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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.
Discovery Early Career Researcher Award - Grant ID: DE220100185
Funder
Australian Research Council
Funding Amount
$438,712.00
Summary
Decoding the evolution of killer T cell immunity across human lifetime. The immune system is a potent weapon for protection against pathogens. T cells have a central role as their receptors monitor the body for threats. The thymus (organ) educates receptors to discriminate between healthy and infected cells. Receptor diversity and T cell strength change throughout human life. This project aims to unravel how T cells gain and lose optimal receptors and strength. The aims are to understand 1) The ....Decoding the evolution of killer T cell immunity across human lifetime. The immune system is a potent weapon for protection against pathogens. T cells have a central role as their receptors monitor the body for threats. The thymus (organ) educates receptors to discriminate between healthy and infected cells. Receptor diversity and T cell strength change throughout human life. This project aims to unravel how T cells gain and lose optimal receptors and strength. The aims are to understand 1) The role of thymic education in diversifying receptors 2) Whether gradual loss of thymic education affects receptor diversity 3) The molecular mechanisms underlying T cell strength. The project is essential for understanding how optimal T cell immunity is formed, critical if we wish to harness this to improve healthy aging.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
Role of Pasteurella surface polysaccharides in pathogenesis and immunity. Livestock infections cause major economic losses worldwide. The bacterium Pasteurella multocida causes multiple diseases in a range of livestock, including hemorrhagic septicaemia in cattle and fowl cholera in poultry. Two surface polysaccharide structures, capsule and lipopolysaccharide, are crucial for P. multocida to cause disease. Our data indicate that varying the amount/content of these structures also affects vaccin ....Role of Pasteurella surface polysaccharides in pathogenesis and immunity. Livestock infections cause major economic losses worldwide. The bacterium Pasteurella multocida causes multiple diseases in a range of livestock, including hemorrhagic septicaemia in cattle and fowl cholera in poultry. Two surface polysaccharide structures, capsule and lipopolysaccharide, are crucial for P. multocida to cause disease. Our data indicate that varying the amount/content of these structures also affects vaccine performance. This project aims to identify how the production of these P. multocida structures are controlled and if changes to these structures affect its ability to infect different animals/birds. Using this information, the project aims to develop state-of-the-art livestock vaccines with superior disease coverage.Read moreRead less
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
Novel Babesia proteins and their roles in the pathogenesis of tick fever. This project aims at gaining a deep understanding of the biology of Babesia parasites and how they cause tick fever in cattle. The project expects to discover novel parasite proteins involved in the development and persistence of tick fever and identify their functional role in infection. The main expected outcome is the discovery of parasite proteins that are critical for infection and pathogenesis of cattle tick fever. T ....Novel Babesia proteins and their roles in the pathogenesis of tick fever. This project aims at gaining a deep understanding of the biology of Babesia parasites and how they cause tick fever in cattle. The project expects to discover novel parasite proteins involved in the development and persistence of tick fever and identify their functional role in infection. The main expected outcome is the discovery of parasite proteins that are critical for infection and pathogenesis of cattle tick fever. The findings will contribute to the development of future novel vaccines to control tick fever, with significant economic benefits for the beef and dairy industries worldwide.Read moreRead less
Recognition of lipid antigens by the immune system. T cells are a critical component of the immune system, protecting against a range of pathogens by detecting and responding to foreign molecules. Despite their importance, there is still much to learn about how T cells function. New types of T cells that respond to bacteria-derived lipid molecules, have recently been identified. This project aims to undertake a molecular and functional investigation into lipid-reactive T cells. This will provide ....Recognition of lipid antigens by the immune system. T cells are a critical component of the immune system, protecting against a range of pathogens by detecting and responding to foreign molecules. Despite their importance, there is still much to learn about how T cells function. New types of T cells that respond to bacteria-derived lipid molecules, have recently been identified. This project aims to undertake a molecular and functional investigation into lipid-reactive T cells. This will provide basic fundamental insight into a poorly understood, but crucial, component of the immune system as well as an opportunity to ultimately develop novel lipid-based vaccines.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
All-in-vitro engineering and single molecule analysis of protein complexes. The production and engineering of proteins are key methodologies in life sciences. The current project aims to develop new approaches to accelerate the production and analysis of proteins and to apply them to increase our understanding of the basic mechanisms of cell self-maintenance.