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: DE140101553
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
A flexible virus-like particle delivery platform for next-generation vaccines. Murine polyomavirus (MPyV) capsid proteins self-assemble into spherical protein shells approximately 45 nm in diameter. Such virus-like particles (VLPs) are of considerable interest as bionanotechnological tools. The unique flexibility provided by MPyV VLPs will be exploited by exploring the ability of the interior cavity to retain bioactive cargos while engineering novel functionality on the exterior surface by 'mix- ....A flexible virus-like particle delivery platform for next-generation vaccines. Murine polyomavirus (MPyV) capsid proteins self-assemble into spherical protein shells approximately 45 nm in diameter. Such virus-like particles (VLPs) are of considerable interest as bionanotechnological tools. The unique flexibility provided by MPyV VLPs will be exploited by exploring the ability of the interior cavity to retain bioactive cargos while engineering novel functionality on the exterior surface by 'mix-and-match' assembly of VLPs from modified components. As a proof of concept for next-generation vaccines that stimulate much needed, broadly protective responses against infectious diseases, model antigens will be delivered to specific immune cells using this nano-container.Read moreRead less
Ultrasensitive electrochemical biosensors. This project aims to develop novel proteins that can convert biochemical cues into electronic signals. Using protein engineering, this project will produce redox protein-based OFF switches. The project expects that the use of the OFF-switches (as opposed to ON switches) will simplify biosensor design and create a new class of sensory architectures. Integration of OFF-switch-based biosensors with an enzymatic signal amplification circuit is expected to y ....Ultrasensitive electrochemical biosensors. This project aims to develop novel proteins that can convert biochemical cues into electronic signals. Using protein engineering, this project will produce redox protein-based OFF switches. The project expects that the use of the OFF-switches (as opposed to ON switches) will simplify biosensor design and create a new class of sensory architectures. Integration of OFF-switch-based biosensors with an enzymatic signal amplification circuit is expected to yield ultrasensitive sensory systems with near-real-time response. The project will address a need for new technologies that enable collection of physiological and environmental information rapidly, and at low cost outside of the specialised laboratories.Read moreRead less
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.
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.
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
Developing an integrated systems and synthetic biology platform to expand the product spectrum of acetogens. This project aims to advance a waste gas fermentation process to enable the production of sustainable aviation fuel molecules for the first time. LanzaTech are world leaders in microbial gas fermentation and have produced ethanol at large scale in China. This project aims to combine the LanzaTech process with systems biology expertise at The University of Queensland to go beyond ethanol t ....Developing an integrated systems and synthetic biology platform to expand the product spectrum of acetogens. This project aims to advance a waste gas fermentation process to enable the production of sustainable aviation fuel molecules for the first time. LanzaTech are world leaders in microbial gas fermentation and have produced ethanol at large scale in China. This project aims to combine the LanzaTech process with systems biology expertise at The University of Queensland to go beyond ethanol to deliver new value-added products such as butanediol and farnesene. To achieve this aim the project will explore, understand and overcome fundamental energy and metabolic limitations in the production microorganism. Achieving the aims will be of direct relevance to SkyNRG and the new Brisbane Bioport on their path to deliver sustainable fuel to Brisbane Airport.Read moreRead less
Toward sustainable diesel production using microbial cells: unravelling isoprenoid pathway regulation through systems biology. The methylerythritol pyrophosphate (MEP) pathway for isoprenoid production is an essential biochemical pathway. It was only fully elucidated a decade ago, and the regulatory controls over this pathway are not understood. The objective of this project is to elucidate the mechanisms by which the MEP pathway is controlled in E. coli using a novel systems biology approach. U ....Toward sustainable diesel production using microbial cells: unravelling isoprenoid pathway regulation through systems biology. The methylerythritol pyrophosphate (MEP) pathway for isoprenoid production is an essential biochemical pathway. It was only fully elucidated a decade ago, and the regulatory controls over this pathway are not understood. The objective of this project is to elucidate the mechanisms by which the MEP pathway is controlled in E. coli using a novel systems biology approach. Understanding control of the MEP pathway is required to gain insight into homeostatic control of this essential pathway, and enable biotechnological engineering of E. coli in order to produce a wide range of industrially useful isoprenoids (including biofuels, pharmaceuticals, industrial chemicals, neutraceuticals, food additives, perfumes and many more).Read moreRead less
In vitro expression of macrocyclic peptides. This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-sele ....In vitro expression of macrocyclic peptides. This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-selective incorporation are inefficient. The project’s strategy relies on the depletion of selected tRNAs from an in vitro protein translation system and their replacement with synthetic tRNAs, charged with unnatural amino acids. It is expected that the developed technology could be used to rapidly generate and screen highly diversified macrocyclic peptide libraries.Read moreRead less
Engineering electrochemical protein biosensors. This project plans to develop novel, sensitive, inexpensive and flexible electric biosensors to monitor potentially any molecule. It plans to use synthetic biology principles to develop a new class of artificial protein receptors that generate electric current upon encountering a molecular target. Using expertise in in vitro protein synthesis, the project plans to integrate biosensor design and electrode prototyping to achieve rapid development of ....Engineering electrochemical protein biosensors. This project plans to develop novel, sensitive, inexpensive and flexible electric biosensors to monitor potentially any molecule. It plans to use synthetic biology principles to develop a new class of artificial protein receptors that generate electric current upon encountering a molecular target. Using expertise in in vitro protein synthesis, the project plans to integrate biosensor design and electrode prototyping to achieve rapid development of low-cost broadly applicable sensory electrodes. To increase the sensitivity of the resulting sensing systems, the electrochemical receptors will be integrated with signal amplification cascades based on artificial autoinhibited proteases. The project aims to address the need for new technologies that enable collection of biological information outside of the laboratory environment.Read moreRead less