Molecular characterisation of hypervirulence and the infectious cycle in Clostridium difficile. Gut diseases caused by the bacterium Clostridium difficile are a significant animal and public health problem in Australia and many other countries. This project will allow us to understand how this bacterium causes disease, leading to the development of much needed preventative and treatment strategies for animals and human patients.
Discovery Early Career Researcher Award - Grant ID: DE200100111
Funder
Australian Research Council
Funding Amount
$373,097.00
Summary
Replication and transfer of novel plasmid classes in Acinetobacter. The project aims to reveal basic biology of plasmids found in Acinetobacter baumannii. A. baumannii is a bacterial pathogen that can rapidly acquire resistance to antibiotics, including last-resort antibiotics. In modern strains, acquisition is often mediated by plasmids. On the basis of DNA sequencing data, A. baumannii plasmids are likely to function differently to well-studied plasmids. However, surprisingly little experiment ....Replication and transfer of novel plasmid classes in Acinetobacter. The project aims to reveal basic biology of plasmids found in Acinetobacter baumannii. A. baumannii is a bacterial pathogen that can rapidly acquire resistance to antibiotics, including last-resort antibiotics. In modern strains, acquisition is often mediated by plasmids. On the basis of DNA sequencing data, A. baumannii plasmids are likely to function differently to well-studied plasmids. However, surprisingly little experimental work has been done to evidence this. By combining microbiological and bioinformatics approaches the project expects to generate new knowledge on the mechanisms of replication and transfer of A. baumannii plasmids. This may lead to new targets for strategies to slow and track the spread of antibiotic resistance.Read moreRead less
Signalling pathways for sexual differentiation of apicomplexan parasites. This project aims to study the sexual development of apicomplexan parasites, which cause major diseases in humans, livestock and wildlife, including malaria. Only sexually differentiated cells can survive in the mosquito vector and hence this development is essential for the parasite's life-cycle. This project will employ a new approach that separates female from male parasites, thus enabling new information to be gleaned ....Signalling pathways for sexual differentiation of apicomplexan parasites. This project aims to study the sexual development of apicomplexan parasites, which cause major diseases in humans, livestock and wildlife, including malaria. Only sexually differentiated cells can survive in the mosquito vector and hence this development is essential for the parasite's life-cycle. This project will employ a new approach that separates female from male parasites, thus enabling new information to be gleaned about the development of these parasites. The expected outcomes are an understanding of the mechanisms of sexual differentiation and a functional characterisation of novel sex-specific molecules. This will provide significant benefits, such as pivotal prerequisites for new approaches to parasite intervention.Read moreRead less
A link between antibiotic resistance and bacterial sporulation. This project aims to define the sporulation process in the bacterium Clostridium difficile, and advance our understanding of a link between antibiotic use and sporulation. To survive in hostile environments, some bacteria produce a dormant and resilient cell form called a spore which can survive for many years in unfavourable environments, but our understanding of how this process occurs is limited. This project will provide a deepe ....A link between antibiotic resistance and bacterial sporulation. This project aims to define the sporulation process in the bacterium Clostridium difficile, and advance our understanding of a link between antibiotic use and sporulation. To survive in hostile environments, some bacteria produce a dormant and resilient cell form called a spore which can survive for many years in unfavourable environments, but our understanding of how this process occurs is limited. This project will provide a deeper understanding of the sporulation process and the long-lasting detrimental impact of antibiotic use. The project expects to provide economic benefits, reduce environmental microbial contamination and contribute to better health of animals and humans.Read moreRead less
Bacterial poly-histidine triad proteins. The poly-histidine triad (Pht) proteins are a poorly characterised family of surface proteins expressed by the genus Streptococcus and other Gram-positive genera. Recent studies suggest an important role for Pht proteins in survival of these bacteria in low zinc (Zn) environments. The project hypothesis is that Pht proteins specifically recruit Zn from the extracellular environment and somehow make it available to ATP binding cassette (ABC) transport syst ....Bacterial poly-histidine triad proteins. The poly-histidine triad (Pht) proteins are a poorly characterised family of surface proteins expressed by the genus Streptococcus and other Gram-positive genera. Recent studies suggest an important role for Pht proteins in survival of these bacteria in low zinc (Zn) environments. The project hypothesis is that Pht proteins specifically recruit Zn from the extracellular environment and somehow make it available to ATP binding cassette (ABC) transport systems located in the bacterial plasma membrane, beneath the cell wall, facilitating Zn uptake by the bacterium. The aim of this project is to conduct comprehensive molecular characterization of the interactions between Pht proteins, Zn and ABC transporters, and the role of the histidine triad motifs in these interactions.Read moreRead less
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
Discovery Early Career Researcher Award - Grant ID: DE120101730
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Targeting cell death pathways in parasites. Schistosomiasis is a disease caused by parasitic worms. Due to the potential for drug resistance, new drugs are needed. This project aims to identify the components needed for parasite survival based on a cell death pathway in schistosomes. Neutralising the activities of these proteins should cause parasite death, providing a new treatment strategy.
Safety in numbers: Bacterial aggregation and adaptation to oxidative stress. This project is a new collaboration which links two molecular microbiologists with the complementary skills required to make new insights into the molecular processes that underpin bacterial aggregation and biofilm formation. Biofilms are of immense significance in medical, industrial and environmental settings and so the fundamental information gained from this project will have wider relevance to the field of microbio ....Safety in numbers: Bacterial aggregation and adaptation to oxidative stress. This project is a new collaboration which links two molecular microbiologists with the complementary skills required to make new insights into the molecular processes that underpin bacterial aggregation and biofilm formation. Biofilms are of immense significance in medical, industrial and environmental settings and so the fundamental information gained from this project will have wider relevance to the field of microbiology. An outcome of this proposal will be fundamental knowledge about the production of surface adhesins that will form the basis for rational treatment of disease in the future. Prevention of aggregation and biofilm formation would make bacterial populations more susceptible to conventional antibiotic treatment.Read moreRead less
Understanding the dynamics of malaria infection. Malaria infection kills around one million patients each year and this project involves an interdisciplinary team who will directly measure how the parasite grows and is killed by the immune system. A better understanding of parasite growth and control will help develop better drugs therapy and vaccination for this important infection.
Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently ....Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently glycosylation of Gram-negative bacterial proteins was not thought to occur, however our recent work with these bacteria, and other groups studying Pseudomonas and Campylobacter, have shown that this process may be widespread. In our previous studies, we have identified and analysed a number of genes involved in pili glycosylation, in bacteria, which make known sugar structures. We have used this information to developed models for how the biochemistry and physiology of the glycosylation system may work. With a well-established structure and many genes already identified, glycosylation in Neisseria represents the best available model system to study this novel and important process. In the proposed study we describe experiments planned to test our models and reveal the molecular detail of this process. This study could lead to major advances in our understanding of this process and, when understood, may have future applications in biotechnology.Read moreRead less