Artificial Self-Replication of Peptide Nanocapsules. Replication is key to the operation of biology, but how molecular replicators arose spontaneously on early Earth remains an open question. The ability of molecules to self-replicate must have come before the development of the highly evolved enzymes that biology currently employs. The aim of this Future Fellowship is to develop a peptide nanocapsule capable of replicating itself nonenzymatically by self-templated ligation, thus offering a plat ....Artificial Self-Replication of Peptide Nanocapsules. Replication is key to the operation of biology, but how molecular replicators arose spontaneously on early Earth remains an open question. The ability of molecules to self-replicate must have come before the development of the highly evolved enzymes that biology currently employs. The aim of this Future Fellowship is to develop a peptide nanocapsule capable of replicating itself nonenzymatically by self-templated ligation, thus offering a platform that possesses the traits needed for Darwinian evolution to emerge. By obtaining a better understanding of the design and function of self-replicating systems, this project is expected to transform our understanding of some of the key chemical principles needed for life's emergence.Read moreRead less
Understanding prokaryotic small proteins from context. Prokaryotic small proteins are increasingly recognised to play important biological roles but have been largely overlooked due to the lack of adequate tools to study them. This project aims to develop new methods to identify and predict the functions of small proteins from microbial communities by studying sequence patterns in their genomes. These predicted functions will be confirmed in the laboratory, leading to a catalogue of newly charac ....Understanding prokaryotic small proteins from context. Prokaryotic small proteins are increasingly recognised to play important biological roles but have been largely overlooked due to the lack of adequate tools to study them. This project aims to develop new methods to identify and predict the functions of small proteins from microbial communities by studying sequence patterns in their genomes. These predicted functions will be confirmed in the laboratory, leading to a catalogue of newly characterised small proteins from a diverse range of habitats and geographies. By creating new ways to study the role of small proteins in the global microbiome, we will provide the foundational knowledge required to leverage these proteins for use in biotechnology. Read moreRead less
Venom-derived blood-brain-barrier shuttles. This project aims to discover new venom peptides capable of crossing the blood-brain barrier and to develop non-toxic peptide-based brain delivery systems. It addresses long-standing challenges and knowledge gaps in the delivery of macromolecules across biological barriers. Expected outcomes include an improved understanding of the strategies nature exploits to reach targets in the brain, mechanistic pathways to cross biological membranes, and innovati ....Venom-derived blood-brain-barrier shuttles. This project aims to discover new venom peptides capable of crossing the blood-brain barrier and to develop non-toxic peptide-based brain delivery systems. It addresses long-standing challenges and knowledge gaps in the delivery of macromolecules across biological barriers. Expected outcomes include an improved understanding of the strategies nature exploits to reach targets in the brain, mechanistic pathways to cross biological membranes, and innovative discovery and chemistry strategies to advance fundamental research across the chemical and biological sciences. Anticipated benefits include technological innovations relevant to Australia’s biotechnology sector and enhanced capacity for cross-disciplinary collaboration.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
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: DE230101236
Funder
Australian Research Council
Funding Amount
$444,154.00
Summary
Chimeric molecules for precision protein modification. This project aims to address fundamental questions on how natural modifications of proteins cause functional changes inside cells. The project expects to generate new knowledge in the areas of organic chemistry and chemical biology through the development of a synthetic platform for the discovery of a novel class of chimeric molecules that can trigger precise modifications of proteins. Expected outcomes include a detailed understanding of ho ....Chimeric molecules for precision protein modification. This project aims to address fundamental questions on how natural modifications of proteins cause functional changes inside cells. The project expects to generate new knowledge in the areas of organic chemistry and chemical biology through the development of a synthetic platform for the discovery of a novel class of chimeric molecules that can trigger precise modifications of proteins. Expected outcomes include a detailed understanding of how specific modifications modulate protein and cellular function. Significant benefits of this interdisciplinary project include access to a new class of molecules for basic research that may also find use for cell engineering applications within the growing biotechnology sector in Australia.Read moreRead less
Defining a new family of sodium channel accessory proteins. Voltage-gated sodium channels are key proteins that function as multi-subunit complexes to regulate neuronal excitability. The project aims to investigate the structure and function of a novel family of accessory subunits by utilizing a class of toxins, derived from the giant Australian stinging tree, that directly binds to these proteins to modulate sodium channel function. The project aims to generate significant new knowledge on the ....Defining a new family of sodium channel accessory proteins. Voltage-gated sodium channels are key proteins that function as multi-subunit complexes to regulate neuronal excitability. The project aims to investigate the structure and function of a novel family of accessory subunits by utilizing a class of toxins, derived from the giant Australian stinging tree, that directly binds to these proteins to modulate sodium channel function. The project aims to generate significant new knowledge on the function of sodium channels as multi-protein complexes. Expected outcomes of this project include development of novel channel-modulating molecules that may have applications as neuroscience tools to address fundamental questions about ion channel function and biology.Read moreRead less
Greening the production of peptides and proteins . This project aims to develop a green and sustainable synthetic platform for the production of peptide and protein molecules. The synthetic methodology that will be developed has the potential to solve a major technological gap in the field by providing an efficient and cost-effective method for manufacturing peptides and proteins with a substantial reduction in reagent and solvent waste over currently employed methods. Expected outcomes include ....Greening the production of peptides and proteins . This project aims to develop a green and sustainable synthetic platform for the production of peptide and protein molecules. The synthetic methodology that will be developed has the potential to solve a major technological gap in the field by providing an efficient and cost-effective method for manufacturing peptides and proteins with a substantial reduction in reagent and solvent waste over currently employed methods. Expected outcomes include the delivery of a breakthrough green technology for accessing high value peptide and protein targets in academia and industry, and the training of industry-ready early career researchers, both of which will benefit Australia’s growing biotechnology and pharmaceutical manufacturing sectors.Read moreRead less