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
Unravelling small RNA regulatory networks to target and control bacteria. Small RNA (sRNA) molecules are critical regulators of bacterial gene expression. These molecules control important phenotypes in the Gram-negative veterinary pathogen Pasteurella multocida. This project aims to identify the range of P. multocida sRNAs and to show how expression of these molecules changes under various growth conditions. Specifically, this project endeavours: to identify the mRNA targets of the sRNAs; to id ....Unravelling small RNA regulatory networks to target and control bacteria. Small RNA (sRNA) molecules are critical regulators of bacterial gene expression. These molecules control important phenotypes in the Gram-negative veterinary pathogen Pasteurella multocida. This project aims to identify the range of P. multocida sRNAs and to show how expression of these molecules changes under various growth conditions. Specifically, this project endeavours: to identify the mRNA targets of the sRNAs; to identify the mechanisms of sRNA-mRNA interaction; to build systems-biology models that describe the sRNA regulatory circuits; to design inhibitors capable of disrupting critical sRNA-mRNA interactions; and to use the new inhibitors to modulate specific phenotypes. The ability to precisely manipulate sRNA regulatory circuits could allow fine control of bacterial phenotypes and could be widely applicable.Read moreRead less
Vaccine against leptospirosis. This project will utilise the information from the determination of the complete genome sequence of Leptospira borgpetersenii serovar Hardjobovis at Monash University. Bioinformatics analysis will be used to allow a global approach to identify all putative vaccine antigens which will be cloned, expressed and purified and their protective capacity investigated.
Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less
Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to tr ....Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to treat a range of pathogenic bacteria, including "Golden Staph".Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230100700
Funder
Australian Research Council
Funding Amount
$429,449.00
Summary
A novel bacterial secretion system for applications in nanobiotechnology. This project aims to characterise a new molecular machine, called the S-Pump. Molecular machines drive the complex biology in all cells and are an exciting area of translational research, with broad potential for industrial applications. This project expects to provide fundamental insights into how bacterial S-Pumps contribute to antimicrobial resistance and enhancing food production. Expected outcomes include new tools fo ....A novel bacterial secretion system for applications in nanobiotechnology. This project aims to characterise a new molecular machine, called the S-Pump. Molecular machines drive the complex biology in all cells and are an exciting area of translational research, with broad potential for industrial applications. This project expects to provide fundamental insights into how bacterial S-Pumps contribute to antimicrobial resistance and enhancing food production. Expected outcomes include new tools for molecular machine discovery and identification of ways to adapt molecular machines for biotechnological applications. This work should enhance Australia-UK ties through collaboration, provide benefits toward nanobiotechnology and economic benefits through more efficient food production.Read moreRead less
Antibacterial Material Design via Mechanism-Based Mathematical Modelling. This Project aims to provide new rules for the design of novel polymer materials with antibacterial properties by employing mechanism-based mathematical modelling.
This Project expects to generate new understanding of those mechanisms which underpin the antibacterial activity of these materials, how bacteria respond to these through metabolic changes and emergence of resistance.These rules will govern material design to yi ....Antibacterial Material Design via Mechanism-Based Mathematical Modelling. This Project aims to provide new rules for the design of novel polymer materials with antibacterial properties by employing mechanism-based mathematical modelling.
This Project expects to generate new understanding of those mechanisms which underpin the antibacterial activity of these materials, how bacteria respond to these through metabolic changes and emergence of resistance.These rules will govern material design to yield new antibacterial materials with improved properties.
Expected outcomes of this project may be a novel mechanism-based mathematical model that will enable the next-generation of antibacterial materials.
This outcome will help address the increasing economic and social burden of antibiotic drug resistance in Australia.
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A link between antibiotic resistance and bacterial sporulation. This project aims to define the sporulation process in the bacterium Clostridium difficile, and advance our understanding of a link between antibiotic use and sporulation. To survive in hostile environments, some bacteria produce a dormant and resilient cell form called a spore which can survive for many years in unfavourable environments, but our understanding of how this process occurs is limited. This project will provide a deepe ....A link between antibiotic resistance and bacterial sporulation. This project aims to define the sporulation process in the bacterium Clostridium difficile, and advance our understanding of a link between antibiotic use and sporulation. To survive in hostile environments, some bacteria produce a dormant and resilient cell form called a spore which can survive for many years in unfavourable environments, but our understanding of how this process occurs is limited. This project will provide a deeper understanding of the sporulation process and the long-lasting detrimental impact of antibiotic use. The project expects to provide economic benefits, reduce environmental microbial contamination and contribute to better health of animals and humans.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