Phase-variable epigenetic regulators in bacterial veterinary pathogens. This project aims to identify phasevarion regulated genes in the major bacterial swine pathogens Streptococcus suis and Actinobacillus pleuropneumoniae. Both species contain randomly switching epigenetic regulators that control expression of multiple genes by epigenetic mechanisms. Identifying phasevarion controlled genes will inform and direct future vaccine development for important livestock species.
Structural Characterisation of the Type IX Secretion System. The Type IX Secretion System present in diverse bacteria of veterinary, agricultural, environmental and industrial importance enables effector proteins to be secreted and attached to the cell surface where they contribute to disease pathogenesis or degrade biopolymers of commercial interest. This project aims to determine the structure and assembly mechanism of this complex secretion nanomachine comprising 15 different proteins using s ....Structural Characterisation of the Type IX Secretion System. The Type IX Secretion System present in diverse bacteria of veterinary, agricultural, environmental and industrial importance enables effector proteins to be secreted and attached to the cell surface where they contribute to disease pathogenesis or degrade biopolymers of commercial interest. This project aims to determine the structure and assembly mechanism of this complex secretion nanomachine comprising 15 different proteins using state of the art microscopy. Knowledge of the structure will greatly enhance our understanding of secretion mechanisms and our ability to both inhibit the system to treat disease in animals or manipulate the system for industrial applications providing future economic and environmental benefits to our nation.Read moreRead less
Slipping out unnoticed: a new bacterial lipoprotein transport system. Worldwide markets for biotechnology-derived products are projected to grow to at least $50 billion per year for the next 10 years. The cornerstone of biotechnology is the production of proteins. The applicant has discovered a new pathway for protein production in bacteria. The primary objective of this project is to use a diverse array of biochemical and biophysical techniques to understand how this new protein production pl ....Slipping out unnoticed: a new bacterial lipoprotein transport system. Worldwide markets for biotechnology-derived products are projected to grow to at least $50 billion per year for the next 10 years. The cornerstone of biotechnology is the production of proteins. The applicant has discovered a new pathway for protein production in bacteria. The primary objective of this project is to use a diverse array of biochemical and biophysical techniques to understand how this new protein production platform works. We will also assess this new pathway for the production of proteins of interest to the biotechnology sector. This project expects to determine how this system can be exploited for use in the growing Australian bioeconomy.Read moreRead less
Autotransporter folding: insights advancing recombinant protein production. Imagine a world in which any protein could be produced using a single production platform. This project aims to make this a reality by reengineering autotransporters, a large family of bacterial virulence factors with a modular structure that makes them amenable to rational design. The project plans to examine the structures and folding behaviour of autotransporters and reengineered derivatives fused to target heterologo ....Autotransporter folding: insights advancing recombinant protein production. Imagine a world in which any protein could be produced using a single production platform. This project aims to make this a reality by reengineering autotransporters, a large family of bacterial virulence factors with a modular structure that makes them amenable to rational design. The project plans to examine the structures and folding behaviour of autotransporters and reengineered derivatives fused to target heterologous proteins using biochemical, biophysical, and structural methods. It is expected that this project will provide fundamental insights into factors that dictate autotransporter folding and stability, which may enhance recombinant protein production and drive discovery of strategies to prevent autotransporter-mediated infection.Read moreRead less
Bacterial vesicles transport their bioactive cargo to the host nucleus. This project aims to investigate how bacterial membrane vesicles transport their cargo to the nucleus of cells and its impact on host cell functions. Bacteria use membrane vesicles as a means of communication with the host, but the full extent of their effects on host cells has yet to be fully elucidated. This project expects to generate new knowledge in the field using cutting-edge imaging and molecular biology approaches. ....Bacterial vesicles transport their bioactive cargo to the host nucleus. This project aims to investigate how bacterial membrane vesicles transport their cargo to the nucleus of cells and its impact on host cell functions. Bacteria use membrane vesicles as a means of communication with the host, but the full extent of their effects on host cells has yet to be fully elucidated. This project expects to generate new knowledge in the field using cutting-edge imaging and molecular biology approaches. The work should provide significant benefits, particularly towards the development of membrane vesicles in gene therapy, gene editing and other applications. Read moreRead less
