YhcB, a crucial player in the control of bacterial cell envelope biogenesis. All life depends on a cell envelope to enclose the chemical reactions that make life possible. But how do cell envelopes grow? How each component of the cell envelope is incorporated into the envelope at the right amount and in the right time to prevent cell death, has been a longstanding question in bacteriology. Using a unique combination of high through put genetic screens and biochemical approaches, this project wil ....YhcB, a crucial player in the control of bacterial cell envelope biogenesis. All life depends on a cell envelope to enclose the chemical reactions that make life possible. But how do cell envelopes grow? How each component of the cell envelope is incorporated into the envelope at the right amount and in the right time to prevent cell death, has been a longstanding question in bacteriology. Using a unique combination of high through put genetic screens and biochemical approaches, this project will characterise a key regulator of cell envelope growth in Gram-negative bacteria. Knowledge arising from this research will provide insight into a fundamental process in bacteria, will develop new technology to probe protein interactions, and will provide novel avenues to solve infection in plants, humans and animals.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL210100258
Funder
Australian Research Council
Funding Amount
$3,331,707.00
Summary
Understanding how bacteria adapt and function in the complex gut ecosystem. This project aims to investigate the role of the gut ecosystem in defining the structure and function of microbes. Given that one of the current challenges in microbiology is our inability to study individual microbes directly from complex, multi-microbial niches, this project aims to develop multidisciplinary methods to study microbes in their native state, to understand how they adapt to live in the gut. This understan ....Understanding how bacteria adapt and function in the complex gut ecosystem. This project aims to investigate the role of the gut ecosystem in defining the structure and function of microbes. Given that one of the current challenges in microbiology is our inability to study individual microbes directly from complex, multi-microbial niches, this project aims to develop multidisciplinary methods to study microbes in their native state, to understand how they adapt to live in the gut. This understanding should provide fundamental insights into adaptation mechanisms that lead to bacterial proliferation, disease and antibiotic resistance. As well as enhancing interdisciplinary collaborations, this work should provide economic benefits by contributing to improved gut health of animals, and more efficient food production.Read moreRead less
Creation of a super-resolution map of the bacterial cytokinesis machinery . Cell division is a fundamental process essential for life. Yet our understanding of this process on a molecular level is limited, mostly hampered by the inability to visualize the different components of the division machinery inside these tiny cells with adequate resolution. To overcome this barrier, capitalizing on recent advancements in imaging and molecular technologies combined with innovative engineering, this proj ....Creation of a super-resolution map of the bacterial cytokinesis machinery . Cell division is a fundamental process essential for life. Yet our understanding of this process on a molecular level is limited, mostly hampered by the inability to visualize the different components of the division machinery inside these tiny cells with adequate resolution. To overcome this barrier, capitalizing on recent advancements in imaging and molecular technologies combined with innovative engineering, this project aims to create a spatial and temporal map of the division machinery inside bacterial cells at unprecedented resolution. The expected outcomes are new knowledge on the mechanism of bacterial division and technological advances in biological imaging, informing applications in a wide variety of sectors.Read moreRead less
Breaking through the Gram-negative cell barrier. This project aims to develop fundamental knowledge of the cell envelope in Gram-negative bacteria, which functions as a permeability barrier to small molecules. Combining innovative functional genomics with biochemistry, this project will determine how small molecules can pass across the cell envelope, and the chemical properties that they need to do so. Some Gram-negative bacteria are human pathogens and cause serious infections, whereas others a ....Breaking through the Gram-negative cell barrier. This project aims to develop fundamental knowledge of the cell envelope in Gram-negative bacteria, which functions as a permeability barrier to small molecules. Combining innovative functional genomics with biochemistry, this project will determine how small molecules can pass across the cell envelope, and the chemical properties that they need to do so. Some Gram-negative bacteria are human pathogens and cause serious infections, whereas others are used in biotechnology for biosynthetic chemical production or bioremediation. This project expects to help the future development of new antibiotics and assist in the design of strains to be used in biotechnological applications.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
Unlocking bacterial shapeshifting and its role in antimicrobial resistance. This project aims to combine advanced imaging with innovative microfluidics to identify how microbial shapeshifting can be exploited as a target for new antimicrobials. Infections that are hard to treat due to increasing antimicrobial resistance not only have an enormous, global impact on mammalian health, including livestock and humans, but also carry a growing economic burden. Advanced understanding of microbial life c ....Unlocking bacterial shapeshifting and its role in antimicrobial resistance. This project aims to combine advanced imaging with innovative microfluidics to identify how microbial shapeshifting can be exploited as a target for new antimicrobials. Infections that are hard to treat due to increasing antimicrobial resistance not only have an enormous, global impact on mammalian health, including livestock and humans, but also carry a growing economic burden. Advanced understanding of microbial life can propel urgently needed progress this area. Specifically, the project outcomes are expected to aid the development of next generation antibiotics. The new fundamental knowledge should also benefit translational prevention, identification and management efforts of a rising national and global health threat.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
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
The molecular mechanism of bacterial ABC toxins. This project aims to establish that the ABC family of bacterial protein toxins, the main virulence factors in many species of naturally-occurring bacterial pathogens of insect pests, represent a protein machinery that cells and other organisms may use to deliver bioactive proteins to specific cells. ABC toxins are the main virulence factors in many species of naturally-occurring bacterial pathogens of insect pests. This project aims to establish t ....The molecular mechanism of bacterial ABC toxins. This project aims to establish that the ABC family of bacterial protein toxins, the main virulence factors in many species of naturally-occurring bacterial pathogens of insect pests, represent a protein machinery that cells and other organisms may use to deliver bioactive proteins to specific cells. ABC toxins are the main virulence factors in many species of naturally-occurring bacterial pathogens of insect pests. This project aims to establish that ABC toxins represent a new protein machinery that may be used more widely throughout cells and other organisms to direct the intercellular delivery of bioactive proteins in a highly cell-specific manner. The project expects these findings to enable the development of biopesticides based on ABC toxins, and generic intercellular protein delivery devices for biotechnological use.Read moreRead less
The mechanistic basis of tropism in an insecticidal pore-forming toxin . This project aims to answer a fundamental question regarding the mechanism of a recently discovered family of insecticidal protein complexes - how do these pore-forming proteins recognise and target specific hosts? The project will use an innovative, cross-disciplinary approach to determine the mechanisms of cellular recognition and uptake on a molecular scale. These outcomes have the potential to influence the use of ABC t ....The mechanistic basis of tropism in an insecticidal pore-forming toxin . This project aims to answer a fundamental question regarding the mechanism of a recently discovered family of insecticidal protein complexes - how do these pore-forming proteins recognise and target specific hosts? The project will use an innovative, cross-disciplinary approach to determine the mechanisms of cellular recognition and uptake on a molecular scale. These outcomes have the potential to influence the use of ABC toxins in many areas of biotechnology, delivering benefits including the development of new bioinsecticides for pest control and crop protection as well as in the development of bespoke protein delivery devices which may find use in biotechnological and therapeutic applications.Read moreRead less