Discovery Early Career Researcher Award - Grant ID: DE180100929
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Stronger together: understanding antibiotic synergy on a molecular level. This project aims to use genomics-based approaches to answer fundamental questions about how antibiotic synergy works. Antibiotic combination therapy presents an opportunity to revive the use of antibiotics in otherwise resistant bacteria, yet currently there is little understanding of the molecular mechanisms underlying antibiotic synergy. Studies indicate that additional mechanisms of action (MOA) occur during synergist ....Stronger together: understanding antibiotic synergy on a molecular level. This project aims to use genomics-based approaches to answer fundamental questions about how antibiotic synergy works. Antibiotic combination therapy presents an opportunity to revive the use of antibiotics in otherwise resistant bacteria, yet currently there is little understanding of the molecular mechanisms underlying antibiotic synergy. Studies indicate that additional mechanisms of action (MOA) occur during synergistic killing beyond those of the original antibiotics. This project will identify genes involved in multiple synergistic treatments and determine how bacterial cells gain resistance. The synergy-specific MOA identified also represent an untapped reservoir of primary drug targets.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL210100071
Funder
Australian Research Council
Funding Amount
$3,246,000.00
Summary
“L-form” bacteria: basic science, antibiotics, evolution and biotechnology. This Fellowship addresses key gaps in knowledge about cell wall deficient bacteria called L-forms: an altered state of bacteria with intriguing properties both structurally and functionally. The main aims of the research program are to improve our understanding of the basic biology of L-forms and employ them as tools in several important ways: for understanding the mechanisms of cell wall synthesis and how antibiotics wo ....“L-form” bacteria: basic science, antibiotics, evolution and biotechnology. This Fellowship addresses key gaps in knowledge about cell wall deficient bacteria called L-forms: an altered state of bacteria with intriguing properties both structurally and functionally. The main aims of the research program are to improve our understanding of the basic biology of L-forms and employ them as tools in several important ways: for understanding the mechanisms of cell wall synthesis and how antibiotics work, as models for early steps in the evolution of cellular life, and as a significant new platform for the production of proteins and fine chemicals. Outcomes and benefits include improved understanding of how to generate new antibiotics, and the development of new platforms for Australian biotechnology and biocommerce.Read moreRead less
Cellular Gene Regulation Networks. The benefit to Australia will be scientific in terms of providing an understanding of how cells integrate transcriptional control systems and the networks that are involved. This will inform research on folate deficiency and aberrant human development and towards identifying genes that are important in improving efficiency of microbial fermentations. Additional and more practical major benefits will follow from the development of tools to analyse interaction ....Cellular Gene Regulation Networks. The benefit to Australia will be scientific in terms of providing an understanding of how cells integrate transcriptional control systems and the networks that are involved. This will inform research on folate deficiency and aberrant human development and towards identifying genes that are important in improving efficiency of microbial fermentations. Additional and more practical major benefits will follow from the development of tools to analyse interactions between control systems, including software of value to the research community. The work will provide postgraduate students with major training in up-to-date genomic technologies, and in the interface between application of bioinformatics and experimental science.
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ARC Centre of Excellence in Synthetic Biology. The ARC Centre of Excellence in Synthetic Biology (CoESB) will provide the technical innovation critical for Australia to develop a vibrant bioeconomy building on the nation’s strengths in agriculture. For thousands of years we have used microbes to create bread, wine, cheese. Now, our Centre will pioneer new approaches to the design of synthetic microbes, enabling the development of custom-designed microbial communities, synthetic organelles and ne ....ARC Centre of Excellence in Synthetic Biology. The ARC Centre of Excellence in Synthetic Biology (CoESB) will provide the technical innovation critical for Australia to develop a vibrant bioeconomy building on the nation’s strengths in agriculture. For thousands of years we have used microbes to create bread, wine, cheese. Now, our Centre will pioneer new approaches to the design of synthetic microbes, enabling the development of custom-designed microbial communities, synthetic organelles and new to nature biological pathways and enzymes. CoESB will combine engineering with molecular biology to design and construct novel biological systems that can convert biomass from agriculture or waste streams to biofuel, bioplastics and other high-value chemicals.Read moreRead less
Elucidating the genetic basis of newly evolved metabolic functions in yeast. Elucidating the genetic basis of newly evolved metabolic functions in yeast. This project intends to research how complex metabolic pathways originate and evolve. This project will use cutting edge genome sequencing and molecular techniques to elucidate the heritable genetic basis of Baker’s yeast, which has been the selectively evolved to use xylose as a sole carbon source: something vital for second generation biofuel ....Elucidating the genetic basis of newly evolved metabolic functions in yeast. Elucidating the genetic basis of newly evolved metabolic functions in yeast. This project intends to research how complex metabolic pathways originate and evolve. This project will use cutting edge genome sequencing and molecular techniques to elucidate the heritable genetic basis of Baker’s yeast, which has been the selectively evolved to use xylose as a sole carbon source: something vital for second generation biofuel production that wild yeast cannot do. This project will combine detailed molecular characterisation of highly adapted yeast strains with a novel "molecular palaeontology" approach to trace the evolutionary process and identify functionally significant loci under selection. Detailed characterisation of this trait will accelerate the development of future yeast strains and test fundamental evolutionary theories.Read moreRead less
Evolution and ecology of integron gene cassettes: exploring the protein universe. Bacteria rapidly adapt to new conditions by sharing diverse genes via lateral genetic transfer, best illustrated by the spread of antibiotic resistance. This study will characterise mobile genes, discovering new gene families and proteins, and will expand existing knowledge of bacterial evolution.
