Deciphering Electron Transfer Pathways in Bacteria. Enzyme catalysed oxidation reactions are key players in the production of naturally occurring biologically active molecules. These processes are tightly regulated by their electron transfer partners. This project aims to characterise new electron transfer ferredoxin proteins from a metabolically diverse bacterium. These ferredoxins, important in many bacteria, contain different non-cysteine amino acids in their iron-sulfur cluster binding motif ....Deciphering Electron Transfer Pathways in Bacteria. Enzyme catalysed oxidation reactions are key players in the production of naturally occurring biologically active molecules. These processes are tightly regulated by their electron transfer partners. This project aims to characterise new electron transfer ferredoxin proteins from a metabolically diverse bacterium. These ferredoxins, important in many bacteria, contain different non-cysteine amino acids in their iron-sulfur cluster binding motifs and are poorly defined. The outcomes will advance understandings of electron transfer, a fundamental process. This will allow strategies to combat human and plant pathogens and unlock the potential of these systems as biocatalysts for the green chemical synthesis of complex and valuable chemicals.Read moreRead less
Carbohydrate language changes in vertebrate-pathogen co-evolution. This project aims to understand protein glycosylation’s role in host-pathogen relationships and cross-species transmission. Species specific sugars extensively modify cell surface and body fluid proteins. These glycans build a universal language that cells use and pathogens abuse. This project will use glycomics and glycoproteomics to uncover how pathogens learned to speak and interpret glyco-languages between different species. ....Carbohydrate language changes in vertebrate-pathogen co-evolution. This project aims to understand protein glycosylation’s role in host-pathogen relationships and cross-species transmission. Species specific sugars extensively modify cell surface and body fluid proteins. These glycans build a universal language that cells use and pathogens abuse. This project will use glycomics and glycoproteomics to uncover how pathogens learned to speak and interpret glyco-languages between different species. This project is expected to develop a glycan dictionary which could reveal host-pathogen co-evolution and glycosylation evolution in the Chordata phylum and counteract zoonoses threats.Read moreRead less
Developing serial crystallography for room temperature structure & dynamics. This project aims to uncover the molecular structural dynamics of a bacterial enzyme responsible for protein folding in bacteria. This project expects to generate new knowledge to guide the development of a new type of antibacterial to circumvent antibiotic resistance. Expected outcomes of this project include new experimental, computational and simulation tools for dynamic X-ray crystallography including new capabiliti ....Developing serial crystallography for room temperature structure & dynamics. This project aims to uncover the molecular structural dynamics of a bacterial enzyme responsible for protein folding in bacteria. This project expects to generate new knowledge to guide the development of a new type of antibacterial to circumvent antibiotic resistance. Expected outcomes of this project include new experimental, computational and simulation tools for dynamic X-ray crystallography including new capabilities at the Australian Synchrotron for very small microcrystals of any biomolecule. This would provide a powerful new tool for the Australian structural biology community that should accelerate fundamental discoveries, including facilitating high-resolution structure determination of membrane proteins and drug development.Read moreRead less
Molecular basis of nucleotide signalling by TIR domain containing proteins. Nicotinamide adenine dinucleotide (NAD+) dependent signalling pathways play important roles in neurodegenerative diseases and bacterial defence systems, and are therefore potential targets for the development of new therapeutics and biotechnology tools. This project aims to increase our understanding of the biology of a novel class of enzymes involved in NAD+ signalling across the domains of life. The project is expected ....Molecular basis of nucleotide signalling by TIR domain containing proteins. Nicotinamide adenine dinucleotide (NAD+) dependent signalling pathways play important roles in neurodegenerative diseases and bacterial defence systems, and are therefore potential targets for the development of new therapeutics and biotechnology tools. This project aims to increase our understanding of the biology of a novel class of enzymes involved in NAD+ signalling across the domains of life. The project is expected to unravel general principles of nucleotide-based signalling, and the expected outcomes will include new molecular mechanisms relevant to cell-death and pathogen defence in mammalian and bacterial systems, which should provide significant benefit for a range of applications in human biology and biotechnology.Read moreRead less
Engineering Bioresponsive Hybrid Nanodevices using RNA, Peptides and Synthetic Polymers. This project aims to develop new microRNA polymer nanoassemblies with enhanced bioresponsive properties. Nanoengineered functional RNA-polymer materials can exploit both the recognition properties of RNA and the responsiveness of the polymer to tailor the structural and physicochemical properties of such systems. Further, targeting ligands (antibody, aptamers) tethered to the RNA-polymer nanoassembly could a ....Engineering Bioresponsive Hybrid Nanodevices using RNA, Peptides and Synthetic Polymers. This project aims to develop new microRNA polymer nanoassemblies with enhanced bioresponsive properties. Nanoengineered functional RNA-polymer materials can exploit both the recognition properties of RNA and the responsiveness of the polymer to tailor the structural and physicochemical properties of such systems. Further, targeting ligands (antibody, aptamers) tethered to the RNA-polymer nanoassembly could augment cellular uptake and delivery. The development of imaging and tracking methodology to accurately measure intracellular miRNA payload and localisation in a 3D tissue mimicking matrix is also planned.Read moreRead less
