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
Enantioselective nitrilases from filamentous fungi. The optical characteristics (chirality) of chemical precursors are important for many fine chemicals. Chiral intermediates are in high demand by the pharmaceutical and agrochemical industries for the preparation of bulk drug intermediates and agricultural products. Nitriles are attractive starting points but their conversion to corresponding amides and carboxylic acids generates significant wastes. Their hydrolysis can be performed under mil ....Enantioselective nitrilases from filamentous fungi. The optical characteristics (chirality) of chemical precursors are important for many fine chemicals. Chiral intermediates are in high demand by the pharmaceutical and agrochemical industries for the preparation of bulk drug intermediates and agricultural products. Nitriles are attractive starting points but their conversion to corresponding amides and carboxylic acids generates significant wastes. Their hydrolysis can be performed under mild conditions by enzymes termed nitrilases. We will work on fungal nitrilases as they present a globally attractive, yet untapped commercial target. The outcome for Applimex will be a suite of biocatalysts specific for the production of key intermediates for drug and agrochemical syntheses.Read moreRead less
Mammalian histidine kinase: its characterisation and role in hepatic cellular proliferation. Protein kinases regulate all aspects of cellular metabolism, but there is a class of protein kinase, histidine kinases, which exists in mammalian cells, about which remarkably little is understood. This project will be the first detailed characterisation of such an enzyme and investigation of its cellular function. The enzyme to be characterised is hepatic and it has been implicated in the regulation of ....Mammalian histidine kinase: its characterisation and role in hepatic cellular proliferation. Protein kinases regulate all aspects of cellular metabolism, but there is a class of protein kinase, histidine kinases, which exists in mammalian cells, about which remarkably little is understood. This project will be the first detailed characterisation of such an enzyme and investigation of its cellular function. The enzyme to be characterised is hepatic and it has been implicated in the regulation of DNA replication in regenerating liver. We shall obtain a detailed picture of the role of this histidine kinase in liver cell biology and an insight into the more general biological role of this class of enzyme.Read moreRead less
A global approach to structure, assembly and function of yeast mitochondrial ATP synthase. ATP synthase is responsible for the synthesis of the ubiquitous energy substance ATP in living cells. This multisubunit enzyme complex is a molecular rotatory motor whose mechanism relies on functional dynamic interactions of the component protein subunits of the complex. Using a combination of powerful and sophisticated molecular biology techniques the functional and dynamic contacts made by subunits wi ....A global approach to structure, assembly and function of yeast mitochondrial ATP synthase. ATP synthase is responsible for the synthesis of the ubiquitous energy substance ATP in living cells. This multisubunit enzyme complex is a molecular rotatory motor whose mechanism relies on functional dynamic interactions of the component protein subunits of the complex. Using a combination of powerful and sophisticated molecular biology techniques the functional and dynamic contacts made by subunits within the complex, or between ATP synthase and other enzyme complex involved in energy production (including other ATP synthase complexes) will be investigated. New and significant insights into one of the most fundamental and challenging enzymes of life will be obtained.Read moreRead less
The Structure Function and Biology of Serpins. The serpin family of proteins control protease activity, in a variety of biological systems, via a dramatic conformational change. We are 4 leaders in the serpin reseacrh field using an integrated approach of biochemistry, biophysics, molecular biology, cell biology, structural biology and bioinformatics to analyse every facet of serpin structure, function and biology. We will apply and develop novel technologies that will determine how these confor ....The Structure Function and Biology of Serpins. The serpin family of proteins control protease activity, in a variety of biological systems, via a dramatic conformational change. We are 4 leaders in the serpin reseacrh field using an integrated approach of biochemistry, biophysics, molecular biology, cell biology, structural biology and bioinformatics to analyse every facet of serpin structure, function and biology. We will apply and develop novel technologies that will determine how these conformational changes are achieved and how they are controlled. Our increased understanding of this inhibitor - enzyme interaction will have implications to other proteins which undergo conformational change and biotechnology.Read moreRead less
