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
Unravelling the mechanisms of sodium-selectivity in biological ion channels. The aim of this project is to determine the origins of protein-mediated sodium ion transport across cell membranes. The project expects to reveal the mechanisms of selective ion conduction in different sodium-selective ion channels using advanced computer simulations, in concert with non-canonical mutation experiments that target the roles of protein chemistry. The expected outcome is improved understanding of how prote ....Unravelling the mechanisms of sodium-selectivity in biological ion channels. The aim of this project is to determine the origins of protein-mediated sodium ion transport across cell membranes. The project expects to reveal the mechanisms of selective ion conduction in different sodium-selective ion channels using advanced computer simulations, in concert with non-canonical mutation experiments that target the roles of protein chemistry. The expected outcome is improved understanding of how proteins discriminate between ion species, challenging theories that have stood for decades. The results should provide benefits in the form of basic understanding relevant to ion transport phenomena in biology and novel materials, with atomic-level views of nervous system function to guide future directions in drug development.
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Investigating Hippo-regulated transcription at single molecule resolution. Signalling pathways operate throughout life to relay signals from the extracellular world to the cellular nucleus, to control transcription and elicit a response. This project aims to understand how the Hippo growth control pathway regulates transcription. Using a combination of biology, biophysics and computational biology, this project aims to quantify behaviour of the Hippo pathway transcription factors at sub-micron r ....Investigating Hippo-regulated transcription at single molecule resolution. Signalling pathways operate throughout life to relay signals from the extracellular world to the cellular nucleus, to control transcription and elicit a response. This project aims to understand how the Hippo growth control pathway regulates transcription. Using a combination of biology, biophysics and computational biology, this project aims to quantify behaviour of the Hippo pathway transcription factors at sub-micron resolution, and how Hippo signalling modulates their behaviour, interaction with the genome and function. We anticipate our discoveries will stimulate new research, e.g. testing of how other signaling pathways regulate transcription. Intended benefits are creation of jobs and new knowledge on fundamental principles of life.Read moreRead less
Uncovering the molecular mechanisms of potassium channel activity. The aim of this project is to determine the mechanisms of protein-mediated potassium ion transport across cell membranes. It will combine advanced simulations, structural biology and electrophysiology to describe the detailed molecular processes underscoring calcium-activated potassium channel conduction, gating and inactivation. The expected outcome is an improved description of how ion channels recognise and respond to physiolo ....Uncovering the molecular mechanisms of potassium channel activity. The aim of this project is to determine the mechanisms of protein-mediated potassium ion transport across cell membranes. It will combine advanced simulations, structural biology and electrophysiology to describe the detailed molecular processes underscoring calcium-activated potassium channel conduction, gating and inactivation. The expected outcome is an improved description of how ion channels recognise and respond to physiological stimuli to control electrical signalling the body. Our results will provide benefits in the form of basic understanding relevant to ion transport phenomena in biological systems, and atomic-level views of nervous system function to guide future directions in pharmacology.Read moreRead less
Laws of attraction and repulsion: a novel family of bacterial chemo-sensors. This project aims to reveal the structural basis for the abilities of a newly characterised, widespread family of chemotaxis receptors to sense and distinguish between attractants and repellents. Many bacteria are motile. Controlling the movement of bacterial populations requires understanding of their chemosensory mechanisms. It is anticipated that this work will generate significant new knowledge in the field of signa ....Laws of attraction and repulsion: a novel family of bacterial chemo-sensors. This project aims to reveal the structural basis for the abilities of a newly characterised, widespread family of chemotaxis receptors to sense and distinguish between attractants and repellents. Many bacteria are motile. Controlling the movement of bacterial populations requires understanding of their chemosensory mechanisms. It is anticipated that this work will generate significant new knowledge in the field of signalling biology that will drive the discovery of novel chemo-effectors and the redesign of receptor specificity. Innovative use of this knowledge could be the development of new classes of repellents that are not toxic. These could be used as a means to prevent infections caused by bacterial build-up on implanted medical devices.Read moreRead less
Structural and functional studies of Helicobacter pylori flagellar motor. This project investigates the bacterial flagellar motor specialised for locomotion in viscous fluids. Its striking feature, revealed by cryo-tomography, is a complex cage-like protein scaffold that is hypothesised to stabilise the wider force-generating ring of the motor to sustain a larger turning force. The aim is to unravel the make-up of this scaffold and the structural basis for its ability to recruit more force-gener ....Structural and functional studies of Helicobacter pylori flagellar motor. This project investigates the bacterial flagellar motor specialised for locomotion in viscous fluids. Its striking feature, revealed by cryo-tomography, is a complex cage-like protein scaffold that is hypothesised to stabilise the wider force-generating ring of the motor to sustain a larger turning force. The aim is to unravel the make-up of this scaffold and the structural basis for its ability to recruit more force-generating units, in order to advance our fundamental knowledge about the mechanism of the bacterial flagellar motor, and about strategies used by nature to increase its performance under high viscosity conditions. This research is expected to add a new paradigm for how polar flagellar motors assemble and function in bacteria.
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