DsbA Foldases From Multidrug Resistant Pathogens As Targets For New Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$743,401.00
Summary
Bacteria that cause common human infections, such as cystitis and diarrhoea, are now resistant to many antibiotics. If no action is taken, by 2050 antibiotic resistant infections will kill more people each year than cancer. This project aims to address this global public health crisis by characterising promising new bacterial targets and inhibitors designed to disarm multidrug resistant pathogens. Longer term this work could provide new infection therapies that are urgently needed.
MOLECULAR BREEDING OF CYTOCHROME P450 ENZYMES. Cytochrome P450s are enzymes that catalyse an impressive array of oxidative transformations. However, there is little available data on how to modify their substrate specificity and generate tailored biocatalysts. We plan to use an emerging technology known as DNA shuffling to create libraries of P450s with varying activities. These will then be screened for enzymes that can catalyse the formation of indigo (a blue dye) and indirubin (a chemother ....MOLECULAR BREEDING OF CYTOCHROME P450 ENZYMES. Cytochrome P450s are enzymes that catalyse an impressive array of oxidative transformations. However, there is little available data on how to modify their substrate specificity and generate tailored biocatalysts. We plan to use an emerging technology known as DNA shuffling to create libraries of P450s with varying activities. These will then be screened for enzymes that can catalyse the formation of indigo (a blue dye) and indirubin (a chemotherapeutic agent). The enzymes that catalyse indigo formation will be useful in the production of coloured transgenic plants and those that produce indirubin will have a role in gene therapy.Read moreRead less
Tailored Biodegradable Polymers for Injection Moulding Applications. This project aims to engineer and scale up production of biodegradable injection molded products with tailored properties, processing and biodegradation. Specifically we will focus on novel materials and processing technologies in tandem with biodegradation understandings to expand the utilization of starch-based polymers. We will then combine fundamental rheological and polymer processing skills with and product development ex ....Tailored Biodegradable Polymers for Injection Moulding Applications. This project aims to engineer and scale up production of biodegradable injection molded products with tailored properties, processing and biodegradation. Specifically we will focus on novel materials and processing technologies in tandem with biodegradation understandings to expand the utilization of starch-based polymers. We will then combine fundamental rheological and polymer processing skills with and product development experience from both universities and the industrial partner (Plantic Technologies) to scale up processing and develop successful biodegradable products. This project will also enable an Australian owned start-up company with a broad shareholder base to generate significant export income through key commercialization.Read moreRead less
BIOCATALYSTS MINED FROM CYTOCHROME P450 LIBRARIES: AN INNOVATIVE TOOL FOR ACCELERATING DRUG DEVELOPMENT. The cytochrome P450s (P450s) are a family of enzymes that are perhaps the most versatile biological catalysts known. DNA shuffling is an emerging technique that takes the genes encoding families of enzymes and creates libraries of catalysts with both improved and novel properties. We will obtain proof of concept that shuffled P450 libraries can be screened and optimized for use as biocatalys ....BIOCATALYSTS MINED FROM CYTOCHROME P450 LIBRARIES: AN INNOVATIVE TOOL FOR ACCELERATING DRUG DEVELOPMENT. The cytochrome P450s (P450s) are a family of enzymes that are perhaps the most versatile biological catalysts known. DNA shuffling is an emerging technique that takes the genes encoding families of enzymes and creates libraries of catalysts with both improved and novel properties. We will obtain proof of concept that shuffled P450 libraries can be screened and optimized for use as biocatalysts in drug development. The methodologies developed here will overcome two critical bottlenecks in current drug development: the optimisation and metabolic profiling of new drug candidates. This will yield important benefits in accelerating the optimisation and safety testing of drugs under development.Read moreRead less
Organophosphate pesticide degradation: evolved enzymes and biomimetics for bioremediation and medicine. Organophosphate (OP) pesticides are an indispensable part of modern agriculture - their use results in dramatically increased crop yields. However, they are toxic and can damage the environment and cause significant health problems. Enzymes are currently being used to treat runoff water that is contaminated with OPs. The same enzymes also have the potential to aid in the treatment of OP poison ....Organophosphate pesticide degradation: evolved enzymes and biomimetics for bioremediation and medicine. Organophosphate (OP) pesticides are an indispensable part of modern agriculture - their use results in dramatically increased crop yields. However, they are toxic and can damage the environment and cause significant health problems. Enzymes are currently being used to treat runoff water that is contaminated with OPs. The same enzymes also have the potential to aid in the treatment of OP poisoning. However, OP degrading enzymes could be improved in many ways - we will evolve these enzymes to enhance their catalytic properties - to enable them to act more efficiently on an increased number of OPs. Read moreRead less
