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Novel chemoenzymatic synthesis and bioconjugation of peptides and proteins. This project aims to solve the critical difficulty of producing the complex peptide insulin and related insulin-like peptides (INSLs) and their analogues. The project will use unique, recyclable enzymes which ligate smaller peptide segments with extraordinary site and substrate selectivity. The expected outcome of the project is novel, cheaper and scalable, enzyme-mediated engineering of this critical class of peptides a ....Novel chemoenzymatic synthesis and bioconjugation of peptides and proteins. This project aims to solve the critical difficulty of producing the complex peptide insulin and related insulin-like peptides (INSLs) and their analogues. The project will use unique, recyclable enzymes which ligate smaller peptide segments with extraordinary site and substrate selectivity. The expected outcome of the project is novel, cheaper and scalable, enzyme-mediated engineering of this critical class of peptides as biological probes and potential therapeutic agents.Read moreRead less
Atomic details of antimicrobial peptides at work in live cells. This project aims to develop methods to determine the detailed structure of biologically important molecules in live cells to better understand how biomolecular structure is related to disease. The structure at the atomic level of the molecules of life is usually characterised by crystal or solution studies in model systems. However, the structure of many biologically important molecules depends on their environment. Using new instr ....Atomic details of antimicrobial peptides at work in live cells. This project aims to develop methods to determine the detailed structure of biologically important molecules in live cells to better understand how biomolecular structure is related to disease. The structure at the atomic level of the molecules of life is usually characterised by crystal or solution studies in model systems. However, the structure of many biologically important molecules depends on their environment. Using new instrumentation and labelling schemes, the project plans to use nuclear magnetic resonance methods to study antibiotics and antimicrobial peptides in live bacteria and human cells. The goal is to resolve how these molecules cross cell membranes and how biomolecular structure is related to activity, which may advance development in biotechnology and therapeutic treatments against drug-resistant infections.Read moreRead less
New Conus-derived alpha-conotoxin analgesics for the treatment of chronic pain: structure, mode of action, delivery and disposition. Current product deficiencies in the area of pain management are forcing the pharmaceutical industry to develop new strategies for achieving analgesia and reduce their dependence on traditional, addictive opiate-based products. Structural modification of cone snail derived peptides will provide exciting new leads for achieving effective analgesia.
Innovations in peptide-based drug design. This project will aim to develop new types of drugs that fill a gap between existing small molecule drugs, which are relatively inexpensive and stable, but often have side-effects, and biologics which are very expensive and require injection. Our new generation of peptide-based drugs promise to be applicable to diseases that are not treatable by current drugs.
Development of effective peptide-based drugs. There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. The aim of this research project is to develop potent and effective peptide-based drugs that are able to resist the body's natural degradation pathways so that they can reach their biological target and act as effective drugs.
Molecular Interactions with an antibiotic target in DNA replication. This project aims to develop and use new technologies to address mechanistic aspects of anti-bacterial compounds in development, and of the development of resistance to them. The project will focus on the sliding clamp subunit of the bacterial replicative polymerase by studying its association with many other proteins in vitro and in vivo, using novel techniques in solid-state NMR, single-molecule fluorescence and molecular mic ....Molecular Interactions with an antibiotic target in DNA replication. This project aims to develop and use new technologies to address mechanistic aspects of anti-bacterial compounds in development, and of the development of resistance to them. The project will focus on the sliding clamp subunit of the bacterial replicative polymerase by studying its association with many other proteins in vitro and in vivo, using novel techniques in solid-state NMR, single-molecule fluorescence and molecular microbiology. The outcomes are expected to be an increased understanding of bacterial DNA replication and mechanisms of antibiotic action and resistance. This project expects to generate new knowledge to assist in combatting antibiotic resistance in Gram-negative bacterial pathogens.Read moreRead less
Development of disulphide-rich peptides for drug design. Peptides are an outstanding source of potential drug leads. This project seeks to build on earlier breakthroughs by developing stable, peptide-based drugs to combat cancer and autoimmune diseases. The peptides, derived from natural sources, are anticipated to provide drug leads that can ultimately lead to treatments for these diseases.
Discovery Early Career Researcher Award - Grant ID: DE210100422
Funder
Australian Research Council
Funding Amount
$447,346.00
Summary
Using toxins to manipulate the gating of voltage-gated sodium channels. The project aims to investigate how sodium channel subtypes contribute to the excitability of sensory neurons by utilising venom-derived peptides that specifically target and alter the function of these channels. This project expects to generate new knowledge in the area of neuroscience using an interdisciplinary approach including synthetic peptide chemistry, pharmacology and electrophysiology. Expected outcomes of this pro ....Using toxins to manipulate the gating of voltage-gated sodium channels. The project aims to investigate how sodium channel subtypes contribute to the excitability of sensory neurons by utilising venom-derived peptides that specifically target and alter the function of these channels. This project expects to generate new knowledge in the area of neuroscience using an interdisciplinary approach including synthetic peptide chemistry, pharmacology and electrophysiology. Expected outcomes of this project include the development of new venom-based research tools and improved techniques for studying sodium channel function. This will provide significant benefits, including advancement of fundamental knowledge in physiology and the development of novel analgesics. Read moreRead less
Novel green scalable chemical peptide synthesis and enzyme immobilization. The Project aims to address the critical issue of developing green processes for the chemical production of peptides including on an industrial scale. It will use unique, biocompatible solid supports that have been invented by our partner SpheriTech Ltd together with other reagents to allow synthesis to be conducted in water rather than toxic organic solvents. Expected outcomes of the Project include an international part ....Novel green scalable chemical peptide synthesis and enzyme immobilization. The Project aims to address the critical issue of developing green processes for the chemical production of peptides including on an industrial scale. It will use unique, biocompatible solid supports that have been invented by our partner SpheriTech Ltd together with other reagents to allow synthesis to be conducted in water rather than toxic organic solvents. Expected outcomes of the Project include an international partnership in highly efficient environmentally-friendly assembly of peptides and of their analogues by both solid phase synthesis and immobilized enzyme-mediated ligation. The clear benefit will be the first novel, water-based, scalable green synthesis of peptides as biological probes and potential therapeutic agents.Read moreRead less
New platform technologies for the chemical synthesis of post-translationally modified proteins. The last decade has seen an explosion in the number of protein drugs approved for use in the clinic, a large proportion of which possess post-translational modifications (PTMs). These modified protein drugs are produced and sold as mixtures which has led to difficulties in understanding the role of specific PTMs on activity and in gaining clinical approval for candidate drugs. This project will provid ....New platform technologies for the chemical synthesis of post-translationally modified proteins. The last decade has seen an explosion in the number of protein drugs approved for use in the clinic, a large proportion of which possess post-translational modifications (PTMs). These modified protein drugs are produced and sold as mixtures which has led to difficulties in understanding the role of specific PTMs on activity and in gaining clinical approval for candidate drugs. This project will provide a fundamental solution to this problem through the development of novel synthetic methods and a powerful new platform technology for accessing PTM proteins in pure form. The utility of this technology will be demonstrated through its use in the total chemical synthesis of a range of PTM proteins for applications in biology and medicine.Read moreRead less