Understanding evolution in natural systems using robotic models. This project aims to build biologically-inspired robotic and computational systems, and then modify these in ways which are either not possible, or have not yet occurred in natural systems. A comparison of these two systems will then allow a quantitative understanding of how well optimised biological structures are and where the limitations to optimisation lie. Expected outcomes include advancing the understanding of evolutionary p ....Understanding evolution in natural systems using robotic models. This project aims to build biologically-inspired robotic and computational systems, and then modify these in ways which are either not possible, or have not yet occurred in natural systems. A comparison of these two systems will then allow a quantitative understanding of how well optimised biological structures are and where the limitations to optimisation lie. Expected outcomes include advancing the understanding of evolutionary processes, and will provide significant benefits, such as aiding the manufacture of efficient autonomous robots.Read moreRead less
Gene regulation by retroelement encoded natural antisense transcripts. Genetic information underpins all life on earth and is processed to make proteins, which determine the characteristics of an organism. However, only about 2% of our whole genome is made up of genes that encode proteins; the other 98% is non-coding and its function remains poorly understood. Aims and Significance: This proposal aims to utilise cutting edge genomic technologies to generate new knowledge about how the non-coding ....Gene regulation by retroelement encoded natural antisense transcripts. Genetic information underpins all life on earth and is processed to make proteins, which determine the characteristics of an organism. However, only about 2% of our whole genome is made up of genes that encode proteins; the other 98% is non-coding and its function remains poorly understood. Aims and Significance: This proposal aims to utilise cutting edge genomic technologies to generate new knowledge about how the non-coding genome regulates the expression of protein coding genes. Expected Outcomes and Benefits: This proposal will provide novel targets and methodology for gene modulation with broad applications from biology to environmental sciences.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
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
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
Autotransporter folding: insights advancing recombinant protein production. Imagine a world in which any protein could be produced using a single production platform. This project aims to make this a reality by reengineering autotransporters, a large family of bacterial virulence factors with a modular structure that makes them amenable to rational design. The project plans to examine the structures and folding behaviour of autotransporters and reengineered derivatives fused to target heterologo ....Autotransporter folding: insights advancing recombinant protein production. Imagine a world in which any protein could be produced using a single production platform. This project aims to make this a reality by reengineering autotransporters, a large family of bacterial virulence factors with a modular structure that makes them amenable to rational design. The project plans to examine the structures and folding behaviour of autotransporters and reengineered derivatives fused to target heterologous proteins using biochemical, biophysical, and structural methods. It is expected that this project will provide fundamental insights into factors that dictate autotransporter folding and stability, which may enhance recombinant protein production and drive discovery of strategies to prevent autotransporter-mediated infection.Read moreRead less