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
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.
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561041
Funder
Australian Research Council
Funding Amount
$347,358.00
Summary
A New Generation Biosensor and Fluorescence Facility for Proteomics. The complete DNA sequence (the genome) is now known for many organisms and advances are being made to identify the complement of messenger RNA (the transcriptome) and the resultant collection of proteins (the proteome). The genome is largely fixed while the transcriptome and proteome differ between cell types in an organism and constantly vary to adapt the cell to changing conditions. The mediators of these variations are prote ....A New Generation Biosensor and Fluorescence Facility for Proteomics. The complete DNA sequence (the genome) is now known for many organisms and advances are being made to identify the complement of messenger RNA (the transcriptome) and the resultant collection of proteins (the proteome). The genome is largely fixed while the transcriptome and proteome differ between cell types in an organism and constantly vary to adapt the cell to changing conditions. The mediators of these variations are proteins, interacting with each other and with signal molecules. The next frontier in molecular biology is to identify and quantify these protein interactions. Our two institutions have a very large cohort of biologists whose research on proteins would be greatly facilitated by the Biacore 3000 and the ISS K2.Read moreRead less
New Proteins from the Mobile Genome: Structure-Led Discovery. The project will provide full descriptions of proteins with the capacity to become mobilised, as well as providing a source of completely novel genes with commercial potential. The proteins and enzymes discovered, and the metabolic processes with which they are identified, will have applications in a wide range of Australian industries: agriculture, forestry, pollution control and pharmaceutical design. This work therefore offers op ....New Proteins from the Mobile Genome: Structure-Led Discovery. The project will provide full descriptions of proteins with the capacity to become mobilised, as well as providing a source of completely novel genes with commercial potential. The proteins and enzymes discovered, and the metabolic processes with which they are identified, will have applications in a wide range of Australian industries: agriculture, forestry, pollution control and pharmaceutical design. This work therefore offers opportunities for many future directions in biotechnology, an area of growing strength in Australia. Read moreRead less
The role of the protease inhibitor Serpinb9 in antigen cross-presentation by dendritic cells. This project will provide fundamental new insights into antigen cross-presentation, a crucial facet of the immune system's response to viral infection or neoplastic cells. It will also provide a basis for future studies into mechanisms of immune tolerance and enhance our understanding of autoimmune disease.
The structure and function of dihydroorotase - an enzyme essential for pyrimidine biosynthesis. Malaria has recently re-emerged as one of the major life threatening diseases worldwide. With increasing travel and climate change, malaria is increasingly endangering Australians at home and abroad. Our work aims to provide the basis for the rational design of a new class of anti-malarial drugs by the systematic and thorough analysis of an essential enzyme in the malarial parasite.
Structure-based inhibitor design of VAP-1/SSAO for the treatment of respiratory dirsorders and other major inflammatory diseases. Inflammatory diseases, such as asthma, rheumatoid arthritis and multiple sclerosis, are widespread and often poorly treated in Australia and elsewhere. Inhibitors of the recently studied VAP-1/SSAO protein are predicted to effectively treat the inflammation symptoms of one or more of these diseases. A structure-based approach to discover these new medicines should pro ....Structure-based inhibitor design of VAP-1/SSAO for the treatment of respiratory dirsorders and other major inflammatory diseases. Inflammatory diseases, such as asthma, rheumatoid arthritis and multiple sclerosis, are widespread and often poorly treated in Australia and elsewhere. Inhibitors of the recently studied VAP-1/SSAO protein are predicted to effectively treat the inflammation symptoms of one or more of these diseases. A structure-based approach to discover these new medicines should provide a means to identify patentable compounds, with high potency, efficacy and safety. If this approach is successful, an Australian pharmaceutical company will be one of the first to the market with this new medicine to treat these chronic diseases.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