Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less
Special Research Initiatives - Grant ID: SR0354892
Funder
Australian Research Council
Funding Amount
$40,000.00
Summary
The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these ....The Australian Protease Network. Proteases are pivotal enzymes during birth, life, ageing and death of all organisms. Proteases regulate most physiological processes by controlling protein activation, synthesis and turnover and are essential for replication and spread of viruses, bacteria and parasites that cause infectious diseases. Blockbuster drugs and diagnostics already target a few proteases. Australians have made innovative contributions individually to understanding and regulating these enzymes. However this initiative aims to network their efforts by value-adding to the current protease research through promoting national and international collaborations to improve our understanding of biology, and encourage exploitation of proteases/inhibitors/receptors for pharmaceutical and industrial applications.Read moreRead less
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
From Chemical Architecture to Protein Surfaces. Creation of small stable molecules that reproduce key functions of important protein surfaces, would be a significant technology breakthrough with many important potential applications in science, medicine & industry. As new scientific tools they could be used to interrogate biological systems & implicate specific protein surfaces in biological/disease mechanisms. As leads to new medicines (pharmaceuticals, vaccines, diagnostics), they could offer ....From Chemical Architecture to Protein Surfaces. Creation of small stable molecules that reproduce key functions of important protein surfaces, would be a significant technology breakthrough with many important potential applications in science, medicine & industry. As new scientific tools they could be used to interrogate biological systems & implicate specific protein surfaces in biological/disease mechanisms. As leads to new medicines (pharmaceuticals, vaccines, diagnostics), they could offer new ways of impacting on infection, diseases of the aged, & preventative medicine (National Research Priorities). As new intellectual property, the technology has the potential to advance basic science at the chemistry-biology interface while providing new economic opportunities for Australia.Read moreRead less
Enhancing the performance of existing industrial enzymes through the application of new chemical modification technology. Enzymes have many uses in industry, replacing undesirable chemicals which adversely effect human & animal health & the environment. Enzymes offer advantages in effectiveness, biodegradability, specificity and safety. The concern with enzymes, in industrial applications, is that enzyme performance is degraded by a harsh chemical and/or physical environment. The aim of this stu ....Enhancing the performance of existing industrial enzymes through the application of new chemical modification technology. Enzymes have many uses in industry, replacing undesirable chemicals which adversely effect human & animal health & the environment. Enzymes offer advantages in effectiveness, biodegradability, specificity and safety. The concern with enzymes, in industrial applications, is that enzyme performance is degraded by a harsh chemical and/or physical environment. The aim of this study is to improve the performance of industrially significant enzymes by enhancing resistance to chemical & physical degradation or inactivation. This will be achieved by modifying the enzymes using new technology that we have developed. This will improve cost effectiveness of existing industrial enzymes & create opportunities for new uses of enzymes.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
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
Development of new herbicides targeting enzymes involved in the biosynthesis of branched-chain amino acids. Modern agriculture is heavily reliant on the use of herbicides. An inevitable consequence of herbicide usage is that resistant weeds will develop. Therefore, there is a continuing need to develop new herbicides to kill these resistant species. Herbicides interact with vulnerable molecular targets in plants, such as photosynthesis or the biosynthesis of certain amino acids. This project wil ....Development of new herbicides targeting enzymes involved in the biosynthesis of branched-chain amino acids. Modern agriculture is heavily reliant on the use of herbicides. An inevitable consequence of herbicide usage is that resistant weeds will develop. Therefore, there is a continuing need to develop new herbicides to kill these resistant species. Herbicides interact with vulnerable molecular targets in plants, such as photosynthesis or the biosynthesis of certain amino acids. This project will attempt to develop new herbicides that act upon two molecular targets that are not exploited by herbicides that are used currently. We will design, synthesize and test a variety of new compounds as potential environmentally-benign herbicides.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560685
Funder
Australian Research Council
Funding Amount
$451,000.00
Summary
Scanning Probe Microscopy for Bioelectrochemistry. New methods to study the fundamental properties of biological samples, in particular proteins, are continuing to advance and impact on society. We will establish a leading edge facility for high-resolution imaging of biomolecules with redox functions. This will enable the continued development of new enzyme based diagnostic tests by understanding the dynamic nature of coupled electron and molecular interactions with redox enzymes in solution. Th ....Scanning Probe Microscopy for Bioelectrochemistry. New methods to study the fundamental properties of biological samples, in particular proteins, are continuing to advance and impact on society. We will establish a leading edge facility for high-resolution imaging of biomolecules with redox functions. This will enable the continued development of new enzyme based diagnostic tests by understanding the dynamic nature of coupled electron and molecular interactions with redox enzymes in solution. The bioelectrochemical imaging facility will be unique in Australia and establish an important cross-disciplinary approach within the international community.Read moreRead less
Chemical synthesis of cancer-associated glycoproteins. Glycosylation of proteins is an extremely common event which plays an important role in a variety of biological processes. Aberrant glycosylation and over-production of glycoproteins is associated with numerous cancer types (including breast, prostate, ovarian and small lung) and are recognised as promising agents for disease diagnosis and vaccine development. A range of cancer-associated glycoproteins will be synthesised in this research p ....Chemical synthesis of cancer-associated glycoproteins. Glycosylation of proteins is an extremely common event which plays an important role in a variety of biological processes. Aberrant glycosylation and over-production of glycoproteins is associated with numerous cancer types (including breast, prostate, ovarian and small lung) and are recognised as promising agents for disease diagnosis and vaccine development. A range of cancer-associated glycoproteins will be synthesised in this research program using a number of novel chemical technologies. These glycoproteins will be used to develop cancer vaccines and diagnostics. Cancer is a severe burden on the Australian community and on the economy, therefore this research will be of significant benefit to Australia.Read moreRead less