New laser and mass spectrometry-based tools for comprehensive structural elucidation of lipids and their biomolecular interactions. Lipid-related disorders such as obesity, diabetes and heart disease are reaching epidemic proportions. We propose the development of specialised instrumentation to identify and quantify lipids (fats) in tissue and culture samples thus providing Australian scientists with unique capabilities to investigate the mechanisms of disease.
The photons take charge: Elucidating the structure and stability of distonic radical anions by mass spectrometry and photoelectron spectroscopy. Recent work has discovered that certain radical anions have electronic configurations that defy chemical convention and exhibit exceptional radical stability. Exploitation of this breakthrough first requires experimental elucidation of the intrinsic electronic structure of these compounds and how it relates to their remarkable properties. This project w ....The photons take charge: Elucidating the structure and stability of distonic radical anions by mass spectrometry and photoelectron spectroscopy. Recent work has discovered that certain radical anions have electronic configurations that defy chemical convention and exhibit exceptional radical stability. Exploitation of this breakthrough first requires experimental elucidation of the intrinsic electronic structure of these compounds and how it relates to their remarkable properties. This project will probe the fundamental structure and energetics of radical anions by modifying instrumentation to enable multi-step gas-phase ion synthesis to be efficiently coupled with anion photoelectron spectroscopy. These investigations are essential to revealing the scope of this phenomenon in free radical chemistry and biology and could inform future development of new catalysts for polymerisation.Read moreRead less
Refinement of dynamic combinatorial chemistry as a drug discovery tool. Medicinal chemistry is constantly being challenged to develop efficient methodologies for the synthesis of compounds for drug discovery. Following completion of the Human Genome project, the cloning and expression of new proteins will proceed at an accelerated rate. In the absence of biochemical knowledge of the target protein there is a growing interest in techniques that expand the structural and biological diversity of co ....Refinement of dynamic combinatorial chemistry as a drug discovery tool. Medicinal chemistry is constantly being challenged to develop efficient methodologies for the synthesis of compounds for drug discovery. Following completion of the Human Genome project, the cloning and expression of new proteins will proceed at an accelerated rate. In the absence of biochemical knowledge of the target protein there is a growing interest in techniques that expand the structural and biological diversity of compound libraries. Dynamic combinatorial chemistry is an innovative technology with the capacity for supporting the shift from focussed to diverse compound libraries. This application seeks funding to refine dynamic combinatorial chemistry into an effective drug discovery tool.Read moreRead less
Developing next-generation mass spectrometry imaging with isomer resolution. Mass spectrometry imaging (MSI) is a rapidly emerging technology for mapping molecular distributions within biological samples. This project will bring together market-leading MSI instrumentation from the industry partner Waters Corporation with unique technologies developed at QUT and UOW to develop an integrated MSI-platform capable of achieving high mass- and spatial-resolution, as well as discrimination of lipid iso ....Developing next-generation mass spectrometry imaging with isomer resolution. Mass spectrometry imaging (MSI) is a rapidly emerging technology for mapping molecular distributions within biological samples. This project will bring together market-leading MSI instrumentation from the industry partner Waters Corporation with unique technologies developed at QUT and UOW to develop an integrated MSI-platform capable of achieving high mass- and spatial-resolution, as well as discrimination of lipid isomers. Resolution of lipid isomers using this instrumentation will afford researchers a first glimpse of isomer-resolved images that will be used to visualise tissue-specific changes resulting from underlying chemical, physical or metabolic processes; changes that are currently invisible to contemporary imaging technologies.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
Developing next generation technologies for unmasking the lipidome. Recent discoveries suggest that the number and structural variety of lipids in nature may be far greater than previously imagined. This complexity arises from the presence of structurally similar, but functionally distinct, lipid isomers that are not readily distinguished using current lipidomics technologies. This project aims to develop unique instrumentation that combines ion mobility and mass spectrometry to enable the rapid ....Developing next generation technologies for unmasking the lipidome. Recent discoveries suggest that the number and structural variety of lipids in nature may be far greater than previously imagined. This complexity arises from the presence of structurally similar, but functionally distinct, lipid isomers that are not readily distinguished using current lipidomics technologies. This project aims to develop unique instrumentation that combines ion mobility and mass spectrometry to enable the rapid separation, identification and quantification of isomeric lipids. These next generation technologies will be deployed in the hope of unmasking the molecular diversity within the lipidomes of two important mammalian cell types, thus providing fundamental new insights into the structure and function of lipids within living systems.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0239037
Funder
Australian Research Council
Funding Amount
$248,000.00
Summary
An Analytical Variable Pressure Scanning Electron Microscope for South-East Queensland. The proposed equipment is an analytical scanning electron microscope (SEM) with the special capability that it can examine and analyse specimen surfaces at high magnifications while specimens remain at low vaccum. This allows hydrated or poorly conducting samples to be examined directly without the specimen preparation usually necessary for SEM. Scanning electron microscopy is already extensively used in re ....An Analytical Variable Pressure Scanning Electron Microscope for South-East Queensland. The proposed equipment is an analytical scanning electron microscope (SEM) with the special capability that it can examine and analyse specimen surfaces at high magnifications while specimens remain at low vaccum. This allows hydrated or poorly conducting samples to be examined directly without the specimen preparation usually necessary for SEM. Scanning electron microscopy is already extensively used in research across multiple disciplines, including mineralogy, materials science and engineering, and life science. The instrument, to be sited at QUT, would be available to researchers from the three Brisbane universities, and would greatly enhance the regional capabilities for characterisation of materials.Read moreRead less
Correction of non-linearity in inductively-coupled-plasma mass-spectrometry. Chemical analyses by mass spectrometers underpin key Australian economic sectors, particularly minerals and agriculture. The quadrupole inductively-coupled-plasma mass-spectrometer has seen a particular rise in prominence over last 25 years. In this collaboration between mass spectrometrists and the leading instrument designer, we will improve the linearity of its detection system for more precise and accurate data. Bet ....Correction of non-linearity in inductively-coupled-plasma mass-spectrometry. Chemical analyses by mass spectrometers underpin key Australian economic sectors, particularly minerals and agriculture. The quadrupole inductively-coupled-plasma mass-spectrometer has seen a particular rise in prominence over last 25 years. In this collaboration between mass spectrometrists and the leading instrument designer, we will improve the linearity of its detection system for more precise and accurate data. Better elemental and isotope ratio data from these high-throughput instruments will open up new real-world applications in many areas of Australian interest, such as biosecurity, forensics, groundwater management, and drug design. The research will also inform design of the next generation instruments by the industry partner.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0237908
Funder
Australian Research Council
Funding Amount
$637,000.00
Summary
Mass Spectrometry Instrumentation for Therapeutic Lead Discovery. Drug discovery is reliant on the application of basic research and advanced technologies to obtain solutions to human suffering caused by diseases. This application seeks funding to support the installation of state-of-the-art mass spectrometry instrumentation at Griffith University and the University of Melbourne. The requested instrumentation will enhance high quality collaborative research programs in drug discovery and eradica ....Mass Spectrometry Instrumentation for Therapeutic Lead Discovery. Drug discovery is reliant on the application of basic research and advanced technologies to obtain solutions to human suffering caused by diseases. This application seeks funding to support the installation of state-of-the-art mass spectrometry instrumentation at Griffith University and the University of Melbourne. The requested instrumentation will enhance high quality collaborative research programs in drug discovery and eradicate significant deficiencies in research infrastructure at both institutions. Access to state-of-the-art mass spectrometry instrumentation will markedly improve our international competitiveness across a broad range of biological and chemical science disciplines.Read moreRead less