The colour of cellular aging: a deep probe of cellular processes. Understanding why we age and whether aging is preventable are profound research challenges, which must be first tackled at a cellular level. Building on our advances in non-invasive colour monitoring of cell function, this project aims to uncover intimate links between cellular processes and aging in cells that must survive for many decades such as oocytes and neurons. We will explore the tantalising possibility to rejuvenate such ....The colour of cellular aging: a deep probe of cellular processes. Understanding why we age and whether aging is preventable are profound research challenges, which must be first tackled at a cellular level. Building on our advances in non-invasive colour monitoring of cell function, this project aims to uncover intimate links between cellular processes and aging in cells that must survive for many decades such as oocytes and neurons. We will explore the tantalising possibility to rejuvenate such aged cells by interfering with molecular master switches of aging. A unique machine learning approach will be applied for finding the most effective interventions. The results will have broad impact beyond the science of aging, in the areas of female fertility, neurodegeneration and immunity.
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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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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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE180100066
Funder
Australian Research Council
Funding Amount
$443,311.00
Summary
Electrophysiology facility for cell phenotyping and drug discovery. This project aims to establish a high-throughput, automated patch clamp facility to enable research at the forefront of cell phenotyping and drug discovery. Ion channels are membrane proteins that underlie cell function and are therefore important drug targets. The patch clamp technique is the most powerful tool available to functionally characterise cells and study the function of ion channels. The significant advance provided ....Electrophysiology facility for cell phenotyping and drug discovery. This project aims to establish a high-throughput, automated patch clamp facility to enable research at the forefront of cell phenotyping and drug discovery. Ion channels are membrane proteins that underlie cell function and are therefore important drug targets. The patch clamp technique is the most powerful tool available to functionally characterise cells and study the function of ion channels. The significant advance provided by the high-throughput, automated patch clamp system is that it allows up to 384 cells to be recorded simultaneously. This project expects to enhance capacity to automate and standardise the quality of recordings, substantially increase the rate of data production, and enable greater access to patch clamp technology.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
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
Shear stimulated Brillouin microscopy for cell mechanobiology. This project aims to develop novel technology for non-contact imaging of micro-mechanical properties in cells and tissues to answer fundamental questions of cell mechnanobiology. Based on principles of Brillouin light scattering, the project takes advantage of a radio-frequency lock-in detection scheme. The project will result in a real-time, high-sensitivity, non-contact 3D imaging solution for spatial characterisation of cell's loc ....Shear stimulated Brillouin microscopy for cell mechanobiology. This project aims to develop novel technology for non-contact imaging of micro-mechanical properties in cells and tissues to answer fundamental questions of cell mechnanobiology. Based on principles of Brillouin light scattering, the project takes advantage of a radio-frequency lock-in detection scheme. The project will result in a real-time, high-sensitivity, non-contact 3D imaging solution for spatial characterisation of cell's local stiffness and compressibility. This will underpin the advancement of knowledge in the area of cell mechanobiology and the investigation of diseases, where microscale changes in cell mechanical properties lead to cell dysfunction and apoptosis.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
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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Rejuvenating adult stem cells. This project aims to uncover intimate links between metabolic regulation and longevity in adult stem cells, the source of all cells in the body. Understanding why we age and whether ageing is preventable are research challenges which must be first attacked at a cellular level. This project will try to rejuvenate aged stem cells by interfering with a prospective molecular master switch of aging and also develop an approach to identify and select youthful stem cells. ....Rejuvenating adult stem cells. This project aims to uncover intimate links between metabolic regulation and longevity in adult stem cells, the source of all cells in the body. Understanding why we age and whether ageing is preventable are research challenges which must be first attacked at a cellular level. This project will try to rejuvenate aged stem cells by interfering with a prospective molecular master switch of aging and also develop an approach to identify and select youthful stem cells. The results are expected to be important beyond informing the science of ageing, in the areas of tissue engineering, wound healing, embryology and cancer.Read moreRead less