Site-specific protein functionalisation at diselenides via photocatalysis . This project aims to develop a new photocatalytic reaction for the on demand functionalisation of proteins. The synthetic methodology will solve a major technological gap in the field by enabling efficient access to proteins with defined modifications at specific locations. Functionalised proteins generated in the project will underpin a detailed understanding of how specific modifications influence the structure and fun ....Site-specific protein functionalisation at diselenides via photocatalysis . This project aims to develop a new photocatalytic reaction for the on demand functionalisation of proteins. The synthetic methodology will solve a major technological gap in the field by enabling efficient access to proteins with defined modifications at specific locations. Functionalised proteins generated in the project will underpin a detailed understanding of how specific modifications influence the structure and function of several important proteins. The project will generate significant new knowledge in the fields of chemistry and biology and will foster interdisciplinary collaboration, nationally and internationally. The breakthrough technology also has the potential to benefit Australia’s biotechnology sector.Read moreRead less
Advances in Peptide Synthesis: Exploiting Underutilised Functional Groups. The translation of therapeutically-relevant classes of peptides to the clinic is often limited by chemists' ability to synthesise these complex biomolecules efficiently and sustainably. This project aims to develop new tools for the preparation of designer peptides that are broadly inspired by an underutilised reactive group found in naturally-occurring peptide sequences. Expected outcomes encompass health and economic be ....Advances in Peptide Synthesis: Exploiting Underutilised Functional Groups. The translation of therapeutically-relevant classes of peptides to the clinic is often limited by chemists' ability to synthesise these complex biomolecules efficiently and sustainably. This project aims to develop new tools for the preparation of designer peptides that are broadly inspired by an underutilised reactive group found in naturally-occurring peptide sequences. Expected outcomes encompass health and economic benefits for the Australian community, including: the first approach to a class of promising antibiotic peptide natural product analogues, the development of a mild electrochemical approach to peptide modification, and the production of a library of novel amino acids for incorporation into potential antibiotic leads.Read moreRead less
Time to shine for constrained peptides as next-generation pharmaceuticals. Current methods for the screening and generation of peptide and protein drugs are laborious, expensive and often incompatible with the biological systems used in pharmaceutical industries. Leveraging recent advancements in chemistry and molecular biology, this project aims to improve the design, synthesis and screening of peptide-based pharmaceuticals. Key research outcomes are innovative biocompatible chemical transforma ....Time to shine for constrained peptides as next-generation pharmaceuticals. Current methods for the screening and generation of peptide and protein drugs are laborious, expensive and often incompatible with the biological systems used in pharmaceutical industries. Leveraging recent advancements in chemistry and molecular biology, this project aims to improve the design, synthesis and screening of peptide-based pharmaceuticals. Key research outcomes are innovative biocompatible chemical transformations for the screening of large peptide libraries, to unleash the revolutionary potential of constrained peptides in drug development. Expected benefits are reliable and cost-effective technologies for the rapid production of biologically active molecules for future targeted use in human and agricultural pharmaceuticals.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE240100502
Funder
Australian Research Council
Funding Amount
$424,875.00
Summary
Building Molecular Complexity Through Enzyme-Enabled Synthesis. Many valuable natural molecules are too complex to be commercially synthesised by current technologies. Despite advances in synthetic chemistry there is great need to adopt the elegant biocatalytic strategies for complex molecule synthesis found in nature, employing sophisticated enzyme catalysts. This interdisciplinary research program aims to address the shortcomings of traditional synthetic methods through the development of enzy ....Building Molecular Complexity Through Enzyme-Enabled Synthesis. Many valuable natural molecules are too complex to be commercially synthesised by current technologies. Despite advances in synthetic chemistry there is great need to adopt the elegant biocatalytic strategies for complex molecule synthesis found in nature, employing sophisticated enzyme catalysts. This interdisciplinary research program aims to address the shortcomings of traditional synthetic methods through the development of enzyme catalysts to rapidly generate complex molecular structures. These novel molecules can be readily converted into pharmaceuticals and agrochemicals leading to advancements in the bio-enabled production and application of organic molecules in these vital fields. Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230100634
Funder
Australian Research Council
Funding Amount
$410,140.00
Summary
Phos-Ligation: A powerful new tool for chemoselective protein modification. The project aims to develop a powerful new method for the generation of pure modified proteins. Tools for modification of proteins are integral to the study of protein structure and function as well as the commercial production of biopharmaceuticals. The extremely cost effective and operationally simple chemistry that will be developed in this project will overcome a number of pitfalls of currently available methods for ....Phos-Ligation: A powerful new tool for chemoselective protein modification. The project aims to develop a powerful new method for the generation of pure modified proteins. Tools for modification of proteins are integral to the study of protein structure and function as well as the commercial production of biopharmaceuticals. The extremely cost effective and operationally simple chemistry that will be developed in this project will overcome a number of pitfalls of currently available methods for protein modification, and will therefore deliver substantial technological innovation to both academia and industry. Through domestic and international collaboration, this new technology will be applied to study proteins involved in the defence of wheat against fungal rust disease and in inflammatory signalling in humans.Read moreRead less
