Improving grain legume seeds for future climates. Grain legumes are essential for sustainable agriculture and human dietary protein, but seed quality is predicted to decline under future scenarios of high CO2 and warmer temperatures. This project aims to improve legume seed quality under future climates by comparing metabolites and physiological traits of chickpea and other legumes to establish mechanisms by which legumes maximise seed nutrient allocation. The anticipated outcomes include new me ....Improving grain legume seeds for future climates. Grain legumes are essential for sustainable agriculture and human dietary protein, but seed quality is predicted to decline under future scenarios of high CO2 and warmer temperatures. This project aims to improve legume seed quality under future climates by comparing metabolites and physiological traits of chickpea and other legumes to establish mechanisms by which legumes maximise seed nutrient allocation. The anticipated outcomes include new metabolite-based breeding markers for the improvement of crops with higher seed proteins, micronutrients and bioactive compounds that are adapted to future climates. Seed nutrient improvement will also include increased biological nitrogen fixation to reduce the need for chemical nitrogen fertilisers.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
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
Unravelling transthyretin amyloid, bounding ahead using wallabies. Each protein in our body has a unique shape that enables it to function correctly. For unknown reasons, some proteins can change their shape, aggregate with other proteins and stick to the outside of cells of major organs or nerves. This prevents those cells from working properly and results in disease. Transthyretin is a protein that changes shape and aggregates in the heart of most people over the age of 70. The disease is call ....Unravelling transthyretin amyloid, bounding ahead using wallabies. Each protein in our body has a unique shape that enables it to function correctly. For unknown reasons, some proteins can change their shape, aggregate with other proteins and stick to the outside of cells of major organs or nerves. This prevents those cells from working properly and results in disease. Transthyretin is a protein that changes shape and aggregates in the heart of most people over the age of 70. The disease is called Senile Systemic Amyloidosis (SSA). It is not known how or why this happens. There is no cure or therapy. This project will use transthyretins from human and wallaby to explore a possible cause of SSA. If our hypothesis is correct, we will propose preventative actions to reduce the incidence of SSA in the future.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
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
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
New Methods for Structural Biology in Solution. New technologies will be developed that are sufficiently rapid and inexpensive to compete with and replace the mutagenesis experiments that biologists usually perform to identify and characterize the functionally important parts of a protein. Nuclear magnetic resonance (NMR) spectroscopy techniques in combination with various selective labelling schemes will be developed with the goal of identification and structural characterization of protein-lig ....New Methods for Structural Biology in Solution. New technologies will be developed that are sufficiently rapid and inexpensive to compete with and replace the mutagenesis experiments that biologists usually perform to identify and characterize the functionally important parts of a protein. Nuclear magnetic resonance (NMR) spectroscopy techniques in combination with various selective labelling schemes will be developed with the goal of identification and structural characterization of protein-ligand interactions at increased rates and enhanced accuracy. In addition, the three-dimensional structures of proteins and protein domains of biologically important functions and unknown fold will be determined by NMR. The project aims at techniques of direct impact in pharmaceutical industry.Read moreRead less