Industrial biotechnology for improved manufacture of medicinal alkaloids. Industrial biotechnology for improved manufacture of medicinal alkaloids. This project aims to develop a new semi-synthetic route for the manufacture of Codeine from Thebaine. Codeine is manufactured by the chemical conversion of poppy-derived Morphine, which is low yielding and environmentally unfriendly. This project will investigate and optimise two key enzymes in the biosynthetic pathway to Codeine and develop an innov ....Industrial biotechnology for improved manufacture of medicinal alkaloids. Industrial biotechnology for improved manufacture of medicinal alkaloids. This project aims to develop a new semi-synthetic route for the manufacture of Codeine from Thebaine. Codeine is manufactured by the chemical conversion of poppy-derived Morphine, which is low yielding and environmentally unfriendly. This project will investigate and optimise two key enzymes in the biosynthetic pathway to Codeine and develop an innovative bioreactor to achieve high yield. It will research industrial biotransformations, providing a greener and cheaper process for increased global access to Codeine. Australian opiate manufacturing is expected to benefit from value adding and increased flexibility introduced by a biotechnology approach.Read moreRead less
The molecular biology and biochemistry of bacterial manganese oxidation. This project will further the understanding of bacterial manganese (Mn2+) oxidation. A multi-disciplinary approach will be used to further investigate the genetics and biochemistry of the Mn2+-oxidising systems of Pseudomonas putida, Leptothrix sp. and Pedomicrobium sp. This work will focus in particular on comparing the Mn2+-oxidising systems from unrelated bacteria. A combination of molecular biology, protein biochemis ....The molecular biology and biochemistry of bacterial manganese oxidation. This project will further the understanding of bacterial manganese (Mn2+) oxidation. A multi-disciplinary approach will be used to further investigate the genetics and biochemistry of the Mn2+-oxidising systems of Pseudomonas putida, Leptothrix sp. and Pedomicrobium sp. This work will focus in particular on comparing the Mn2+-oxidising systems from unrelated bacteria. A combination of molecular biology, protein biochemistry and spectroscopy will be used. This will be the first time that the enzymes of bacterial Mn2+-oxidation will have been characterised in such detail and will lead to a greater understanding of the process of bacterial manganese oxidation.Read moreRead less
The protein O-glycosylation pathway of Neisseria: a model system for O-glycosylation of bacterial proteins with potential use in biotechnology. Proteins can be modified by the addition of sugar molecules. This process, called glycosylation, has been studied for some time in humans and other higher organisms, but is relatively new in the field of bacteria. This study will use the bacterium Neisseria as a model system for this process and work to harness the system for use in biotechnology.
Algal direct-air CO2 capture through interfacial enzyme immobilisation . Capturing CO2 directly from the atmosphere is challenging due to inherently slow mass transfer kinetics. This project aims to overcome this using an enzyme that can rapidly solubilise CO2 from air into water, to produce algae. By engineering the enzyme immobilisation at the air-water interface, this project will activate and protect the enzymes, increasing their lifespan and reducing costs. By understanding mass transfer an ....Algal direct-air CO2 capture through interfacial enzyme immobilisation . Capturing CO2 directly from the atmosphere is challenging due to inherently slow mass transfer kinetics. This project aims to overcome this using an enzyme that can rapidly solubilise CO2 from air into water, to produce algae. By engineering the enzyme immobilisation at the air-water interface, this project will activate and protect the enzymes, increasing their lifespan and reducing costs. By understanding mass transfer and enzyme activity in the interfacial immobilisation media, floating enzyme rafts can be developed for deployment over expansive areas, facilitating large-scale conversion of atmospheric CO2 into algae-derived fuels, feeds and chemicals.Read moreRead less
Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test th ....Pre-clinical evaluation of snake venom proteins with therapeutic potential. Australia harbors some of the most toxic snakes in the world. Their venoms contain a range of substances that are designed to rapidly immobilize and kill their prey. These include agents that lead to enhanced blood clotting; excess bleeding. We have isolated and characterized a large number of the components involved over the last several years. The aim here is to carry out pre-clinical trials in animal models to test the efficacy of three proteins as anti-bleeding agents and investigate several other novel components. The ultimate outcome will be the development of novel drugs that will have application in the treatment of human disorders. Read moreRead less