Total chemical synthesis of a redesigned enzyme, HIV-1 PR, containing an artificial tunable catalytic apparatus. The research project proposed represents a novel approach using total chemical synthesis to study the enzyme action of the HIV-1 PR, an aspartyl protease essential for the replication of AIDS virus. The redesign of the catalytic apparatus will allow us to investigate molecular aspects of its action. The synthetic polypeptide chain will be folded and characterised for the correct folde ....Total chemical synthesis of a redesigned enzyme, HIV-1 PR, containing an artificial tunable catalytic apparatus. The research project proposed represents a novel approach using total chemical synthesis to study the enzyme action of the HIV-1 PR, an aspartyl protease essential for the replication of AIDS virus. The redesign of the catalytic apparatus will allow us to investigate molecular aspects of its action. The synthetic polypeptide chain will be folded and characterised for the correct folded structure by NMR, and assayed for enzymatic activity. It can be expected that significant new insights into the molecular basis of the properties of the HIV-1 PR will be obtained. This will be an important contribution to biomedical research.Read moreRead less
CHARACTERISATION OF NOVEL BIOACTIVES FROM AUSTRALIAN HONEY WITH THERAPEUTIC POTENTIAL. Honey from specific Australian flowering plants has been identified that contain significant therapeutic properties in wound healing and other treatments. The research project proposed will identify and fully characterise the bioactive components of selected Australian honey (Medihoney) with antibiotic and growth promoting activites. These aims will be supported by high resolution mass spectrometry interfaced ....CHARACTERISATION OF NOVEL BIOACTIVES FROM AUSTRALIAN HONEY WITH THERAPEUTIC POTENTIAL. Honey from specific Australian flowering plants has been identified that contain significant therapeutic properties in wound healing and other treatments. The research project proposed will identify and fully characterise the bioactive components of selected Australian honey (Medihoney) with antibiotic and growth promoting activites. These aims will be supported by high resolution mass spectrometry interfaced with HPLC and or affinity chip surfaces, 750 MHz NMR analysis and a range of relevant bioassays on specific organisms and cell lines. These outcomes will not only enhance the value of current honey-based products but have the potential to identify new therapeutic lead molecules.Read moreRead less
Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may ....Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.Read moreRead less
Structure-based discovery of anti-parainfluenza viral agents. Respiratory diseases, for example croup and bronchitis, in children are caused in the main by human parainfluenza viruses (hPIVs) types 1-3. No vaccines or specific antiviral therapy against hPIV infections exist. This project targets an essential protein in the virus' lifecycle. The essential triple role of the protein in virus spread makes it an attractive target for the development of hPIV-specific drugs. This project aims to prod ....Structure-based discovery of anti-parainfluenza viral agents. Respiratory diseases, for example croup and bronchitis, in children are caused in the main by human parainfluenza viruses (hPIVs) types 1-3. No vaccines or specific antiviral therapy against hPIV infections exist. This project targets an essential protein in the virus' lifecycle. The essential triple role of the protein in virus spread makes it an attractive target for the development of hPIV-specific drugs. This project aims to produce lead-like compounds that inhibit the protein's function and may provide novel drug candidates for further development. Furthermore the role of human host cell-associated carbohydrates in parainfluenza infection will be better understood.Read moreRead less
Disruption of Sex Pheromone Biosynthesis: A Novel Control Method for Pestiferous Fruit Flies by. Fruit flies from the genus Bactrocera are economically important worldwide. B. tryoni, (Queensland fruit fly) is the most damaging horticultural pest in Australia and B. oleae (olive fly) is a major European pest. These flies use chemicals of similar but distinct structure for communication and particularly for finding mates. This research will examine the pathways and enzymes these flies use to sy ....Disruption of Sex Pheromone Biosynthesis: A Novel Control Method for Pestiferous Fruit Flies by. Fruit flies from the genus Bactrocera are economically important worldwide. B. tryoni, (Queensland fruit fly) is the most damaging horticultural pest in Australia and B. oleae (olive fly) is a major European pest. These flies use chemicals of similar but distinct structure for communication and particularly for finding mates. This research will examine the pathways and enzymes these flies use to synthesise sex pheromones. We propose that understanding the chemical and biochemical steps employed by the flies will allow us to design inhibitors to prevent pheromone production and thus provide a novel, species specific method for controlling fruit flies.Read moreRead less
