Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins ....Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins of high biochemical or biomedical importance, and the approach will be applied to established drug targets.Read moreRead less
Design of tuneable microstructures for additive manufacturing. The project intends to develop methods to tune the microstructure of materials in additive manufacturing so that components can be manufactured with maximum productivity and properties. Additive manufacturing is leading the mass customisation of manufacturing. Designed tunable microstructures enable structure and properties to be tailored for specific applications. One of the greatest challenges, however, is how to control the scale ....Design of tuneable microstructures for additive manufacturing. The project intends to develop methods to tune the microstructure of materials in additive manufacturing so that components can be manufactured with maximum productivity and properties. Additive manufacturing is leading the mass customisation of manufacturing. Designed tunable microstructures enable structure and properties to be tailored for specific applications. One of the greatest challenges, however, is how to control the scale and morphology of the microstructure. This project aims to use the interdependence model of grain refinement to control and design grain sizes. The project first plans to investigate the near-rapid solidification conditions in aluminium alloys. It then plans to re-design the harder-to-manufacture titanium alloys to improve grain size control.Read moreRead less
Mitigating the Severity of Level Crossing Accidents and Derailments. Ongoing increases in the number of level crossings and heavy road vehicles cause more frequent and severe level crossing accidents and derailments. Despite the use of active warning systems, each year, on average, 100 level crossing accidents occur in Australia. With a view to mitigating these crashes, this research aims to formulate theories for reduction in crash energy and effective wheel constraints to prevent derailment by ....Mitigating the Severity of Level Crossing Accidents and Derailments. Ongoing increases in the number of level crossings and heavy road vehicles cause more frequent and severe level crossing accidents and derailments. Despite the use of active warning systems, each year, on average, 100 level crossing accidents occur in Australia. With a view to mitigating these crashes, this research aims to formulate theories for reduction in crash energy and effective wheel constraints to prevent derailment by modifying the levels of road and rail crossings and providing guard rails in the recesses of these modified level crossings. The theories are intended be developed using nonlinear dynamic computational methods and laboratory experiments. The outcomes are expected to enable reduction in the severity of level crossing accidents and hence save lives and costs of derailment.Read moreRead less
Nanostructured solid acid catalysts for sustainable chemical manufacturing. This project aims to develop next-generation solid acid catalysts for energy- and atom-efficient transformations of waste biomass and carbon dioxide to sustainable chemicals and fuels. Catalysis is a transformative technology, key to both life and lifestyle, contributing to 90% of chemical manufacturing processes and >20% of all industrial products, and will be a key enabler for the emerging Australian bioeconomy. The ex ....Nanostructured solid acid catalysts for sustainable chemical manufacturing. This project aims to develop next-generation solid acid catalysts for energy- and atom-efficient transformations of waste biomass and carbon dioxide to sustainable chemicals and fuels. Catalysis is a transformative technology, key to both life and lifestyle, contributing to 90% of chemical manufacturing processes and >20% of all industrial products, and will be a key enabler for the emerging Australian bioeconomy. The expected development of new high performance catalysts for the production of renewable transportation fuels and sustainable chemical feedstocks will underpin commercially viable low carbon technologies using waste resources, and should provide significant benefits to Australian science, industry, and the environment.
