Explaining the differences in affinity and of carbohydrate binding of the glycogen-sensing enzyme, AMP-protein activated kinase (AMPK). This project will provide fundamental molecular knowledge of how a complex enzyme, AMPK is controlled by the major sugar molecule, glycogen. Our research will increase our understanding of its role in metabolic diseases such as Type 2 diabetes and obesity.
Structural and functional characterisation of compounds that inhibit the malarial aminopeptidases. Malaria is the world's most prevalent parasitic disease. Due to the rapid spread of drug resistant parasites there is a need to develop new antimalarial drugs. In this proposal we will characterise new targets and novel methods of inhibition that will form the basis of a new mechanism for antimalarial drugs.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE110100078
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
Establishment of a comprehensive regional biophysical analysis facility. Interactions between molecules are needed for cells to function correctly. This facility will permit comprehensive molecular characterisation as well as research into the fundamentals of how molecules interact.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE140100096
Funder
Australian Research Council
Funding Amount
$180,000.00
Summary
Biomolecular Interaction Facility. Biomolecular interaction facility: A biomolecular interaction facility located in Perth is essential to support the research performed by a growing community of key protein researchers. The infrastructure provided by this integrated facility will act as a hub for analysis of samples produced by high-throughput protein production methods and will provide high-level training with cutting-edge equipment for researchers at all levels. It will underpin faster and be ....Biomolecular Interaction Facility. Biomolecular interaction facility: A biomolecular interaction facility located in Perth is essential to support the research performed by a growing community of key protein researchers. The infrastructure provided by this integrated facility will act as a hub for analysis of samples produced by high-throughput protein production methods and will provide high-level training with cutting-edge equipment for researchers at all levels. It will underpin faster and better fundamental and translational research in the areas of structural biology, biotechnology, biomedical science, plant science and nanotechnology, supporting the activities of researchers and their collaborators in Australia and worldwide.Read moreRead less
Mechanism of AMPK activation by drugs and metabolites. This project aims to identify the molecular basis of activation mechanisms in the AMP-activated protein kinase (AMPK), an enzyme that regulates burning and storage of fuels such as fat and sugars, autophagy and controls appetite and energy expenditure. This project expects to provide insights into how energy metabolism and physiological functions are linked.
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
Structural basis of the neuroendocrine enzyme GAD65-mediated autoimmunity in Type 1 Diabetes. More than 80 per cent of patients with Type 1 Diabetes develop antibodies against the neuroendocrine enzyme GAD65. This project will use state-of-the art techniques to study the interaction of GAD65 with antibodies in molecular detail. This will provide key insights into the molecular mechanisms of autoimmune disease.
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