Integrated Nanoplatform for Multiomics Analysis of Cell-to-Cell Interaction. This project aims to develop an integrated nanoplatform for analysis of exosomes produced by host-pathogen interaction at the single cell level. This will be accomplished by engineering an innovative device involving plasmonic nanoparticles to probe exosomes molecular profiles over time. The intended outcome is a generic and robust platform for detailed molecular analysis of the consequences of cell-to-cell interactions ....Integrated Nanoplatform for Multiomics Analysis of Cell-to-Cell Interaction. This project aims to develop an integrated nanoplatform for analysis of exosomes produced by host-pathogen interaction at the single cell level. This will be accomplished by engineering an innovative device involving plasmonic nanoparticles to probe exosomes molecular profiles over time. The intended outcome is a generic and robust platform for detailed molecular analysis of the consequences of cell-to-cell interactions. Single cell scale will greatly improve detection accuracy for heterogeneous cell populations. Benefits will include new knowledge of cell-to-cell communication and intellectual property in manufacturing, which will foster collaborations across institutions and Australian industry by providing new technological solutions.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0346876
Funder
Australian Research Council
Funding Amount
$1,584,000.00
Summary
800 MHz NMR Spectrometer for Molecular Structure-Function Analyses. An 800 MHz high-resolution nuclear magnetic resonance (NMR) spectrometer equipped with a triple-resonance cryoprobe is required to support the research of 5 universities in the NSW/ACT area. The high magnetic field of the spectrometer is necessary for the study of proteins, protein-ligand complexes and other biomolecular systems of molecular weight >30,000. Projects previously inaccessible due to sensitivity, solubility or resol ....800 MHz NMR Spectrometer for Molecular Structure-Function Analyses. An 800 MHz high-resolution nuclear magnetic resonance (NMR) spectrometer equipped with a triple-resonance cryoprobe is required to support the research of 5 universities in the NSW/ACT area. The high magnetic field of the spectrometer is necessary for the study of proteins, protein-ligand complexes and other biomolecular systems of molecular weight >30,000. Projects previously inaccessible due to sensitivity, solubility or resolution problems will become tractable. The increased turn-around times afforded by the high sensitivity of the cryo-enabled spectrometer make it possible to provide access for Australian institutions that would not otherwise have access to comparable equipment.Read moreRead less
Proteomics of the Influenza Virus for In-field Surveillance. The influenza virus continues to pose a serious health risk to Australians and remains a leading cause of death. The molecular characterisation of emerging strains of the virus lies at the heart of current surveillance procedures vital to vaccine preparation and the development of new anti-viral drugs. This research will advance a world-first proteomics surveillance of the virus developed in this laboratory that will enable it to be ch ....Proteomics of the Influenza Virus for In-field Surveillance. The influenza virus continues to pose a serious health risk to Australians and remains a leading cause of death. The molecular characterisation of emerging strains of the virus lies at the heart of current surveillance procedures vital to vaccine preparation and the development of new anti-viral drugs. This research will advance a world-first proteomics surveillance of the virus developed in this laboratory that will enable it to be characterised in-field at the site(s) of infection outbreaks. This rapid response is vital, particularly in the event of a pandemic or a deliberate release of the virus in a bioterrorist attack.Read moreRead less
The Application of Chemical Force Microscopy for Monitoring DNA Hybridization: A New Sensing Concept Capable of Detecting Single Molecules. This proposal outlines a method of monitoring DNA sequences with such high sensitivity that a single molecule may be detected. Such sensitivity is achieved using an atomic force microscope (AFM) to measure surface forces. Modifying an AFM tip with a single strand of DNA allows the complementary strand (the target) to be recognized via hybridization to form ....The Application of Chemical Force Microscopy for Monitoring DNA Hybridization: A New Sensing Concept Capable of Detecting Single Molecules. This proposal outlines a method of monitoring DNA sequences with such high sensitivity that a single molecule may be detected. Such sensitivity is achieved using an atomic force microscope (AFM) to measure surface forces. Modifying an AFM tip with a single strand of DNA allows the complementary strand (the target) to be recognized via hybridization to form the double helix. The occurrence of hybridization is determined by differences in surface force measurements compared with when only the single strand of DNA is present. In this way DNA samples can be analyzed without amplification; a major advance for DNA diagnostics.Read moreRead less
Gas Phase Dynamics of a Biological Molecular Machine: Fundamentals, Stoichiometries and Stabilities. Over the last twenty years advanced molecular measurement techniques have enabled the characterization of individual biological molecules (proteins and DNA) within different types of cells and diseased tissues. This project uses a new technique that literally "weighs" groups of proteins and/or DNA to help us understand how such large molecules fit together and function within cells (sometimes ref ....Gas Phase Dynamics of a Biological Molecular Machine: Fundamentals, Stoichiometries and Stabilities. Over the last twenty years advanced molecular measurement techniques have enabled the characterization of individual biological molecules (proteins and DNA) within different types of cells and diseased tissues. This project uses a new technique that literally "weighs" groups of proteins and/or DNA to help us understand how such large molecules fit together and function within cells (sometimes referred to as molecular machinery). More detailed knowledge of processes such as those involved in copying DNA when new cells are produced will, in the long term, improve our understanding and treatment of conditions or diseases that result from errors in molecular machinery. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100194
