Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668534
Funder
Australian Research Council
Funding Amount
$770,000.00
Summary
High resolution bioanalytical Fourier transform mass spectrometer combined with liquid chromatograph. This project extends a network of advanced technology for bioanalysis that enables discoveries in biotechnology, molecular medicine and biochemistry. The proposed equipment includes the most powerful mass spectrometer (MS) currently available for bioanalysis to complement an existing network of instruments at four universities in Sydney. These include 3 of 4 nodes of the Australian Proteome Anal ....High resolution bioanalytical Fourier transform mass spectrometer combined with liquid chromatograph. This project extends a network of advanced technology for bioanalysis that enables discoveries in biotechnology, molecular medicine and biochemistry. The proposed equipment includes the most powerful mass spectrometer (MS) currently available for bioanalysis to complement an existing network of instruments at four universities in Sydney. These include 3 of 4 nodes of the Australian Proteome Analysis Facility (APAF). The new technology is a missing link in bioanalytical capability where other instruments are not sufficiently sensitive. The instrument will be managed by MS specialists at the Bioanalytical Mass Spectrometry Facility at UNSW (www.bmsf.unsw.edu.au) where access by and training of users is well established.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
Regulation of proteolysis by specialised adaptor proteins. Training research scientists of the future forms an integral part of this research program and this collaboration will provide an excellent opportunity for young Australian scientists to be exposed to the very professional and competitive environment of basic research, as it exists in Germany. It will expose early career researchers to new ideas and emerging methodologies arming them with valuable skills, which they will transfer to Aust ....Regulation of proteolysis by specialised adaptor proteins. Training research scientists of the future forms an integral part of this research program and this collaboration will provide an excellent opportunity for young Australian scientists to be exposed to the very professional and competitive environment of basic research, as it exists in Germany. It will expose early career researchers to new ideas and emerging methodologies arming them with valuable skills, which they will transfer to Australia. The involvement of Prof. Turgay in the Deutsche Forschungsgemeinschaft (DFG) Priority Programme: Proteolysis in Prokaryotes also provides a unique opportunity for these young researchers to interact with several of the worlds leading scientists in the area of proteolysis, enhancing Australia's reputation at the forefront of science.Read moreRead less
Differential Expression Proteomics: Identification and Quantitation of Peptides and Proteins by Fixed Charge Derivatization and Tandem Mass Spectrometry. The aim of this proposal is to develop novel strategies for the rapid, sensitive and selective identification and quantitation of proteins present in complex mixtures. Specifically, isotopically labeled fixed charge derivatives of peptides containing selected amino acids will be developed that direct the formation of product ions following tan ....Differential Expression Proteomics: Identification and Quantitation of Peptides and Proteins by Fixed Charge Derivatization and Tandem Mass Spectrometry. The aim of this proposal is to develop novel strategies for the rapid, sensitive and selective identification and quantitation of proteins present in complex mixtures. Specifically, isotopically labeled fixed charge derivatives of peptides containing selected amino acids will be developed that direct the formation of product ions following tandem mass spectrometry toward a single fragmentation channel. This approach will provide enhanced selectivity and sensitivity of up to 2 orders of magnitude over existing approaches, and will allow examination, at the protein level, of the complex cellular changes that occur following transformation of cells from a normal to a diseased state.Read moreRead less
Using the fractionation of hydrogen and carbon isotopes to analyse the mechanisms of the primary processes of photosynthesis. The primary processes of CO2 fixation and reduction in photosynthesis leave their signatures in the isotopic composition of organic matter. Although these signatures are used widely in geochemistry, biology and climatology to infer the dynamics and history of the biosphere, the information they provide about the mechanisms of the processes that produce them has not been e ....Using the fractionation of hydrogen and carbon isotopes to analyse the mechanisms of the primary processes of photosynthesis. The primary processes of CO2 fixation and reduction in photosynthesis leave their signatures in the isotopic composition of organic matter. Although these signatures are used widely in geochemistry, biology and climatology to infer the dynamics and history of the biosphere, the information they provide about the mechanisms of the processes that produce them has not been exploited fully. We propose to map the underlying biochemistry responsible for fractionation of hydrogen isotopes, to assess its ability to indicate the water relations of plants, and to use carbon-isotope discrimination to probe the catalytic chemistry of the CO2-fixing enzyme, Rubisco.Read moreRead less
