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
Regulation of 3D Cell Migration by Microtubule-Dependent Processes. The overarching aim of this research is to elucidate the molecular mechanisms that cells use to move in 3D environments: a basic biological function essential to development and homeostasis. During these processes, cells interact with their surroundings where they translate biophysical forces into biochemical signals to adapt their shape to move. This requires distinct signalling, controlled in space and time, to regulate the cr ....Regulation of 3D Cell Migration by Microtubule-Dependent Processes. The overarching aim of this research is to elucidate the molecular mechanisms that cells use to move in 3D environments: a basic biological function essential to development and homeostasis. During these processes, cells interact with their surroundings where they translate biophysical forces into biochemical signals to adapt their shape to move. This requires distinct signalling, controlled in space and time, to regulate the crosstalk between organelles and the cytoskeleton. To date, the role of microtubules remains elusive. Using interdisciplinary approaches combining advanced imaging technology with novel cell biology methods, the project aims to uncover fundamental knowledge about how cells interact with their environment.Read moreRead less
The role of HP1 alpha dimerisation in maintaining chromatin structure. Heterochromatin protein 1 alpha (HP1a) is an architectural protein that decorates three-dimensional genome organisation and through self-association into HP1a dimers regulates global gene expression. While there is extensive biochemical evidence on how HP1a molecules bind DNA, dimerise and bridge nucleosomes close together, we still do not know how HP1a regulates higher order chromatin structure in the context of a living cel ....The role of HP1 alpha dimerisation in maintaining chromatin structure. Heterochromatin protein 1 alpha (HP1a) is an architectural protein that decorates three-dimensional genome organisation and through self-association into HP1a dimers regulates global gene expression. While there is extensive biochemical evidence on how HP1a molecules bind DNA, dimerise and bridge nucleosomes close together, we still do not know how HP1a regulates higher order chromatin structure in the context of a living cell. Thus, by use of cutting-edge fluorescence microscopy methods, the overall aim of this research project is to determine the biophysical mechanism by which the HP1a monomer to dimer transition spatially and temporally modulates live cell chromatin network organisation to ensure faithful transmission of the genome.Read moreRead less
Tracking DNA repair dynamics in the nuclear landscape of a living cell. This project aims to track DNA repair factor recruitment in the nuclear landscape of a living cell and quantify the role of nucleus architecture in maintenance of genome integrity. By coupling advanced fluorescence microscopy with a novel DNA double strand break inducible cell system, this project expects to uncover how the nucleus spatially coordinates DNA damage detection, assessment and repair in real time. This research ....Tracking DNA repair dynamics in the nuclear landscape of a living cell. This project aims to track DNA repair factor recruitment in the nuclear landscape of a living cell and quantify the role of nucleus architecture in maintenance of genome integrity. By coupling advanced fluorescence microscopy with a novel DNA double strand break inducible cell system, this project expects to uncover how the nucleus spatially coordinates DNA damage detection, assessment and repair in real time. This research is important because DNA damage threatens organism survival and this project has the potential to define how this genomic threat is resolved at the single molecule level. The benefit of this research is a fundamental insight into DNA repair biology and development of imaging technology to quantify genome function.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100046
Funder
Australian Research Council
Funding Amount
$289,381.00
Summary
A fast fluorescence lifetime imaging microscope to track protein dynamics. This project aims to establish a fast fluorescence lifetime imaging microscope that can track the intracellular journey of a protein throughout the entire structural framework of a living cell. By coupling single particle tracking technology with a cutting-edge fluorescence lifetime camera, this one-of-a-kind microscope will enable protein mobility and interaction to be spatially mapped with unprecedented temporal resolut ....A fast fluorescence lifetime imaging microscope to track protein dynamics. This project aims to establish a fast fluorescence lifetime imaging microscope that can track the intracellular journey of a protein throughout the entire structural framework of a living cell. By coupling single particle tracking technology with a cutting-edge fluorescence lifetime camera, this one-of-a-kind microscope will enable protein mobility and interaction to be spatially mapped with unprecedented temporal resolution. The benefit of this technology is that it will enable scientists in Australia to image, for the first time, the biophysical mechanism by which a protein navigates intracellular architecture to regulate a complex biological function at the single molecule level.Read moreRead less
