Generation of Novel Fermentation Products and their Exploitation in the Synthesis of Biologically Active Organic Compounds with Therapeutic Potential. Collections of new micro-organisms and their metabolites suitable for use in the chemical synthesis programs will emerge from the proposed research. This will provide a potentially highly-valuable national resource that could serve the needs of many laboratories around Australia by allowing them to establish more direct routes to target molecules ....Generation of Novel Fermentation Products and their Exploitation in the Synthesis of Biologically Active Organic Compounds with Therapeutic Potential. Collections of new micro-organisms and their metabolites suitable for use in the chemical synthesis programs will emerge from the proposed research. This will provide a potentially highly-valuable national resource that could serve the needs of many laboratories around Australia by allowing them to establish more direct routes to target molecules being sought in the development of new therapeutic agents and/or materials. The combined application of molecular biological, microbiological and chemical synthesis techniques in a concerted manner in the one location will lead to a raft of new opportunities for the biotech and pharmaceutical industries in Australia.Read moreRead less
Biosynthesis of nonribosomal peptide toxins in cyanobacteria: A functional characterisation of microcystin synthetase. Microcystins are potent toxins and tumour promoters produced by cyanobacteria associated with blue-green algal blooms. This non-ribosomal peptide is produced by microcystin synthetase, a unique enzyme complex comprised of peptide synthetases, polyketide synthases, and integrated accessory enzymes. We have identified and characterised the extensive gene cluster encoding this enzy ....Biosynthesis of nonribosomal peptide toxins in cyanobacteria: A functional characterisation of microcystin synthetase. Microcystins are potent toxins and tumour promoters produced by cyanobacteria associated with blue-green algal blooms. This non-ribosomal peptide is produced by microcystin synthetase, a unique enzyme complex comprised of peptide synthetases, polyketide synthases, and integrated accessory enzymes. We have identified and characterised the extensive gene cluster encoding this enzyme. This project describes the biochemical characterisation of specific enzyme activities within microcystin synthetase and how they determine the final structure and toxicity of the many forms of microcystin. Interactions between this enzyme complex and its substrate amino acids will provide information for the genetic engineering of this and similar natural products.Read moreRead less
Controlled Crystallisation of Bioactives. The new technologies developed in this project for bioactive recovery and particle design will allow the development of new value added products for Australia's growing biotechnology industry, especially in pharmaceuticals, neutraceuticals and functional foods. Two PhD students will receive excellent research training to then move into research and development in these industries.
Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less
Design of Polymeric Devices for Biotechnological Applications. The research project focuses on the development of functional polymer particles for diagnostic applications. Advanced polymer chemistry will be used to synthesize devices for reliable and fast diagnostic systems. The outcome of this work will help promoting and maintaining good health in Australia by developing novel technologies and advanced materials based on polymer science.
