Ultrasensitive chemical analysis of single cells by mass spectrometry. This project aims to significantly improve the analysis of single cells by mass spectrometry with ultrahigh sensitivity. Molecular differences between cells in large populations can be important in many processes, including cell differentiation and signalling. However, most measurements result in the chemical heterogeneity between cells being masked by the bulk population. Recent discoveries now make it feasible to measure th ....Ultrasensitive chemical analysis of single cells by mass spectrometry. This project aims to significantly improve the analysis of single cells by mass spectrometry with ultrahigh sensitivity. Molecular differences between cells in large populations can be important in many processes, including cell differentiation and signalling. However, most measurements result in the chemical heterogeneity between cells being masked by the bulk population. Recent discoveries now make it feasible to measure thousands of proteins and small molecules from single cells. This project aims to leverage these breakthroughs to allow heterogeneity to be characterised in single cells with unprecedented molecular detail. This is expected to be important for future biological discovery, as well as disease prediction and drug discovery.Read moreRead less
Homogenous Antibody-Metal Conjugates For Immuno-Mass Spectrometry Imaging. This project aims to use bespoke metal labels and high-resolution mass spectrometry imaging to address current shortcomings in approaches that visualise and measure proteins in cells and tissue. It expects to substantially increase the utility of immuno-mass spectrometry imaging technology to analyses that are refractory to current techniques and workflows. Expected outcomes include metal probes that facilitate the spatia ....Homogenous Antibody-Metal Conjugates For Immuno-Mass Spectrometry Imaging. This project aims to use bespoke metal labels and high-resolution mass spectrometry imaging to address current shortcomings in approaches that visualise and measure proteins in cells and tissue. It expects to substantially increase the utility of immuno-mass spectrometry imaging technology to analyses that are refractory to current techniques and workflows. Expected outcomes include metal probes that facilitate the spatial quantification of multiple biomolecules on a single histological section, providing significant benefits to bioscience laboratories that require complex workflows to visualise and obtain quantitative data on the expression of biomolecules.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
Probing antimicrobial drug resistance by multimodal molecular analysis. This project aims to investigate drug resistance in microbial agents. With the emergence of "super bugs" there is a need to understand the biochemistry of antimicrobial resistance. Combining vibrational spectroscopic approaches and metabolomic techniques, the project will investigate cell populations, single cells and subcellular structures in search of biomarkers for drug resistance. The discovery of such biomarkers could l ....Probing antimicrobial drug resistance by multimodal molecular analysis. This project aims to investigate drug resistance in microbial agents. With the emergence of "super bugs" there is a need to understand the biochemistry of antimicrobial resistance. Combining vibrational spectroscopic approaches and metabolomic techniques, the project will investigate cell populations, single cells and subcellular structures in search of biomarkers for drug resistance. The discovery of such biomarkers could lead to improved disease management and eradication programs through identification and treatment of drug resistant pathogens in individuals that have the potential to re-infect the community.Read moreRead less
Polymer Inclusion Membranes for Electrokinetic Sampling and Separation. This proposal aims to understand the chemical and physical properties governing the transport of ions into and within advanced extracting polymeric materials, known as polymer inclusion membranes, under the influence of an applied voltage. These membranes are dry-to-touch and represent a new and potentially powerful analytical platform for environmental, medical and industry sample preparation. By understanding the transport ....Polymer Inclusion Membranes for Electrokinetic Sampling and Separation. This proposal aims to understand the chemical and physical properties governing the transport of ions into and within advanced extracting polymeric materials, known as polymer inclusion membranes, under the influence of an applied voltage. These membranes are dry-to-touch and represent a new and potentially powerful analytical platform for environmental, medical and industry sample preparation. By understanding the transport mechanism, new membranes will be developed, capable of purifying and concentrating diverse targets chemicals from liquid and solid samples. These processes can take place during sample transportation to a centralised laboratory thus simplifying and streamlining analysis upon arrival to decrease drastically its costs.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