Integrated Nanoplatform for Multiomics Analysis of Cell-to-Cell Interaction. This project aims to develop an integrated nanoplatform for analysis of exosomes produced by host-pathogen interaction at the single cell level. This will be accomplished by engineering an innovative device involving plasmonic nanoparticles to probe exosomes molecular profiles over time. The intended outcome is a generic and robust platform for detailed molecular analysis of the consequences of cell-to-cell interactions ....Integrated Nanoplatform for Multiomics Analysis of Cell-to-Cell Interaction. This project aims to develop an integrated nanoplatform for analysis of exosomes produced by host-pathogen interaction at the single cell level. This will be accomplished by engineering an innovative device involving plasmonic nanoparticles to probe exosomes molecular profiles over time. The intended outcome is a generic and robust platform for detailed molecular analysis of the consequences of cell-to-cell interactions. Single cell scale will greatly improve detection accuracy for heterogeneous cell populations. Benefits will include new knowledge of cell-to-cell communication and intellectual property in manufacturing, which will foster collaborations across institutions and Australian industry by providing new technological solutions.Read moreRead less
Next-generation epigenetic analysis: direct reading of DNA methylation. This project aims to develop a new molecular tool to directly and dynamically read chemical modifications on genomic DNA (epigenetics) by utilizing advanced nanomaterials with the unique features of Raman spectroscopy. Epigenetics affects cellular processes and controls genetic programs by turning them “on” and “off" but there is currently no direct method to measure modifications on DNA. A new technology will be designed to ....Next-generation epigenetic analysis: direct reading of DNA methylation. This project aims to develop a new molecular tool to directly and dynamically read chemical modifications on genomic DNA (epigenetics) by utilizing advanced nanomaterials with the unique features of Raman spectroscopy. Epigenetics affects cellular processes and controls genetic programs by turning them “on” and “off" but there is currently no direct method to measure modifications on DNA. A new technology will be designed to avoid complicated procedures/chemistry for DNA epigenetic analysis providing a specific molecular fingerprint. The anticipated outcomes include a new technique and advanced knowledge in nanomaterials and DNA functions, thus strengthening the economic viability of Australian manufacturing and biotechnology sectors.Read moreRead less
Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our ....Mapping networks governing cell state plasticity: how, where and when? Single cell organisms are the basic unit of life, yet, if they had not developed the ability to change cell states we would not exist today. Changing cell states lies at the core of almost every developmental and disease process in multicellular organisms. Building upon our fundamental discovery that stem cells and non-stem cells readily interconvert, we will now incorporate innovative cell systems and the development of our new multi-layered systems biology strategy to elucidate the first comprehensive understanding of the cell biology that underlies cell state changes. These studies are a major step toward understanding the fundamentals of life. Read moreRead less
Deciphering new regulators of lipid metabolism: a focus on lipid droplets . Lipid droplets store lipids in cells and the mitochondria break down this lipid to generate energy. Both organelles are critical for energy metabolism and cell survival. This project aims to determine the proteins that regulate the interaction between mitochondria and lipid droplets, and how these proteins regulate metabolism. It is anticipated that this project will identify the essential components of lipid droplet-mit ....Deciphering new regulators of lipid metabolism: a focus on lipid droplets . Lipid droplets store lipids in cells and the mitochondria break down this lipid to generate energy. Both organelles are critical for energy metabolism and cell survival. This project aims to determine the proteins that regulate the interaction between mitochondria and lipid droplets, and how these proteins regulate metabolism. It is anticipated that this project will identify the essential components of lipid droplet-mitochondria interactions and their impact on regulating cellular lipid metabolism. The intended outcome of this project is to provide fundamental new knowledge in understanding how organelles interact and how lipid metabolism is regulated. This knowledge has applications for the primary industries and biotechnology sector.Read moreRead less