Conotoxin diversification and evolution of venom peptides in cone snails. The marine snails of the genus Conus have evolved one of the most complex venoms that has emerged as a rich source of novel bioactive peptides. However, < 0.1% of their true potential has been characterised to-date. Using advanced genomic, proteomic, structural and pharmacological approaches pioneered in our laboratory, this study will decipher how conotoxin diversification from ancestral worm hunters facilitated the shift ....Conotoxin diversification and evolution of venom peptides in cone snails. The marine snails of the genus Conus have evolved one of the most complex venoms that has emerged as a rich source of novel bioactive peptides. However, < 0.1% of their true potential has been characterised to-date. Using advanced genomic, proteomic, structural and pharmacological approaches pioneered in our laboratory, this study will decipher how conotoxin diversification from ancestral worm hunters facilitated the shift in diet to modern fish and mollusc hunting species by determining the evolutionary trajectories of positively selected conotoxins. Investigation of the structure and function of these highly optimised venom peptides will provide new research tools and potential leads to new pharmaceuticals and agrochemicals.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE150101481
Funder
Australian Research Council
Funding Amount
$373,000.00
Summary
Aquatic invasion of venomous snakes. Animal venoms target multiple physiological pathways to rapidly disrupt homeostasis and cause paralysis and death of prey animals. Physiological protein-encoding genes are recruited into the envenoming function, which then evolve to be highly effective on their molecular targets. The expansion of venom complexity due to the predator-prey chemical 'arms race' has given rise to a plethora of toxin types. While examples of venoms that have become subsequently st ....Aquatic invasion of venomous snakes. Animal venoms target multiple physiological pathways to rapidly disrupt homeostasis and cause paralysis and death of prey animals. Physiological protein-encoding genes are recruited into the envenoming function, which then evolve to be highly effective on their molecular targets. The expansion of venom complexity due to the predator-prey chemical 'arms race' has given rise to a plethora of toxin types. While examples of venoms that have become subsequently streamlined and/or simplified in response to a change in environment and/or specialisation of diet are plenty, the underlying mechanisms remain elusive. This project aims to unravel how animal venoms become streamlined and uncover the underexplored vast pharmacopeia of aquatic venoms.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE160101142
Funder
Australian Research Council
Funding Amount
$360,000.00
Summary
Unravelling the structural evolution of centipede toxins. The project intends to improve understanding of venom evolution in centipedes, and uncover new families of peptides with potential application in the agrochemical and pharmaceutical sectors. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range studied, and many groups of venomous a ....Unravelling the structural evolution of centipede toxins. The project intends to improve understanding of venom evolution in centipedes, and uncover new families of peptides with potential application in the agrochemical and pharmaceutical sectors. Venoms have emerged as a rich source of pharmacological tools with potential for development into therapeutics and bioinsecticides. However, venoms-based discovery has been limited by the narrow taxonomical range studied, and many groups of venomous animals remain overlooked. One such group is centipedes, whose venoms contain diverse novel toxins. This project aims to provide an insight into centipede toxin evolution, and establish a structure-based approach to understanding their evolution and structural diversification. The outcomes may contribute to our understanding of protein evolution and support the development of new products.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
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
Development of effective peptide-based drugs. There is huge interest in the development of bioactive peptides and proteins for the treatment of a wide range of diseases. The aim of this research project is to develop potent and effective peptide-based drugs that are able to resist the body's natural degradation pathways so that they can reach their biological target and act as effective drugs.
Development of disulphide-rich peptides for drug design. Peptides are an outstanding source of potential drug leads. This project seeks to build on earlier breakthroughs by developing stable, peptide-based drugs to combat cancer and autoimmune diseases. The peptides, derived from natural sources, are anticipated to provide drug leads that can ultimately lead to treatments for these diseases.
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
The chemistry and biology of circular proteins. This project aims to develop plant-derived ultra-stable cyclic peptides for pharmaceutical and agricultural applications. The project will use innovative new methodologies for discovery, chemical synthesis and engineering of these molecules. It is expected that the project will contribute to high value biotechnology and agricultural industries in Australia. The proposed outcomes will include fundamental new knowledge on the biosynthesis of circular ....The chemistry and biology of circular proteins. This project aims to develop plant-derived ultra-stable cyclic peptides for pharmaceutical and agricultural applications. The project will use innovative new methodologies for discovery, chemical synthesis and engineering of these molecules. It is expected that the project will contribute to high value biotechnology and agricultural industries in Australia. The proposed outcomes will include fundamental new knowledge on the biosynthesis of circular proteins in plants, new approaches for their discovery and technologies for applying them as drug leads and agricultural products.Read moreRead less