Unravelling small RNA regulatory networks to target and control bacteria. Small RNA (sRNA) molecules are critical regulators of bacterial gene expression. These molecules control important phenotypes in the Gram-negative veterinary pathogen Pasteurella multocida. This project aims to identify the range of P. multocida sRNAs and to show how expression of these molecules changes under various growth conditions. Specifically, this project endeavours: to identify the mRNA targets of the sRNAs; to id ....Unravelling small RNA regulatory networks to target and control bacteria. Small RNA (sRNA) molecules are critical regulators of bacterial gene expression. These molecules control important phenotypes in the Gram-negative veterinary pathogen Pasteurella multocida. This project aims to identify the range of P. multocida sRNAs and to show how expression of these molecules changes under various growth conditions. Specifically, this project endeavours: to identify the mRNA targets of the sRNAs; to identify the mechanisms of sRNA-mRNA interaction; to build systems-biology models that describe the sRNA regulatory circuits; to design inhibitors capable of disrupting critical sRNA-mRNA interactions; and to use the new inhibitors to modulate specific phenotypes. The ability to precisely manipulate sRNA regulatory circuits could allow fine control of bacterial phenotypes and could be widely applicable.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230100700
Funder
Australian Research Council
Funding Amount
$429,449.00
Summary
A novel bacterial secretion system for applications in nanobiotechnology. This project aims to characterise a new molecular machine, called the S-Pump. Molecular machines drive the complex biology in all cells and are an exciting area of translational research, with broad potential for industrial applications. This project expects to provide fundamental insights into how bacterial S-Pumps contribute to antimicrobial resistance and enhancing food production. Expected outcomes include new tools fo ....A novel bacterial secretion system for applications in nanobiotechnology. This project aims to characterise a new molecular machine, called the S-Pump. Molecular machines drive the complex biology in all cells and are an exciting area of translational research, with broad potential for industrial applications. This project expects to provide fundamental insights into how bacterial S-Pumps contribute to antimicrobial resistance and enhancing food production. Expected outcomes include new tools for molecular machine discovery and identification of ways to adapt molecular machines for biotechnological applications. This work should enhance Australia-UK ties through collaboration, provide benefits toward nanobiotechnology and economic benefits through more efficient food production.Read moreRead less
Characterising O-linked glycosylation across Burkholderia. Protein glycosylation, the chemical addition of sugars to proteins, enables the augmentation of protein properties. Across the Burkholderia genus we have shown O-linked glycosylation is both conserved as well as essential for bacterial fitness. Yet, we have little understanding of how glycosylation modulates the proteome of this genus. This project aims to characterise the glycoproteomes of Burkholderia species and track the impact of gl ....Characterising O-linked glycosylation across Burkholderia. Protein glycosylation, the chemical addition of sugars to proteins, enables the augmentation of protein properties. Across the Burkholderia genus we have shown O-linked glycosylation is both conserved as well as essential for bacterial fitness. Yet, we have little understanding of how glycosylation modulates the proteome of this genus. This project aims to characterise the glycoproteomes of Burkholderia species and track the impact of glycosylation on both the proteome and protein stability. By understanding how glycosylation shapes the proteome we will gain a greater understanding of the role of bacterial glycosylation in Burkholderia physiology as well as how we may better utilise microbial glycosylation for glycoprotein production.Read moreRead less
Antibacterial Material Design via Mechanism-Based Mathematical Modelling. This Project aims to provide new rules for the design of novel polymer materials with antibacterial properties by employing mechanism-based mathematical modelling.
This Project expects to generate new understanding of those mechanisms which underpin the antibacterial activity of these materials, how bacteria respond to these through metabolic changes and emergence of resistance.These rules will govern material design to yi ....Antibacterial Material Design via Mechanism-Based Mathematical Modelling. This Project aims to provide new rules for the design of novel polymer materials with antibacterial properties by employing mechanism-based mathematical modelling.
This Project expects to generate new understanding of those mechanisms which underpin the antibacterial activity of these materials, how bacteria respond to these through metabolic changes and emergence of resistance.These rules will govern material design to yield new antibacterial materials with improved properties.
Expected outcomes of this project may be a novel mechanism-based mathematical model that will enable the next-generation of antibacterial materials.
This outcome will help address the increasing economic and social burden of antibiotic drug resistance in Australia.
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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