Seeing is believing: Microscopy-capable single-molecule bioelectronics. This project aims to create new biophysical tools for single-molecule sensing by advancing the state-of-the-art in nanoscale bioelectronic devices. The goal is to generate novel bioelectronic devices optimised for fabrication on microscope coverslip (170 micron glass) for compatibility with new low-cost platforms for advanced biological microscopy. Expected outcomes include the first organic electrochemical transistors inter ....Seeing is believing: Microscopy-capable single-molecule bioelectronics. This project aims to create new biophysical tools for single-molecule sensing by advancing the state-of-the-art in nanoscale bioelectronic devices. The goal is to generate novel bioelectronic devices optimised for fabrication on microscope coverslip (170 micron glass) for compatibility with new low-cost platforms for advanced biological microscopy. Expected outcomes include the first organic electrochemical transistors interfaced to constrained area lipid bilayers for studying membrane proteins at single-molecule level and nanoscale transistors for electrostatically detecting motile microtubules in in-vitro molecular motor assays for biocomputation. The intended benefit is innovation in capabilities and manufacturing of bioelectronics.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
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
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
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.
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: LE180100037
Funder
Australian Research Council
Funding Amount
$223,039.00
Summary
Cryogenic quantum microscope facility. This project aims to establish a cryogenic, quantum microscope facility in Australia. Quantum sensing is a new field that harnesses the properties of individual quantum systems to realise new types of detection and imaging with unprecedented combination of sensitivity and spatial resolution. The potential innovations, applications and benefits to society are far reaching across the full spectrum of scientific and engineering activity, from the development o ....Cryogenic quantum microscope facility. This project aims to establish a cryogenic, quantum microscope facility in Australia. Quantum sensing is a new field that harnesses the properties of individual quantum systems to realise new types of detection and imaging with unprecedented combination of sensitivity and spatial resolution. The potential innovations, applications and benefits to society are far reaching across the full spectrum of scientific and engineering activity, from the development of atomic-scale imaging of protein structures for drug discovery, to the study of chemical, physical, and biological processes and materials for advanced technology and manufacturing.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL130100119
Funder
Australian Research Council
Funding Amount
$3,110,000.00
Summary
New views of life: quantum imaging in biology. This project will create and apply new technology, based on the quantum properties of diamond, to attack important problems in biology; from how cells differentiate at the beginning of life, to understanding brain function. The results of this project will directly benefit society through the development of new technology for nano-medicine and drug discovery.