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
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
The toxins of water-borne cyanobacteria: regulation and exploitation of their biosynthesis. Water quality is a major concern in Australia, as is the global need for new natural products with antibiotic activity. The mechanisms by which cyanobacteria produce toxins that reduce the quality of water may very well be the answer to the lack of novel medicinal compounds currently being discovered in nature. Encompassed in this one program are the aims of ameliorating the effects of toxic algal blooms ....The toxins of water-borne cyanobacteria: regulation and exploitation of their biosynthesis. Water quality is a major concern in Australia, as is the global need for new natural products with antibiotic activity. The mechanisms by which cyanobacteria produce toxins that reduce the quality of water may very well be the answer to the lack of novel medicinal compounds currently being discovered in nature. Encompassed in this one program are the aims of ameliorating the effects of toxic algal blooms as well as introducing the means for the design and synthesis of a range of novel bioactive products. The benefits include better water quality and biosafety management options, a new generation of drug design and discovery, and the associated transformation of environmental and medical research and education in Australia.Read moreRead less
A sustainable cellular factory for the production of antibiotics by photosynthetic bacteria. The range and rate of natural product discovery is the limiting factor in developing new pharmaceuticals. Traditional methods for the screening of these compounds or for their chemical synthesis are rapidly becoming inadequate as an increasing number of specific therapies, for cancers and infectious diseases for instance, are required. The research proposed will enable the design and production of "unnat ....A sustainable cellular factory for the production of antibiotics by photosynthetic bacteria. The range and rate of natural product discovery is the limiting factor in developing new pharmaceuticals. Traditional methods for the screening of these compounds or for their chemical synthesis are rapidly becoming inadequate as an increasing number of specific therapies, for cancers and infectious diseases for instance, are required. The research proposed will enable the design and production of "unnatural" products, including novel antibiotics, via combinatorial biosynthesis in photosynthetic microorgansims. The outcomes include graduate student training and Australian innovation in an enormous global market that is awaiting the next generation of medicines and associated pharmaceutical production technologies.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0454052
Funder
Australian Research Council
Funding Amount
$733,595.00
Summary
Tandem Matrix-Assisted Laser Desorption/Ionisation Time-Of-Flight Mass Spectrometer and Robots for High Throughput Proteomics Analysis. This proposal seeks to establish the capacity to perform high-energy tandem mass spectrometry on a high throughput basis, through purchase and coordinated operation of a Matrix-Assisted Laser Desorption/Ionisation - Time of Flight / Time of Flight - Mass Spectrometer and ancillary equipment, to enhance the proteomics expertise, infrastructure and research plans ....Tandem Matrix-Assisted Laser Desorption/Ionisation Time-Of-Flight Mass Spectrometer and Robots for High Throughput Proteomics Analysis. This proposal seeks to establish the capacity to perform high-energy tandem mass spectrometry on a high throughput basis, through purchase and coordinated operation of a Matrix-Assisted Laser Desorption/Ionisation - Time of Flight / Time of Flight - Mass Spectrometer and ancillary equipment, to enhance the proteomics expertise, infrastructure and research plans of a network of institutions from Queensland and New South Wales and their collaborators. Access to such instrumentation is critical to high level achievement in proteomics, a key platform technology for National Research Priorities relating to Frontier Technologies. No comparable instrument currently exists in Australia.Read moreRead less