of the biology of insulin-like growth factor 1 and its derivatives for the development of new therapeutics. This project will investigate the biology of insulin-like growth factor 1, a key molecule in growth, development and, in particular, the wound healing process. Its success will lead to improved treatments for non-healing (chronic) wounds and, potentially, new anti-cancer treatments.
TREX-mediated nuclear mRNA export in neuronal differentiation and function. This project aims to study nucleus-to-cytoplasm information flow and the cellular toolbox required for this process. To ensure competitive growth and survival, plant and animal cells have sophisticated mechanisms of information transfer. One such process is efficient export of molecules from the cell nucleus (the coding space) to the cell cytoplasm (the protein synthesis space). This project will use a cell-based system ....TREX-mediated nuclear mRNA export in neuronal differentiation and function. This project aims to study nucleus-to-cytoplasm information flow and the cellular toolbox required for this process. To ensure competitive growth and survival, plant and animal cells have sophisticated mechanisms of information transfer. One such process is efficient export of molecules from the cell nucleus (the coding space) to the cell cytoplasm (the protein synthesis space). This project will use a cell-based system that can precisely control different aspects of the toolbox performance to understand this process. The knowledge and resources generated can be used to develop products or services with tangible economic and health benefits.Read moreRead less
Differential roles of gene family members in development of a cell lineage. This project aims to investigate how a family of genes influence cells in the testis to become mature sperm. Testicular cells regulate gene activity via the Snail family of proteins during sperm development, and interruption of their activities reduces fertility in mice and fruit flies. The project aims to use genetic, cell biological and biochemical studies in Drosophila and mice to compare different Snail family protei ....Differential roles of gene family members in development of a cell lineage. This project aims to investigate how a family of genes influence cells in the testis to become mature sperm. Testicular cells regulate gene activity via the Snail family of proteins during sperm development, and interruption of their activities reduces fertility in mice and fruit flies. The project aims to use genetic, cell biological and biochemical studies in Drosophila and mice to compare different Snail family proteins in spermatogenesis. The outcomes will define the different roles of highly similar proteins from the same family in differentiation of a single cell lineage. This is important in generating functional tissues using in vitro laboratory approaches or understanding how normal development and developmental disorders arise.Read moreRead less
Programmed cell death in host-microbe interactions. This project aims to address how host cell death, as part of the immune defence system, controls invading microbes. By following host-microbe interactions at high resolution, the project will generate new knowledge in the area of infection and immunity based on an interdisciplinary approach to discover new cell death factors. The expected outcome of this project will enhance the imaging capacity and develop new technologies in Australia by buil ....Programmed cell death in host-microbe interactions. This project aims to address how host cell death, as part of the immune defence system, controls invading microbes. By following host-microbe interactions at high resolution, the project will generate new knowledge in the area of infection and immunity based on an interdisciplinary approach to discover new cell death factors. The expected outcome of this project will enhance the imaging capacity and develop new technologies in Australia by building on international collaborations, providing significant benefits to the health of the community and potential to develop innovative applications in biomedical industries.Read moreRead less