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
Synthesis and assembly of bacterial repeat unit polysaccharides. Bacteria make an enormous range of surface polysaccharides. The complexity was first appreciated as antigenic diversity, but we now have hundreds of chemical structures and perhaps a hundred sequences of their gene clusters, but the number in nature must be many thousands. Our knowledge of gene function is growing but is not keeping up with the discovery of new sequences and structures. The aim is to determine structure and functio ....Synthesis and assembly of bacterial repeat unit polysaccharides. Bacteria make an enormous range of surface polysaccharides. The complexity was first appreciated as antigenic diversity, but we now have hundreds of chemical structures and perhaps a hundred sequences of their gene clusters, but the number in nature must be many thousands. Our knowledge of gene function is growing but is not keeping up with the discovery of new sequences and structures. The aim is to determine structure and function of key O antigen processing genes and the functions of a range of glycosyl transferases, and to use the information to generate novel gene clusters to synthesise novel polysaccharidesRead moreRead less
Elucidation of bacterial glycosylytransferase specificity. The benefits are involvement in the growth area of polysaccharide research, with potential for major industrial spin off. Polysaccharides are critical in all organisms as signalling, structural and storage compounds. Bacteria make a wide variety with extensive use of unusual sugars, some with uses from oil emulsifiers to food thickeners. The project is on the enzymes that assemble bacterial polysaccharides. We are world leaders in genet ....Elucidation of bacterial glycosylytransferase specificity. The benefits are involvement in the growth area of polysaccharide research, with potential for major industrial spin off. Polysaccharides are critical in all organisms as signalling, structural and storage compounds. Bacteria make a wide variety with extensive use of unusual sugars, some with uses from oil emulsifiers to food thickeners. The project is on the enzymes that assemble bacterial polysaccharides. We are world leaders in genetics of the gene clusters especially synthesis of the unusual sugars. We now aim to fill a major gap by determining which enzymes make which bonds, leading to options for new gene combinations and novel structures. We have a lead in research in this area and Australia gains if we maintain that lead.Read moreRead less
Genetic modification and lyophilisation of microorganisms for the generation of bacteriological internal quality controls. The development of internal quality control micro-organisms in precise numbers is necessary for the evolution of standard methodology in microbiology, which until now, remains obsolete, because it relies on inaccurate methods to produce quantitative and qualitative results. The research described here is largely based on molecular techniques to genetically tag micro-organism ....Genetic modification and lyophilisation of microorganisms for the generation of bacteriological internal quality controls. The development of internal quality control micro-organisms in precise numbers is necessary for the evolution of standard methodology in microbiology, which until now, remains obsolete, because it relies on inaccurate methods to produce quantitative and qualitative results. The research described here is largely based on molecular techniques to genetically tag micro-organisms with fluorescent proteins and pigment producing enzymes, and on the manipulation of growth and storage conditions to maximize the survival of micro-organisms during lyophilisation. Successful completion and application of the proposed project through existing patents owned by BTF, will revolutionise the way microbiological tests are performed worldwide.Read moreRead less
Role of the proteasome in eradication of misfolded proteins in fungal cell factories. Filamentous fungi contribute to the well being of modern society as surrogate hosts for the synthesis of vaccines, hormones and enzymes for their application to health, agriculture, industry and the environment. However, attempts to express foreign proteins to the full potential of a given system have been disappointing. It is vital to understand unexplored molecular and physiological factors such as protein ....Role of the proteasome in eradication of misfolded proteins in fungal cell factories. Filamentous fungi contribute to the well being of modern society as surrogate hosts for the synthesis of vaccines, hormones and enzymes for their application to health, agriculture, industry and the environment. However, attempts to express foreign proteins to the full potential of a given system have been disappointing. It is vital to understand unexplored molecular and physiological factors such as protein quality control in the cell to take advantage of the global opportunities that recombinant gene expression indisputably offers in the form of unrestricted supply of proteins of social and economic value. The project will create novel IP and licensing opportunities for Australia.Read moreRead less
