Structure-guided optimisation of light-driven microalgae cell factories. Every two hours Earth receives more solar energy than is required to power our entire global economy for a year. This project aims to engineer advanced single cell green algae for high-efficiency solar light capture, to power next-generation light-driven bio-manufacture. The significance is to advance industry-scale production of sustainable products using microalgae. This is economically, socially and environmentally benef ....Structure-guided optimisation of light-driven microalgae cell factories. Every two hours Earth receives more solar energy than is required to power our entire global economy for a year. This project aims to engineer advanced single cell green algae for high-efficiency solar light capture, to power next-generation light-driven bio-manufacture. The significance is to advance industry-scale production of sustainable products using microalgae. This is economically, socially and environmentally beneficial. Project outcomes are designed to advance the technology from high-value bio-manufacture in microalgae, such as pharmaceuticals (e.g. biologicals), to mid-value products (e.g. fine chemicals) through to low-cost products, such as renewable fuels to help deliver key UN Sustainable Development Goals.Read moreRead less
On the Hunt: Boosting Productivity of Cell Factories by Advanced Searches . This project aims to advance our fundamental understanding of molecular mechanisms underlying protein secretion in yeast, an industrial workhorse and a model organism. It will develop a unique multifaceted research platform to identify and analyse superior yeast strains with the desired traits at the single-cell level. Expected outcomes include a new analytical tool for high-throughput strain analysis and advanced knowle ....On the Hunt: Boosting Productivity of Cell Factories by Advanced Searches . This project aims to advance our fundamental understanding of molecular mechanisms underlying protein secretion in yeast, an industrial workhorse and a model organism. It will develop a unique multifaceted research platform to identify and analyse superior yeast strains with the desired traits at the single-cell level. Expected outcomes include a new analytical tool for high-throughput strain analysis and advanced knowledge of yeast molecular biology that can be applied to improve cell factories for the next generation of fuels, food and pharmaceuticals. This will provide significant economic and social benefits by boosting biotech industry growth, facilitating the transition to a sustainable society and improving Australia’s biosecurity.Read moreRead less
Biosynthetic Hooks for an Enigmatic Marine Toxin. This project aims to characterise the genetic basis for the production of tetrodotoxin; a potent neurotoxin of ecological and biomedical significance. We hypothesise that tetrodotoxin is produced by microorganisms and transferred via the food web to fish, molluscs and other marine animals. Our integrated genomic and synthetic biology approach, targeting key biosynthesis genes, will reveal pathways for the production of tetrodotoxin and other pote ....Biosynthetic Hooks for an Enigmatic Marine Toxin. This project aims to characterise the genetic basis for the production of tetrodotoxin; a potent neurotoxin of ecological and biomedical significance. We hypothesise that tetrodotoxin is produced by microorganisms and transferred via the food web to fish, molluscs and other marine animals. Our integrated genomic and synthetic biology approach, targeting key biosynthesis genes, will reveal pathways for the production of tetrodotoxin and other potentially valuable compounds. In addition to providing unprecedented insight into the ecology and biosynthesis of this enigmatic toxin, the data generated will enable improved management of seafood safety and provide a foundation for the future development of novel neuroactive compounds.Read moreRead less
Discovery and directed evolution of small molecule biosensors. This project aims to address the need for novel small molecule biosensing capability in diverse fields including food and wine production, environmental monitoring, biocatalysis, and diagnostics using a synthetic biology approach. The significance of this work is the development of new biosensors by a strong interdisciplinary team contributing bioinformatics to identify new biosensors, innovative protein engineering approaches, and c ....Discovery and directed evolution of small molecule biosensors. This project aims to address the need for novel small molecule biosensing capability in diverse fields including food and wine production, environmental monitoring, biocatalysis, and diagnostics using a synthetic biology approach. The significance of this work is the development of new biosensors by a strong interdisciplinary team contributing bioinformatics to identify new biosensors, innovative protein engineering approaches, and cutting-edge directed evolution methodologies. Intended outcomes include enhanced institutional capacity for interdisciplinary collaboration; discovery of fundamentally important bacterial sensors; and development of synthetic regulatory circuits enabling outgrowth of non-biological biocatalysis industries.Read moreRead less
