Discovery Early Career Researcher Award - Grant ID: DE120103152
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Development of next generation drugs against Helicobacter pylori. Gastric cancer is the second leading cause of cancer-related death in the world and infection by Helicobacter pylori bacteria is the main cause of this disease. The aim of this project is to develop new approaches to treat Helicobacter pylori infection that will give superior results and lower side effects than available therapies.
A new source of bivalent molecules from nature. This project aims to describe a new class of naturally occurring multivalent molecules termed secreted cysteine-rich repeat proteins (SCREPs). Multivalency is a key feature of molecular interaction in biology, underlying the high specificity and potency found in many proteins. Focusing on bivalent peptides, the project will generate a database of bioactive SCREPs with similarity to known bioactive peptides, and develop new recombinant methods for t ....A new source of bivalent molecules from nature. This project aims to describe a new class of naturally occurring multivalent molecules termed secreted cysteine-rich repeat proteins (SCREPs). Multivalency is a key feature of molecular interaction in biology, underlying the high specificity and potency found in many proteins. Focusing on bivalent peptides, the project will generate a database of bioactive SCREPs with similarity to known bioactive peptides, and develop new recombinant methods for their production. The project will use advanced nuclear magnetic resonance spectroscopy to characterise members of this new class, providing new insights into the design of bivalent and multivalent peptides and establishing a new source of molecules with applications in the rapidly growing biotechnology sector.Read moreRead less
A Tough Resilin Based Hydrogel Platform for Repair and Regeneration. This project seeks to develop novel hydrogels that mimic the properties of the body. In the field of repair and regeneration, our challenge is to make hydrogels that retain the fatigue and resilience properties of the natural body part, but are comprised of nontoxic material. Resilin is a remarkable material exhibiting a broad range of stimuli-responsive behaviour and outstanding elasticity. The project aim is to create a tough ....A Tough Resilin Based Hydrogel Platform for Repair and Regeneration. This project seeks to develop novel hydrogels that mimic the properties of the body. In the field of repair and regeneration, our challenge is to make hydrogels that retain the fatigue and resilience properties of the natural body part, but are comprised of nontoxic material. Resilin is a remarkable material exhibiting a broad range of stimuli-responsive behaviour and outstanding elasticity. The project aim is to create a tough and responsive hydrogel platform from this disordered protein family through greater understanding of structure and mechanical function and incorporating adequate stiffness, strength and biocompatibility. Such tough hydrogels would be applicable to a range of biotechnological applications (eg intervertebral disc repair or artificial skin tissue engineering).Read moreRead less
Biosynthetic LEGO: enzymatic redesign to produce new vancomycin analogues. This project aims to uncover the reengineering potential of the biosynthetic machinery that produces glycopeptide antibiotics by advancing our understanding of how the core peptide production line functions. Natural product biosynthesis often produces complex peptide structures, with one important example being the glycopeptide antibiotics. This project expects to generate new knowledge about enzymatic peptide biosynthesi ....Biosynthetic LEGO: enzymatic redesign to produce new vancomycin analogues. This project aims to uncover the reengineering potential of the biosynthetic machinery that produces glycopeptide antibiotics by advancing our understanding of how the core peptide production line functions. Natural product biosynthesis often produces complex peptide structures, with one important example being the glycopeptide antibiotics. This project expects to generate new knowledge about enzymatic peptide biosynthesis using a highly interdisciplinary approach and previously developed tools. The anticipated outcomes of this project will be an enhanced understanding of how such complex peptide biosynthesis is performed, which is knowledge vital for future efforts to reengineer such biosynthetic peptide assembly lines as a series of modular LEGO blocks to produce new bioactive peptides.Read moreRead less
Novel conotoxins that target ion channels and receptors. This project will discover peptides from cone snail venom that are potential drug candidates. The project will expand our knowledge of these biological active peptides and their mode of action. It will also protect key molecules through patent applications, providing a competitive edge for Australian biotechnology.
Development of potent and specific modulators of the human sodium channel Nav1.7. There are few effective drugs available for the treatment of chronic pain. This team recently discovered that spider venoms are a rich source of inhibitors of Nav1.7, a new target for anti-pain drugs. The goal of this project is to develop potent blockers of Nav1.7 that can be used to critically assess the role of this ion channel in mediating pain.
Aquatic chemo-modulators: a novel source for potent molecular probes. This project aims to investigate peptides that modulate prey behaviour. Chemical signalling constitutes much of the language of life underwater. Certain cone snails evolved a hunting strategy, where they release potent peptides to modulate fish behaviour through yet unknown mechanisms. The snail then expands its mouth and eats the fish without resistance. This project will investigate the mechanisms at play using transcriptomi ....Aquatic chemo-modulators: a novel source for potent molecular probes. This project aims to investigate peptides that modulate prey behaviour. Chemical signalling constitutes much of the language of life underwater. Certain cone snails evolved a hunting strategy, where they release potent peptides to modulate fish behaviour through yet unknown mechanisms. The snail then expands its mouth and eats the fish without resistance. This project will investigate the mechanisms at play using transcriptomics, proteomics, peptide synthesis, behavioural pharmacology and nuclear magnetic resonance. This will advance the knowledge of aquatic chemo-modulators on a functional, structural and evolutionary level, and provide a source of molecular probes with unique pharmacology and applications in human physiology, developmental biology and aquacultures.Read moreRead less
Structure and activity determination of membrane-active peptides. Membrane-active peptides, such as antimicrobial and amyloid (Ab) peptides, play an important role in disease. With the growth of antibiotic resistance and increase in Alzheimer’s disease, which is epitomised by plaques of Ab, new drugs are required. Although Ab is toxic in neuronal cell cultures and disrupts cell membranes, the mechanism is unknown. Antimicrobial peptides that target bacterial membranes have evolved as a defence m ....Structure and activity determination of membrane-active peptides. Membrane-active peptides, such as antimicrobial and amyloid (Ab) peptides, play an important role in disease. With the growth of antibiotic resistance and increase in Alzheimer’s disease, which is epitomised by plaques of Ab, new drugs are required. Although Ab is toxic in neuronal cell cultures and disrupts cell membranes, the mechanism is unknown. Antimicrobial peptides that target bacterial membranes have evolved as a defence mechanism against infection and, since membranes show little genetic adaptation, could be drug candidates. Model membranes will be developed to elucidate the mechanism of action and key molecular features that determine affinity for membrane lipids of an antimicrobial peptide and full length Ab peptides.Read moreRead less
Novel cysteine-rich conotoxin frameworks from Australian cone snails. This project aims to discover conotoxins that are potential drug leads or useful pharmacological tools. It aims to increase both the discovery of novel conotoxin cysteine-rich frameworks through integrated transcriptomics and proteomics (venomics), conotoxin synthesis and 3-D structure determination, and to generate conotoxin disulfide bond mimetics and conotoxin dendrimers to increase stability, potency and selectivity. The w ....Novel cysteine-rich conotoxin frameworks from Australian cone snails. This project aims to discover conotoxins that are potential drug leads or useful pharmacological tools. It aims to increase both the discovery of novel conotoxin cysteine-rich frameworks through integrated transcriptomics and proteomics (venomics), conotoxin synthesis and 3-D structure determination, and to generate conotoxin disulfide bond mimetics and conotoxin dendrimers to increase stability, potency and selectivity. The work is designed to be based on a venomics platforms to accelerate conotoxin framework discovery while using novel mimetics and dendrimeric constructs to improve their biophysical properties. The expected outcomes include an expansion of novel conotoxin sequences and novel frameworks to generate lead molecules for potential development.Read moreRead less