Development of ozone-induced dissociation for lipidomics workflows. An Australian invention (ozone induced dissociation) will be developed in collaboration with a major instrument manufacturer. This project will provide Australian researchers with unique capabilities to investigate the role of lipids (fats) in human disease and will place them at the forefront of lipid research internationally.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989078
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Unique, state-of-the-art lipidomics infrastructure. The new technologies provided through this grant will significantly enhance our understanding of lipids and their role in normal cell biology and disease. These new insights will be vital in improving our understanding of lipid-related disorders such obesity, type 2 diabetes and cardiovascular disease and helping to improve their treatment and prevention.
Multiplexed bio-imaging mass spectrometry. This project aims to develop technology for simultaneous three-dimensional imaging of trace elements and molecules in biological tissues. This technology is an essential analytical and diagnostic advance to uncover latent mechanistic biology and will reveal subtle metabolic interactions between cells. The project will use laser ablation-inductively coupled plasma-mass spectrometry and lanthanide-conjugated probes to map the zinc metabolic pathway in the ....Multiplexed bio-imaging mass spectrometry. This project aims to develop technology for simultaneous three-dimensional imaging of trace elements and molecules in biological tissues. This technology is an essential analytical and diagnostic advance to uncover latent mechanistic biology and will reveal subtle metabolic interactions between cells. The project will use laser ablation-inductively coupled plasma-mass spectrometry and lanthanide-conjugated probes to map the zinc metabolic pathway in the ageing mouse brain. It is expected to result in a complete imaging solution for quantitative spatial determination of all important elements, co-factors, metabolites and other functional molecules to investigate metabolic pathways which current technologies find difficult or impossible to track. Ultimately this technology is expected to underpin investigations of diseases where trace metal and chemical species dysfunction is implicated.Read moreRead less
Biophysical characterization of protein interactions within a transcription factor network. Gene expression is regulated in part by interactions between pairs and groups of proteins known as transcription factors and co-regulators. These proteins assemble into complexes at gene promoters and enhancers and thereby control the expression of that gene. Little is known at the molecular level of how these complexes form and how different interactions cooperate or compete with each other. In this prop ....Biophysical characterization of protein interactions within a transcription factor network. Gene expression is regulated in part by interactions between pairs and groups of proteins known as transcription factors and co-regulators. These proteins assemble into complexes at gene promoters and enhancers and thereby control the expression of that gene. Little is known at the molecular level of how these complexes form and how different interactions cooperate or compete with each other. In this proposal we aim to define a complex between two transcriptional regulators (HOP and SRF) involved in cardiac development and to begin to define other interactions that make up a transcriptional network essential for development of a normal heart.Read moreRead less
Characterization of erythroid differentiation related factor (EDRF): a novel a-globin binding protein. Hemoglobin, a four-subunit protein comprising two alpha and two beta polypeptide chains, is the essential oxygen transporter found in all mammals. Problems with the synthesis of hemoglobin can give rise to a range of common and serious human disorders, including thalassaemia and anemia. We have discovered a protein, EDRF, that appears to interact directly with alpha-globin (but not beta-globin) ....Characterization of erythroid differentiation related factor (EDRF): a novel a-globin binding protein. Hemoglobin, a four-subunit protein comprising two alpha and two beta polypeptide chains, is the essential oxygen transporter found in all mammals. Problems with the synthesis of hemoglobin can give rise to a range of common and serious human disorders, including thalassaemia and anemia. We have discovered a protein, EDRF, that appears to interact directly with alpha-globin (but not beta-globin) and to play a role in the regulation of hemoglobin production. We now seek to understand the nature of this interaction at a molecular level and mechanistic level.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
Cellular Gene Regulation Networks. The benefit to Australia will be scientific in terms of providing an understanding of how cells integrate transcriptional control systems and the networks that are involved. This will inform research on folate deficiency and aberrant human development and towards identifying genes that are important in improving efficiency of microbial fermentations. Additional and more practical major benefits will follow from the development of tools to analyse interaction ....Cellular Gene Regulation Networks. The benefit to Australia will be scientific in terms of providing an understanding of how cells integrate transcriptional control systems and the networks that are involved. This will inform research on folate deficiency and aberrant human development and towards identifying genes that are important in improving efficiency of microbial fermentations. Additional and more practical major benefits will follow from the development of tools to analyse interactions between control systems, including software of value to the research community. The work will provide postgraduate students with major training in up-to-date genomic technologies, and in the interface between application of bioinformatics and experimental science.
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