Rational design of array-based nanozyme sensors. The project aims to obtain a deep understanding of molecular interactions at the nano-bio interface, and use this knowledge to develop a robust sensor technology for the rapid detection of foodborne pathogens in complex samples. The project proposes to employ an innovative approach that mimics the senses of smell and taste, where an array of aptamers are expected to work in synergy to precisely identify a target, providing an edge over current sen ....Rational design of array-based nanozyme sensors. The project aims to obtain a deep understanding of molecular interactions at the nano-bio interface, and use this knowledge to develop a robust sensor technology for the rapid detection of foodborne pathogens in complex samples. The project proposes to employ an innovative approach that mimics the senses of smell and taste, where an array of aptamers are expected to work in synergy to precisely identify a target, providing an edge over current sensing technologies. Expected outcomes include a ready-to-go analytical tool for the detection of food contaminants. This should provide significant economic, health, and social benefits through supporting Australian food and health sectors, and the potential commercialisation of sensor technologies.Read moreRead less
Precise, Cytosolic Dendrimer Delivery Systems. This project aims to use precisely targeted dendrimer technology to improve the delivery of poorly permeable molecules to their subcellular sites of action. Our cutting edge approach combines innovative phage screening techniques and advanced dendrimer synthesis. The outcomes of this proposal will be: 1) a targeting system that is manufacturable at scale and reasonable cost, 2) a dendrimer delivery system that is rapidly internalised into specifc ta ....Precise, Cytosolic Dendrimer Delivery Systems. This project aims to use precisely targeted dendrimer technology to improve the delivery of poorly permeable molecules to their subcellular sites of action. Our cutting edge approach combines innovative phage screening techniques and advanced dendrimer synthesis. The outcomes of this proposal will be: 1) a targeting system that is manufacturable at scale and reasonable cost, 2) a dendrimer delivery system that is rapidly internalised into specifc target cells and 3) bio-responsive dendrimers that promote delivery of their cargo into the cytosol. This work will strengthen a highly successful collaboration between the Australian biotech company Starpharma and Monash University, to design the next generation of nanomaterials delivery systems.Read moreRead less
Homogenous Antibody-Metal Conjugates For Immuno-Mass Spectrometry Imaging. This project aims to use bespoke metal labels and high-resolution mass spectrometry imaging to address current shortcomings in approaches that visualise and measure proteins in cells and tissue. It expects to substantially increase the utility of immuno-mass spectrometry imaging technology to analyses that are refractory to current techniques and workflows. Expected outcomes include metal probes that facilitate the spatia ....Homogenous Antibody-Metal Conjugates For Immuno-Mass Spectrometry Imaging. This project aims to use bespoke metal labels and high-resolution mass spectrometry imaging to address current shortcomings in approaches that visualise and measure proteins in cells and tissue. It expects to substantially increase the utility of immuno-mass spectrometry imaging technology to analyses that are refractory to current techniques and workflows. Expected outcomes include metal probes that facilitate the spatial quantification of multiple biomolecules on a single histological section, providing significant benefits to bioscience laboratories that require complex workflows to visualise and obtain quantitative data on the expression of biomolecules.Read moreRead less
Next Generation Fluorescent Tools for Measuring Autophagy Dynamics in Cells. This project aims to create new molecular tools for detecting a crucial cell survival process called autophagy. Specifically, this project will develop small molecule fluorescent probes that are specific to autophagy, for the first time, by interacting with the key autophagy marker proteins or cargos. This will allow researchers to visualise and quantify autophagy activity in living cells without disrupting the system, ....Next Generation Fluorescent Tools for Measuring Autophagy Dynamics in Cells. This project aims to create new molecular tools for detecting a crucial cell survival process called autophagy. Specifically, this project will develop small molecule fluorescent probes that are specific to autophagy, for the first time, by interacting with the key autophagy marker proteins or cargos. This will allow researchers to visualise and quantify autophagy activity in living cells without disrupting the system, which is not currently possible. This project represents a major technical and knowledge advance that will improve our understanding of autophagy in fundamental biology and ultimately contribute to the development of new intervention strategies for diseases like neurodegeneration and cancers.Read moreRead less
Designer Nanoparticles Enable mRNA Protein Factories. Intracellular delivery of mRNA facilitates target protein production, which could build protein factories that are essential in biomanufacturing industries. However, the instability of mRNA greatly lowers the protein production performance, limiting the commercial translation potential. This project aims to develop a new generation of nanoparticle delivery system to enhance mRNA stability against intracellular unstable cue, enzymatic digestio ....Designer Nanoparticles Enable mRNA Protein Factories. Intracellular delivery of mRNA facilitates target protein production, which could build protein factories that are essential in biomanufacturing industries. However, the instability of mRNA greatly lowers the protein production performance, limiting the commercial translation potential. This project aims to develop a new generation of nanoparticle delivery system to enhance mRNA stability against intracellular unstable cue, enzymatic digestion and thermal stress. This will be achieved by tailoring the nanochemistry at multi-scales. Expected outcomes include new knowledge in custom-design of functional nanomaterials for mRNA delivery, and new technology that will bring commercial benefits to the partner organisation and the biopharma sector.Read moreRead less