Synthetic biology tools for just-in-time control of biosynthetic pathways. Synthetic biology enables sustainable synthesis of precious chemicals, ranging from drugs to biomaterials. Using microbes, high production levels are usually attained by overexpressing the genes that make the desired product, but this simple approach often fails for antibiotics and other compounds that are toxic to microbes. Using synthetic biology this project builds genetic circuits enabling smart, just-in-time activati ....Synthetic biology tools for just-in-time control of biosynthetic pathways. Synthetic biology enables sustainable synthesis of precious chemicals, ranging from drugs to biomaterials. Using microbes, high production levels are usually attained by overexpressing the genes that make the desired product, but this simple approach often fails for antibiotics and other compounds that are toxic to microbes. Using synthetic biology this project builds genetic circuits enabling smart, just-in-time activation of target genes, which is pervasive in natural pathways. Using these circuits we will boost 1) the production of a valuable antibiotic and 2) calcite precipitation in self-healing concrete. This approach enables the biosynthesis of many other chemicals, leading to cleaner and greener bio-factories.Read moreRead less
Engineering Fungal Nonribosomal Peptide Synthetases for Novel Alkaloids. This project aims to use protein-domain shuffling aided by structural biology to decode and engineer a class of modular megaenzymes, called nonribosomal peptide synthetases (NRPSs), in fungi. These are responsible for the biosynthesis of peptide-derived bioactive molecules, such as the antibiotic penicillin and the immunosuppressant cyclosporin. Expected outcomes of this project include a fungal NRPS engineering platform fo ....Engineering Fungal Nonribosomal Peptide Synthetases for Novel Alkaloids. This project aims to use protein-domain shuffling aided by structural biology to decode and engineer a class of modular megaenzymes, called nonribosomal peptide synthetases (NRPSs), in fungi. These are responsible for the biosynthesis of peptide-derived bioactive molecules, such as the antibiotic penicillin and the immunosuppressant cyclosporin. Expected outcomes of this project include a fungal NRPS engineering platform for generating new molecules with desirable biological activities that can be readily scaled up for sustainable bioproduction. This will provide significant benefits to Australia through the development of cutting-edge biotechnologies as well as the discovery of new pharmaceuticals, veterinary products and agrichemicals.Read moreRead less
Structural and molecular studies of endocrine disruption in Australia fauna. Contamination of waterways with compounds that disrupt hormone (endocrine) function is a major environmental problem and threat to the health and fertility of animals. Specifically, we lack an understanding of how these potent endocrine disrupting compounds function in native species. Using an innovative combination of structural and molecular biology approaches we will elucidate the mechanisms of action of environmenta ....Structural and molecular studies of endocrine disruption in Australia fauna. Contamination of waterways with compounds that disrupt hormone (endocrine) function is a major environmental problem and threat to the health and fertility of animals. Specifically, we lack an understanding of how these potent endocrine disrupting compounds function in native species. Using an innovative combination of structural and molecular biology approaches we will elucidate the mechanisms of action of environmental endocrine disrupting compounds in native aquatic species - model fish and the platypus; and develop novel technologies for their detection. This work will provide an understanding of the environmental threat of these pollutants to our unique wildlife and will guide future waterway management. Read moreRead less
Remodelling encapsulin nanocages to help enhance plant carbon fixation. Nature has evolved mechanisms in microbial systems to improve photosynthetic efficiency by saturating the enzyme Rubisco with carbon dioxide. These carbon concentrating mechanisms are genetically complex, precluding successful introduction into crops. Our simpler approach is to use encapsulins, a new source of robust bacterial pore-containing nanocages made from a single gene. This project will optimise the development of sy ....Remodelling encapsulin nanocages to help enhance plant carbon fixation. Nature has evolved mechanisms in microbial systems to improve photosynthetic efficiency by saturating the enzyme Rubisco with carbon dioxide. These carbon concentrating mechanisms are genetically complex, precluding successful introduction into crops. Our simpler approach is to use encapsulins, a new source of robust bacterial pore-containing nanocages made from a single gene. This project will optimise the development of synthetic encapsulin-Rubisco carbon-fixing nanoreactors and transform them into leaf chloroplasts to test their impact on plant photosynthesis and growth. Our genetically simpler solution will aid ongoing global efforts to deliver overdue step change improvements in agricultural productivity.Read moreRead less
Advancing plant synthetic gene circuit capability, robustness, and use. This project aims to advance our ability to control gene expression in plants using synthetic gene circuits. By expanding the toolkit and optimizing circuit components, we aim to achieve more complex capabilities and robust implementation. Furthermore, we will apply gene circuit technologies to enhance plant frost tolerance. The expected project outcomes include a significant advance in gene circuit capabilities, a better un ....Advancing plant synthetic gene circuit capability, robustness, and use. This project aims to advance our ability to control gene expression in plants using synthetic gene circuits. By expanding the toolkit and optimizing circuit components, we aim to achieve more complex capabilities and robust implementation. Furthermore, we will apply gene circuit technologies to enhance plant frost tolerance. The expected project outcomes include a significant advance in gene circuit capabilities, a better understanding of their behavior in plant cells, and the ability to use them to confer advantageous traits. The benefits of this research include new plant biotechnology tools that will underpin future crop yield improvements, and advances in plant-based pharmaceuticals and materials.Read moreRead less