Mechanistic Studies of Dimethylsulfide Dehydrogenase: A Novel Bacterial Molybdoenzyme. The aim of this proposal is to use electrochemical, spectroscopic and molecular biological techniques to understand the mechanism of action of the enzyme dimethylsulfide dehydrogenase. This enzyme is representative of an major group of molybdenum-containing enzymes that have importance in microbial biotransformations. The project will provide fundamental information about a multi-redox centre protein that has ....Mechanistic Studies of Dimethylsulfide Dehydrogenase: A Novel Bacterial Molybdoenzyme. The aim of this proposal is to use electrochemical, spectroscopic and molecular biological techniques to understand the mechanism of action of the enzyme dimethylsulfide dehydrogenase. This enzyme is representative of an major group of molybdenum-containing enzymes that have importance in microbial biotransformations. The project will provide fundamental information about a multi-redox centre protein that has potential application in biosensors and biocatalysis.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0344441
Funder
Australian Research Council
Funding Amount
$390,000.00
Summary
New Generation Metalloenzyme Magnetic Circular Dichroism Spectrometer Systems. Funding is sought to enhance the existing collaborations between UQ, ANU, Sydney and other universities in the study of metal-centred molecules of biological interest through the construction of advanced magnetic circular dichroism (MCD) spectrometers. These facilities will be the best instruments of their kind, and will enable researchers at Australian institutions to enhance the quality of their research and remain ....New Generation Metalloenzyme Magnetic Circular Dichroism Spectrometer Systems. Funding is sought to enhance the existing collaborations between UQ, ANU, Sydney and other universities in the study of metal-centred molecules of biological interest through the construction of advanced magnetic circular dichroism (MCD) spectrometers. These facilities will be the best instruments of their kind, and will enable researchers at Australian institutions to enhance the quality of their research and remain internationally competitive through the application of modern MCD spectroscopic techniques to the study of metal-centred biomolecules. These facilities will drive a number of programs in the area of metalloenzyme and photosystem II research.Read moreRead less
Enzyme Electrochemical Communication. The ways that redox enzymes communicate with an electrochemical electrode are poorly understood and most systems rely on small molecule mediators as electron shuttles to complete the circuit. The few examples where direct (unmediated) enzyme electrochemistry has been achieved have relied on empirical experimental approaches in electrode modification. In this project a rational approach will be taken, starting with a mediated enzyme electrochemical system whi ....Enzyme Electrochemical Communication. The ways that redox enzymes communicate with an electrochemical electrode are poorly understood and most systems rely on small molecule mediators as electron shuttles to complete the circuit. The few examples where direct (unmediated) enzyme electrochemistry has been achieved have relied on empirical experimental approaches in electrode modification. In this project a rational approach will be taken, starting with a mediated enzyme electrochemical system which is then systematically deconstructed to produce a minimal enzyme-electrode that is stabilised by non-covalent forces and functions without a mediator. This rational approach will provide new routes to the direct enzyme electrochemistry of other enzyme systems as yet unexplored.Read moreRead less
Short circuiting redox enzymes. Enzymes that catalyse oxidation or reduction reactions can be integrated with an electrode in the development of biosensors. A key challenge is enabling an electrical current between the enzyme and the electrode and this project aims to probe this phenomenon to provide an enzyme system that operates with greater efficiency than in nature.
