Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost a ....Single-session Introduction of Mutations in Parallel Lines (SIMPL). This project aims to develop a novel method for markedly accelerating production of genetically modified mice, which are a key 'tool' for studying biological processes and diseases. The work plans to take CRISPR, the latest gene-editing technique, to the next level by developing a novel CRISPR-based method to generate different mouse strains with distinct variations of the same gene sequences, at a fraction of the present cost and time. This project should overcome a major barrier to studying gene function with unprecedented detail, thereby opening new avenues for future research into biological processes. Thus, the outcomes from this project should impact on the entire field of biomedical research, and advance Australia's biotech industry.Read moreRead less
Age-related mechanisms of amino acid signalling in skeletal muscle. This project aims to increase our understanding of the role of glycine receptor-mediated signalling and its metabolism in the amino acid sensing capacity of mTORC1, a key enzyme regulating muscle protein synthesis. Ageing is associated with a progressive decline in skeletal muscle mass, weakness, and impaired regeneration after injury. Impaired anabolic signalling after food intake has been proposed as a key contributor, yet the ....Age-related mechanisms of amino acid signalling in skeletal muscle. This project aims to increase our understanding of the role of glycine receptor-mediated signalling and its metabolism in the amino acid sensing capacity of mTORC1, a key enzyme regulating muscle protein synthesis. Ageing is associated with a progressive decline in skeletal muscle mass, weakness, and impaired regeneration after injury. Impaired anabolic signalling after food intake has been proposed as a key contributor, yet the metabolic pathways responsible for nutrient sensing and regulation of protein synthesis remain unresolved. The project will assess defective amino acid sensing and protein synthesis in old mammals, identifying the role of glycine signalling in these processes. The project expects to underpin development of muscle-specific modulators of muscle homeostasis with broad relevance to Australia’s ageing population.Read moreRead less
Boosting C4 photosynthesis to climate proof crop yields. Building next generation C4 crops, such as maize, sugarcane and sorghum, to cope with drought and heat stress is requisite to ensure the supply of food and fodder. Here we will increase the content and / or catalytic efficiency of the primary carboxylase of C4 photosynthesis (PEPC) that supplies CO2 to the carbon concentrating mechanism and ensures high photosynthetic rates. We will develop new SynBio tools to create and test novel PEPC is ....Boosting C4 photosynthesis to climate proof crop yields. Building next generation C4 crops, such as maize, sugarcane and sorghum, to cope with drought and heat stress is requisite to ensure the supply of food and fodder. Here we will increase the content and / or catalytic efficiency of the primary carboxylase of C4 photosynthesis (PEPC) that supplies CO2 to the carbon concentrating mechanism and ensures high photosynthetic rates. We will develop new SynBio tools to create and test novel PEPC isoforms with desirable properties. Ultimately, the project aims to identify isoforms that improve plant fitness under stress conditions. Optimising PEPC activity will provide next generation solutions to improve water balance and carbon assimilation to keep C4 crops productive under future climates.Read moreRead less
Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisa ....Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisation or decay to control development. RNA-driven processes program morphogenesis and differentiation of spermatids, but via mechanisms only poorly understood. Uncovering the function of extensive cytoplasmic polyadenylation, which is essential for murine fertility, may fuel the next wave of RNA biotech applications. Read moreRead less
Combining new synthetic biology tools to boost crop CO2 capture and growth. A solution for improving crop yield is to enhance the carbon dioxide fixation properties of the enzyme Rubisco whose inefficient activity often limits plant growth. This project makes use of new synthetic biology capabilities to artificially evolve Rubisco in the laboratory and select for new versions with improved performance. These beneficial changes will be introduced into crop Rubisco using targeted gene editing appr ....Combining new synthetic biology tools to boost crop CO2 capture and growth. A solution for improving crop yield is to enhance the carbon dioxide fixation properties of the enzyme Rubisco whose inefficient activity often limits plant growth. This project makes use of new synthetic biology capabilities to artificially evolve Rubisco in the laboratory and select for new versions with improved performance. These beneficial changes will be introduced into crop Rubisco using targeted gene editing approaches and the improvements in photosynthesis, growth and yield evaluated. This information will aid complimentary biotechnological efforts seeking to supercharge photosynthesis and help deliver the second Green Revolution needed to meet the improvement required in future agriculture productivity and resource use.Read moreRead less
