A microscopical examination of curdlan production by an Agrobacterium sp. We will investigate the secretion of the insoluble polysaccharide curdlan, a (1,3)-beta-glucan, from the surfaces of Agrobacterium cells and the assembly of the individual polysaccharide chains into microfibrils. Using state-of-the-art techniques in time lapse and electron microscopy we will compare the images of wild type curdlan-producing cells with those of mutants impaired in the production of curdlan. The outputs will ....A microscopical examination of curdlan production by an Agrobacterium sp. We will investigate the secretion of the insoluble polysaccharide curdlan, a (1,3)-beta-glucan, from the surfaces of Agrobacterium cells and the assembly of the individual polysaccharide chains into microfibrils. Using state-of-the-art techniques in time lapse and electron microscopy we will compare the images of wild type curdlan-producing cells with those of mutants impaired in the production of curdlan. The outputs will be information on the mechanics of curdlan production that will complement that emerging from our molecular biological and biochemical studies. These will have implications for understanding bacterial polysaccharide production in general and may have a commercial outcome in enhanced curdlan production.Read moreRead less
Stuctural analysis of RNA polymerase elongation complexes. RNA polymerase (RNAP) is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. Many additional factors are required to ensure that this enzyme functions correctly in the cell. The aim of this project is to obtain structural information on a bacterial RNAP complexed with an essential transcription factor called NusA. Using this information ....Stuctural analysis of RNA polymerase elongation complexes. RNA polymerase (RNAP) is an essential enzyme in all living cells. Its role is to convert the genetic information stored in genes into a message that can be converted into protein. Many additional factors are required to ensure that this enzyme functions correctly in the cell. The aim of this project is to obtain structural information on a bacterial RNAP complexed with an essential transcription factor called NusA. Using this information, plus data already obtained on the structure of this enzyme complexed with another essential factor called sigma, we will design small molecules to inhibit the interaction of these essential factors with polymerase. These molecules will serve as leads for the development of new antibiotics.Read moreRead less
Ubiquinone in Giardia: Amitochondrial component in an amitochondriate parasite. Giardia intestinalis is a fascinating organism, it is one of the most primitive nucleated organisms known and is responsible for ~280 million infections annually. Ubiquinone is usually associated with mitochondrial function, however it has been found in Giardia, which lacks this organelle. Our initial studies show that in Giardia, ubiquinone plays essential roles in electron transport pathways associated with membr ....Ubiquinone in Giardia: Amitochondrial component in an amitochondriate parasite. Giardia intestinalis is a fascinating organism, it is one of the most primitive nucleated organisms known and is responsible for ~280 million infections annually. Ubiquinone is usually associated with mitochondrial function, however it has been found in Giardia, which lacks this organelle. Our initial studies show that in Giardia, ubiquinone plays essential roles in electron transport pathways associated with membrane energisation and oxidative stress management. Elucidation of these mechanisms will have a major impact on the understanding of Giardia and other anaerobic organisms as well as being of significant evolutionary and medical importance.
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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
Structure and function of novel transporters in alphaproteobacteria. First, detailed knowledge of a set of membrane transporters and the way their activity might be inhibited, will have implications for the treatment of human disease. Second, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the transfer of technical capabilities not currently available in Australia. Third, our studies on non-pathogenic ....Structure and function of novel transporters in alphaproteobacteria. First, detailed knowledge of a set of membrane transporters and the way their activity might be inhibited, will have implications for the treatment of human disease. Second, excellent outcomes are provided for the training of postgraduate students and research staff. This project entails cutting edge technology, and the transfer of technical capabilities not currently available in Australia. Third, our studies on non-pathogenic species of alpha-proteobacteria provides for a timely advance in our knowledge of their biology: other species of alpha-proteobacteria were amongst the first organisms trialled for biological weapons by the USA and the former Soviet Union, and those pathogenic species are rated as Class 3 organisms.Read moreRead less
Dynamic signaling pathways of dispersal in bacterial biofilms. This Breakthrough Science project will result in an increased understanding of the molecular processes that govern biofilm development and dispersal. While the outcomes will be directly applicable where P. aeruginosa infections continue to cause health-threatening conditions, such as in Cystic Fibrosis chronic infections, it will also be instrumental for the rational design of novel products and strategies to control biofilms of othe ....Dynamic signaling pathways of dispersal in bacterial biofilms. This Breakthrough Science project will result in an increased understanding of the molecular processes that govern biofilm development and dispersal. While the outcomes will be directly applicable where P. aeruginosa infections continue to cause health-threatening conditions, such as in Cystic Fibrosis chronic infections, it will also be instrumental for the rational design of novel products and strategies to control biofilms of other single species or of mixed species populations in many other settings. Countless environmental, industrial and clinical applications will benefit from improved antimicrobial strategies and reduced usage of antibiotics.Read moreRead less
Gating, specificity and regulation of the YggB channel protein from Corynebacterium glutamicum. The proposed research will greatly contribute to our understanding of the functioning of a bacterial membrane channel/transporter, which has played a significant role in biotechnology of commercially important amino acids. A direct national benefit will result from establishing collaboration with a leading German laboratory providing expertise in protein biochemistry and molecular microbiology not ava ....Gating, specificity and regulation of the YggB channel protein from Corynebacterium glutamicum. The proposed research will greatly contribute to our understanding of the functioning of a bacterial membrane channel/transporter, which has played a significant role in biotechnology of commercially important amino acids. A direct national benefit will result from establishing collaboration with a leading German laboratory providing expertise in protein biochemistry and molecular microbiology not available in Australia. The acquired knowledge will present an original contribution which will have a strong impact on a very competitive field of molecular microbiology and biotechnology.Read moreRead less
Sensing atmosphere: Understanding the HNOX-protein gas-sensing capability and how it is affected by heme-oxidation. The project investigates how gas sensing heme-proteins from the novel HNOX (Heme-Nitric Oxide) family are able to discriminate between different gaseous ligands such as O2 and NO and how oxidation of the heme alters this response. The gas-sensing capability of the HNOX proteins is crucial for organisms ranging from bacteria to humans. Thus, understanding of these signalling mechani ....Sensing atmosphere: Understanding the HNOX-protein gas-sensing capability and how it is affected by heme-oxidation. The project investigates how gas sensing heme-proteins from the novel HNOX (Heme-Nitric Oxide) family are able to discriminate between different gaseous ligands such as O2 and NO and how oxidation of the heme alters this response. The gas-sensing capability of the HNOX proteins is crucial for organisms ranging from bacteria to humans. Thus, understanding of these signalling mechanisms will have a strong impact on many scientific fields from the control of pathogen growth to human blood pressure regulation. This collaboration will establish Australian scientists and as world-leading in the field of NO and redox signalling. This development will also be of substantial benefit for the training of the next generation of Australian students and scientists.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