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
MOLECULAR APPROACHES TO OVERCOME SCABIES AND ASSOCIATED DISEASE. Scabies causes childhood pyoderma predisposing to severe disease in later life. It is a major increasing health burden in Indigenous people of Northern Australia. Drug resistance is developing in mites and bacteria. The lack of clinical material has hampered molecular research and this work will use comparative genomics of parasitic and free living mites and microbiome analysis to understand fundamental aspects of mite biology and ....MOLECULAR APPROACHES TO OVERCOME SCABIES AND ASSOCIATED DISEASE. Scabies causes childhood pyoderma predisposing to severe disease in later life. It is a major increasing health burden in Indigenous people of Northern Australia. Drug resistance is developing in mites and bacteria. The lack of clinical material has hampered molecular research and this work will use comparative genomics of parasitic and free living mites and microbiome analysis to understand fundamental aspects of mite biology and pathogenesis. The understanding of proteins that are essential for mite survival and interfere with host defences will allow the informed design of peptide inhibitors as a new strategy to develop alternative treatment options.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE160100127
Funder
Australian Research Council
Funding Amount
$355,000.00
Summary
Superresolution fluorescence imaging in microbiology. Superresolution fluorescence imaging in microbiology:
This project involves the purchase of new, and upgrade of existing, fluorescence imaging tools to facilitate the study of intracellular processes in microbial systems at significantly higher spatial and temporal resolutions than hitherto possible. Visualisation of the structure and dynamics of intracellular molecular assemblies at maximal resolution is required to understand protein funct ....Superresolution fluorescence imaging in microbiology. Superresolution fluorescence imaging in microbiology:
This project involves the purchase of new, and upgrade of existing, fluorescence imaging tools to facilitate the study of intracellular processes in microbial systems at significantly higher spatial and temporal resolutions than hitherto possible. Visualisation of the structure and dynamics of intracellular molecular assemblies at maximal resolution is required to understand protein function inside living cells. The new equipment is designed to provide a fast super-resolution imaging system to study the intracellular dynamics of proteins in vitro and a super-resolution microscope to visualise structures and assemblies inside microbes with a resolution of tens of nanometres, putting in vitro biochemistry into the context of a living cell. Read moreRead less
Arsenite oxidation by a novel bacterium that is a candidate for arsenic bioremediation. The arsenic munching microbe NT-26 could help in the fight to clean up arsenic-contaminated mining waste and drinking water. Arsenic poses an environmental problem in countries such as Australia, USA and Canada owing primarily to mining activities. The problem in countries such as Bangladesh and West Bengal are even more serious as these people are dying of arsenic-related diseases as they rely on water conta ....Arsenite oxidation by a novel bacterium that is a candidate for arsenic bioremediation. The arsenic munching microbe NT-26 could help in the fight to clean up arsenic-contaminated mining waste and drinking water. Arsenic poses an environmental problem in countries such as Australia, USA and Canada owing primarily to mining activities. The problem in countries such as Bangladesh and West Bengal are even more serious as these people are dying of arsenic-related diseases as they rely on water containing arsenic as their primary source of drinking water. The outcomes of this research should provide the necessary information for removing arsenic from all types of waters.Read moreRead less
Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently ....Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently glycosylation of Gram-negative bacterial proteins was not thought to occur, however our recent work with these bacteria, and other groups studying Pseudomonas and Campylobacter, have shown that this process may be widespread. In our previous studies, we have identified and analysed a number of genes involved in pili glycosylation, in bacteria, which make known sugar structures. We have used this information to developed models for how the biochemistry and physiology of the glycosylation system may work. With a well-established structure and many genes already identified, glycosylation in Neisseria represents the best available model system to study this novel and important process. In the proposed study we describe experiments planned to test our models and reveal the molecular detail of this process. This study could lead to major advances in our understanding of this process and, when understood, may have future applications in biotechnology.Read moreRead less
Stuctural analysis of RNA polymerase elongation complexes. RNA polymerase (RNAP) is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. Many additional factors are required to ensure that this enzyme functions correctly in the cell. The aim of this project is to obtain structural information on a bacterial RNAP complexed with an essential transcription factor called NusA. Using this information ....Stuctural analysis of RNA polymerase elongation complexes. RNA polymerase (RNAP) is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. Many additional factors are required to ensure that this enzyme functions correctly in the cell. The aim of this project is to obtain structural information on a bacterial RNAP complexed with an essential transcription factor called NusA. Using this information, plus data already obtained on the structure of this enzyme complexed with another essential factor called sigma, we will design small molecules to inhibit the interaction of these essential factors with polymerase. These molecules will serve as leads for the development of new antibiotics.Read moreRead less
DNA end resection: from basic mechanisms to genome editing. The project aims to understand processes underlying genome editing, a bioengineering process that introduces specific mutations into genomic DNA. Homologous recombination and nonhomologous end-joining pathways play a crucial role in repairing broken DNA strands, which are a toxic form of DNA damage. The proteins that function in the repair process have been recently identified, but it remains unclear how they function on a mechanistic l ....DNA end resection: from basic mechanisms to genome editing. The project aims to understand processes underlying genome editing, a bioengineering process that introduces specific mutations into genomic DNA. Homologous recombination and nonhomologous end-joining pathways play a crucial role in repairing broken DNA strands, which are a toxic form of DNA damage. The proteins that function in the repair process have been recently identified, but it remains unclear how they function on a mechanistic level and how either of the two main pathways is selected. The project aims to define how the activity of a key control protein, Sae2 (Sporulation in the Absence of Spo Eleven), is regulated by posttranslational modifications, and how this activates homologous recombination. The project plans to first use Saccharomyces cerevisiae yeast as a model and then to extend research into the human system in an attempt to improve the efficiency of genome editing. 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
The protein O-glycosylation pathway in Neisseria meningitidis. Neisseria meningitidis causes bacterial meningitis, a sudden and severe disease of particular concern to children in both the developed and developing worlds. This project will contribute to an understanding of how these bacteria evade the immune system by modifying the proteins displayed on their surface, which will help in the development of a vaccine.