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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
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
In vivo molecular imaging using engineered affinity reagents and fluorescent laser scanning confocal endomicroscopy. The goal of this project is to develop laser scanning confocal endomicroscopy as a tool for basic scientific discovery and rapid detection of disease biomarkers. The cutting-edge instrument and associated technologies will provide scientists with unprecedented access to dynamic biological processes as they occur in real-time. In addition, it will enable the development of virtual ....In vivo molecular imaging using engineered affinity reagents and fluorescent laser scanning confocal endomicroscopy. The goal of this project is to develop laser scanning confocal endomicroscopy as a tool for basic scientific discovery and rapid detection of disease biomarkers. The cutting-edge instrument and associated technologies will provide scientists with unprecedented access to dynamic biological processes as they occur in real-time. In addition, it will enable the development of virtual biopsies and instant diagnosis without the need for costly and time-consuming histopathological reports. Thus, it will not only drive transformative research but also transform health care delivery. It will also be a major boost to the Australian biotechnology industry with potential for enormous economic benefits.Read moreRead less
New methods for the chemical synthesis of a library of glycopeptide-based tri-component cancer vaccines. A novel method for the synthesis of tumour-associated glycopeptides will be developed in this research as well as the preparation of a library of glycopeptide-based cancer vaccines. These vaccines will be tested in immunological studies with a view to elucidating new immune-based therapies for the treatment of cancer.
Discovery Early Career Researcher Award - Grant ID: DE140101632
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
Development of Innovative Chemical Tools for Studying Glycosyltransferases . This project aims to develop chemical probes capable of selectively binding and inhibiting two classes of carbohydrate processing enzymes known as O-linked beta-N-acetylglucosamine transferase and sialyltransferases. These enzymes are overexpressed in various cancers and play critical roles in cancer progression. Probes will be developed to analyse the activities of these enzymes in cancer cells.
Discovery Early Career Researcher Award - Grant ID: DE150101863
Funder
Australian Research Council
Funding Amount
$372,000.00
Summary
Strained alkenes as chemical probes for cysteine sulfenic acid. This project aims to introduce strained alkenes as probes for cysteine sulfenic acid, a poorly understood biomarker for oxidative stress. This probe will enable rapid detection of cysteine sulfenic acid and meet an urgent need for tools to map cysteine redox signalling. Moreover, since many enzymes feature a cysteine sulfenic acid at their active site, the strained alkene probes will also serve as useful inhibitor probes of these en ....Strained alkenes as chemical probes for cysteine sulfenic acid. This project aims to introduce strained alkenes as probes for cysteine sulfenic acid, a poorly understood biomarker for oxidative stress. This probe will enable rapid detection of cysteine sulfenic acid and meet an urgent need for tools to map cysteine redox signalling. Moreover, since many enzymes feature a cysteine sulfenic acid at their active site, the strained alkene probes will also serve as useful inhibitor probes of these enzymes. Such inhibitor probes will provide critical information for potential therapeutic applications in human conditions associated with oxidative stress such as ageing, cancer, and heart disease.Read moreRead less
New peptide ligation technology for the rapid assembly of modified proteins. The project aims to develop novel technologies to enable the synthesis of modified proteins that are of widespread biological and therapeutic interest. More than 70 per cent of all human proteins are modified with a range of functionalities after translation from the ribosome. Although these modifications are of crucial importance for biological activity, characterising the effect of a given modification on function is ....New peptide ligation technology for the rapid assembly of modified proteins. The project aims to develop novel technologies to enable the synthesis of modified proteins that are of widespread biological and therapeutic interest. More than 70 per cent of all human proteins are modified with a range of functionalities after translation from the ribosome. Although these modifications are of crucial importance for biological activity, characterising the effect of a given modification on function is difficult due to problems in obtaining the protein in pure form. The goal of this project is to develop a peptide ligation methodology to access pure modified proteins in a rapid manner through the exploitation of a new reaction recently discovered in our laboratory. The project plans to explore the scope and mechanism of the new reaction as well as its application in the total chemical synthesis and structure-function studies of important modified proteins.Read moreRead less
Fine-tuning the conformations of cyclic peptides: a paradigm for optimising synthetic efficiency and biological activity. This proposal develops a strategy for optimising the synthesis and properties of an important class of drug molecules known as cyclic peptides. Such molecules show great promise as therapeutic agents, but they can be very difficult to synthesise and their three-dimensional shapes can be difficult to control. This project simultaneously addresses both of these problems, by exp ....Fine-tuning the conformations of cyclic peptides: a paradigm for optimising synthetic efficiency and biological activity. This proposal develops a strategy for optimising the synthesis and properties of an important class of drug molecules known as cyclic peptides. Such molecules show great promise as therapeutic agents, but they can be very difficult to synthesise and their three-dimensional shapes can be difficult to control. This project simultaneously addresses both of these problems, by exploiting a series of unusual amino acid building blocks that have a variety of shapes and different levels of conformational flexibility. This strategy will enable the development of a wide variety of therapeutically-relevant cyclic peptides, and to exemplify this concept a panel of cyclic peptides will be created that are specifically targeted for activity against solid tumours.Read moreRead less