The protein O-glycosylation pathway of Neisseria: a model system for O-glycosylation of bacterial proteins with potential use in biotechnology. Proteins can be modified by the addition of sugar molecules. This process, called glycosylation, has been studied for some time in humans and other higher organisms, but is relatively new in the field of bacteria. This study will use the bacterium Neisseria as a model system for this process and work to harness the system for use in biotechnology.
The role of N-linked protein glycosylation in Campylobacter jejuni. It is estimated that 300,000 Campylobacter jejuni (C. jejuni) infections occur in Australia annually, causing a vast economic loss. This project will assist in the understanding of the role of glycosylation and will significantly aid in determining how C. jejuni colonises humans and poultry and lead to the discovery of interventions to reduce the organism in poultry for human consumption.
Bacterial poly-histidine triad proteins. The poly-histidine triad (Pht) proteins are a poorly characterised family of surface proteins expressed by the genus Streptococcus and other Gram-positive genera. Recent studies suggest an important role for Pht proteins in survival of these bacteria in low zinc (Zn) environments. The project hypothesis is that Pht proteins specifically recruit Zn from the extracellular environment and somehow make it available to ATP binding cassette (ABC) transport syst ....Bacterial poly-histidine triad proteins. The poly-histidine triad (Pht) proteins are a poorly characterised family of surface proteins expressed by the genus Streptococcus and other Gram-positive genera. Recent studies suggest an important role for Pht proteins in survival of these bacteria in low zinc (Zn) environments. The project hypothesis is that Pht proteins specifically recruit Zn from the extracellular environment and somehow make it available to ATP binding cassette (ABC) transport systems located in the bacterial plasma membrane, beneath the cell wall, facilitating Zn uptake by the bacterium. The aim of this project is to conduct comprehensive molecular characterization of the interactions between Pht proteins, Zn and ABC transporters, and the role of the histidine triad motifs in these interactions.Read moreRead less
Molecular insights into bacterial metal ion homeostasis and toxicity. This project aims to measure bacterial cellular metal concentrations, elucidate mechanisms cells use to adapt to changing extracellular metal concentrations, and reveal the molecular targets of metal toxicity. Metal ions are essential to all forms of life, and half of all proteins use metal ions for cellular chemical processes. However, how cells precisely balance sufficient metal ions for essential cellular chemistry without ....Molecular insights into bacterial metal ion homeostasis and toxicity. This project aims to measure bacterial cellular metal concentrations, elucidate mechanisms cells use to adapt to changing extracellular metal concentrations, and reveal the molecular targets of metal toxicity. Metal ions are essential to all forms of life, and half of all proteins use metal ions for cellular chemical processes. However, how cells precisely balance sufficient metal ions for essential cellular chemistry without accumulating a toxic excess (metal homeostasis) is poorly understood. Discovering the roles of metal ions in bacterial cells will be key to defining the chemical biology of living systems and will provide information essential to understanding how microbes adapt to changing environments.Read moreRead less
New molecular tools to study the mechanisms of bacterial metal homeostasis. This project aims to provide new insight into how metal ion uptake is regulated. It will precisely measure the cellular concentrations of metal ions, reveal the roles of metal ions in essential cellular processes, and identify the molecular targets of metal toxicity. Metal ions are essential to all forms of life and are used by up to half of all proteins to facilitate cellular chemical processes. The intended outcome of ....New molecular tools to study the mechanisms of bacterial metal homeostasis. This project aims to provide new insight into how metal ion uptake is regulated. It will precisely measure the cellular concentrations of metal ions, reveal the roles of metal ions in essential cellular processes, and identify the molecular targets of metal toxicity. Metal ions are essential to all forms of life and are used by up to half of all proteins to facilitate cellular chemical processes. The intended outcome of the research is to provide new fundamental knowledge of the roles of metal ions in bacterial cells; knowledge that will be key to defining the chemical biology of living systems and will provide information essential to understanding how microbes adapt to changing environments.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.
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
Mitochondria: a target for intracellular bacterial pathogens. This project aims to understand how intracellular bacterial pathogens target mitochondria. Coxiella burnetii is a unique and significant pathogen of humans and commercially important animals that uses effector proteins to control host cell functions. A cohort of these effectors target mitochondria. Since mitochondria are key players in cell health, the intended outcome of this research is to understand the role of the mitochondrially- ....Mitochondria: a target for intracellular bacterial pathogens. This project aims to understand how intracellular bacterial pathogens target mitochondria. Coxiella burnetii is a unique and significant pathogen of humans and commercially important animals that uses effector proteins to control host cell functions. A cohort of these effectors target mitochondria. Since mitochondria are key players in cell health, the intended outcome of this research is to understand the role of the mitochondrially-targeted effector proteins. The project will determine the importance of mitochondrial protein trafficking for Coxiella pathogenesis and how mitochondrial function is altered during infection. This will provide understanding of how bacterial pathogens manipulate organelles like mitochondria for their survival.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: DE230100356
Funder
Australian Research Council
Funding Amount
$450,241.00
Summary
Bacterial membrane remodelling and the interaction with peptides. This project aims to elucidate the fundamental mechanism of lipid remodelling in Gram-negative outer membrane, which is critical both in preventing noxious compounds and evading host immune defence. For the first time, the complex interplays between bacterial cellular metabolism and membrane remodelling will be defined through systems pharmacology, and the precise membrane-peptide interaction will be examined by computational and ....Bacterial membrane remodelling and the interaction with peptides. This project aims to elucidate the fundamental mechanism of lipid remodelling in Gram-negative outer membrane, which is critical both in preventing noxious compounds and evading host immune defence. For the first time, the complex interplays between bacterial cellular metabolism and membrane remodelling will be defined through systems pharmacology, and the precise membrane-peptide interaction will be examined by computational and biophysical approaches. Novel knowledge will be generated to improve our understanding on how bacteria remodel their outer membrane in response to environmental stress. This will benefit the future design of much-needed antimicrobial strategies including products and technologies to target bacterial membrane. Read moreRead less