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Mastering pyrimidine editing in RNA. Many plants and animals can alter their genetic information via RNA (ribonucleic acid) editing, a process that is often essential for the growth and development of the organism. This ability provides accurate control over gene expression and has great potential as a biotechnological tool in agriculture and medicine. RNA editing could be used to switch genes on or off in biotechnological production systems with an unprecedented degree of precision, or to corre ....Mastering pyrimidine editing in RNA. Many plants and animals can alter their genetic information via RNA (ribonucleic acid) editing, a process that is often essential for the growth and development of the organism. This ability provides accurate control over gene expression and has great potential as a biotechnological tool in agriculture and medicine. RNA editing could be used to switch genes on or off in biotechnological production systems with an unprecedented degree of precision, or to correct genetic diseases. This project aims to understand two RNA editing pathways in plants, one of which is found nowhere else and likely to involve a novel enzymatic mechanism. We will use the understanding gained to develop novel RNA processing tools usable in any living organism.Read moreRead less
Engineering self-assembled intracellular biological condensates. Cells depend on proteins linking together to build cellular structure, but how weak interactions build stable structure is a mystery. New evidence suggests proteins come together and then change state, employing liquid-like behaviour that builds vital nanoscale structure, such as nuclear bodies called paraspeckles. This project will unlock the secrets of this mysterious behavior of proteins, using paraspeckles as a model. We will u ....Engineering self-assembled intracellular biological condensates. Cells depend on proteins linking together to build cellular structure, but how weak interactions build stable structure is a mystery. New evidence suggests proteins come together and then change state, employing liquid-like behaviour that builds vital nanoscale structure, such as nuclear bodies called paraspeckles. This project will unlock the secrets of this mysterious behavior of proteins, using paraspeckles as a model. We will use this information for nanotechnology application to build a synthetic paraspeckle inspired structure with bespoke function. Benefits will include new concepts in how vital cell structure is assembled and disassembled, and nanotechnology and synthetic biology tools to manipulate cellular processes.Read moreRead less
IDENTIFYING CONTROL ELEMENTS IN CHLOROPLAST GENE EXPRESSION. Energy from sunlight is captured by photosynthesis in plants, providing the basis for the terrestrial food chain. This process takes place in chloroplasts, subcellular structures that derived from photosynthetic bacteria a billion years ago. Chloroplasts have their own DNA, containing genes encoding the most important photosynthetic proteins. This project aims to provide the world’s best resources for the study of chloroplast genes. In ....IDENTIFYING CONTROL ELEMENTS IN CHLOROPLAST GENE EXPRESSION. Energy from sunlight is captured by photosynthesis in plants, providing the basis for the terrestrial food chain. This process takes place in chloroplasts, subcellular structures that derived from photosynthetic bacteria a billion years ago. Chloroplasts have their own DNA, containing genes encoding the most important photosynthetic proteins. This project aims to provide the world’s best resources for the study of chloroplast genes. In the process, we will discover how these important genes are regulated to provide photosynthetic proteins in the right amounts, in the right cells, at the right time. The knowledge and resources gained will facilitate improvement of photosynthetic function in future agricultural crops.Read moreRead less
Sculpting a masterpiece: synthesis and evolution of minimal yeast genomes. This project aims to better understand genome complexity by engineering minimal yeast genomes that have fewer genes, and are therefore easier to characterise and engineer. Yeast is a model organism and industrial food, fuel, and chemical producer. This project expects to increase our basic understanding of yeast genomes, and develop new tools for engineering whole genomes. Expected outcomes of this project include the eng ....Sculpting a masterpiece: synthesis and evolution of minimal yeast genomes. This project aims to better understand genome complexity by engineering minimal yeast genomes that have fewer genes, and are therefore easier to characterise and engineer. Yeast is a model organism and industrial food, fuel, and chemical producer. This project expects to increase our basic understanding of yeast genomes, and develop new tools for engineering whole genomes. Expected outcomes of this project include the engineering and characterisation of the world's first minimal yeast genome, and the development of novel industrial yeast strains. This will provide significant benefits for both fundamental genetics and biochemistry research, and the industrial use of yeast for bio-manufacturing of sustainable foods, fuels, and chemicals.Read moreRead less
Lipid droplet membrane tethers at atomic resolution. Eukaryotic cells are distinguished by the presence of membrane-bound compartments called organelles. This project will use structural biology to determine how essential proteins called sorting nexins (SNXs) regulate membrane interactions required for lipid droplet formation. These interactions are essential for life, controlling protein and lipid homeostasis needed for cell survival. The major outcome of this proposal will be a fundamental und ....Lipid droplet membrane tethers at atomic resolution. Eukaryotic cells are distinguished by the presence of membrane-bound compartments called organelles. This project will use structural biology to determine how essential proteins called sorting nexins (SNXs) regulate membrane interactions required for lipid droplet formation. These interactions are essential for life, controlling protein and lipid homeostasis needed for cell survival. The major outcome of this proposal will be a fundamental understanding of how SNXs control this process, and the work will significantly strengthen our international collaboration in this emerging area. The knowledge has potential future translation in the treatment of neurodegenerative disorders where dysregulation of these proteins is known to cause disease.Read moreRead less
