CONBIOS

Cone snail toxins as therapeutic agents: Decoding biological mechanisms of conotoxin folding

Coordinatore	KOBENHAVNS UNIVERSITET    more  Organization address postcode: 1017 contact info Titolo: Mrs. Nome: Tine Cognome: Mathiesen Email: send email Telefono: 4535322810 Fax: 4535324612
Nazionalità Coordinatore	Denmark [DK]
Totale costo	294˙456 €
EC contributo	294˙456 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2012-IOF
Funding Scheme	MC-IOF
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-05-01   -   2017-03-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	KOBENHAVNS UNIVERSITET	DK	coordinator	294˙456.30

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 Obiettivo del progetto (Objective)

'Predatory marine cone snails use extraordinarily complex venoms to capture prey. Most of the ~500,000 biologically active venom components are small, disulfide-rich peptides called conotoxins. They target receptors and ion channels of the nervous system with remarkable potency and specificity. Due to their enormous diversity and target specificity, conotoxins have become invaluable tools in molecular pharmacology and as therapeutic agents. However, their chemical synthesis is hampered by multiple disulfide bonds and additional post-translational modifications, which result in low folding yields and accumulation of aggregated or misfolded products. Recently observed differences between in vitro and in vivo synthesis strongly indicate that folding and modification of conotoxins in the endoplasmic reticulum of the venom glandular cells are tightly regulated processes. Understanding mechanisms that govern the proper assembly of conotoxins at a molecular level is a prerequisite for designing more efficient production systems for conotoxins and other disulfide-rich peptides of biological and pharmacological importance. By using next-generation sequencing, bottom-up proteomics, protein-protein interaction and molecular silencing technologies, this study will elucidate crucial pathways for the oxidative folding and modification of conotoxins. These results will be used to develop a cell-based expression system for conotoxins that are difficult or impossible to synthesise chemically, thus providing novel agents for pharmacotherapeutic studies. While our knowledge on the proper folding of larger protein substrates is constantly improving, research into the generation of small, disulfide-containing peptides is a newly emerging field. By bringing together world-leading scientists in conotoxin pharmacology and protein folding, this project will develop excellent scientific and leadership competences at a high level for a young talented European scientist.'