The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less
Autocyclases: A new class of self-cyclising proteins. The biotechnology sector is emerging as an important economic strength in Australia. While the improved efficacy and selectivity of biomolecules has seen them emerge as alternatives to existing chemicals in health and agriculture, the stability of biomolecules remains a major limiting factor. A general strategy for improving protein stability is by joining the ends of the peptide chain in a cyclisation reaction. While a wide range of cyclic p ....Autocyclases: A new class of self-cyclising proteins. The biotechnology sector is emerging as an important economic strength in Australia. While the improved efficacy and selectivity of biomolecules has seen them emerge as alternatives to existing chemicals in health and agriculture, the stability of biomolecules remains a major limiting factor. A general strategy for improving protein stability is by joining the ends of the peptide chain in a cyclisation reaction. While a wide range of cyclic peptides and proteins are being developed in Australia and around the world, the cyclisation reaction presents a significant challenge. In this proposal we detail a novel method for protein cyclisation as a general, low-cost and green production method for making a diverse range of biomolecules. Read moreRead less
Microbiome Regulation of the Host Mitochondrial Genome. This project aims to describe newly discovered processes by which bacteria that reside in the gut of an animal influences host mitochondria, the powerhouses of the cell. Using advanced genetic and molecular methodologies, this project aims to generate new knowledge on improving mitochondrial function as well as advance our understanding of the emerging field of microbiome research. Expected outcomes include a novel and universal technology ....Microbiome Regulation of the Host Mitochondrial Genome. This project aims to describe newly discovered processes by which bacteria that reside in the gut of an animal influences host mitochondria, the powerhouses of the cell. Using advanced genetic and molecular methodologies, this project aims to generate new knowledge on improving mitochondrial function as well as advance our understanding of the emerging field of microbiome research. Expected outcomes include a novel and universal technology platform in which to engineer small molecules and probiotics to improve mitochondrial health and enhance fitness in a range of animals. This should provide significant benefits, through both scientifically relevant outcomes and economic benefits through technological advancements.Read moreRead less
Mapping and defining inter-organ cross talk during exercise. This project aims to examine precisely how organs communicate and interact. These interactions are particularly important during exercise, when continued movement demands intricate organ communication, and have major ramifications for the whole organism as it ages. Precisely how this communication takes place is unclear, but we now know that the movement of cargo with extracellular vesicles (EVs) plays an integral role in organ to orga ....Mapping and defining inter-organ cross talk during exercise. This project aims to examine precisely how organs communicate and interact. These interactions are particularly important during exercise, when continued movement demands intricate organ communication, and have major ramifications for the whole organism as it ages. Precisely how this communication takes place is unclear, but we now know that the movement of cargo with extracellular vesicles (EVs) plays an integral role in organ to organ communication. This project expects to build upon unprecedented recent developments we have made in the biology of inter-organ communication via EVs. The expected outcomes will have broad impact across life science and biotechnology.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
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
An integrated nano-bioengineered chip for enhanced molecular evolution. This project aims to develop a novel molecular evolution platform technology for the rapid selection of high value target binding molecules from diverse molecular libraries using an electrically activated nanofluidic chip coated with target. Significant outcomes from the project is the controlled selection of target binding molecules that is not possible with current methods and improved understanding of nanoforce driven mol ....An integrated nano-bioengineered chip for enhanced molecular evolution. This project aims to develop a novel molecular evolution platform technology for the rapid selection of high value target binding molecules from diverse molecular libraries using an electrically activated nanofluidic chip coated with target. Significant outcomes from the project is the controlled selection of target binding molecules that is not possible with current methods and improved understanding of nanoforce driven molecular collisions on nano-bioengineered surfaces. This provides significant benefits, creating new knowledge in nanomaterials and advanced manufacturing of nanofabricated devices, creating commercial interest and positioning Australia at the forefront of molecular discovery technology, a highly valuable global market.
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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