Metabolic engineering of Zymomonas mobilis for higher value fermentation products. This project will provide an opportunity to revolutionise the Australian chemical and sugar industries. Unlike the traditional methods of the petrochemical industry, bioconversion of carbohydrates to chemicals such as succinic acid via fermentation is cosiderably environmental friendly. For the sugar industry this project will provide an opportunity to produce not only conventional sugar products but also high val ....Metabolic engineering of Zymomonas mobilis for higher value fermentation products. This project will provide an opportunity to revolutionise the Australian chemical and sugar industries. Unlike the traditional methods of the petrochemical industry, bioconversion of carbohydrates to chemicals such as succinic acid via fermentation is cosiderably environmental friendly. For the sugar industry this project will provide an opportunity to produce not only conventional sugar products but also high value commodities via the process integration of succinic acid production using agricultural residues such as bagasse. This will contribute to significant levels of job creation in Australia, and further benefits will be that such products will be important both for import replacement and export potential.Read moreRead less
Metabolic engineering to develop recombinant Zymomonas mobilis for the production of fuel ethanol and fermentation chemicals. This project will provide an opportunity to revolutionise the Australian chemical and sugar industries. Unlike the traditional methods of the petrochemical industry, bioconversion of carbohydrates to chemicals, such as succinic acid via fermentation is more considerably environmentally friendly. For the sugar industry this project will provide an opportunity to produce no ....Metabolic engineering to develop recombinant Zymomonas mobilis for the production of fuel ethanol and fermentation chemicals. This project will provide an opportunity to revolutionise the Australian chemical and sugar industries. Unlike the traditional methods of the petrochemical industry, bioconversion of carbohydrates to chemicals, such as succinic acid via fermentation is more considerably environmentally friendly. For the sugar industry this project will provide an opportunity to produce not only conventional sugar products but also high value commodities via the process integration of succinic acid production using agricultural residues, such as bagasse. This will contribute to significant levels of job creation in Australia, with the further benefit that such products will be important for both import replacement and export potential.Read moreRead less
Exploration of a mechanistic link between eukaryotic transcription and translation. Gene transcription is functionally coupled to other aspects of eukaryotic mRNA metabolism, emphasizing a need for integrated approaches to analyse the gene expression pathway. We have shown in previous work that yeast cells, when responding to external stimuli, show a tight correlation between changes in the transcriptome composition and homodirectional alterations in the translation state of mRNAs. This phenomen ....Exploration of a mechanistic link between eukaryotic transcription and translation. Gene transcription is functionally coupled to other aspects of eukaryotic mRNA metabolism, emphasizing a need for integrated approaches to analyse the gene expression pathway. We have shown in previous work that yeast cells, when responding to external stimuli, show a tight correlation between changes in the transcriptome composition and homodirectional alterations in the translation state of mRNAs. This phenomenon of ?potentiation? may serve to amplify signal-induced changes in the transcriptome at the translational level. This project will begin to unravel the molecular mechanisms underlying potentiation using experiments designed to distinguish between transcription- and translation-driven mechanisms.Read moreRead less
The biology of integrons and their role in bacterial adaptation. Bacteria evolve in ways that animals and plants do not. One of the tools available is the ability to share genes amongst individuals in a community. One example of this is the very rapid spread of antibiotic resistance genes in pathogens. Here we will be studying a genetic element that greatly contributes to this horizontal spread of genes. This will lead to a better understanding of how bacteria work, the direct benefits of whic ....The biology of integrons and their role in bacterial adaptation. Bacteria evolve in ways that animals and plants do not. One of the tools available is the ability to share genes amongst individuals in a community. One example of this is the very rapid spread of antibiotic resistance genes in pathogens. Here we will be studying a genetic element that greatly contributes to this horizontal spread of genes. This will lead to a better understanding of how bacteria work, the direct benefits of which includes the discovery of new pathways and genes for the biotechnology industry and greater understanding of how bacteria cause disease in us, other animals and in commercial crops.Read moreRead less