Thioamide ligations: new technologies for peptide and protein synthesis. This project aims to develop novel amide-bond forming reactions for the chemical synthesis of peptides and proteins. New peptide ligation strategies, including an asparagine-based ligation and a residue-independent ligation will be developed that exploit the recent discovery of silver-promoted coupling reactions of thioamides. A novel late-stage, chemo-selective assembly of N-glycosylated asparagine residues in peptides and ....Thioamide ligations: new technologies for peptide and protein synthesis. This project aims to develop novel amide-bond forming reactions for the chemical synthesis of peptides and proteins. New peptide ligation strategies, including an asparagine-based ligation and a residue-independent ligation will be developed that exploit the recent discovery of silver-promoted coupling reactions of thioamides. A novel late-stage, chemo-selective assembly of N-glycosylated asparagine residues in peptides and proteins will also be developed. The outcomes of this research will lead to breakthroughs in synthetic methodologies for the assembly and functionalisation of peptides and proteins, thereby enabling access to a range of homogeneous, post translationally modified proteins though total chemical synthesis. These research outcomes will expand Australia's research capability and global competitiveness in the field of biotechnology, delivering significant benefits to the third largest manufacturing sector in Australia.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
Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an i ....Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an initial screen, distinct variants and combinations of these genes were identified. This project aims to interrogate how variation in these critical genes impacts on the function of cytotoxic lymphocytes, providing insights into the evolutionary drivers of immune recognition mechanisms.Read moreRead less
Understanding peptide bond formation in non-ribosomal peptide biosynthesis. This project aims to uncover the origins of selectivity exhibited by the biosynthetic machinery that produces non-ribosomal peptides through advancing our understanding of how the central peptide synthesis domain functions. This project intends to generate new knowledge about peptide biosynthesis using a highly interdisciplinary approach and essential tools that have been developed. The anticipated outcomes of this proje ....Understanding peptide bond formation in non-ribosomal peptide biosynthesis. This project aims to uncover the origins of selectivity exhibited by the biosynthetic machinery that produces non-ribosomal peptides through advancing our understanding of how the central peptide synthesis domain functions. This project intends to generate new knowledge about peptide biosynthesis using a highly interdisciplinary approach and essential tools that have been developed. The anticipated outcomes of this project will be an enhanced understanding of the structural basis for substrate selection exhibited during peptide synthesis, revealing the specificity code of these key domains. This knowledge is vital for future efforts to reengineer such biosynthetic peptide assembly lines to produce new bioactive peptides.Read moreRead less
Gut Absorption of Constrained Peptides for Local and Systemic Targeting. Aims: This project aims to investigate how peptides are absorbed across the intestinal wall and distributed to organs and fluids in a rodent model by combining bio-analysis and pharmacokinetics with high-resolution microscopy and imaging.
Significance: This project expects to generate the most comprehensive survey to date of the pathways and mechanisms of peptide absorption, biodistribution and immune cell targeting, by ....Gut Absorption of Constrained Peptides for Local and Systemic Targeting. Aims: This project aims to investigate how peptides are absorbed across the intestinal wall and distributed to organs and fluids in a rodent model by combining bio-analysis and pharmacokinetics with high-resolution microscopy and imaging.
Significance: This project expects to generate the most comprehensive survey to date of the pathways and mechanisms of peptide absorption, biodistribution and immune cell targeting, by implementing innovative approaches.
Expected Outcomes: Expected outcomes include significant new knowledge and a new multi-disciplinary platform for measuring peptide absorption.
Benefits: This should provide significant benefits by informing the future design of peptides for supplements, therapeutics and carriers. Read moreRead less
A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societa ....A new platform technology for gene therapy . The project aims to make a landmark contribution to biological science by enabling programmed delivery of therapeutic payloads from biocompatible materials. It will employ a novel synthetic biology approach to form two distinct peptide-enabled molecular architectures in a single system. This is expected to deliver a platform technology that will allow successful programmed delivery of viral vectors. The project is likely to deliver significant societal benefit as a fundamental scientific platform, improving Australia's capacity and impact in the agriculture and the healthcare sectors. The platform technology has the potential to increase the quality of life for patients and their carers, while also produce fitter, healthier livestock.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE240100134
Funder
Australian Research Council
Funding Amount
$796,206.00
Summary
Super-resolution platform to accelerate biological and molecular research. This application aims to establish a new molecular analysis platform integrating a microfluid capillary electrophoresis interface directly to a mass spectrometer with advanced data scanning technology. This enables label-free detection, quantitation and characterisation of intact proteins, lipids and metabolites with unprecedented sensitivity, resolution and throughput. It will enhance ARC projects spanning natural produc ....Super-resolution platform to accelerate biological and molecular research. This application aims to establish a new molecular analysis platform integrating a microfluid capillary electrophoresis interface directly to a mass spectrometer with advanced data scanning technology. This enables label-free detection, quantitation and characterisation of intact proteins, lipids and metabolites with unprecedented sensitivity, resolution and throughput. It will enhance ARC projects spanning natural product discovery, biotechnology, agriculture, and animal, plant and marine biology, as well as single-cell proteomics, lipidomics and metabolomics. It will ensure Australia remains at the forefront of molecular and biological research and create new training and collaborative opportunities both nationally and internationally.Read moreRead less
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
Discovery Early Career Researcher Award - Grant ID: DE220101329
Funder
Australian Research Council
Funding Amount
$435,000.00
Summary
Advanced Chemical Protein Synthesis and Applications. This project aims to develop enhanced methods for the chemical assembly of peptides, oligonucleotides and proteins. This will lead to the creation of new knowledge in chemistry and structural biology, and underpin advances in the drug discovery process, pharmaceutical manufacture and biocatalysis. Once complete, it is expected that lower cost, greener processes for manufacturing drugs such as Enfuvirtide (for HIV) will ensue. A new generatio ....Advanced Chemical Protein Synthesis and Applications. This project aims to develop enhanced methods for the chemical assembly of peptides, oligonucleotides and proteins. This will lead to the creation of new knowledge in chemistry and structural biology, and underpin advances in the drug discovery process, pharmaceutical manufacture and biocatalysis. Once complete, it is expected that lower cost, greener processes for manufacturing drugs such as Enfuvirtide (for HIV) will ensue. A new generation of hyper-stable, environmentally friendly catalysts will also be developed. This could enable domestic production of fine chemicals and essential medicines, and thus create high-tech jobs in a more diversified, resilient economy. Ultimately, it could lead to improved outcomes in human health.Read moreRead less