Understanding pore formation by the complement membrane attack complex. The project aims to improve our understanding of the function of the membrane attack complex (MAC). MAC is a large protein complex used by the human immune system to target invading bacteria and parasites by punching holes in the lipid membranes of target cells. The MAC is part of a superfamily of proteins, the MACPF (membrane attack complex/perforin superfamily)/CDC (cholesterol-dependent cytolysins) superfamily, used by an ....Understanding pore formation by the complement membrane attack complex. The project aims to improve our understanding of the function of the membrane attack complex (MAC). MAC is a large protein complex used by the human immune system to target invading bacteria and parasites by punching holes in the lipid membranes of target cells. The MAC is part of a superfamily of proteins, the MACPF (membrane attack complex/perforin superfamily)/CDC (cholesterol-dependent cytolysins) superfamily, used by animals (in venoms and immunity), fungi (in defence) and pathogenic bacteria (in disease). The aim of this project is to image to the highest possible resolution how the MAC form pores in the context of bacterial cells and explore the way it inserts into cells in real time. Intended project outcomes may lay the foundation for applied future research into improved antibiotic delivery and novel pesticide development.Read moreRead less
Anticipating, Combating and Exploiting the Evolution of Pesticide Resistance in Australian Agricultural Pests and Disease Vectors. Synthetic insecticides have resulted in an explosion in food production through effective insect control. However, insects have begun to evolve resistance against one of the most widely used classes of insecticides (organophosphates) via mutations in carboxylesterases (CBEs). To address this problem, the ability to anticipate further evolution, combat it and exploit ....Anticipating, Combating and Exploiting the Evolution of Pesticide Resistance in Australian Agricultural Pests and Disease Vectors. Synthetic insecticides have resulted in an explosion in food production through effective insect control. However, insects have begun to evolve resistance against one of the most widely used classes of insecticides (organophosphates) via mutations in carboxylesterases (CBEs). To address this problem, the ability to anticipate further evolution, combat it and exploit it for our own benefit is needed. This project aims to anticipate evolution by simulating it in the laboratory, allowing for the best preparation for change. New pesticides will be designed to combat insecticide resistance based upon the molecular structure of an insect CBE. This project aims to exploit these newly evolved enzymes to create biosensors and decontamination agents.Read moreRead less
Molecular evolution of a model oligomeric enzyme from bacterial extremophiles. The national benefits of this research program include insight into the sustainability of marine microorganisms that play an important role in Australia's diverse ecosystem, the development and applications of frontier technologies including high-performance computing on the world's largest supercomputer facility for life science research, and knowledge impacting on the discovery of novel antibiotics that target patho ....Molecular evolution of a model oligomeric enzyme from bacterial extremophiles. The national benefits of this research program include insight into the sustainability of marine microorganisms that play an important role in Australia's diverse ecosystem, the development and applications of frontier technologies including high-performance computing on the world's largest supercomputer facility for life science research, and knowledge impacting on the discovery of novel antibiotics that target pathogenic bacteria, like Golden Staph. This program will also train several young Australians in highly sought after skills, including bacteriology, biophysics, enzymology, molecular biology, molecular modelling, protein chemistry and structural biology. Read moreRead less
Transformer 3D Nanostructures: Stimuli Responsive Polymers. This research program will develop smart nanostructures that will be capable of producing high value added products using cheap polymer materials but achieving a much greater design capacity for end-use functions. The knowledge gained from this project will have potential applications in many areas where nanomaterials and polymers are used, including high strength coatings, conducting coatings for the electronic industry, drug and vacci ....Transformer 3D Nanostructures: Stimuli Responsive Polymers. This research program will develop smart nanostructures that will be capable of producing high value added products using cheap polymer materials but achieving a much greater design capacity for end-use functions. The knowledge gained from this project will have potential applications in many areas where nanomaterials and polymers are used, including high strength coatings, conducting coatings for the electronic industry, drug and vaccine delivery devices, tissue scaffolds, nanosensors, and gene delivery. These polymer techniques will enable Australian Industry to significantly improve product performance by providing advanced features and capabilities previously unavailable.Read moreRead less
High performance chromatography based on nanostructured monolithic polymers. The proposed project will generate highly significant, fundamental advances in separation science by developing new stationary phases and separation technologies suitable for the analysis of very complex samples which cannot be addressed by current methods. These technologies will be applied in a wide range of areas of national importance including pharmaceutical analysis and drug discovery; environmental, clinical, and ....High performance chromatography based on nanostructured monolithic polymers. The proposed project will generate highly significant, fundamental advances in separation science by developing new stationary phases and separation technologies suitable for the analysis of very complex samples which cannot be addressed by current methods. These technologies will be applied in a wide range of areas of national importance including pharmaceutical analysis and drug discovery; environmental, clinical, and forensic analysis; energy generation and foods. The project will also lead to very significant new intellectual property having extremely high commercial potential worldwide, and thereby generates the promise of considerable direct financial returns to Australia.Read moreRead less