Project description
On the road to the discovery of toxin mimetics that could cure disease
Toxins have generated a lot of interest as promising biomedical research tools and therapeutics for various human diseases. The EU-funded ToxMim project will test whether a small group of toxins that disrupt physiology by mimicking the action of endogenous signalling peptides represent suitable candidates for drug discovery and development. Proof-of-concept was provided by the project team's discovery of a toxin that mimics insulin, used by a marine cone snail to induce low blood sugar in its prey. The study will use next-generation sequencing combined with computational and experimental venom discovery and pharmacology to develop a set of tools that enable the systematic identification and characterisation of toxin mimetics of human signalling peptides with an emphasis on those implicated in disease.
Objective
Venomous animals use a myriad of toxins to specifically disrupt the physiology and behavior of their prey. Because of their high stability, potency, and specificity, toxins are important tools for biomedical research and have been developed as therapeutics for various human diseases. However, contributions to date pale in comparison to future prospects. We hypothesize that a small and essentially overlooked group of toxins, “ToxMims”, represent the most promising candidates for drug discovery and development. ToxMims potently disrupt the prey’s physiology by specifically mimicking the action of endogenous signaling peptides. Because many of these signaling peptides are critical players in human health and disease, ToxMims are exceptionally promising drug leads. Proof-of-concept is provided by our recent discovery of a toxin mimetic of insulin that is used by a marine cone snail to induce dangerously low blood sugar in fish prey. Because of its advantageous properties over human insulin, the venom insulin has rapidly become a novel drug lead for the treatment of diabetes. Despite their significant biomedical potential, ToxMims are rare and difficult to systematically detect using currently available methodologies. By leveraging recent advances in next-generation sequencing combined with our proven expertise in computational and experimental venom discovery and pharmacology, this project aims to develop a set of tools to enable the systematic identification and characterization of any ToxMim of the ~350 human signaling peptides with an emphasis on those implicated in disease. If successful, this research will not only identify a set of unique drug leads with profound impact on human health but elucidate previously unknown mechanisms of receptor activation, inhibition and signaling. Furthermore, this project will foster European excellence in venom research and develop scientific leadership competences for an independent, early-career researcher returning to Europe.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- natural sciencesbiological sciencesbiochemistrybiomolecules
- medical and health sciencesclinical medicineendocrinologydiabetes
- medical and health sciencesbasic medicinephysiology
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Programme(s)
Topic(s)
Funding Scheme
ERC-STG - Starting GrantHost institution
1165 Kobenhavn
Denmark