Single molecule spectroscopy-guided design of thermostable industrial enzymes. The production and engineering of proteins are key methodologies in life sciences. The current project aims to develop new approaches to accelerate the production and analysis of proteins and to apply them to discover improved proteins for use as feedstock supplements.
All-in-vitro engineering and single molecule analysis of protein complexes. The production and engineering of proteins are key methodologies in life sciences. The current project aims to develop new approaches to accelerate the production and analysis of proteins and to apply them to increase our understanding of the basic mechanisms of cell self-maintenance.
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
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
The rational design and construction of new genetic circuits for applications in synthetic biology. By designing, building and testing new gene control modules, this project will gain an understanding of the design principles required for the construction of biological circuits with predictable and controllable behaviour. The ability to build such circuits will have significant economic benefit in areas such as metabolic engineering and biomedicine.
Development of a novel high yield cell-free protein expression system. Recombinant proteins are used as vaccines, drugs, and research tools, as well as food and detergent additives, comprising a A$100 billion international market. Their production requires laborious, expensive, and time-consuming construction of transgenic organisms or cells. Alternatively, recombinant proteins can be produced in extracts prepared from cells or organisms. The aim of this proposal is to develop a new technology t ....Development of a novel high yield cell-free protein expression system. Recombinant proteins are used as vaccines, drugs, and research tools, as well as food and detergent additives, comprising a A$100 billion international market. Their production requires laborious, expensive, and time-consuming construction of transgenic organisms or cells. Alternatively, recombinant proteins can be produced in extracts prepared from cells or organisms. The aim of this proposal is to develop a new technology that will make cell-free production of recombinant proteins rapid, cheap, and scalable. This will advance Australia’s intellectual leadership in the area of biotechnology and will bring numerous economic benefits by accelerating pharmaceutical development. 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
Synthetic biology tools for integration into bacterial chromosomes. The aim of the project is to develop a set of versatile chromosomal integration tools for bacteria, enabling rapid development of novel biological outputs. A major goal in the emerging discipline of synthetic biology is to apply engineering principles to the design and construction of new biological entities such as proteins, genetic circuits and cells. Custom-designed genetic circuits, integrated in an appropriate host genome, ....Synthetic biology tools for integration into bacterial chromosomes. The aim of the project is to develop a set of versatile chromosomal integration tools for bacteria, enabling rapid development of novel biological outputs. A major goal in the emerging discipline of synthetic biology is to apply engineering principles to the design and construction of new biological entities such as proteins, genetic circuits and cells. Custom-designed genetic circuits, integrated in an appropriate host genome, hold enormous economic potential for applications ranging from biomedicine to biofuel production. This project aims to help synthetic biologists to embed made-to-order circuits in appropriate host cells to act as living factories, potentially replacing industrial processes which are currently environmentally and economically costly.Read moreRead less
Developing orthogonal synthetic signaling cascades. This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set ....Developing orthogonal synthetic signaling cascades. This project proposes a generic approach for the construction of molecular switches based on artificially autoinhibited proteases. The bottom-up design of protein-based signaling networks is a key goal of synthetic biology. Yet, this remains elusive due to our inability to tailor-make signal transducers and receptors that can be readily compiled into defined signaling networks. Using structure-guided design and directed protein evolution, a set of protease-based signal transducers and ligand activated allosteric receptors will be created. The developed components are intended to be used to construct artificial signaling networks in mammalian cells that are orthogonal to the endogenous signaling cascades.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160100608
Funder
Australian Research Council
Funding Amount
$359,000.00
Summary
Investigating the structural basis of human antibody stability. This project plans to use protein engineering and X-ray crystallography to investigate the effects of stabilising mutations on antigen binding and the antibody-antigen interaction. Monoclonal antibodies are high-affinity reagents that have transformed the study of biological processes. However, antibodies often display inherent instability, which limits applicability. Mutations have recently been identified that render human antibod ....Investigating the structural basis of human antibody stability. This project plans to use protein engineering and X-ray crystallography to investigate the effects of stabilising mutations on antigen binding and the antibody-antigen interaction. Monoclonal antibodies are high-affinity reagents that have transformed the study of biological processes. However, antibodies often display inherent instability, which limits applicability. Mutations have recently been identified that render human antibodies resistant to aggregation. Preliminary data indicates that stabilising mutations improves the biophysical properties of monoclonals without affecting the native antibody structure. The project aims to provide detailed insights into the molecular basis of antibody stability.Read moreRead less