Autocyclases: A new class of self-cyclising proteins. The biotechnology sector is emerging as an important economic strength in Australia. While the improved efficacy and selectivity of biomolecules has seen them emerge as alternatives to existing chemicals in health and agriculture, the stability of biomolecules remains a major limiting factor. A general strategy for improving protein stability is by joining the ends of the peptide chain in a cyclisation reaction. While a wide range of cyclic p ....Autocyclases: A new class of self-cyclising proteins. The biotechnology sector is emerging as an important economic strength in Australia. While the improved efficacy and selectivity of biomolecules has seen them emerge as alternatives to existing chemicals in health and agriculture, the stability of biomolecules remains a major limiting factor. A general strategy for improving protein stability is by joining the ends of the peptide chain in a cyclisation reaction. While a wide range of cyclic peptides and proteins are being developed in Australia and around the world, the cyclisation reaction presents a significant challenge. In this proposal we detail a novel method for protein cyclisation as a general, low-cost and green production method for making a diverse range of biomolecules. Read moreRead less
Understanding the mechanisms of peptide cyclisation. This project aims to identify, study, engineer and apply a new class of biocatalysts (called asparaginyl endopeptidase enzymes) as versatile tools for manufacturing of advanced therapeutics and bio-insecticides. The expected outcomes include fundamental new knowledge on the mechanism of action of these catalysts, an expanded toolbox for precision engineering of biomolecules and new strategies for production of high-value pharmaceuticals and cr ....Understanding the mechanisms of peptide cyclisation. This project aims to identify, study, engineer and apply a new class of biocatalysts (called asparaginyl endopeptidase enzymes) as versatile tools for manufacturing of advanced therapeutics and bio-insecticides. The expected outcomes include fundamental new knowledge on the mechanism of action of these catalysts, an expanded toolbox for precision engineering of biomolecules and new strategies for production of high-value pharmaceuticals and crop protecting agents. The project is significant because it will contribute to high value biotechnology and agricultural industries in Australia, with the potential for economic, environmental, training and societal benefits.Read moreRead less
Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to ....Gain from pain: new tools from venomous animals for exploring pain pathways. This project aims to explore animal venoms for new pain-causing toxins, to determine their structure and mechanism of action. Many venomous animals use their venom defensively and envenomation is frequently associated with rapid and often excruciating pain. In most cases the molecular mechanisms by which they achieve this is unknown. Using biochemical, pharmacological and biophysical techniques, this project expects to uncover toxins that employ new mechanisms of pain signalling, leading to new insights into pain physiology.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE200100800
Funder
Australian Research Council
Funding Amount
$415,693.00
Summary
Legume meristem signalling peptides: an untapped niche. This project aims to characterise novel signalling peptides regulating legume stem cell niches to enhance molecular-genetic networks and uncover potential key targets for crop improvement. Legumes represent agricultural sustainability through their decreased fertiliser requirements resulting in reduced carbon and nitrogen footprints. However, their unique gene signalling networks are poorly understood in comparison to traditional cereal cro ....Legume meristem signalling peptides: an untapped niche. This project aims to characterise novel signalling peptides regulating legume stem cell niches to enhance molecular-genetic networks and uncover potential key targets for crop improvement. Legumes represent agricultural sustainability through their decreased fertiliser requirements resulting in reduced carbon and nitrogen footprints. However, their unique gene signalling networks are poorly understood in comparison to traditional cereal crops. The proposed research intends to generate new knowledge in peptide signalling, plant development and legume symbiosis using multidisciplinary techniques. Expected project outcomes will increase understanding of peptide signalling in legume growth and adaption with useful findings for crop enhancement.Read moreRead less
Ultrasensitive electrochemical biosensors. This project aims to develop novel proteins that can convert biochemical cues into electronic signals. Using protein engineering, this project will produce redox protein-based OFF switches. The project expects that the use of the OFF-switches (as opposed to ON switches) will simplify biosensor design and create a new class of sensory architectures. Integration of OFF-switch-based biosensors with an enzymatic signal amplification circuit is expected to y ....Ultrasensitive electrochemical biosensors. This project aims to develop novel proteins that can convert biochemical cues into electronic signals. Using protein engineering, this project will produce redox protein-based OFF switches. The project expects that the use of the OFF-switches (as opposed to ON switches) will simplify biosensor design and create a new class of sensory architectures. Integration of OFF-switch-based biosensors with an enzymatic signal amplification circuit is expected to yield ultrasensitive sensory systems with near-real-time response. The project will address a need for new technologies that enable collection of physiological and environmental information rapidly, and at low cost outside of the specialised laboratories.Read moreRead less
Genetic code expansion of a eukaryotic in vitro translation system. The genetic code programs biosynthesis of polypeptides with efficiency vastly superior to chemical engineering. As the chemical diversity of natural amino acids in proteins is limited, finding ways to include “unnatural” amino acids can supercharge biology with a range of new protein activities. While the genetic code can be expanded to make space for unnatural amino acids, the rarity of free codons and reliance on prokaryotic ....Genetic code expansion of a eukaryotic in vitro translation system. The genetic code programs biosynthesis of polypeptides with efficiency vastly superior to chemical engineering. As the chemical diversity of natural amino acids in proteins is limited, finding ways to include “unnatural” amino acids can supercharge biology with a range of new protein activities. While the genetic code can be expanded to make space for unnatural amino acids, the rarity of free codons and reliance on prokaryotic organisms limit the applicability of this approach. We will develop a new higher-organism cell-free protein production system that can incorporate multiple unnatural amino acids into defined points of proteins. This, enabling and broadly applicable technology, will be tested by constructing opioid biosensors.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150100784
Funder
Australian Research Council
Funding Amount
$373,254.00
Summary
Molecular probe development for the oxytocin and vasopressin receptors. The oxytocin and vasopressin receptors are part of a 600 million year old signalling system that is widely distributed in the kingdom of life. It is involved in many fundamental physiological functions, however we still lack a complete toolbox of selective probes to delineate the individual receptor subtypes. This project aims to introduce a novel and innovative strategy that uses state-of-the art discovery techniques to ide ....Molecular probe development for the oxytocin and vasopressin receptors. The oxytocin and vasopressin receptors are part of a 600 million year old signalling system that is widely distributed in the kingdom of life. It is involved in many fundamental physiological functions, however we still lack a complete toolbox of selective probes to delineate the individual receptor subtypes. This project aims to introduce a novel and innovative strategy that uses state-of-the art discovery techniques to identify selective ligands in nature. Leads will be developed into molecular probes to facilitate in-depth studies of this system. This strategy is applicable to other systems and the outcomes will contribute to a significant advancement of knowledge in chemical biology.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE120102857
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Innovative chemical tools for the isolation, biochemical and structural analysis of biological macromolecular assemblies. This project will develop a new approach for determining the three dimensional structures of protein complexes. This project will demonstrate this approach by determining the structure of a protein complex involved in gene regulation and disease.
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