Tuneable “Nano-Shearing”: An Innovative Mechanism for the Accurate and Specific Capture of Cells and Molecules. Recent investigations have discovered a tuneable electro-hydrodynamic force which drives lateral fluid motion within a few nanometers of an electrode surface. Because the magnitude of this fluid shear force can be tuned externally (for example, via the application of an AC electric field), it provides a new capability to physically displace weakly (non-specifically) bound cellular and ....Tuneable “Nano-Shearing”: An Innovative Mechanism for the Accurate and Specific Capture of Cells and Molecules. Recent investigations have discovered a tuneable electro-hydrodynamic force which drives lateral fluid motion within a few nanometers of an electrode surface. Because the magnitude of this fluid shear force can be tuned externally (for example, via the application of an AC electric field), it provides a new capability to physically displace weakly (non-specifically) bound cellular and molecular analytes. By performing research to further understand and develop this tuneable effect, this project aims to build and test a new platform technology to enable highly efficient capture and specific detection of low concentration pathogenic molecules and circulating tumour cells (CTCs).Read moreRead less
Self-assembled phases as effective and selective materials for analysis. This project aims to develop a suite of self-assembled amphiphilic molecules to form distinctive materials for analytical chemistry. The cost-effective, easy to prepare, selective and environmentally benign materials will be for non-volatile bioactive and chiral molecular targets that are commonly encountered every day or are difficult to study. The project will open a new research area and will further uplift the internati ....Self-assembled phases as effective and selective materials for analysis. This project aims to develop a suite of self-assembled amphiphilic molecules to form distinctive materials for analytical chemistry. The cost-effective, easy to prepare, selective and environmentally benign materials will be for non-volatile bioactive and chiral molecular targets that are commonly encountered every day or are difficult to study. The project will open a new research area and will further uplift the international standing of Australia in the field. The project will provide a high level of training and expertise for Australia-based chemists.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
Noncanonical epitope recognition by CD8+ T lymphocytes. This proposed research program will provide significant fundamental insight in the areas of immunology and vaccine design. Vaccines for many diseases remain elusive, and this project aims to improve our understanding of the precise regions within pathogens that are the targets for the killer T cells of the immune system. These regions, called epitopes, are likely to be key ingredients in many future vaccines. Although immunologists have gat ....Noncanonical epitope recognition by CD8+ T lymphocytes. This proposed research program will provide significant fundamental insight in the areas of immunology and vaccine design. Vaccines for many diseases remain elusive, and this project aims to improve our understanding of the precise regions within pathogens that are the targets for the killer T cells of the immune system. These regions, called epitopes, are likely to be key ingredients in many future vaccines. Although immunologists have gathered much information about such epitopes, recent studies have shown that some unexpected regions of pathogens are targets for killer T cells. This project will break new ground by utilising unbiased procedures to assess the relative contribution of these noncanonical epitopes to immunity.Read moreRead less
Photodissociation mass spectrometry for lipidome analysis. This project aims to develop and apply novel bioanalytical mass spectrometry-based methods and workflows to illuminate the otherwise hidden structural diversity and molecular complexity of the lipidome. The structure of individual lipids define their specific biological functions. A major requirement of analytical methods employed for lipid analysis on a lipidome-wide scale, therefore, is to enable the detailed structural characterisatio ....Photodissociation mass spectrometry for lipidome analysis. This project aims to develop and apply novel bioanalytical mass spectrometry-based methods and workflows to illuminate the otherwise hidden structural diversity and molecular complexity of the lipidome. The structure of individual lipids define their specific biological functions. A major requirement of analytical methods employed for lipid analysis on a lipidome-wide scale, therefore, is to enable the detailed structural characterisation of the, potentially, tens of thousands of individual molecular lipid species that may be present within a sample of interest. This project will develop and optimise novel, ultraviolet photodissociation-tandem mass spectrometry methods which will be integrated within an automated lipidome analysis workflow, to enable comprehensive global lipidome profiling and to reveal the structural diversity of lipids involved in fundamental cellular signalling processes.Read moreRead less
The RGG/RG motif as an RNA chaperone: advancing CRISPR-Cas RNA technology. This project investigates the way in which protein molecules interact effectively with RNA molecules and also aims to enhance the CRISPR-Cas13a system for RNA detection. Innovative approaches will be used to test the role of a particular protein motif, called the RGG/RG motif, in remodelling RNA structure and enhancing the Cas13a protein. This knowledge is expected to shift our understanding of protein-RNA interactions th ....The RGG/RG motif as an RNA chaperone: advancing CRISPR-Cas RNA technology. This project investigates the way in which protein molecules interact effectively with RNA molecules and also aims to enhance the CRISPR-Cas13a system for RNA detection. Innovative approaches will be used to test the role of a particular protein motif, called the RGG/RG motif, in remodelling RNA structure and enhancing the Cas13a protein. This knowledge is expected to shift our understanding of protein-RNA interactions that are fundamental to almost every aspect of cell biology. The project is intended to benefit Australia through contributing to fundamental knowledge in the field, facilitating the development of new CRISPR-Cas biotechnologies for RNA detection and through the training of young researchers in frontier technologies. Read moreRead less
Spectroscopic investigations into nano-scale drug interactions and molecular processes in single living cells and isolated molecules. This project will develop micro-spectroscopy and nano-spectroscopy molecular imaging based techniques to spatially locate and determine the bonding sites of a new range of chemotherapeutic drugs designed to treat cancer and malaria. This project will adopt a translational approach looking first at drug interactions directly with molecules such as DNA. Secondly, in ....Spectroscopic investigations into nano-scale drug interactions and molecular processes in single living cells and isolated molecules. This project will develop micro-spectroscopy and nano-spectroscopy molecular imaging based techniques to spatially locate and determine the bonding sites of a new range of chemotherapeutic drugs designed to treat cancer and malaria. This project will adopt a translational approach looking first at drug interactions directly with molecules such as DNA. Secondly, investigating these interactions in living cells and finally applying the technology to tissue samples. The outcome of this research will be new drug screening technologies and methodologies to address two of the most devastating diseases to afflict human kind, offering hope to the countless millions suffering from these diseases.Read moreRead less
Understanding and controlling bioavailability: passive dosing of persistent organic pollutants into recombinant cell bioassays. Bioassays with mammalian cell lines may replace animal testing in chemical risk assessment if issues with limited sensitivity can be overcome for very hydrophobic chemicals such as polychlorinated dibenzodioxins. The project will solve this problem by developing a polymer-release dosing technique that assures defined and constant exposure.
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
Lectin based open tubular micro-reactors for probing protein-protein binding. This project seeks to develop non-invasive technology for the measurement and quantitation of lectin-carbohydrate binding events, in the first instance glycopeptides and glycoproteins. The goal is not only to provide accurate protein-protein association and dissociation constant data within the developed system, but to do so within an enclosed micro-fluidic environment, with the added advantages of also providing ‘trap ....Lectin based open tubular micro-reactors for probing protein-protein binding. This project seeks to develop non-invasive technology for the measurement and quantitation of lectin-carbohydrate binding events, in the first instance glycopeptides and glycoproteins. The goal is not only to provide accurate protein-protein association and dissociation constant data within the developed system, but to do so within an enclosed micro-fluidic environment, with the added advantages of also providing ‘trap and release’ extraction capabilities, and being easily coupled to both chromatographic and mass spectrometry systems. Read moreRead less