Hitting bacteria with a Bam: Lectin-Like Antimicrobials as New Antibiotics. Antibiotic resistance in disease-causing bacteria is a rapidly growing problem, making the development of new antibiotics of critical importance. This project aims to develop naturally produced lectin-like protein antibiotics as novel antimicrobial agents. To achieve this, the project will produce an extensive library of these antibiotics and test them for potency and specificity. Using cutting-edge techniques, it will d ....Hitting bacteria with a Bam: Lectin-Like Antimicrobials as New Antibiotics. Antibiotic resistance in disease-causing bacteria is a rapidly growing problem, making the development of new antibiotics of critical importance. This project aims to develop naturally produced lectin-like protein antibiotics as novel antimicrobial agents. To achieve this, the project will produce an extensive library of these antibiotics and test them for potency and specificity. Using cutting-edge techniques, it will determine how these antibiotics kill cells on a molecular and cellular level. It is anticipated this research will create the tools and knowledge required to exploit lectin-like protein antibiotics to fight bacterial infection, which will lead to their use in the prevention of crop and livestock losses due to disease.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
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
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
How does glycosylation shape protein function within Burkholderia? Protein glycosylation, the chemical addition of sugars to proteins, is an important but poorly understood aspect of bacterial physiology. This project aims to build on our recent discovery of the conservation of O-linked glycosylation across the Burkholderia genus to understand the function of this modification. Using cutting-edge proteomics, novel expression systems and molecular approaches this project will reveal the role of g ....How does glycosylation shape protein function within Burkholderia? Protein glycosylation, the chemical addition of sugars to proteins, is an important but poorly understood aspect of bacterial physiology. This project aims to build on our recent discovery of the conservation of O-linked glycosylation across the Burkholderia genus to understand the function of this modification. Using cutting-edge proteomics, novel expression systems and molecular approaches this project will reveal the role of glycosylation in Burkholderia species. This innovative project will provide a comprehensive understanding of how glycosylation contributes to Burkholderia protein function and how these systems can be harnessed for the creation of bespoke glycoconjugatesRead moreRead less
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
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
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