Design, Synthesis and Biological Evaluation of Rotavirus Inhibitors. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 400,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. The ....Design, Synthesis and Biological Evaluation of Rotavirus Inhibitors. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 400,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.Read moreRead less
Liposaccharide based peptide and vaccine delivery systems: improving the bioavailability and immunogenicity of Luteinizing Hormone-Releasing Hormone. This project aims to develop new lipid- and sugar-based drug delivery systems for Luteinizing-hormone-releasing hormone (LHRH), a hormone which regulates the level of enzymes involved in fertility conditions and prostate cancers. This technology could be extended to significantly increase the number of drugs available on the market, such as peptide ....Liposaccharide based peptide and vaccine delivery systems: improving the bioavailability and immunogenicity of Luteinizing Hormone-Releasing Hormone. This project aims to develop new lipid- and sugar-based drug delivery systems for Luteinizing-hormone-releasing hormone (LHRH), a hormone which regulates the level of enzymes involved in fertility conditions and prostate cancers. This technology could be extended to significantly increase the number of drugs available on the market, such as peptide drugs and vaccines.Read moreRead less
Investigation of novel sialic acid mimetics to target the spread of cancer. The mortality rates for many cancers afflicting the world's population are extremely high and these rates are consistent with the Australian experience. It is generally accepted that colon cancer, and cancers as a whole, are a significant healthcare issue and have immense socioeconomic impact. Alternative treatments preventing the spread of cancers would be of very significant benefit. This fellowship will provide the ....Investigation of novel sialic acid mimetics to target the spread of cancer. The mortality rates for many cancers afflicting the world's population are extremely high and these rates are consistent with the Australian experience. It is generally accepted that colon cancer, and cancers as a whole, are a significant healthcare issue and have immense socioeconomic impact. Alternative treatments preventing the spread of cancers would be of very significant benefit. This fellowship will provide the opportunity for the discovery and development of such treatments that are based on the processes that utilise carbohydrates to facilitate the spread of tumours.Read moreRead less
Design and discovery of novel conotoxins that target ion channels and receptors. The national benefits that may arise include (i) new knowledge of biologically active peptides and their mode of action that will be protected through patent applications and provide a competitive edge for Australian biotechnology (ii) the training of a new generation of skilled researchers in chemical and structural biology that will sustain the biotechnology industry (iii) economic benefits from licensing and roya ....Design and discovery of novel conotoxins that target ion channels and receptors. The national benefits that may arise include (i) new knowledge of biologically active peptides and their mode of action that will be protected through patent applications and provide a competitive edge for Australian biotechnology (ii) the training of a new generation of skilled researchers in chemical and structural biology that will sustain the biotechnology industry (iii) economic benefits from licensing and royalty returns on drug leads that may arise from this program (iv) environmental benefits from the development of more sensitive analytical methods that obviate over collection of endangered species and (v) social benefits from a reduction in suffering from diseases for which drugs are developed as a result of this program.Read moreRead less
Heparan sulphate mimetics: Versatile tools for chemical biology. This project aims to develop chemical tools to study heparan sulphate-binding proteins. Heparan sulphate is a complex polysaccharide that is ubiquitously expressed on mammalian cells and interacts with proteins to mediate numerous biological and pathological functions. These interactions are poorly understood. This project will use homogeneous, structurally defined compounds to study heparan sulphate and its binding partners in bio ....Heparan sulphate mimetics: Versatile tools for chemical biology. This project aims to develop chemical tools to study heparan sulphate-binding proteins. Heparan sulphate is a complex polysaccharide that is ubiquitously expressed on mammalian cells and interacts with proteins to mediate numerous biological and pathological functions. These interactions are poorly understood. This project will use homogeneous, structurally defined compounds to study heparan sulphate and its binding partners in biology. This is expected to lead to a better, molecular-level understanding of these fundamental processes, and may have future applications in biotechnology and drug development.Read moreRead less