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
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
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.
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.
Regulation of proteolysis by specialised adaptor proteins. Training research scientists of the future forms an integral part of this research program and this collaboration will provide an excellent opportunity for young Australian scientists to be exposed to the very professional and competitive environment of basic research, as it exists in Germany. It will expose early career researchers to new ideas and emerging methodologies arming them with valuable skills, which they will transfer to Aust ....Regulation of proteolysis by specialised adaptor proteins. Training research scientists of the future forms an integral part of this research program and this collaboration will provide an excellent opportunity for young Australian scientists to be exposed to the very professional and competitive environment of basic research, as it exists in Germany. It will expose early career researchers to new ideas and emerging methodologies arming them with valuable skills, which they will transfer to Australia. The involvement of Prof. Turgay in the Deutsche Forschungsgemeinschaft (DFG) Priority Programme: Proteolysis in Prokaryotes also provides a unique opportunity for these young researchers to interact with several of the worlds leading scientists in the area of proteolysis, enhancing Australia's reputation at the forefront of science.Read moreRead less
The biogenesis of bacterial outer membranes: how bacteria build their surface coating. This project will determine how bacteria build their outer membranes. The outer membrane protects 'probiotic bacteria' in the human intestine and enables 'pathogenic' bacteria to cause infectious diseases. The project presents outstanding training opportunities with the use of cutting edge technology and the development of skills not common in Australia.
Molecular characterisation of hypervirulence and the infectious cycle in Clostridium difficile. Gut diseases caused by the bacterium Clostridium difficile are a significant animal and public health problem in Australia and many other countries. This project will allow us to understand how this bacterium causes disease, leading to the development of much needed preventative and treatment strategies for animals and human patients.