Light-driven biocatalytic cell factories. This project aims to develop single-cell algae optimised for high-efficiency green hydrogen production from cheap, sustainable resources - sunlight and water. The success of this project would be a game changer for industry by dramatically improving light to fuel conversion efficiencies. The expected high-efficiency cells would be a valuable resource for a wide range of other light-driven advanced bio-manufacture applications from high-value biopharmaceu ....Light-driven biocatalytic cell factories. This project aims to develop single-cell algae optimised for high-efficiency green hydrogen production from cheap, sustainable resources - sunlight and water. The success of this project would be a game changer for industry by dramatically improving light to fuel conversion efficiencies. The expected high-efficiency cells would be a valuable resource for a wide range of other light-driven advanced bio-manufacture applications from high-value biopharmaceuticals (e.g. <10 Hectare scale) through to renewable fuels (e.g. 10-1000 Hectare regional scale). The benefits would include advanced green chemical and biochemical manufacturing, diversified sources for green H2 production, regional development, industry growth, job security and exports.Read moreRead less
The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyami ....The “New” Biochemistry of Polyamines: When Metabolic Pathways Collide. Basic biochemistry and the metabolic regulation of proliferation remain as the fundamental building blocks of knowledge in cell biology that have enabled breakthrough advances in biology and medicine. Polyamines are unique and ubiquitous low-Mr amines that play vital roles in many biological processes, including proliferation, DNA/RNA synthesis, etc. This proposal will mechanistically dissect the "new" biochemistry of polyamines, as we have discovered that polyamines are regulated by iron at 2-major levels, involving >10-key polyamine pathway proteins. This proposal represents first-in-field studies specifically designed to dissect mechanisms involved in this relationship. Our Central Hypothesis is that iron regulates polyamine metabolism.Read moreRead less
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
Engineer enzyme nanoparticles as antibiotic alternatives for agriculture. Antibiotic usage in agriculture contributes to spread of resistant bacteria. Existing antibiotic alternatives to minimize such usage are focused on growth promotion of animals and infection prevention, but lack efficient treatment. This project aims to engineer enzyme nanoparticles, with synergy from multiple enzymes, to confer better antibacterial abilities against livestock pathogens. It will combine protein engineering, ....Engineer enzyme nanoparticles as antibiotic alternatives for agriculture. Antibiotic usage in agriculture contributes to spread of resistant bacteria. Existing antibiotic alternatives to minimize such usage are focused on growth promotion of animals and infection prevention, but lack efficient treatment. This project aims to engineer enzyme nanoparticles, with synergy from multiple enzymes, to confer better antibacterial abilities against livestock pathogens. It will combine protein engineering, nanotechnology and biophysics to develop new enzyme nanoparticles that can be manufactured at low-cost through self-assembly process. The intended outcome is knowledge on molecular engineering of enzyme nanoparticles and innovative agriculture biotechnology for treatment of bacterial infectious diseases in livestock.Read moreRead less
Safer gene editing tools for Australian livestock and biotech industries. Editing the genome of an organism in an efficient and safe fashion is critical for the livestock and biotechnology industries. While CRISPR-Cas9 has become the method of choice for genome editing, it is known to introduce unwanted "on-target" and "off-target" mutations, limiting its utility. To address this the CI team created a novel genome editing platform technology termed Crackling-CAST that is almost 100% accurate, w ....Safer gene editing tools for Australian livestock and biotech industries. Editing the genome of an organism in an efficient and safe fashion is critical for the livestock and biotechnology industries. While CRISPR-Cas9 has become the method of choice for genome editing, it is known to introduce unwanted "on-target" and "off-target" mutations, limiting its utility. To address this the CI team created a novel genome editing platform technology termed Crackling-CAST that is almost 100% accurate, while retaining the efficiency of the classical Cas9 system. This project will exemplify the capabilities of the novel gene targeting platform in cell types used by the biotechnology and livestock sectors, ensuring its global uptake by these industries and delivering significant economic benefits for Australia. Read moreRead less