Insect development : the role of cytochrome P450s. Pest insects vector human diseases such as malaria and impose a massive burden in agriculture due to control costs and production losses. The intelligent control of insect pests requires an understanding of their development that is controlled by hormones. This project will provide an in depth understanding of insect hormone synthesis/degradation that is controlled by a class of enzymes, the cytochrome P450s. This will increase the potential ....Insect development : the role of cytochrome P450s. Pest insects vector human diseases such as malaria and impose a massive burden in agriculture due to control costs and production losses. The intelligent control of insect pests requires an understanding of their development that is controlled by hormones. This project will provide an in depth understanding of insect hormone synthesis/degradation that is controlled by a class of enzymes, the cytochrome P450s. This will increase the potential for new insect-specific control strategies with a decreased environmental impact.Read moreRead less
New Insights into the Structure and Function of Pyruvate Carboxylase. Pyruvate carboxylase plays an essential roles in insulin secretion by pancreatic islets and in normal brain function, but excess expression of this enzyme in liver and adipose tissue is associated with diabetes and obesity.
Understanding the function of each structural feature in the reaction mechanism of an enzyme is essential to designing safe and effective pharmaceuticals that are required to modulate its activity.
Th ....New Insights into the Structure and Function of Pyruvate Carboxylase. Pyruvate carboxylase plays an essential roles in insulin secretion by pancreatic islets and in normal brain function, but excess expression of this enzyme in liver and adipose tissue is associated with diabetes and obesity.
Understanding the function of each structural feature in the reaction mechanism of an enzyme is essential to designing safe and effective pharmaceuticals that are required to modulate its activity.
This project, which will use cutting edge techniques in an experimental model, seeks to characterise this important enzyme's function so that better treatments can be developed in future for diabetes and obesity.
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How organisms coordinate energy supply and demand. The metabolic stress sensing protein kinase called the AMP activated protein kinase controls metabolism of all eukaryotes to meet the needs of energy demand and nutrient supply. It is responsible for accelerating metabolism (glucose transport, glycolysis and fatty acid oxidation) in response to energy demand and with caloric restriction it regulates gene transcription to adapt to energy supply. This project is to provide a comprehensive unders ....How organisms coordinate energy supply and demand. The metabolic stress sensing protein kinase called the AMP activated protein kinase controls metabolism of all eukaryotes to meet the needs of energy demand and nutrient supply. It is responsible for accelerating metabolism (glucose transport, glycolysis and fatty acid oxidation) in response to energy demand and with caloric restriction it regulates gene transcription to adapt to energy supply. This project is to provide a comprehensive understanding of the AMP activated protein kinase (enzyme isoforms, genes, physiological roles and regulation). This knowledge will have major benefits in biopharmaceutical development, the livestock, plant and sport/racing industries.Read moreRead less
Structural and Functional Aspects of the Allosteric Regulation of Pyruvate Carboxylase by Acyl-CoA Compounds. Pyruvate carboxylase occupies a central location in intermediary metabolism catalysing the formation of oxaloacetate, a key component of the Krebs' tricarboxylic acid cycle especially in its synthetic modes in gluconeogenesis, lipogenesis and in the synthesis of neurotransmitters.
This project aims: (i) To produce crystals of pyruvate carboxylase for determining its structure by X-ra ....Structural and Functional Aspects of the Allosteric Regulation of Pyruvate Carboxylase by Acyl-CoA Compounds. Pyruvate carboxylase occupies a central location in intermediary metabolism catalysing the formation of oxaloacetate, a key component of the Krebs' tricarboxylic acid cycle especially in its synthetic modes in gluconeogenesis, lipogenesis and in the synthesis of neurotransmitters.
This project aims: (i) To produce crystals of pyruvate carboxylase for determining its structure by X-ray diffraction; (ii) To use affinity-labelling to determine the amino acid residues in the binding site of the enzyme's allosteric activator, acetyl-CoA; (iii) To construct chimeric enzymes from different species to define regions of the enzyme which affect its responses to its important allosteric activator, acetyl-CoA.
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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
Enantioselective nitrilases from filamentous fungi. The optical characteristics (chirality) of chemical precursors are important for many fine chemicals. Chiral intermediates are in high demand by the pharmaceutical and agrochemical industries for the preparation of bulk drug intermediates and agricultural products. Nitriles are attractive starting points but their conversion to corresponding amides and carboxylic acids generates significant wastes. Their hydrolysis can be performed under mil ....Enantioselective nitrilases from filamentous fungi. The optical characteristics (chirality) of chemical precursors are important for many fine chemicals. Chiral intermediates are in high demand by the pharmaceutical and agrochemical industries for the preparation of bulk drug intermediates and agricultural products. Nitriles are attractive starting points but their conversion to corresponding amides and carboxylic acids generates significant wastes. Their hydrolysis can be performed under mild conditions by enzymes termed nitrilases. We will work on fungal nitrilases as they present a globally attractive, yet untapped commercial target. The outcome for Applimex will be a suite of biocatalysts specific for the production of key intermediates for drug and agrochemical syntheses.Read moreRead less
Genetic modification and lyophilisation of microorganisms for the generation of bacteriological internal quality controls. The development of internal quality control micro-organisms in precise numbers is necessary for the evolution of standard methodology in microbiology, which until now, remains obsolete, because it relies on inaccurate methods to produce quantitative and qualitative results. The research described here is largely based on molecular techniques to genetically tag micro-organism ....Genetic modification and lyophilisation of microorganisms for the generation of bacteriological internal quality controls. The development of internal quality control micro-organisms in precise numbers is necessary for the evolution of standard methodology in microbiology, which until now, remains obsolete, because it relies on inaccurate methods to produce quantitative and qualitative results. The research described here is largely based on molecular techniques to genetically tag micro-organisms with fluorescent proteins and pigment producing enzymes, and on the manipulation of growth and storage conditions to maximize the survival of micro-organisms during lyophilisation. Successful completion and application of the proposed project through existing patents owned by BTF, will revolutionise the way microbiological tests are performed worldwide.Read moreRead less
Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such meta ....Metalloproteins and metalloenzymes. Most of the chemical reactions and physical movements in living systems are carried out by proteins. The information for producing proteins from amino acids is stored in the genes, but many biological processes depend on additional atoms or molecules ('cofactors') that are added to a protein after it is assembled. For example, more than 30% of all proteins contain metal atoms which are essential for their function. We are studying the structures of such metalloproteins and metalloenzymes so that we can better understand their activities with long term aims of creating new molecules for biotechnology and/or drugs.Read moreRead less
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
Biochemical Reconstitution Of The Ubiquitin Ligase Pathway Defective In Fanconi Anaemia
Funder
National Health and Medical Research Council
Funding Amount
$562,742.00
Summary
Fanconi Anemia (FA) is characterised by loss of vital blood cells but also 700x risk of developing leukaemia and other cancers. FA is caused by an inherited defect in one of 15 different genes that provide a signal and repair mechanism protecting cells from cancer causing mutations. By reconstructing this signaling mechanism in the test tube we will determine how it contributes to cancer protection, and highlight potential strategies for treatment of FA and leukaemia in the general population.