Mechanism of action of a novel multifunctional bacterial secretion system. This project aims to examine the functional role of holin/lysin secretion systems in the complex lifestyles of important animal bacterial pathogens. This project will generate new knowledge in how bacteria interact with each other, the environment or their hosts through the secretion of proteins or other particles. The results of this research will provide a deeper understanding of the multifunctional roles that these un ....Mechanism of action of a novel multifunctional bacterial secretion system. This project aims to examine the functional role of holin/lysin secretion systems in the complex lifestyles of important animal bacterial pathogens. This project will generate new knowledge in how bacteria interact with each other, the environment or their hosts through the secretion of proteins or other particles. The results of this research will provide a deeper understanding of the multifunctional roles that these unusual secretion systems play and how they contribute to niche adaptation and disease. New insights will lead to identifying targets for future veterinary disease interventions or biotechnological applications.Read moreRead less
Unraveling autotransporter function in bacterial aggregates and biofilms. Autotransporters are a large family of bacterial proteins that play a central role in pathogenesis. They promote the formation of cell clusters and biofilms, which are mechanisms for bacterial resistance to host immune factors and antibiotics. Currently, the precise mode of action of autotransporters is unknown. This project will examine the interplay between the structure and function of key autotransporter proteins. It ....Unraveling autotransporter function in bacterial aggregates and biofilms. Autotransporters are a large family of bacterial proteins that play a central role in pathogenesis. They promote the formation of cell clusters and biofilms, which are mechanisms for bacterial resistance to host immune factors and antibiotics. Currently, the precise mode of action of autotransporters is unknown. This project will examine the interplay between the structure and function of key autotransporter proteins. It is expected that the outcomes of this research will establish how these proteins mediate aggregation and biofilm formation. It may also provide three-dimensional structures of proteins that are strongly immunogenic and may represent targets for future vaccine design, as well as identify molecules that inhibit autotransporter function.Read moreRead less
Structures to Solve Conflicts of DNA Replication and RNA Transcription. This project aims to understand how new DNA is made so quickly and without mistakes in cells that are about to divide, in spite of competition from other processes happening at the same time on the DNA that should stop or interfere with it, such as the synthesis of RNA. The project expects to use the latest available methods to uncover what the microscopic natural machines that make DNA and RNA look like, and how they compet ....Structures to Solve Conflicts of DNA Replication and RNA Transcription. This project aims to understand how new DNA is made so quickly and without mistakes in cells that are about to divide, in spite of competition from other processes happening at the same time on the DNA that should stop or interfere with it, such as the synthesis of RNA. The project expects to use the latest available methods to uncover what the microscopic natural machines that make DNA and RNA look like, and how they compete with each other for access to DNA. Potential outcomes include the identification of processes that can be compromised by small molecules that may be developed into new antibiotics. This would be of great benefit - new antibiotics are urgently needed as one approach to countering the threat of antimicrobial resistance.Read moreRead less
How auto-transporter proteins mediate bacterial interactions. This project aims to investigate the structure-function relationships that underpin key auto-transporter roles in bacterial cell adhesion, aggregation and biofilm formation. Auto-transporter proteins are extremely common in bacteria where they play a central role in controlling bacterial interactions with other bacteria, with human cells, and with surfaces. This project will define the molecular mechanisms underlying these processes. ....How auto-transporter proteins mediate bacterial interactions. This project aims to investigate the structure-function relationships that underpin key auto-transporter roles in bacterial cell adhesion, aggregation and biofilm formation. Auto-transporter proteins are extremely common in bacteria where they play a central role in controlling bacterial interactions with other bacteria, with human cells, and with surfaces. This project will define the molecular mechanisms underlying these processes. This will have significant benefits, such as providing the basis for the development of approaches to block auto-transporter functions that contribute to the establishment of persistent and difficult to treat bacterial infections.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
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
Mechanism of secretion of large clostridial toxins . This project aims to investigate how the large clostridial toxins are secreted from important animal bacterial pathogens. This project expects to generate new knowledge about how bacteria interact with hosts through protein secretion, using a collaborative and interdisciplinary approach and cutting-edge techniques. Expected outcomes of this project include building a deep understanding of the role of export machinery in toxin secretion from ba ....Mechanism of secretion of large clostridial toxins . This project aims to investigate how the large clostridial toxins are secreted from important animal bacterial pathogens. This project expects to generate new knowledge about how bacteria interact with hosts through protein secretion, using a collaborative and interdisciplinary approach and cutting-edge techniques. Expected outcomes of this project include building a deep understanding of the role of export machinery in toxin secretion from bacteria, and the identification of new systems by which this is achieved. This should provide significant benefits, such as gaining new insights into new bacterial protein export mechanisms, with the aim of identifying targets for future veterinary disease interventions or biotechnological applications.Read moreRead less
How bacteria form resistant aggregates and biofilms. This research aims to use interdisciplinary approaches to advance fundamental knowledge on bacterial aggregates and biofilms. These bacterial clusters are a significant problem as they have extraordinary resistance to disinfectants and antibiotics, and currently no effective methods are available to disrupt them. The expected outcomes of this project are to dissect how autotransporters, the most common group of bacterial cell-surface proteins, ....How bacteria form resistant aggregates and biofilms. This research aims to use interdisciplinary approaches to advance fundamental knowledge on bacterial aggregates and biofilms. These bacterial clusters are a significant problem as they have extraordinary resistance to disinfectants and antibiotics, and currently no effective methods are available to disrupt them. The expected outcomes of this project are to dissect how autotransporters, the most common group of bacterial cell-surface proteins, promote aggregation and biofilm formation, and to develop inhibitors that prevent the formation of these damaging bacterial clusters. Ultimately, this new knowledge will help address the increasing economic and social burden of industrial, environmental and biomedical biofilms.Read moreRead less
Molecular mechanisms of regulatory proteolysis in Escherichia coli. This project will examine how microorganisms, such as bacteria, remodel their internal proteins by selectively dismantling them in order to survive. Knowledge gained here could be used to manipulate these organisms for social and economic benefit by improving health outcomes and the production of resources.