Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding ....Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding the effect of editing on how endogenous RNA is perceived by the innate immune system.Read moreRead less
High-throughput microfluidic approach to mapping hierarchies of interactions in the gene regulation machinery. The exploration of protein-protein interactions networks is becoming an extremely active area of research in life sciences. The current project will develop new approaches to accelerate the discovery of novel interacting proteins participating in gene regulation, in order to understand how cells differentiate into different tissues and organs.
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
Harnessing the potential of metals in biocatalysis. The project aims to use an integrated, multi-disciplinary approach to study the properties of a group of related but functionally diverse enzymes; binuclear metallohydrolases (BMHs). These enzymes are of great relevance to protein engineers aiming to produce potent agents for bioremediation and pharmacologists interested in developing drugs. Elucidating and modulating the mode of action of BMHs is thus our main objective and should provide esse ....Harnessing the potential of metals in biocatalysis. The project aims to use an integrated, multi-disciplinary approach to study the properties of a group of related but functionally diverse enzymes; binuclear metallohydrolases (BMHs). These enzymes are of great relevance to protein engineers aiming to produce potent agents for bioremediation and pharmacologists interested in developing drugs. Elucidating and modulating the mode of action of BMHs is thus our main objective and should provide essential information to fully exploit the potential of these enzymes for practical applications. In particular, understanding how metal ions interact with BMHs and how this contributes to their reactivity is crucial to optimally understand their biotechnological potential.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
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
Evolved enzymes and biomimetics for organophosphate degradation. Organophosphate (OP) pesticides are an indispensable part of modern agriculture - their use results in dramatically increased crop yields. However, they are toxic and can damage the environment and cause significant health problems. This project intends to evolve enzymes capable of dealing with problems caused by OPs.