Engineering synthetic genetic codes. Large, high quality libraries of new drugs are absolutely essential resources to find new medicines. However, their use is restricted to a few pharmaceutical giants. We will engineer cells to make a wide variety of drug-like polymers, providing a drug discovery resource accessible to almost any scientific laboratory. As each cell could make a different polymer, billions of different potential drugs could be produced in a single tube. This technology provides ....Engineering synthetic genetic codes. Large, high quality libraries of new drugs are absolutely essential resources to find new medicines. However, their use is restricted to a few pharmaceutical giants. We will engineer cells to make a wide variety of drug-like polymers, providing a drug discovery resource accessible to almost any scientific laboratory. As each cell could make a different polymer, billions of different potential drugs could be produced in a single tube. This technology provides an opportunity to put the future of drug discovery in the hands of the wider scientific community and new tools for Australian industries.Read moreRead less
Re-engineering the genetic code. Large, high quality libraries of new drugs are absolutely essential resources to find new medicines. However, their use is restricted to a few pharmaceutical giants. We will engineer cells to make a wide variety of drug-like polymers, providing a drug discovery resource accessible to almost any scientific laboratory. As each cell could make a different polymer, billions of different potential drugs could be produced in a single tube. This technology provides an o ....Re-engineering the genetic code. Large, high quality libraries of new drugs are absolutely essential resources to find new medicines. However, their use is restricted to a few pharmaceutical giants. We will engineer cells to make a wide variety of drug-like polymers, providing a drug discovery resource accessible to almost any scientific laboratory. As each cell could make a different polymer, billions of different potential drugs could be produced in a single tube. This technology provides an opportunity to put the future of drug discovery in the hands of the wider scientific community and provides new tools for Australian industries.Read moreRead less
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
Functional Genomics to Predict and Enhance Response to Interferon. The increasing number and huge cost impost of new therapies to health providers, both worldwide and nationally, has not yet resulted in a concomitant increase in strategies to optimise their use. Many of the new therapies are proteins (recombinant human proteins or humanised monoclonal antibodies). The improved use of one of Australia's most expensive commonly used protein drugs, pegylated interferon ribavirin (Peg-IFN-R), could ....Functional Genomics to Predict and Enhance Response to Interferon. The increasing number and huge cost impost of new therapies to health providers, both worldwide and nationally, has not yet resulted in a concomitant increase in strategies to optimise their use. Many of the new therapies are proteins (recombinant human proteins or humanised monoclonal antibodies). The improved use of one of Australia's most expensive commonly used protein drugs, pegylated interferon ribavirin (Peg-IFN-R), could potentially produce savings to the Pharmaceutical Benefits Scheme (PBS), and improve delivery of healthcare to thousands of Australians.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
A Unique Target in the Purine Biosynthesis of the Pathogen Helicobacter pylori. The uptake systems of purine and analogues of the human pathogen Helicobacter pylori will be characterised because they can be utilised to introduce cytotoxic compounds into the cells. The first step in de novo purine biosynthesis of the bacterium is catalysed by two different enzymes, which are components of other biosynthetic pathways. These unique properties make them excellent potential therapeutic targets. Their ....A Unique Target in the Purine Biosynthesis of the Pathogen Helicobacter pylori. The uptake systems of purine and analogues of the human pathogen Helicobacter pylori will be characterised because they can be utilised to introduce cytotoxic compounds into the cells. The first step in de novo purine biosynthesis of the bacterium is catalysed by two different enzymes, which are components of other biosynthetic pathways. These unique properties make them excellent potential therapeutic targets. Their individual combined activities in purine biosynthesis will be characterised in situ and in vitro. Isogenic mutants with inactivated genes encoding for these enzymes will be constructed to investigate their role in the survival of the organism.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
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
Genetic and molecular analysis of long-distance gene silencing in Arabidopsis. Gene silencing is a surveillance mechanism in plants and animals to ensure that all genes are switched on or off at the right time. It is also a defence mechanism against viruses. Perturbation of gene silencing can be a cause of genetic diseases, and conversely, gene silencing has immense potential as a therapeutic tool for correcting genetic diseases and curing viral diseases. When silencing is triggered against a ge ....Genetic and molecular analysis of long-distance gene silencing in Arabidopsis. Gene silencing is a surveillance mechanism in plants and animals to ensure that all genes are switched on or off at the right time. It is also a defence mechanism against viruses. Perturbation of gene silencing can be a cause of genetic diseases, and conversely, gene silencing has immense potential as a therapeutic tool for correcting genetic diseases and curing viral diseases. When silencing is triggered against a gene or virus in plants, genetic signals are transmitted throughout the organism to systemically switch off the specific gene or virus. Expected long-term national/community benefits from understanding gene silencing are wide-ranging, from improved crops through to drugs and gene therapy.Read moreRead less
Identification of the targets of a novel metalloproteinase inhibitor used for the treatment of human head lice. Human head lice are difficult to control. This project examines a new type of ovicidal treatment that prevents louse eggs from hatching. The goal is to understand precisely how this treatment is ovicidal, so that even more effective products might be designed. Beyond the benefits of providing a safe and reliable treatment option for a troublesome pest, the development of this product ....Identification of the targets of a novel metalloproteinase inhibitor used for the treatment of human head lice. Human head lice are difficult to control. This project examines a new type of ovicidal treatment that prevents louse eggs from hatching. The goal is to understand precisely how this treatment is ovicidal, so that even more effective products might be designed. Beyond the benefits of providing a safe and reliable treatment option for a troublesome pest, the development of this product will be a significant step forward for the Australian pharmaceutical industry.Read moreRead less