NMR Studies of Second Generation Polynuclear Platinum Compounds. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration between Prof. Berners-Price and the inventor of these ne ....NMR Studies of Second Generation Polynuclear Platinum Compounds. Cancer affects one in four Australians and 50% of cancer patients are treated with cisplatin. BBR3464 is a new type of platinum anticancer drug that has shown promise in clinical trials, including results in cancers that do not respond to cisplatin treatment. Second-generation analogues, now under development, may offer significant advantages. This international collaboration between Prof. Berners-Price and the inventor of these new drugs puts Australian research at the forefront of the clinical development. There is the potential for the generation of new IP from new strategies in the design of improved anticancer drugs. The project builds strong international links and provides international training for Australian PhD students.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
NMR studies on DNA interactions of polynuclear platinum. BBR3464 is representative of a class of structurally unique platinum anticancer drugs, and is currently undergoing clinical trials. The anticancer activity most likely depends on binding to DNA, but the mechanism is different from that of the widely used drug, cisplatin. This project uses NMR spectroscopy to follow in detail the stepwise formation of DNA adducts. Further extension to reactions of polynuclear platinum complexes with sulfur ....NMR studies on DNA interactions of polynuclear platinum. BBR3464 is representative of a class of structurally unique platinum anticancer drugs, and is currently undergoing clinical trials. The anticancer activity most likely depends on binding to DNA, but the mechanism is different from that of the widely used drug, cisplatin. This project uses NMR spectroscopy to follow in detail the stepwise formation of DNA adducts. Further extension to reactions of polynuclear platinum complexes with sulfur nucleophiles will aid in understanding their metabolism and toxicity. The results of this work will aid in the selection of back-up clinical candidates and the design of drugs that target specific sequences of DNA for use in novel gene-based therapies.Read moreRead less
The development of a two-colour flow cytometric assay for the detection of whole cell biosensors in environmental samples. Macquarie University and the University of Copenhagen have expertise in fluorescence detection and whole cell biosensors respectively. The project will take advantage of these skills and develop a sensitive assay for monitoring biosensor bacteria in soil. The technology will be significant as it will enable real time analysis of antibiotic production in situ through the de ....The development of a two-colour flow cytometric assay for the detection of whole cell biosensors in environmental samples. Macquarie University and the University of Copenhagen have expertise in fluorescence detection and whole cell biosensors respectively. The project will take advantage of these skills and develop a sensitive assay for monitoring biosensor bacteria in soil. The technology will be significant as it will enable real time analysis of antibiotic production in situ through the detection of GFP expression. This work will then be used to isolate new antibiotic produces and will be extended to research into the bioavailability of toxic compounds and stress. An existing collaboration between the two institutions will be extended enabling the transfer and application of biosensor technology to Australia.Read moreRead less
Biologically active peptides from Australian and Russian Amphibians. Bowie's group has identified many host-defence peptides from Australian anurans, including antimicrobial and anticancer active peptides, and neuropeptides that inhibit the formation of the ubiquitous chemical messenger nitric oxide. Lebedev's group from Moscow have initiated a collaboration with us to investigate active peptides from unstudied Russian frogs and newts. Preliminary investigations show these are very different f ....Biologically active peptides from Australian and Russian Amphibians. Bowie's group has identified many host-defence peptides from Australian anurans, including antimicrobial and anticancer active peptides, and neuropeptides that inhibit the formation of the ubiquitous chemical messenger nitric oxide. Lebedev's group from Moscow have initiated a collaboration with us to investigate active peptides from unstudied Russian frogs and newts. Preliminary investigations show these are very different from those isolated from Australian anurans and some already show potential for development as pharmaceuticals.Read moreRead less
New inhibitors of HIV based on cellular enzymes. Over 39 million people are infected with HIV worldwide. However, none of the most highly affected countries have yet reached the peak in AIDS-related illness and death, thus the global impact of HIV/AIDS will get significantly worse, before it gets better.
