A novel magnetic resonance imaging (MRI) technique to characterise white matter microstructure in the brain. Integrity of the cellular architecture of brain white matter (WM) is vital to normal signal conduction and is disrupted in diseases such as multiple sclerosis. Due to their characteristic molecular arrangements, WM microstructures have distinct magnetic susceptibility characteristics that can be detected with high-field and ultra high-field magnetic resonance imaging (MRI). The objective ....A novel magnetic resonance imaging (MRI) technique to characterise white matter microstructure in the brain. Integrity of the cellular architecture of brain white matter (WM) is vital to normal signal conduction and is disrupted in diseases such as multiple sclerosis. Due to their characteristic molecular arrangements, WM microstructures have distinct magnetic susceptibility characteristics that can be detected with high-field and ultra high-field magnetic resonance imaging (MRI). The objective of this project is to develop and validate a novel method of mapping susceptibility effects at high (sub-voxel) resolution with MRI. The outcomes will be a more comprehensive understanding of the relationship between changes in MRI signal and WM microarchitecture and improved susceptibility mapping that may lead to earlier diagnosis and more effective therapeutic monitoring.Read moreRead less
Probing Anaesthetic Effects with New Functional Imaging Paradigms. This project seeks new insights into the effects of anaesthetics on brain function and repair. Anaesthesia is used in small-animal imaging to immobilise the animal, but in many cases the anaesthesia itself affects the neurophysiological parameters under study. It has also been shown that many anaesthetics enhance recovery after brain injury in small animals. This project plans to exploit a novel functional brain-imaging technique ....Probing Anaesthetic Effects with New Functional Imaging Paradigms. This project seeks new insights into the effects of anaesthetics on brain function and repair. Anaesthesia is used in small-animal imaging to immobilise the animal, but in many cases the anaesthesia itself affects the neurophysiological parameters under study. It has also been shown that many anaesthetics enhance recovery after brain injury in small animals. This project plans to exploit a novel functional brain-imaging technique for conscious animals to gain new insights into the effects of anaesthetics on brain function and recovery from injury. The knowledge gained is expected to improve knowledge of anaesthetic action, guide future anaesthetic use in small animal imaging to improve the accuracy of image-derived research data, and help to clarify how anaesthetics confer neuroprotective effects in brain injury.Read moreRead less
Spatiotemporal dynamics and analysis of functional magnetic resonance imaging. Functional magnetic resonance imaging (fMRI) produces signals generated by brain activity in fine detail, but links between activity and images are poorly understood, posing a barrier to full use of the technology. Predictions from our new theory of such links will be made, tested experimentally and used to improve fMRI and discover new phenomena.
Background-free imaging of single membrane-receptors with nanophosphors. This project aims to develop nanophosphor beacons and real-time, ultrahigh-sensitivity functional imaging to provide a picture of the brain. Time-gated detection microscopy will give these nanophosphors a superior optical contrast. The nanophosphors’ antibody-targeting will image single AMPA membrane receptors in their full biological context, crucial to understanding neuronal signalling. Simultaneous imaging of receptor tr ....Background-free imaging of single membrane-receptors with nanophosphors. This project aims to develop nanophosphor beacons and real-time, ultrahigh-sensitivity functional imaging to provide a picture of the brain. Time-gated detection microscopy will give these nanophosphors a superior optical contrast. The nanophosphors’ antibody-targeting will image single AMPA membrane receptors in their full biological context, crucial to understanding neuronal signalling. Simultaneous imaging of receptor trafficking and activity in neurons will help to uncover details of the dynamic activity in the brain. This technology is expected to help understand the inner workings of the brain and provide insights into its functioning.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100641
Funder
Australian Research Council
Funding Amount
$422,079.00
Summary
Brillouin microscopy for high-speed imaging of rigidity within cells. This project aims to improve the sensitivity and speed of Brillouin microscopes. Brillouin microscopes use light to measure the stiffness of samples in 3D without requiring physical access, allowing their use in inaccessible locations such as the interior of cells or within intact tissue. However, Brillouin microscopes are too slow to be used in most research. This project introduces a new approach based on different optical p ....Brillouin microscopy for high-speed imaging of rigidity within cells. This project aims to improve the sensitivity and speed of Brillouin microscopes. Brillouin microscopes use light to measure the stiffness of samples in 3D without requiring physical access, allowing their use in inaccessible locations such as the interior of cells or within intact tissue. However, Brillouin microscopes are too slow to be used in most research. This project introduces a new approach based on different optical physics that is expected to enable faster and more precise imaging. The microscope will be used to study the movement of amoeba, where it is expected to reveal the controlled stiffening and fluidising of the different regions of protoplasm believed to underlie the cell mobility.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
Discovery Early Career Researcher Award - Grant ID: DE150100091
Funder
Australian Research Council
Funding Amount
$341,000.00
Summary
Traffic on DNA: interplay between RNA polymerases and DNA-bound proteins. The DNA inside the cell is not just a repository of information, but is an active player in how that information is used. Proteins bind to defined locations on the DNA to control which genes are active, and genes are expressed by RNA polymerases that track along the DNA. Collisions between RNA polymerases and DNA-bound proteins can remove the proteins or block the polymerase. How can these essential processes safely coexis ....Traffic on DNA: interplay between RNA polymerases and DNA-bound proteins. The DNA inside the cell is not just a repository of information, but is an active player in how that information is used. Proteins bind to defined locations on the DNA to control which genes are active, and genes are expressed by RNA polymerases that track along the DNA. Collisions between RNA polymerases and DNA-bound proteins can remove the proteins or block the polymerase. How can these essential processes safely coexist on the DNA? The project aims to integrate systematic experiments using well-defined genetic components and mathematical modelling to understand the 'design' features of DNA and proteins that minimise these traffic problems. A better understanding could inform new strategies for manipulation of gene expression.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
Nuclear architecture in a living cell facilitates navigation of the genome. This project aims to investigate the role of nuclear architecture in regulating genome function by development of a new microscopy method to quantify the diffusive route of fluorescent proteins in live cells. The anticipated outcomes of this project include an insight into how chromatin dynamics facilitate DNA target search and an analytical tool for cell biologists to probe how genomes work in their natural environment ....Nuclear architecture in a living cell facilitates navigation of the genome. This project aims to investigate the role of nuclear architecture in regulating genome function by development of a new microscopy method to quantify the diffusive route of fluorescent proteins in live cells. The anticipated outcomes of this project include an insight into how chromatin dynamics facilitate DNA target search and an analytical tool for cell biologists to probe how genomes work in their natural environment (the cell nucleus).Read moreRead less