Molecular analysis of glutathione transferase interactions with drugs and physiological ligands. Proteins called glutathione transferases protect us from toxic molecules that we ingest, breathe in or are by-products of normal metabolism. The same proteins also bind to many types of drugs leading them to be excreted from the body. In this project molecular structures of glutathione transferases bound to anti-cancer drugs will be determined as the basis for devising inhibitors of the protein that ....Molecular analysis of glutathione transferase interactions with drugs and physiological ligands. Proteins called glutathione transferases protect us from toxic molecules that we ingest, breathe in or are by-products of normal metabolism. The same proteins also bind to many types of drugs leading them to be excreted from the body. In this project molecular structures of glutathione transferases bound to anti-cancer drugs will be determined as the basis for devising inhibitors of the protein that will make drugs much more effective.Read moreRead less
Structural studies of glutathione transferases: a model system for functional genomics and drug design. Glutathione S-transferases (GSTs) are a large family of multi-functional proteins that play a vital role in an organism's defence against toxic chemicals. However, they also attack a variety of drugs and hence are a prime target for the development of isoform-specific inhibitors. We will determine the 3D atomic structures of GSTs in complex with a range of substrates and inhibitors as a basis ....Structural studies of glutathione transferases: a model system for functional genomics and drug design. Glutathione S-transferases (GSTs) are a large family of multi-functional proteins that play a vital role in an organism's defence against toxic chemicals. However, they also attack a variety of drugs and hence are a prime target for the development of isoform-specific inhibitors. We will determine the 3D atomic structures of GSTs in complex with a range of substrates and inhibitors as a basis for the design of compounds to improve the efficacy of anti-cancer and other drugs. This is an ambitious, wide-ranging project involving collaborators around the world. We expect the results will not only greatly increase our knowledge of an important enzyme family, but will also have applications in protein folding, catalysis, protein engineering, evolution, drug design and functional genomics. Read moreRead less
Global genetic regulation of carbon metabolism in filamentous fungi. Fungi are of great importance in medicine, agriculture and industry. They are used extensively for food, antibiotic and chemical production and, increasingly, for generating cheap substrates for bioethanol. However many are serious pathogens of plants and humans. Understanding how fungi control their metabolism is of fundamental importance for their more effective use or control. This project takes advantage of a fungus that is ....Global genetic regulation of carbon metabolism in filamentous fungi. Fungi are of great importance in medicine, agriculture and industry. They are used extensively for food, antibiotic and chemical production and, increasingly, for generating cheap substrates for bioethanol. However many are serious pathogens of plants and humans. Understanding how fungi control their metabolism is of fundamental importance for their more effective use or control. This project takes advantage of a fungus that is easily studied in the laboratory by advanced genetic techniques to identify the ways in which genes are turned on and off in response to changes in the nutrients available. By comparing DNA sequences the results are readily applied to fungi of economic importance.Read moreRead less
Particle motion and particle-convective heat transfer near the walls of fluidized beds. Background: Fluidized bed technology has important industrial applications ranging from petrol production to mineral processing for metal production. Such processes take advantage of the high rates of heat transfer in gas-fluidized beds.
Objective of project: To improve understanding and modelling of heat transfer in gas fluidized beds through the application of state-of-the-art experimental (Positron Emiss ....Particle motion and particle-convective heat transfer near the walls of fluidized beds. Background: Fluidized bed technology has important industrial applications ranging from petrol production to mineral processing for metal production. Such processes take advantage of the high rates of heat transfer in gas-fluidized beds.
Objective of project: To improve understanding and modelling of heat transfer in gas fluidized beds through the application of state-of-the-art experimental (Positron Emission Particle Tracking) and modelling (Discrete Element Method simulation) techniques.
Expected outcomes of project: New knowledge of the mechanisms of fluidized bed heat transfer. Improved the prediction of heat transfer coefficients with consequent improvements in the design and operation of fluidized bed processes.