Autocyclases: A new class of self-cyclising proteins. The biotechnology sector is emerging as an important economic strength in Australia. While the improved efficacy and selectivity of biomolecules has seen them emerge as alternatives to existing chemicals in health and agriculture, the stability of biomolecules remains a major limiting factor. A general strategy for improving protein stability is by joining the ends of the peptide chain in a cyclisation reaction. While a wide range of cyclic p ....Autocyclases: A new class of self-cyclising proteins. The biotechnology sector is emerging as an important economic strength in Australia. While the improved efficacy and selectivity of biomolecules has seen them emerge as alternatives to existing chemicals in health and agriculture, the stability of biomolecules remains a major limiting factor. A general strategy for improving protein stability is by joining the ends of the peptide chain in a cyclisation reaction. While a wide range of cyclic peptides and proteins are being developed in Australia and around the world, the cyclisation reaction presents a significant challenge. In this proposal we detail a novel method for protein cyclisation as a general, low-cost and green production method for making a diverse range of biomolecules. Read moreRead less
Understanding how cells regulate self eating during starvation and stress. This project aims to investigate how autophagosomes are built during autophagy by using advanced multi-modal imaging and unique gene-edited human cell lines. This project expects to generate new knowledge on how a family of evolutionary conserved proteins regulate autophagosome formation during starvation and stress conditions. Expected outcomes include the development of frontier imaging technologies that can be subseque ....Understanding how cells regulate self eating during starvation and stress. This project aims to investigate how autophagosomes are built during autophagy by using advanced multi-modal imaging and unique gene-edited human cell lines. This project expects to generate new knowledge on how a family of evolutionary conserved proteins regulate autophagosome formation during starvation and stress conditions. Expected outcomes include the development of frontier imaging technologies that can be subsequently utilised for the advancement of any field of cell biology. This should provide significant benefits by placing Australia at the forefront of cell biology technologies and increasing our understanding of how plant and human cells can protect themselves during starvation and stress.
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Australian Laureate Fellowships - Grant ID: FL180100019
Funder
Australian Research Council
Funding Amount
$2,906,976.00
Summary
An in situ structural study of Drosophila embryonic patterning. This project aims to develop and deploy an in situ structural biology approach, which enables direct visualisation of large macromolecular structures in cells, to be used in combination with molecular genetics, proteomics and computational biology. In situ structural biology has the potential to revolutionise discovery across life science, providing direct insight into macromolecular structure and function. This project will establi ....An in situ structural study of Drosophila embryonic patterning. This project aims to develop and deploy an in situ structural biology approach, which enables direct visualisation of large macromolecular structures in cells, to be used in combination with molecular genetics, proteomics and computational biology. In situ structural biology has the potential to revolutionise discovery across life science, providing direct insight into macromolecular structure and function. This project will establish the field of in situ structural biology in Australia by studying how a model organism, the fruit fly Drosophila melanogaster controls the development of how the head and tail of the embryo are specified. The project will further develop new instrumentation and approaches that will bring in situ biology to the wider scientific community.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
The structural basis for MPEG1 mediated assembly of immune complexes. Macrophage Expressed Gene-1 (MPEG1) is an ancient pore forming perforin-like immune effector that is found throughout multicellular life. In humans MPEG1 is found in Macrophages (a type of immune cell) and functions to eliminate a wide range of different infectious microbes. In this study we will study how different modifications and molecular interactions drive MPEG1 function. Crucially our work will provide a framework to ....The structural basis for MPEG1 mediated assembly of immune complexes. Macrophage Expressed Gene-1 (MPEG1) is an ancient pore forming perforin-like immune effector that is found throughout multicellular life. In humans MPEG1 is found in Macrophages (a type of immune cell) and functions to eliminate a wide range of different infectious microbes. In this study we will study how different modifications and molecular interactions drive MPEG1 function. Crucially our work will provide a framework to understand how MPEG1 interacts with the interferon signalling pathway. These data will provide fundamental insight into how perforin-like proteins are controlled and will broadly inform new approaches to modify immune function and molecular signalling events.Read moreRead less