Host-pathogen interactions: the role of mimicry. The proposed research program, using a combination of structure and functional analysis will provide insight into the mechanism of nucleotide hydrolysis by the enzymes NTPDases. This study will not only improve our fundamental understanding of NTPDase action but could lead to the rational design of antimicrobials.
Designing effective Gram negative bacterial vaccines. There is a need for the development of novel vaccines for use in animals and humans. This project will to address this need by studying the functions of bacterial 'blebs' as potent inducers of the host immune system and by developing these nano-sized particles for use as safe and cost-effective vaccine candidates.
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
The biogenesis of bacterial outer membranes; how bacteria build their surface membranes. The outer membrane protects probiotic bacteria in the human intestine and enables pathogenic bacteria to cause infectious diseases. We will determine bacteria build their outer membranes - outstanding training opportunities come through cutting edge technology and the development of skills not common in Australia.
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
Transport and innate immune properties of DNA in bacterial nano-sized vesicles. All types of living organisms release nano-sized membrane vesicles or “blebs” which they use for intercellular communication and transport of molecules. This project will determine how bacteria package DNA within these vesicles, how this DNA is transported into host cells and how it triggers immune responses in these cells.
The host specificity of bacterial pathogens. The vast majority of microorganisms that cause diseases in animals are host specific. In other words, they cause disease exclusively in a particular animal species, but are harmless for others. Despite considerable recent advances in our understanding of the mechanisms used by microorganisms in general to cause disease, in most cases the underlying basis of host-specificity is not known. In this project, we will use two animal pathogens, rabbit-spe ....The host specificity of bacterial pathogens. The vast majority of microorganisms that cause diseases in animals are host specific. In other words, they cause disease exclusively in a particular animal species, but are harmless for others. Despite considerable recent advances in our understanding of the mechanisms used by microorganisms in general to cause disease, in most cases the underlying basis of host-specificity is not known. In this project, we will use two animal pathogens, rabbit-specific enteropathogenic E. coli and the closely related bacterium, Citrobacter rodentium, which specifically infect rabbits and mice respectively, to investigate the molecular basis of host specificity.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
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