The role of dysregulated signalling by TORC1 in mitochondrial disease. The mitochondria are tiny subcellular compartments responsible for producing over 90 per cent of the cell's energy. Mitochondrial defects feature both in genetic diseases that directly affect the mitochondria and in most neurodegenerative diseases. These incurable diseases are expected to eclipse cancer as the second major cause of death worldwide by 2040. Using a simple model organism, Dictyostelium, previous research showed ....The role of dysregulated signalling by TORC1 in mitochondrial disease. The mitochondria are tiny subcellular compartments responsible for producing over 90 per cent of the cell's energy. Mitochondrial defects feature both in genetic diseases that directly affect the mitochondria and in most neurodegenerative diseases. These incurable diseases are expected to eclipse cancer as the second major cause of death worldwide by 2040. Using a simple model organism, Dictyostelium, previous research showed that dysregulated intracellular signalling by a cellular energy-sensing alarm protein is responsible for diverse cellular pathologies in mitochondrially diseased cells. This project will determine the role in these pathways of a second cellular stress-sensing protein complex, TORC1. New treatment possibilities may emerge.Read moreRead less
Harnessing horizontal gene transfer for sustainable nitrogen fixation. This project aims to investigate natural deoxyribonucleic acid (DNA) transfer from nitrogen-fixing bacteria to indigenous bacteria in Australian soils. This project expects to significantly expand our understanding of the molecular and genetic factors contributing to the evolution of ineffective symbiotic bacteria in these soils. An expected outcome of this project is support development of genetically stable bacterial inocul ....Harnessing horizontal gene transfer for sustainable nitrogen fixation. This project aims to investigate natural deoxyribonucleic acid (DNA) transfer from nitrogen-fixing bacteria to indigenous bacteria in Australian soils. This project expects to significantly expand our understanding of the molecular and genetic factors contributing to the evolution of ineffective symbiotic bacteria in these soils. An expected outcome of this project is support development of genetically stable bacterial inoculants for use in agriculture. Inoculation of legumes with nitrogen-fixing symbiotic bacteria is a cheap and environmentally-friendly alternative to chemical fertilisers and contributes $3-4 billion per annum to Australian economy.Read moreRead less
Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basi ....Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basis and evolution of this important polymorphism. O-antigens are used for typing Shigella and also elicit strong immunity. The molecular data will help establish DNA based typing and vaccine development.Read moreRead less
Evolutionary and ecological complexity in an experimentally controlled environment. Understanding the capacity and mechanism of microbial evolution provides the framework for developing new strategies for preventing infectious disease. If we know how evolution works, it will be possible to hamper the capacity to evolve as a mechanism of preventing new diseases and controlling existing ones. This project will provide a mechanistic description of evolution in real time under controlled conditions. ....Evolutionary and ecological complexity in an experimentally controlled environment. Understanding the capacity and mechanism of microbial evolution provides the framework for developing new strategies for preventing infectious disease. If we know how evolution works, it will be possible to hamper the capacity to evolve as a mechanism of preventing new diseases and controlling existing ones. This project will provide a mechanistic description of evolution in real time under controlled conditions. This detailed information will be used in the education of the public and in debates about evolution. The project will also train at least five students in molecular and evolutionary microbiology, essential for facing future challenges.
Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190101053
Funder
Australian Research Council
Funding Amount
$421,656.00
Summary
Archaeal vesicles: new insights into viral evolution and DNA transfer. This project aims to determine the basis for plasmid and membrane vesicle generation and DNA transfer at the cellular and molecular level. Recent discovery of plasmid vesicles, which transfer plasmid DNA between host cells using viral capsid-like membrane vesicles, suggests they may be an evolutionary precursor for virus particles. The expected project outcomes include the first substantive characterisation of membrane vesicl ....Archaeal vesicles: new insights into viral evolution and DNA transfer. This project aims to determine the basis for plasmid and membrane vesicle generation and DNA transfer at the cellular and molecular level. Recent discovery of plasmid vesicles, which transfer plasmid DNA between host cells using viral capsid-like membrane vesicles, suggests they may be an evolutionary precursor for virus particles. The expected project outcomes include the first substantive characterisation of membrane vesicles in the phylum Euryarchaeota, how plasmid vesicles are generated and transmitted, and new insights into how viruses may evolve. This may lead to new avenues for preventing viral transmission and supporting development of new and improved applications biotechnology and the safe delivery of vaccines or genes in animals and humans.Read moreRead less
Exploiting microbial metabolites to understand fungal biology. The project aims to investigate the principles of hyphal growth in fungi, by studying the mechanisms of action of a bacteria-derived compound that inhibits hyphae. Changing cell shape between yeast and hyphae is a prototype developmental switch enabling fungi to escape stressful environments, while hyphal invasion promotes fungal infections of animals and plants that endanger food security and biodiversity. By using interdisciplinary ....Exploiting microbial metabolites to understand fungal biology. The project aims to investigate the principles of hyphal growth in fungi, by studying the mechanisms of action of a bacteria-derived compound that inhibits hyphae. Changing cell shape between yeast and hyphae is a prototype developmental switch enabling fungi to escape stressful environments, while hyphal invasion promotes fungal infections of animals and plants that endanger food security and biodiversity. By using interdisciplinary approaches of microbiology and chemistry, the expected outcomes are to generate deep knowledge of an important microbial process and how it could be modulated, characterise a new bacterial compound and build research capacity at the nexus of biology and chemistry to benefit discoveries in academia and industry.Read moreRead less
Exploring and harnessing mobile DNA: Integrons and gene cassettes in natural populations of Bacteria. Bacteria respond rapidly to environmental change by acquiring new genes via lateral gene transfer. The integron/gene cassette system is important in this process as it is found in an increasingly broad range of bacteria. As well as being common, we have shown that the system is associated with an unprecedented amount of genetic novelty. Here we explore the limits of this novelty and its con ....Exploring and harnessing mobile DNA: Integrons and gene cassettes in natural populations of Bacteria. Bacteria respond rapidly to environmental change by acquiring new genes via lateral gene transfer. The integron/gene cassette system is important in this process as it is found in an increasingly broad range of bacteria. As well as being common, we have shown that the system is associated with an unprecedented amount of genetic novelty. Here we explore the limits of this novelty and its contribution to bacterial evolution. In so doing we have the potential to identify new commercially important genes and develop enabling technologies. These discoveries could produce beneficial outcomes for exploitation by a wide range of Australian industries.Read moreRead less
Defining how bacteriophage shape the biofilm lifecycle of bacteria. Bacteriophages are viruses that infect bacteria and they represent a significant selective pressure that drives the evolution of bacteria. We will study the genetic mechanisms by which genes encoded by a bacteriophage can contribute to increased survival of bacteria in the environment.
THE BIOLOGY OF COLD ADAPTED EXTREMOPHILES: AN INTEGRATED GENOMIC-PROTEIN ANALYSIS APPROACH. Extremophiles are microorganisms that can thrive in otherwise inhospitable environments. Most extremophiles are Archaea; an order of life separate from Bacteria and Eucaryotes. The project will generate the first genome sequence that was initiated in Australia, and the first genome sequence of any cold adapted organism. Associated functional studies include global analyses of protein expression (proteo ....THE BIOLOGY OF COLD ADAPTED EXTREMOPHILES: AN INTEGRATED GENOMIC-PROTEIN ANALYSIS APPROACH. Extremophiles are microorganisms that can thrive in otherwise inhospitable environments. Most extremophiles are Archaea; an order of life separate from Bacteria and Eucaryotes. The project will generate the first genome sequence that was initiated in Australia, and the first genome sequence of any cold adapted organism. Associated functional studies include global analyses of protein expression (proteomics) and mRNA expression using micro-arrays, and work targeted at RNA binding proteins and protein folding systems involved in the thermally sensitive process of protein synthesis. The nature and scope of the work will impact on fundamental cellular processes and provide enormous innovative biotechnological potential.Read moreRead less
Mechanisms of action and expression of bioactive compounds produced by the surface associated marine bacterium Pseudoalteromonas tunicata. The marine surface-associated bacterium Pseudoalteromonas tunicata produces a number of bioactive metabolites that inhibit the colonisation and growth of common fouling organisms such as bacteria, fungi, algae and invertebrate larvae. The antibacterial and antifungal compounds represent novel metabolites active against a remarkable range of both medically and ....Mechanisms of action and expression of bioactive compounds produced by the surface associated marine bacterium Pseudoalteromonas tunicata. The marine surface-associated bacterium Pseudoalteromonas tunicata produces a number of bioactive metabolites that inhibit the colonisation and growth of common fouling organisms such as bacteria, fungi, algae and invertebrate larvae. The antibacterial and antifungal compounds represent novel metabolites active against a remarkable range of both medically and agriculturally important bacteria and fungi. This project aims to explore the identity, mode of action and regulation of expression of these compounds. This research proposal addresses several significant biological concepts and will lead to the development of novel environmentally friendly antifouling and antimicrobial technologies.Read moreRead less