An Integrated Approach Towards Development of Highly Specific Chemotherapeutics. Many diseases are caused or can be treated by modifying the activities of particular enzymes. Molecules that affect enzymatic activities have potential as therapeutic agents. A successful approach to the discovery of new drug molecules is to design them based on very detailed knowledge of how the target enzyme works. In this project, a highly motivated team of scientists will use state of the art instruments and the ....An Integrated Approach Towards Development of Highly Specific Chemotherapeutics. Many diseases are caused or can be treated by modifying the activities of particular enzymes. Molecules that affect enzymatic activities have potential as therapeutic agents. A successful approach to the discovery of new drug molecules is to design them based on very detailed knowledge of how the target enzyme works. In this project, a highly motivated team of scientists will use state of the art instruments and their combined creativity to understand the intimate details of how one large group of enzymes work. The enzymes selected are the bimetallic hydrolases, many of which are associated with disorders including osteoporosis, mental illnesses, cystic fibrosis and various types of cancer.Read moreRead less
Development of therapeutic agents that target carbonic anhydrase enzymes. This research will discover new chemical entities (compounds) that may lead to therapies for the treatment of cancer, glaucoma and malaria. The research underpins a mechanism to add value to our compounds before partnering with industry to transform the discoveries made here to deliverable therapies that could benefit the health of millions, thus offering a potentially high value contribution to the Australian economy. The ....Development of therapeutic agents that target carbonic anhydrase enzymes. This research will discover new chemical entities (compounds) that may lead to therapies for the treatment of cancer, glaucoma and malaria. The research underpins a mechanism to add value to our compounds before partnering with industry to transform the discoveries made here to deliverable therapies that could benefit the health of millions, thus offering a potentially high value contribution to the Australian economy. The experience and commitment of the multi-disciplinary network of researchers offers exceptional training and employment opportunities for tomorrow's scientists in techniques for discovery and characterisation of novel chemicals, and their interaction with disease targets.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
Understanding and Inhibiting the P450 CYP24 enzyme, a target for cancer chemotherapeutics. This project falls within the National Research Priority of Promoting and Maintaining Good Health in the category of ageing well and productively. CYP24 inhibition provides a particular target for breast and prostate cancer which are the second leading cause of death in women and men, respectively. The proposed research will result in the production of CYP24 inhibitors that will be assessed in vivo at th ....Understanding and Inhibiting the P450 CYP24 enzyme, a target for cancer chemotherapeutics. This project falls within the National Research Priority of Promoting and Maintaining Good Health in the category of ageing well and productively. CYP24 inhibition provides a particular target for breast and prostate cancer which are the second leading cause of death in women and men, respectively. The proposed research will result in the production of CYP24 inhibitors that will be assessed in vivo at the Hanson Institute in Adelaide as potential anti-cancer drugs. Finally, there is a significant benefit in technology transfer to Australia from our collaborators in the USA in the field of computer aided inhibitor design.Read moreRead less
Disruption of Sex Pheromone Biosynthesis: A Novel Control Method for Pestiferous Fruit Flies by. Fruit flies from the genus Bactrocera are economically important worldwide. B. tryoni, (Queensland fruit fly) is the most damaging horticultural pest in Australia and B. oleae (olive fly) is a major European pest. These flies use chemicals of similar but distinct structure for communication and particularly for finding mates. This research will examine the pathways and enzymes these flies use to sy ....Disruption of Sex Pheromone Biosynthesis: A Novel Control Method for Pestiferous Fruit Flies by. Fruit flies from the genus Bactrocera are economically important worldwide. B. tryoni, (Queensland fruit fly) is the most damaging horticultural pest in Australia and B. oleae (olive fly) is a major European pest. These flies use chemicals of similar but distinct structure for communication and particularly for finding mates. This research will examine the pathways and enzymes these flies use to synthesise sex pheromones. We propose that understanding the chemical and biochemical steps employed by the flies will allow us to design inhibitors to prevent pheromone production and thus provide a novel, species specific method for controlling fruit flies.Read moreRead less
Structure-based design of anti-osteoporotic drug leads: an integrated approach. One of the major consequences of Australia's aging population is that age-related diseases, such as osteoporosis, are increasing. Apart from the significant human suffering caused by this disease, there is an immense financial burden on the community, patients and their families. Current treatments for osteoporosis are often ineffective and also have major side-effects. An enzyme has been identified which plays a cru ....Structure-based design of anti-osteoporotic drug leads: an integrated approach. One of the major consequences of Australia's aging population is that age-related diseases, such as osteoporosis, are increasing. Apart from the significant human suffering caused by this disease, there is an immense financial burden on the community, patients and their families. Current treatments for osteoporosis are often ineffective and also have major side-effects. An enzyme has been identified which plays a crucial role in the progression of this disease by increasing the rate of bone-thinning. We will make compounds to slow down this enzyme. This project will provide the basis for the future development of new and improved drugs to treat osteoporosis.Read moreRead less