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Voltage-dependent structural changes in voltage-gated sodium channels. This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to mem ....Voltage-dependent structural changes in voltage-gated sodium channels. This project aims to provide insights into the structural rearrangements experienced by Nav channels, which are key components of animal nervous systems. Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to membrane potential changes. Recently reported crystal structures of bacterial Nav channels have greatly advanced the field, but these channels contain four identical VSDs and have different inactivation properties. Thus, much remains to be learnt about the conformational plasticity of eukaryotic Nav channel VSDs. The project plans to use animal toxins to capture eukaryotic VSDs in defined states of the gating cycle for detailed structural analysis using nuclear magnetic resonance and X-ray crystallography.Read moreRead less
Protein Structure and Dynamics by Electron/Nuclear Paramagnetic Resonance. This interdisciplinary project aims to establish new magnetic resonance methods for the analysis of protein structure and motion at low concentrations and in physiological conditions that are otherwise difficult or impossible to study. It brings together four different research groups with expertise in advanced biochemistry, modern magnetic spectroscopy and high-performance computing. The project expects to develop tools ....Protein Structure and Dynamics by Electron/Nuclear Paramagnetic Resonance. This interdisciplinary project aims to establish new magnetic resonance methods for the analysis of protein structure and motion at low concentrations and in physiological conditions that are otherwise difficult or impossible to study. It brings together four different research groups with expertise in advanced biochemistry, modern magnetic spectroscopy and high-performance computing. The project expects to develop tools to study protein structure, protein-protein association and protein-ligand interactions of established drug-targets. Expected outcomes include new techniques that quickly inform how drugs work, providing significant benefits to many researchers studying biomolecules, and supporting Australia’s growing biotechnology sector. Read moreRead less
Selectively targeting cancer and infectious disease with fragment-based drug discovery. Finding better compounds as starting points is one of the major challenges for drug discovery research. Fragments are small, weak binding molecules that can be upsized into drug leads with better properties when compared to starting with larger molecules. This project addresses two weaknesses of current fragment based drug discovery (FBDD) methods: first, the limitations associated with screening fragments; a ....Selectively targeting cancer and infectious disease with fragment-based drug discovery. Finding better compounds as starting points is one of the major challenges for drug discovery research. Fragments are small, weak binding molecules that can be upsized into drug leads with better properties when compared to starting with larger molecules. This project addresses two weaknesses of current fragment based drug discovery (FBDD) methods: first, the limitations associated with screening fragments; and second, the quality of commercial fragment libraries. This project anticipates that the findings will establish a commanding role for both mass spectrometry and three-dimensional fragments in advancing FBDD approaches. It also expects to identify fragments with favourable development prospects towards the next generation of therapeutics.Read moreRead less
Molecular mechanisms of signalling by plant immune receptors. This project aims to understand how resistance proteins function and to find new sources of these proteins. Plant diseases account for 15% loss of global crop production, representing a threat to food security. Fungicides, one key form of protection, represent environmental concerns. The other key form of protection corresponds to resistance gene breeding, which is limited by lengthy breeding processes, restricted choice of genes from ....Molecular mechanisms of signalling by plant immune receptors. This project aims to understand how resistance proteins function and to find new sources of these proteins. Plant diseases account for 15% loss of global crop production, representing a threat to food security. Fungicides, one key form of protection, represent environmental concerns. The other key form of protection corresponds to resistance gene breeding, which is limited by lengthy breeding processes, restricted choice of genes from sexually compatible species and short effective time spans in the field. Building on previous research, this project aims to characterise the molecular basis of the Toll/interleukin-1 receptor domain-mediated nicotinamide adenine dinucleotide (NAD+) cleavage and the structural architecture of plant NLR complexes. This knowledge will support the long-term objective of protecting crops from pathogens.Read moreRead less
Understanding the molecular function of plant disease resistance proteins, pathogen effectors and their interaction to protect Australian agriculture. This project aims to understand the processes that enable resistant plants to detect and respond to pathogen attack. The acquired knowledge will form the foundation for durable plant disease resistance measures that can be applied to a wide range of crop diseases in an environmentally sustainable manner.
Structural basis of plant immune receptor signaling. Plants detect invading pathogens and trigger immune responses in a process called “effector-triggered immunity”, in which pathogen effector (avirulence) proteins are recognized by plant resistance proteins, typically so-called “plant NLRs”. Ongoing work in the applicants’ laboratories has shown that oligomerization into “resistosomes” and NAD+ (nicotinamide adenine dinucleotide) cleavage play central roles in the process. Building on these dat ....Structural basis of plant immune receptor signaling. Plants detect invading pathogens and trigger immune responses in a process called “effector-triggered immunity”, in which pathogen effector (avirulence) proteins are recognized by plant resistance proteins, typically so-called “plant NLRs”. Ongoing work in the applicants’ laboratories has shown that oligomerization into “resistosomes” and NAD+ (nicotinamide adenine dinucleotide) cleavage play central roles in the process. Building on these data, the project aims to characterize the structures of the signaling molecules resulting from TIR (Toll/interleukin-1 receptor) domain-mediated NAD+ cleavage and the structural architecture of plant NLR resistosomes. This knowledge will support the long-term objective of protecting crops from pathogens.Read moreRead less