Animal venoms are complex cocktails of peptides that have enormous potential as novel therapeutic leads. Replicating in vitro the diversity of venoms by generating large synthetic combinatorial peptide libraries will solve the challenge of working with limited amounts of natural products and permit high-throughput investigation of their pharmacology. A new investigation paradigm associating transcriptomics and proteomics is the only way to achieve this goal and to address the complexity of this unexplored 40,000,000 peptide resource. The vision of the VENOMICS project is to develop, integrate and implement cutting-edge and innovative technologies in a high-throughput approach to investigate the enormous structural and pharmacological diversity of venom peptides. We will use the largest venom and venom gland collection in the world to generate a comprehensive sequence database of bioactive peptides, and produce a 10,000 reticulated peptide bank to be used in drug discovery efforts and development of novel therapeutics. A 1000-fold improvement in throughput over the current situation (1 to 2 candidates generated per year) is reasonably foreseen.
Implementation of the project will require both improvements and the integration of exisiting technologies in a high-throughput workflow comprising venom and tissue sourcing, mass spectrometry-based automated de novo peptide sequencing, transcriptomics of venom gland-derived RNA or cDNA/EST libraries, bioinformatics, implementation of a sequence database, and highly parallel synthetic or recombinant production including peptide refolding. The last step will be the validation of the approach in functional assays targeting specific pathologies. VENOMICS is a high-impact project with societal (new drugs against life threatening diseases), scientific and technological (filling the drug discovery pipeline), political (European leadership in the field) and economic (new opportunities for the biologics market) benefits.
Fields of science
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Funding SchemeCP-FP - Small or medium-scale focused research project