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
Force-from-lipids biophysical principle underlying mechanotransduction. The major aim of this project is to determine evolutionary conserved physical principles of mechanotransduction in living cells through structure and function studies of PIEZO mechanoreceptor channels playing a crucial role in senses such as touch and pain in animals and humans. Mutations in these channels can cause numerous genetic disorders, including hereditary anaemias and joint contractures. Since they have been shown t ....Force-from-lipids biophysical principle underlying mechanotransduction. The major aim of this project is to determine evolutionary conserved physical principles of mechanotransduction in living cells through structure and function studies of PIEZO mechanoreceptor channels playing a crucial role in senses such as touch and pain in animals and humans. Mutations in these channels can cause numerous genetic disorders, including hereditary anaemias and joint contractures. Since they have been shown to respond to mechanical stimuli in the same manner as mechanoreceptor channels of organisms from bacteria to humans the intended outcome of this project is to uncover the unifying principles of mechanotransduction anchored in the laws of physics and chemistry that have guided the force-dependent design of all life forms.Read moreRead less
Non-Canonical Amino Acids for Protein Analysis and Peptide Inhibitors. This interdisciplinary project aims to establish new tools to experimentally confirm 3D structure predictions of proteins that are otherwise difficult to study. A combination of innovative biochemistry, modern spectroscopy, and high-performance computing will be applied to study protein-protein and protein-ligand interactions. The project expects to generate new techniques and to test them on established drug targets. Expecte ....Non-Canonical Amino Acids for Protein Analysis and Peptide Inhibitors. This interdisciplinary project aims to establish new tools to experimentally confirm 3D structure predictions of proteins that are otherwise difficult to study. A combination of innovative biochemistry, modern spectroscopy, and high-performance computing will be applied to study protein-protein and protein-ligand interactions. The project expects to generate new techniques and to test them on established drug targets. Expected outcomes include new tools which quickly inform medicinal chemists how drugs interact with their targets and how they can be improved. The developed tools should provide significant benefit to many researchers by accelerating the early stage of drug discovery, and support Australia’s fast growing biotechnology sector.Read moreRead less
New methods for drug discovery by NMR spectroscopy. This project aims to advance nuclear magnetic resonance (NMR) spectroscopy methods in the field of drug discovery. It addresses a long-standing bottleneck for medicinal chemists in drug development: the rapid determination of how ligand molecules bind to proteins, where they bind and their orientation in the binding site. The methods include techniques for the attachment of NMR tags to ligands and target proteins, installation of new unnatural ....New methods for drug discovery by NMR spectroscopy. This project aims to advance nuclear magnetic resonance (NMR) spectroscopy methods in the field of drug discovery. It addresses a long-standing bottleneck for medicinal chemists in drug development: the rapid determination of how ligand molecules bind to proteins, where they bind and their orientation in the binding site. The methods include techniques for the attachment of NMR tags to ligands and target proteins, installation of new unnatural amino acids in proteins, and software for automated assignment of NMR spectra and 3D structure modelling of proteins using sparse distance restraints measured by electron paramagnetic resonance (EPR) spectroscopy. The outcome is to benefit the early stages of drug discovery in the biotech industries.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
Molecular basis for susceptibility and immunity to Fusarium wilt disease. Fusarium wilt is a devastating disease of many important crop plants, including banana, cotton and tomato. There are significant gaps in our understanding of this disease that need to be addressed to enable better disease management. This project aims to identify and analyse tomato proteins targeted by Fusarium effector proteins (virulence factors), determine how corresponding tomato receptors (resistance proteins) recogni ....Molecular basis for susceptibility and immunity to Fusarium wilt disease. Fusarium wilt is a devastating disease of many important crop plants, including banana, cotton and tomato. There are significant gaps in our understanding of this disease that need to be addressed to enable better disease management. This project aims to identify and analyse tomato proteins targeted by Fusarium effector proteins (virulence factors), determine how corresponding tomato receptors (resistance proteins) recognise these effectors, and identify the signalling pathways and critical defence responses activated by these receptors. The intention is to close the gaps in our understanding and use the knowledge gained to develop new strategies for disease control by interfering with fungal pathogenicity and enhancing plant resistance.Read moreRead less
Uncovering an evolutionary advanced mechanism of gene expression control. This project aims to uncover a new mechanism that activates gene expression in mammals, which involves unexpected connections between the core components of chromosomes and essential enzymatic machines required for the expression of genes. This project will generate new knowledge on the poorly understood process of how the extensive genomic information of multicellular organisms is selectively chosen to enable the expressi ....Uncovering an evolutionary advanced mechanism of gene expression control. This project aims to uncover a new mechanism that activates gene expression in mammals, which involves unexpected connections between the core components of chromosomes and essential enzymatic machines required for the expression of genes. This project will generate new knowledge on the poorly understood process of how the extensive genomic information of multicellular organisms is selectively chosen to enable the expression of only the required subset of genes. This will revolutionise our understanding of the mechanisms of gene control thereby shaping the field in the future. Significantly, this will allow new ways to manipulate gene expression that will impact biotechnology by providing new efficient ways to produce proteins or RNA. Read moreRead less
Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematic ....Molecular mechanisms of mechanosensation and shape regulation in cells. This project aims to explore how cells physically sense and respond to the surrounding environment on a molecular level. Physical distortion of erythrocytes doubles their glucose consumption and increases cation membrane flux five-fold. This mechanism involves opening of the mechanosenstive ion channel Piezo1. This project will include a kinetic description of these phenomena, with a goal to establish a predictive mathematical model of the regulation of cell-shape and volume. The project will provide an understanding of mechanisms operating when cells and tissues are succumbing to trauma and invasion, and how to control these processes on a molecular level.Read moreRead less
Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between the ....Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between these two important processes and will fill a significant gap in our understanding of how splicing quality control and nuclear RNA surveillance work. The project will also identify sequence features that trigger abortive splicing reactions and will thus help to improve the design of synthetic mRNAs.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