Structural and functional studies on prokaryote serpins. Proteins are the machines of life, many of which undergo complex movements to achieve function. The basic research described in this proposal will result in major outcomes in understanding how proteins fold, undergo complex changes in conformation, and misfold to dysfunctional states. As a result, the study will contribute fundamental knowledge that will underpin research in the fields of structural biology, protein design and protein fo ....Structural and functional studies on prokaryote serpins. Proteins are the machines of life, many of which undergo complex movements to achieve function. The basic research described in this proposal will result in major outcomes in understanding how proteins fold, undergo complex changes in conformation, and misfold to dysfunctional states. As a result, the study will contribute fundamental knowledge that will underpin research in the fields of structural biology, protein design and protein folding. Through providing insight into protein misfolding, the work will will contribute to our understanding of degenerative misfolding pathologies that affect the ageing population and thus targets the 'ageing well ageing productively' priority goal.Read moreRead less
Characterisation of a powerful molecular motor, the FtsK DNA translocase. The FtsK protein is a fast and powerful molecular motor, a pump that can, and does, move an entire bacterial chromosome. This project will uncover the detail of the mechanism used by this motor to convert the cell's chemical energy source Adenosine Triphosphate (ATP) into movement of DNA; revealing the molecular detail of a fast and powerful motor.
Modulation of cellular metabolism by protein and peptide peroxides. Oxidation of peptides and proteins by a wide range of reactive radicals and other oxidants, in the presence of oxygen, generates protein peroxides. These species are now recognised to be key intermediates in both the deterioration of foods (e.g. development of rancidity and off-flavours, changes in colour and texture) and a number of human diseases, including cancer, heart disease and ageing. How these peroxides cause biological ....Modulation of cellular metabolism by protein and peptide peroxides. Oxidation of peptides and proteins by a wide range of reactive radicals and other oxidants, in the presence of oxygen, generates protein peroxides. These species are now recognised to be key intermediates in both the deterioration of foods (e.g. development of rancidity and off-flavours, changes in colour and texture) and a number of human diseases, including cancer, heart disease and ageing. How these peroxides cause biological perturbations is poorly understood. The proposed studies will provide valuable information as to how these peroxides affect cellular metabolism and provide key leads as to strategies which may prevent such damage.Read moreRead less
Mechanistic studies on the oxidation of amino acids, peptides and proteins and its biological consequences. Exposure of amino acids and proteins to radicals, oxidants, UV light, and metal ions results in oxidation, with consequent alteration to protein structure and function. It has been shown that these reactions occur during food spoilage, exposure of plants to excess UV light, and in a number of human diseases (e.g. heart disease and cancer). Despite evidence for a key role for protein oxidat ....Mechanistic studies on the oxidation of amino acids, peptides and proteins and its biological consequences. Exposure of amino acids and proteins to radicals, oxidants, UV light, and metal ions results in oxidation, with consequent alteration to protein structure and function. It has been shown that these reactions occur during food spoilage, exposure of plants to excess UV light, and in a number of human diseases (e.g. heart disease and cancer). Despite evidence for a key role for protein oxidation in these events, the fundamental chemistry and biochemistry of protein oxidation is incompletely understood. This is addressed in this project. Knowledge of the mechanisms of these reactions is a vital pre-requisite to the rational design of preventative strategies that might enhance food quality, minimise UV damage and enhance human health.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882295
Funder
Australian Research Council
Funding Amount
$225,000.00
Summary
X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic re ....X-ray crystallography resource for membrane proteins and large macromolecular complexes. Structural biology is the underpinning of biotechnology, biopharmaceuticals and rational therapeutic design. The most successful technique for determining the structures of proteins and large macromolecular complexes is x-ray crystallography. This proposal will set up a network of state of the art resources in the Sydney region to capitalise on expertise in these areas. The facilities will foster basic research and collaborations with industry, which will enhance Australia's profile and commercialisation of research. The facility will enhance the usage of the Australian synchrotron, producing flagship projects on the edge of technical possibilities.Read moreRead less