Transcriptional control of antigenic variation in the malaria parasite Plasmodium falciparum. Malaria is a major health concern for the Australian Defence Personnel recently deployed in East Timor, Afghanistan and the Solomon Islands and is endemic in our immediate neighbours Indonesia and Papua New Guinea. Australia is susceptible to malaria and climate change could extend the mosquitos range to large population centres of Northern Australia causing malaria in Australia. This study would clarif ....Transcriptional control of antigenic variation in the malaria parasite Plasmodium falciparum. Malaria is a major health concern for the Australian Defence Personnel recently deployed in East Timor, Afghanistan and the Solomon Islands and is endemic in our immediate neighbours Indonesia and Papua New Guinea. Australia is susceptible to malaria and climate change could extend the mosquitos range to large population centres of Northern Australia causing malaria in Australia. This study would clarify how malaria parasites evade the host's immune response and help to protect Australia by providing drug targets for the control of this invasive disease.Read moreRead less
Redox-Tuneable Sensitisers for Photodynamic Therapy of Malignant and Non-Malignant Proliferative Diseases. Cancer is currently Australia's leading cause of death with 85 231 new cases reported during 2000, costing the health system >$2 billion annually. Photodynamic Therapy is a promising anti-cancer therapy which combines the action of a photosensitising drug and light to destroy tumours. This project will lead to the development of new photosensitisers which will enable the specific targeting ....Redox-Tuneable Sensitisers for Photodynamic Therapy of Malignant and Non-Malignant Proliferative Diseases. Cancer is currently Australia's leading cause of death with 85 231 new cases reported during 2000, costing the health system >$2 billion annually. Photodynamic Therapy is a promising anti-cancer therapy which combines the action of a photosensitising drug and light to destroy tumours. This project will lead to the development of new photosensitisers which will enable the specific targeting of tumours while protecting healthy tissue from damage. Post-treatment skin photosensitivity will be minimised by antioxidant features integrated into the photosensitisers. The development of improved photosensitisers during this project will ultimately lead to improved treatment and new alternatives for Australian cancer sufferers.Read moreRead less
Composite biomaterials for modulation of dermal fibroblast function. The successful outcome of this research will revolutionize the way scars are treated for the large number of people who suffer burns and even minor trauma that leads to disfigurement. By using advanced chemical synthesis, biochemical analysis, cell biology and polymer materials science, an intelligent gel sheet will be devised that is able to control the formation of scar tissue and also reduce the effect of existing scars. Thi ....Composite biomaterials for modulation of dermal fibroblast function. The successful outcome of this research will revolutionize the way scars are treated for the large number of people who suffer burns and even minor trauma that leads to disfigurement. By using advanced chemical synthesis, biochemical analysis, cell biology and polymer materials science, an intelligent gel sheet will be devised that is able to control the formation of scar tissue and also reduce the effect of existing scars. This will produce improved quality of life for sufferers of severe scarring and have major economic benefits in reduced health costs. Read moreRead less
From Chemical Architecture to Protein Surfaces. Creation of small stable molecules that reproduce key functions of important protein surfaces, would be a significant technology breakthrough with many important potential applications in science, medicine & industry. As new scientific tools they could be used to interrogate biological systems & implicate specific protein surfaces in biological/disease mechanisms. As leads to new medicines (pharmaceuticals, vaccines, diagnostics), they could offer ....From Chemical Architecture to Protein Surfaces. Creation of small stable molecules that reproduce key functions of important protein surfaces, would be a significant technology breakthrough with many important potential applications in science, medicine & industry. As new scientific tools they could be used to interrogate biological systems & implicate specific protein surfaces in biological/disease mechanisms. As leads to new medicines (pharmaceuticals, vaccines, diagnostics), they could offer new ways of impacting on infection, diseases of the aged, & preventative medicine (National Research Priorities). As new intellectual property, the technology has the potential to advance basic science at the chemistry-biology interface while providing new economic opportunities for Australia.Read moreRead less
Design and characterisation of a polysaccharide-based biomaterial for tissue adhesion. This proposal aims to design a new bio-adhesive material and study the mechanisms of action for tissue adhesion. Current suture technology is inadequate for anything but simple repairs and the alternative offered by surgical glues available today is at most augmentation of suturing. Combination of a strong adhesive biomaterial with factors for accelerating wound healing will generate a novel material technolo ....Design and characterisation of a polysaccharide-based biomaterial for tissue adhesion. This proposal aims to design a new bio-adhesive material and study the mechanisms of action for tissue adhesion. Current suture technology is inadequate for anything but simple repairs and the alternative offered by surgical glues available today is at most augmentation of suturing. Combination of a strong adhesive biomaterial with factors for accelerating wound healing will generate a novel material technology that, by uniting wound closure with sealing, addresses an unmet need in surgery.
The primary outcomes of these investigations will be:
1. advancement of knowledge in theories of tissue-biomaterial adhesion mechanisms
2. knowledge of effects of visible light from laser diodes on cells and isolated tissue
3. a biocompatible, visible light activated adhesive film for tissue repair based on chitosan polysaccharides
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