Pluses and minuses of lipid mass spectrometry. This project aims to investigate the structural diversity of lipids. Lipids are among the most structurally diverse of all the biomolecules and thus deciphering their many functions requires bio-analytical technologies capable of uniquely identifying and quantifying individual molecules in a milieu of many thousands of analogues. Mass spectrometry is the pre-eminent technique for contemporary lipid analysis but is challenged by the preference of cer ....Pluses and minuses of lipid mass spectrometry. This project aims to investigate the structural diversity of lipids. Lipids are among the most structurally diverse of all the biomolecules and thus deciphering their many functions requires bio-analytical technologies capable of uniquely identifying and quantifying individual molecules in a milieu of many thousands of analogues. Mass spectrometry is the pre-eminent technique for contemporary lipid analysis but is challenged by the preference of certain lipids to ionise with a polarity that affords sensitive detection but does not permit detailed structure elucidation. This project will develop advanced instrumentation capable of on-demand polarity switching of ionised lipids such that the detection and interrogation of molecular structure can take place in the optimal charge state.Read moreRead less
New biosensing strategies based on bipolar electrochemiluminescence. Chemical analysis is a vital activity in our society, which is to a large extent confined to scientific laboratories and carried out with complex instrumentation. The breakthrough technology envisioned in this proposal will pave the way for simple, low-cost tests which can be used by non-scientists. The development of small, portable sensors for applications ranging from pollution monitoring to health testing, will enable ordi ....New biosensing strategies based on bipolar electrochemiluminescence. Chemical analysis is a vital activity in our society, which is to a large extent confined to scientific laboratories and carried out with complex instrumentation. The breakthrough technology envisioned in this proposal will pave the way for simple, low-cost tests which can be used by non-scientists. The development of small, portable sensors for applications ranging from pollution monitoring to health testing, will enable ordinary people to gain knowledge about the concentrations of molecular compounds in their environments and in themselves. This will stimulate economic and social benefits related to environmental testing and early disease diagnosis and generate new commercial opportunities for the Australian biotechnology industry.Read moreRead less
How electric fields can facilitate reversible protein binding to surfaces. The aim of this project is to develop the first biosensors that prevent nonspecific protein adsorption and allow reversible protein binding. The project expects to achieve this using a combination of novel surface chemistry and pulsed electric fields that dynamically change a sensing interface. The impact of electric fields on the binding of proteins to this interface will be followed using a novel single molecule fluores ....How electric fields can facilitate reversible protein binding to surfaces. The aim of this project is to develop the first biosensors that prevent nonspecific protein adsorption and allow reversible protein binding. The project expects to achieve this using a combination of novel surface chemistry and pulsed electric fields that dynamically change a sensing interface. The impact of electric fields on the binding of proteins to this interface will be followed using a novel single molecule fluorescence microscope previously developed that can locate the position of proteins with 2 nanometer resolution. The expected outcomes of this project is a class of biosensor that can continuously monitor protein biomarkers for wearable sensors that provide information on a user’s wellness and nutrition.Read moreRead less
Parameterisation of voltammetry in a machine learning environment. Important devices in modern society such as batteries, fuel cells and medical sensors exploit special properties of complex electrochemical reactions. The aim of this multidisciplinary project is to develop an integrated approach to intelligent collection and analysis of large electrochemical data sets in a machine-learning environment. As a result, it will become possible for the first time to globally model and quantitatively p ....Parameterisation of voltammetry in a machine learning environment. Important devices in modern society such as batteries, fuel cells and medical sensors exploit special properties of complex electrochemical reactions. The aim of this multidisciplinary project is to develop an integrated approach to intelligent collection and analysis of large electrochemical data sets in a machine-learning environment. As a result, it will become possible for the first time to globally model and quantitatively parameterise all aspects of the dynamic electrochemistry associated with exceptionally complex electrochemical reactions in a statistically significant framework. Problems to be addressed are of biological and chemical significance. An end product will be a commercially viable, user-friendly instrumentation package.Read moreRead less