In Australia, HIV is again on the rise. Ironically, improved treatments that have extended life expectancy will cause the number of HIV infected Australians to rise for many years to come. ....New inhibitors of HIV based on cellular enzymes. Over 39 million people are infected with HIV worldwide. However, none of the most highly affected countries have yet reached the peak in AIDS-related illness and death, thus the global impact of HIV/AIDS will get significantly worse, before it gets better.
In Australia, HIV is again on the rise. Ironically, improved treatments that have extended life expectancy will cause the number of HIV infected Australians to rise for many years to come. Therefore many Australians will suffer from the combined impact of the AIDS illness itself, opportunistic infections, the side-effects of treatment and natural aging. We aim to develop new drugs to combat this disease to help people everywhere lead happier, healthier and more productive lives.Read moreRead less
Inhibitors of enzymes in the lysine biosynthetic pathway. Recent reports of increasing bacterial resistance to antibiotics highlight the need for continual development of new antibacterial agents. Inhibitors of the biosynthesis of the amino acid lysine - an essential component of bacterial proteins and cell wall - may provide a novel class of antibiotics. This project describes investigations of the mechanism of the first two enzymes in the lysine biosynthetic pathway and the design and synthesi ....Inhibitors of enzymes in the lysine biosynthetic pathway. Recent reports of increasing bacterial resistance to antibiotics highlight the need for continual development of new antibacterial agents. Inhibitors of the biosynthesis of the amino acid lysine - an essential component of bacterial proteins and cell wall - may provide a novel class of antibiotics. This project describes investigations of the mechanism of the first two enzymes in the lysine biosynthetic pathway and the design and synthesis of inhibitors of these enzymes.Read moreRead less
Sensing atmosphere: Understanding the HNOX-protein gas-sensing capability and how it is affected by heme-oxidation. The project investigates how gas sensing heme-proteins from the novel HNOX (Heme-Nitric Oxide) family are able to discriminate between different gaseous ligands such as O2 and NO and how oxidation of the heme alters this response. The gas-sensing capability of the HNOX proteins is crucial for organisms ranging from bacteria to humans. Thus, understanding of these signalling mechani ....Sensing atmosphere: Understanding the HNOX-protein gas-sensing capability and how it is affected by heme-oxidation. The project investigates how gas sensing heme-proteins from the novel HNOX (Heme-Nitric Oxide) family are able to discriminate between different gaseous ligands such as O2 and NO and how oxidation of the heme alters this response. The gas-sensing capability of the HNOX proteins is crucial for organisms ranging from bacteria to humans. Thus, understanding of these signalling mechanisms will have a strong impact on many scientific fields from the control of pathogen growth to human blood pressure regulation. This collaboration will establish Australian scientists and as world-leading in the field of NO and redox signalling. This development will also be of substantial benefit for the training of the next generation of Australian students and scientists.Read moreRead less
Synthesis and Characterization of Novel Hybrid star polymers grown from carbohydrate clusters. The aim of the project is to make complex polymer architectures based on stars grown from sugar clusters. The star molecules are expected to have unique properties for transporting guest molecules in drug delivery systems. The outcome will be the development of totally biodegradable, non-toxic cluster/star structures capable of complexing to drugs. This is the first attempt to utilise these clusters ....Synthesis and Characterization of Novel Hybrid star polymers grown from carbohydrate clusters. The aim of the project is to make complex polymer architectures based on stars grown from sugar clusters. The star molecules are expected to have unique properties for transporting guest molecules in drug delivery systems. The outcome will be the development of totally biodegradable, non-toxic cluster/star structures capable of complexing to drugs. This is the first attempt to utilise these clusters, with sugar-based vinyl monomers for star synthesis.Read moreRead less
Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to tr ....Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to treat a range of pathogenic bacteria, including "Golden Staph".Read moreRead less