Discovery Early Career Researcher Award - Grant ID: DE160101281
Funder
Australian Research Council
Funding Amount
$300,036.00
Summary
Biomimetic lipidic self-assembly materials for protein encapsulation. This project intends to improve understanding of the interactions between proteins and lipidic materials to guide the development of new biomaterials. Proteins and peptides play an increasingly important role as drugs, vaccines and diagnostics. However, these fragile, often large, macromolecules come with challenges for drug delivery. Lipid-based materials are ideal matrices for encapsulation of functionally active proteins. T ....Biomimetic lipidic self-assembly materials for protein encapsulation. This project intends to improve understanding of the interactions between proteins and lipidic materials to guide the development of new biomaterials. Proteins and peptides play an increasingly important role as drugs, vaccines and diagnostics. However, these fragile, often large, macromolecules come with challenges for drug delivery. Lipid-based materials are ideal matrices for encapsulation of functionally active proteins. They also offer advantages as drug delivery vehicles including controlled release properties. The combination of strategies creates an ideal delivery system for protein therapeutics. The project aims to characterise the physicochemical interactions between the protein and the lipid matrix. This may guide the development of novel lipidic materials for the encapsulation and controlled release of protein therapeutics.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
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
Solid phase synthesis of side-chain cross-linked peptide oligomers. This research will provide a unique opportunity to investigate the biological pathways and causative factors leading to diseases such as Alzheimer’s disease. Such information will guide the design and development of therapeutic strategies and diagnostic reagents.
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
Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is ....Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is focused on studying structural features of a range of peptides and their contributions to both activity and to resistance against degradation, with the aim to develop stabilised bioactive peptide sequences for in vivo applications, allowing the full potential of peptides as drugs to be realised.Read moreRead less
Development and application of new peptide ligation methods for the synthesis and structure-function studies of glycoproteins. Novel synthetic technologies will be developed in this project to facilitate the preparation of glycoproteins, which are of widespread biological and therapeutic interest. These methods will enable the preparation of pure glycoproteins for detailed biochemical and functional studies eventually leading to therapeutic and diagnostic applications.
Functional studies of tyrosine sulfation using synthetic sulfoproteins. This project aims to address a lack of knowledge about how post-translational sulfation of tyrosine residues influences protein function. The project will develop a synthetic platform for the rapid and efficient generation of libraries of site-selectively sulfated proteins. The new methods will be used to study bioactive sulfated proteins secreted by ticks that dampen the inflammatory response and prevent blood from clotting ....Functional studies of tyrosine sulfation using synthetic sulfoproteins. This project aims to address a lack of knowledge about how post-translational sulfation of tyrosine residues influences protein function. The project will develop a synthetic platform for the rapid and efficient generation of libraries of site-selectively sulfated proteins. The new methods will be used to study bioactive sulfated proteins secreted by ticks that dampen the inflammatory response and prevent blood from clotting. Underpinned by the ability to access synthetic sulfoproteins, expected outcomes include a detailed understanding of how tyrosine sulfation can modulate function and stability of antibodies and proteins with anticoagulant and anti-inflammatory activities. Significant benefits of the project will include breakthrough technologies for the preparation of homogeneously modified proteins, which will strengthen Australia’s growing biotechnology sector.Read moreRead less
Grafted peptide constructs - a new platform for delivering stable bioactive peptides. The project will develop a new strategy to overcome the lack of bioavailability of peptides. The project will design an effective drug delivery vehicle and facilitate drug development as highly active peptides will become attractive drug targets.