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Polyanionic carbon ligands in metal complexes as new reagents in organometallic and inorganic chemistry. The proposed research will benefit Australia by creating a knowledge base in an internationally important area of chemistry. It addresses fundamental questions in organometallic chemistry that will be of great significance for chemical synthesis as well as for a greater understanding of structure and bonding. Through an integrated and interdisciplinary approach, the exploitation of technologi ....Polyanionic carbon ligands in metal complexes as new reagents in organometallic and inorganic chemistry. The proposed research will benefit Australia by creating a knowledge base in an internationally important area of chemistry. It addresses fundamental questions in organometallic chemistry that will be of great significance for chemical synthesis as well as for a greater understanding of structure and bonding. Through an integrated and interdisciplinary approach, the exploitation of technologies arising from this research programme will be explored. In addition to the academic community, these technologies will benefit hi-tech industries including pharmaceutical and fine chemical concerns which will gain from the use of polymetalated carbon species in organic and inorganic synthesis, catalysis and the development of new materials.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160101548
Funder
Australian Research Council
Funding Amount
$373,052.00
Summary
Enantioselective catalysis using P-chiral phosphines and phosphinamines. This project aims to develop new methods to synthesise organic molecules. The synthesis of organic molecules for medicines, polymers and other applications depends on the use of catalysts to promote chemical reactions. The use of small organic catalysts, rather than those based on transition metals or enzymes, offers many advantages in the form of low toxicity, low cost, ease of use and minimal environmental impact. This pr ....Enantioselective catalysis using P-chiral phosphines and phosphinamines. This project aims to develop new methods to synthesise organic molecules. The synthesis of organic molecules for medicines, polymers and other applications depends on the use of catalysts to promote chemical reactions. The use of small organic catalysts, rather than those based on transition metals or enzymes, offers many advantages in the form of low toxicity, low cost, ease of use and minimal environmental impact. This project aims to deliver new methods for synthesis using new approaches in organocatalysis. The methods will be used to synthesise important molecules, including novel catalysts, biocompatible polyester materials and chiral phosphines, which are widely used in chemical industry but difficult and expensive to produce.Read moreRead less
Emulsion Stability and Solvent Extraction Equipment Design in the Pharmaceutical Industry. The project aims at developing reliable prediction of large scale performance of liquid extraction columns. This will be done through a study of the columns in operation at GlaxoSmithKline's operation at Port Fairy alkaloids plant. In addition a detailed study of the influence of impurities on the coalescence rate of liquid dispersions will be undertaken as this is an important rate limiting step in colu ....Emulsion Stability and Solvent Extraction Equipment Design in the Pharmaceutical Industry. The project aims at developing reliable prediction of large scale performance of liquid extraction columns. This will be done through a study of the columns in operation at GlaxoSmithKline's operation at Port Fairy alkaloids plant. In addition a detailed study of the influence of impurities on the coalescence rate of liquid dispersions will be undertaken as this is an important rate limiting step in column performance. The benefit to GlaxoSmithKline will be a more efficient and optimised plant. The benefit to Australian processing industries is a reliable method of relating small scale trials to full size column performance which is a significent problem in the minerals industry at present.Read moreRead less
Next Generation of Separation Equipment for Natural Product Extraction. The benefit to GlaxoSmithKline will be the potential to upgrade to a more efficient plant which is important for maintaining their competitive position in this global business. The benefit to other Australian processing industries will be an improved understanding of the performance of membrane contactors when used for natural product separation and more specifically a reliable method for controlling fouling in this type of ....Next Generation of Separation Equipment for Natural Product Extraction. The benefit to GlaxoSmithKline will be the potential to upgrade to a more efficient plant which is important for maintaining their competitive position in this global business. The benefit to other Australian processing industries will be an improved understanding of the performance of membrane contactors when used for natural product separation and more specifically a reliable method for controlling fouling in this type of equipment which is a currently a significant industry problem.Read moreRead less
Design, Evaluation, and Selection of Novel Pt(IV) Complexes as Anticancer Agents. Platinum anticancer drugs are arguably the most widely used anticancer agents in the world but serious problems remain with toxicity and resistance. Platinum(IV) compounds have numerous advantages in terms of stability and thereby, lower toxicity. In this project we will exploit these advantages along with others that we have discovered recently and our understanding of the chemistry and biology of platinum(IV) to ....Design, Evaluation, and Selection of Novel Pt(IV) Complexes as Anticancer Agents. Platinum anticancer drugs are arguably the most widely used anticancer agents in the world but serious problems remain with toxicity and resistance. Platinum(IV) compounds have numerous advantages in terms of stability and thereby, lower toxicity. In this project we will exploit these advantages along with others that we have discovered recently and our understanding of the chemistry and biology of platinum(IV) to develop novel platinum(IV) compounds to the point where the industry partner can commercialise them.Read moreRead less
Characterisation of insulin-independent glucose uptake mediated by guanine nucleotide-binding proteins (G-proteins) coupled receptors. This project will provide first class postdoctoral training for Dr Sato in the laboratory of A/Prof Bengtsson one of the pioneers in the field of cell metabolism. He will learn new approaches to the study of cell signalling including the use of ribonucleic acid interference (RNAi) technologies and of a series of functionally altered mutants of phosphatidylinosito ....Characterisation of insulin-independent glucose uptake mediated by guanine nucleotide-binding proteins (G-proteins) coupled receptors. This project will provide first class postdoctoral training for Dr Sato in the laboratory of A/Prof Bengtsson one of the pioneers in the field of cell metabolism. He will learn new approaches to the study of cell signalling including the use of ribonucleic acid interference (RNAi) technologies and of a series of functionally altered mutants of phosphatidylinositol (PI) 3-kinase that he will bring back to Monash University. A better understanding of the cell signalling mechanisms involved in glucose transport will be of enormous benefit in developing new approaches to the treatment of diseases such as type II diabetes.Read moreRead less