A scalable and portable question-answering system. The current availability of large volumes of free text digitally stored demands the development of methodologies that can automatically find specific answers to user questions about this "unstructured" information. The goal of this project is to develop a scalable portable and domain-independent real-time natural-language question-answering system that explores the logical contents of the text. To achieve this we will fuse current approaches to ....A scalable and portable question-answering system. The current availability of large volumes of free text digitally stored demands the development of methodologies that can automatically find specific answers to user questions about this "unstructured" information. The goal of this project is to develop a scalable portable and domain-independent real-time natural-language question-answering system that explores the logical contents of the text. To achieve this we will fuse current approaches to question answering with approaches that look at the logical contents of the questions and answer candidates. A central part of the project will be the characterisation of the optimal logical forms, the determination of efficient methods to create and store sentence logical forms of potentially large volumes of text, and the treatment of difficult questions by incorporating summarisation and text generation techniques.Read moreRead less
Functional and structural diversity of the cathepsin L peptidase from the human blood fluke Schistosoma mansoni. Peptidases are enzymes that are important in many infectious and physiological disease states. For example, they are used by infectious pathogens to enter human tissues and survive inside their bodies. The same type of enzymes also contribute to tissue damage in many pathological processes in humans such as cancer, arithritis and osteoporosis. There is an urgent need to define their s ....Functional and structural diversity of the cathepsin L peptidase from the human blood fluke Schistosoma mansoni. Peptidases are enzymes that are important in many infectious and physiological disease states. For example, they are used by infectious pathogens to enter human tissues and survive inside their bodies. The same type of enzymes also contribute to tissue damage in many pathological processes in humans such as cancer, arithritis and osteoporosis. There is an urgent need to define their structure and properties so that we can employ rational approaches to develop new drugs that can combat these diseases and ailments. Read moreRead less
Aminopeptidases involved in regulating the amino acid pool in malaria parasites. Aminopeptidases are pivotal to the normal functions of all cells. Abnormalities in their function and/or structure results in tissue damage in many pathological processes in humans such as cancer, neuronal diseases and hormonal action. They are also critical to viral, bacterial and parasitic infections as they are employed to remove amino acids from the host for use in building their own proteins. This project bring ....Aminopeptidases involved in regulating the amino acid pool in malaria parasites. Aminopeptidases are pivotal to the normal functions of all cells. Abnormalities in their function and/or structure results in tissue damage in many pathological processes in humans such as cancer, neuronal diseases and hormonal action. They are also critical to viral, bacterial and parasitic infections as they are employed to remove amino acids from the host for use in building their own proteins. This project brings national and international expertise together to define the structure and biological properties of these essential enzymes so that in the future we can employ rational approaches to develop new drugs that can combat these diseases and ailments.Read moreRead less
Sodium homeostasis and the molecular basis for neurotoxin production by bacteria and algae. An understanding of the physiology of saxitoxin-producing microorgansims in response to salt stress is critical for the prevention of toxic blooms and for risk assessment of contaminated water bodies. This is nowhere more relevant than in the depleted and increasingly saline water resources of inland Australia. This project will develop genetic tests to assay for saxitoxin-producers and to monitor toxin p ....Sodium homeostasis and the molecular basis for neurotoxin production by bacteria and algae. An understanding of the physiology of saxitoxin-producing microorgansims in response to salt stress is critical for the prevention of toxic blooms and for risk assessment of contaminated water bodies. This is nowhere more relevant than in the depleted and increasingly saline water resources of inland Australia. This project will develop genetic tests to assay for saxitoxin-producers and to monitor toxin production in response to the environment, representing an easier, more economic and ethical alternative to current tests. The market for this type of predictive test includes environmental, anti-bioterrorism and fishery organisations. These genes will also allow the bioengineering of novel therapeutic drugs based on neuroactive alkaloids.Read moreRead less
Bacterial innovation and evolution: Molecular prospecting by targeting integrons and gene cassettes. Bacteria can respond rapidly to environmental change by acquiring new genes via lateral gene transfer. A DNA element called the integron can capture, mobilise and express genes, thereby playing a role in the transfer process. We have discovered that integrons are surprisingly abundant in the environment and are associated with a hitherto unsuspected diversity of novel genes. In this study we will ....Bacterial innovation and evolution: Molecular prospecting by targeting integrons and gene cassettes. Bacteria can respond rapidly to environmental change by acquiring new genes via lateral gene transfer. A DNA element called the integron can capture, mobilise and express genes, thereby playing a role in the transfer process. We have discovered that integrons are surprisingly abundant in the environment and are associated with a hitherto unsuspected diversity of novel genes. In this study we will assess the diversity of environmental integrons and examine their contribution to bacterial evolution. Further, we aim to use integron systems to prospect for novel genes and contract new enzyme pathways by directed evolution.
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