Identification of novel biomarkers in tears for prostate cancer diagnosis and prognosis. The purpose of this study is to identify novel biomarkers in the tears of patients with CaP. The use of the several techniques will increase the chance of success and enable us to find more diagnostic markers. If successful, the identified proteins may be used to diagnose and determine the stage of cancer. This will help guide clinicians in choosing the best treatment methods for an individual patient. The m ....Identification of novel biomarkers in tears for prostate cancer diagnosis and prognosis. The purpose of this study is to identify novel biomarkers in the tears of patients with CaP. The use of the several techniques will increase the chance of success and enable us to find more diagnostic markers. If successful, the identified proteins may be used to diagnose and determine the stage of cancer. This will help guide clinicians in choosing the best treatment methods for an individual patient. The markers may also be used to monitor the disease progress and the effects of treatment. The results from this study may improve the prognosis of CaP patients.Read moreRead less
Identification of novel biomarkers for diabetic retinopathy in tears. There are around 134,000 people with diabetic retinopathy in Australia. The disease affects patients' physical and mental state and economical and social cost is enormous. This research aims to find new biomarkers for the disease which may lead to better treatment and management. Patient's quality of life may be significantly improved by early diagnosis and treatment and the burden to the community reduced. This project also g ....Identification of novel biomarkers for diabetic retinopathy in tears. There are around 134,000 people with diabetic retinopathy in Australia. The disease affects patients' physical and mental state and economical and social cost is enormous. This research aims to find new biomarkers for the disease which may lead to better treatment and management. Patient's quality of life may be significantly improved by early diagnosis and treatment and the burden to the community reduced. This project also gives industrial partners the opportunity to develop new products to diagnose and monitor the disease.Read moreRead less
Function and modulation of the protein quality control network in mammalian mitochondria. This project has potential technological benefit in the areas of biotechnology and molecular medicine especially in relation to age-related cellular degeneration. As a result of our research outputs, strategies could be developed to either delay the onset or reduce the severity of diseases related to mitochondrial dysfunction. Training research scientists of the future, forms an integral part of our researc ....Function and modulation of the protein quality control network in mammalian mitochondria. This project has potential technological benefit in the areas of biotechnology and molecular medicine especially in relation to age-related cellular degeneration. As a result of our research outputs, strategies could be developed to either delay the onset or reduce the severity of diseases related to mitochondrial dysfunction. Training research scientists of the future, forms an integral part of our research program and our association with world leaders in the field provide excellent opportunity for exchange of personnel, ideas and emerging methodologies. This project will lead the way in this field and consequently will expand Australia's reputation at the forefront of scientific advancement. Read moreRead less
AAA+ proteases: substrate binding, translocation and modulation by novel adaptor proteins. Protein quality control is essential for the proper maintenance of the cell. It ensures the correct folding of newly synthesised proteins, the refolding or degradation of misfolded and aggregated proteins, and the controlled degradation of regulatory proteins. These functions are collectively performed by molecular chaperones and proteases. This project will define the molecular basis of substrate selectiv ....AAA+ proteases: substrate binding, translocation and modulation by novel adaptor proteins. Protein quality control is essential for the proper maintenance of the cell. It ensures the correct folding of newly synthesised proteins, the refolding or degradation of misfolded and aggregated proteins, and the controlled degradation of regulatory proteins. These functions are collectively performed by molecular chaperones and proteases. This project will define the molecular basis of substrate selectivity for ATP-dependent proteases and determine the relationship between chaperones and proteases. A major focus will be directed towards the mechanistic analysis of novel AAA+ cofactors such as ClpS, which we recently discovered. A detailed analysis of such proteins is central to understanding how chaperones and protease (a) recognize their substrates and (b) compete for different substrates in vivo.Read moreRead less
New Methods for Structural Biology in Solution. This project aims to expand the range of applications of nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research, where NMR spectroscopy is already used routinely for the identification of chemical compounds that bind to protein targets. The techniques developed aim at providing rapid and broadly applicable tools for 3D structure determinations of chemical compounds bound to their protein target, identification of protein-protein i ....New Methods for Structural Biology in Solution. This project aims to expand the range of applications of nuclear magnetic resonance (NMR) spectroscopy in pharmaceutical research, where NMR spectroscopy is already used routinely for the identification of chemical compounds that bind to protein targets. The techniques developed aim at providing rapid and broadly applicable tools for 3D structure determinations of chemical compounds bound to their protein target, identification of protein-protein interaction sites and characterization of protein motions. The limits of NMR spectroscopy will be pushed to analyse systems of significantly increased molecular weights. The project includes applications to drug targets such as the dengue virus NS2B/NS3 protease.Read moreRead less