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 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
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
Novel ultraviolet radiation filters from extreme environments. This project aims to exploit uncultured microorganisms to produce and characterise novel ultraviolet radiation-filter biosynthesis pathways. Current ultraviolet radiation-filtering compounds are toxic and persistent. There is a need for biodegradable, ultraviolet radiation filters that are safe for use across a variety of health and industrial applications. Over millions of years, the damaging effect of ultraviolet radiation has exer ....Novel ultraviolet radiation filters from extreme environments. This project aims to exploit uncultured microorganisms to produce and characterise novel ultraviolet radiation-filter biosynthesis pathways. Current ultraviolet radiation-filtering compounds are toxic and persistent. There is a need for biodegradable, ultraviolet radiation filters that are safe for use across a variety of health and industrial applications. Over millions of years, the damaging effect of ultraviolet radiation has exerted selective pressure on organisms that has driven the evolutionary diversity of natural radiation-filtering compounds. This project expects to characterise and harness the microbial diversity of unique high ultraviolet radiation ecosystems via synthetic biology to produce industrially and pharmacologically useful ultraviolet radiation filters.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