Funder
Australian Research Council
Funding Amount
$374,200.00
Summary
Quantitative three-dimensional imaging of membrane proteins. This project aims to address the challenge of in-situ quantification of membrane proteins through the emerging field of antibody-imaging mass spectrometry. The project will develop new protocols for quantitative three-dimensional imaging that aim to negate histological artifacts created by freeze-thaw and cryo-sectioning. Membrane proteins are involved in numerous cellular functions and this project expects to increase our knowledge o ....Quantitative three-dimensional imaging of membrane proteins. This project aims to address the challenge of in-situ quantification of membrane proteins through the emerging field of antibody-imaging mass spectrometry. The project will develop new protocols for quantitative three-dimensional imaging that aim to negate histological artifacts created by freeze-thaw and cryo-sectioning. Membrane proteins are involved in numerous cellular functions and this project expects to increase our knowledge of these fundamental biological processes by providing new insights into the study of these essential biomolecules. Tracking protein heterogeneity in three-dimensions will provide significant benefits to our understanding of systems biology and will benefit numerous area, including the pharmaceutical industry.Read moreRead less
A Gas Phase Study of Macromolecular Biological Complexes. Following the completion of the human genome project, increased attention has focussed on the elucidation of structure and function of biopolymers in cells. The project aims to use electrospray ionisation mass spectrometry (a rapidly developing analytical technique) to detail the processes governing the formation of macromolecular complexes (DNA-protein and DNA-metal-protein) in the gas phase. We aim to explore the relevance of gas pha ....A Gas Phase Study of Macromolecular Biological Complexes. Following the completion of the human genome project, increased attention has focussed on the elucidation of structure and function of biopolymers in cells. The project aims to use electrospray ionisation mass spectrometry (a rapidly developing analytical technique) to detail the processes governing the formation of macromolecular complexes (DNA-protein and DNA-metal-protein) in the gas phase. We aim to explore the relevance of gas phase studies of these large macromolecular complexes to interactions between biopolymers in solution and cells. Ultimately, this will aid in the development of improved therapeutics tha t act on DNA and/or DNA-binding proteins and provide new information on biological processes such as replicaton.Read moreRead less
Aptamer imaging mass spectrometry for biomarker quantification. This project aims to develop novel methods for quantifying bio-markers in histological specimens using aptamers, lanthanide visualising tags and laser ablation plasma mass spectrometry. Aptamers are short synthetic strands of nucleic acid with complex three dimensional structures that bind targets with exquisite specificity. This technology meets a major gap in current imaging modalities, has wide application to basic biology and di ....Aptamer imaging mass spectrometry for biomarker quantification. This project aims to develop novel methods for quantifying bio-markers in histological specimens using aptamers, lanthanide visualising tags and laser ablation plasma mass spectrometry. Aptamers are short synthetic strands of nucleic acid with complex three dimensional structures that bind targets with exquisite specificity. This technology meets a major gap in current imaging modalities, has wide application to basic biology and diagnostics, and will eliminate the subjective interpretation of immunohistochemical stains.Read moreRead less
High-throughput microfluidic approach to mapping hierarchies of interactions in the gene regulation machinery. The exploration of protein-protein interactions networks is becoming an extremely active area of research in life sciences. The current project will develop new approaches to accelerate the discovery of novel interacting proteins participating in gene regulation, in order to understand how cells differentiate into different tissues and organs.
Bioinorganic chemistry between immune cell and pathogen. This project aims to investigate the bioinorganic chemistry that occurs when immune system cells encounter pathogens and they try to kill one another, or in the case of a pathogen, to also modify the genetics of the mammalian cell to enable its intracellular survival. Pathogenic bacteria and fungi accumulate chromium (Cr) in their membranes and it was recently discovered that Cr is likely to be an important virulence factor. Similarly, H ....Bioinorganic chemistry between immune cell and pathogen. This project aims to investigate the bioinorganic chemistry that occurs when immune system cells encounter pathogens and they try to kill one another, or in the case of a pathogen, to also modify the genetics of the mammalian cell to enable its intracellular survival. Pathogenic bacteria and fungi accumulate chromium (Cr) in their membranes and it was recently discovered that Cr is likely to be an important virulence factor. Similarly, Hyperaccummulation of Nickel (Ni) is also involved in virulence. The project will investigate the roles of Cr and Ni in virulence using advanced spectroscopic imaging and biochemical techniques. These insights will provide new knowledge on the innate immune system and may lead to more efficacious treatments for serious infections.Read moreRead less