Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. ....Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. Knowledge about this new aspect of protein degradation could provide a powerful tool to test the effect of the stabilisation or removal of specific proteins in the cell and also to develop new technologies in protein production.Read moreRead less
Structures and Functions of Bacterial Replisomal Proteins. DNA replication in all organisms requires many proteins to interact in a structure called the replisome. The bacterial replisome is assembled about the DnaB helicase, a motor protein that moves along DNA, separating the strands of duplex regions in its path. This project aims to develop understanding of the chemistry of DnaB and other replisomal proteins: their structures, how they work, and how they interact to assemble the replisome. T ....Structures and Functions of Bacterial Replisomal Proteins. DNA replication in all organisms requires many proteins to interact in a structure called the replisome. The bacterial replisome is assembled about the DnaB helicase, a motor protein that moves along DNA, separating the strands of duplex regions in its path. This project aims to develop understanding of the chemistry of DnaB and other replisomal proteins: their structures, how they work, and how they interact to assemble the replisome. This has the potential to lead to design of new antibacterial drugs.
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New fragment-based drug design technology by NMR spectroscopy. A new nuclear magnetic resonance (NMR) spectroscopic strategy will be developed for rapid determination of the structure and binding mode of low-molecular weight compounds bound to target proteins. Structural information obtained in this way will greatly accelerate drug development by fragment-based drug design, and NMR spectroscopy is the only method that can deliver this information in solution at atomic resolution. The impact of t ....New fragment-based drug design technology by NMR spectroscopy. A new nuclear magnetic resonance (NMR) spectroscopic strategy will be developed for rapid determination of the structure and binding mode of low-molecular weight compounds bound to target proteins. Structural information obtained in this way will greatly accelerate drug development by fragment-based drug design, and NMR spectroscopy is the only method that can deliver this information in solution at atomic resolution. The impact of the project for pharmaceutical research is further enhanced by extending the range of proteins amenable to NMR analysis by the development of new labelling strategies using stable isotopes, lanthanides and an unnatural amino acid in a state-of-the-art protein production system.Read moreRead less
The metabolic and enzymatic regulation of C4 photosynthesis and its impact on photosynthetic productivity. Australia's tropical pastures are dominated by plants utilising the C4 photosynthetic pathway. World wide C4 grasslands contribute to approximately 20% of global primary productivity. C4 plants also include important crop species such as maize, sorghum and sugar cane and are considered ideal species for bio-fuel production. This project will use a novel functional genomic/metabolomics appro ....The metabolic and enzymatic regulation of C4 photosynthesis and its impact on photosynthetic productivity. Australia's tropical pastures are dominated by plants utilising the C4 photosynthetic pathway. World wide C4 grasslands contribute to approximately 20% of global primary productivity. C4 plants also include important crop species such as maize, sorghum and sugar cane and are considered ideal species for bio-fuel production. This project will use a novel functional genomic/metabolomics approach to provide fundamental insights into the biochemical regulation of C4 photosynthesis under different environmental conditions. This will aid in the development of mathematical models of C4 photosynthesis required in climate models of CO2 exchange and enhance our ability to improve photosynthetic performance of agricultural species.Read moreRead less
Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several labora ....Molecular Interactions in the Eubacterial Replisome: A Paradigm for Study of Dynamic Macromolecular Machines. Many pathogenic bacteria have developed resistance to antibiotics in common use, and new drugs are urgently required to kill them. Copying of their chromosomes before they divide into two new cells is essential for bacteria to live, so DNA synthesis is a good process to target for development of new antibiotics. This project will use state-of-the-art equipment available in several laboratories in Australia and overseas to develop new understanding of how the molecular machine that copies DNA works. This k nowledge could lead to new drugs, and will give us new information about how cellular machines function.Read moreRead less
Directed evolution used to probe protein structure and function; new enzymes for bio-remediation and industry. The aim of the research is to generate new and useful enzymes for bio-remediation and other practical applications. For example, we are evolving enzymes to better degrade organophosphate pesticides that are environmental pollutants. Apart from producing useful enzymes, the proposed research aims at gaining a better understanding of how enzymes work and how they evolve. We intend to dete ....Directed evolution used to probe protein structure and function; new enzymes for bio-remediation and industry. The aim of the research is to generate new and useful enzymes for bio-remediation and other practical applications. For example, we are evolving enzymes to better degrade organophosphate pesticides that are environmental pollutants. Apart from producing useful enzymes, the proposed research aims at gaining a better understanding of how enzymes work and how they evolve. We intend to determine the structure of many related enzymes that have been evolved to have enhanced activities. This data will be used to analyze the intricate relationship between sequence, structure and enzyme activity.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
Exploring the catalytic role of the Rubisco small subunit: a new target for improving carbon dioxide-fixation in plants. This project uses new biotechnological tools to improve the performance of the photosynthetic protein Rubisco, the primary carbon dioxide-fixing enzyme in plants. By supercharging photosynthesis, this research will help to boost yield and reduce water and nitrogen use in crops.
Rubisco for all climates: unlocking the enzyme's structure-function relations for more efficient photosynthesis. This projects biotechnological research will identify structural features in the carbon dioxide (CO2)-capturing enzyme from plants that improve its performance, particularly at warmer temperatures. This knowledge is vital for predicting the influence of climate change on crop productivity and paving the way for supercharging photosynthesis to boost crop performance.
A genomic and phenomic investigation of a mitochondrial glutathione transferase. The aim of this study is to understand of the genomics, structure and function of glutathione transferase Kappa (GSTK), a novel GST found in mitochondria. The investigations will achieve several outcomes. (1)an understanding of the organisation of GSTK gene(s) in humans and mice; (2) determination of the role of GSTK in mitochondria, by investigating the phenotype of knockout mice; (3) determination of the crysta ....A genomic and phenomic investigation of a mitochondrial glutathione transferase. The aim of this study is to understand of the genomics, structure and function of glutathione transferase Kappa (GSTK), a novel GST found in mitochondria. The investigations will achieve several outcomes. (1)an understanding of the organisation of GSTK gene(s) in humans and mice; (2) determination of the role of GSTK in mitochondria, by investigating the phenotype of knockout mice; (3) determination of the crystal structure of human GSTK; (4) An understanding of GSTK's substrate specificity, reaction kinetics and structure/function relationships. Since GSTK is confined to mitochondria, and may not be related to other GSTs, we may also identify novel functionsRead moreRead less