DEtermination of Orphan Receptor PHysiological Agonists and sigNals

Projektinformationen

DE-ORPHAN

ID Finanzhilfevereinbarung: 639125

DOI

10.3030/639125

Projekt abgeschlossen

EK-Unterschriftsdatum 17 April 2015

Startdatum 1 Mai 2015

Enddatum 30 April 2020

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 1 499 926,25

EU-Beitrag

€ 1 499 926,25

Koordiniert durch

KOBENHAVNS UNIVERSITET
Denmark

Periodic Reporting for period 4 - DE-ORPHAN (DEtermination of Orphan Receptor PHysiological Agonists and sigNals)

Berichtszeitraum: 2019-11-01 bis 2020-04-30

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

G protein-coupled receptors (GPCR) make up both the largest signalling system and drug target families in human, thus of high importance for physiology and medicine. DE-ORPHAN has identified physiological agonist hormones and research tool compounds poorly characterised ‘orphan’ receptors. These receptor ligands open up for exploration of the new physiological signalling systems and present new druggable targets, ligands and mechanisms.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

We have developed computational methods to identify; physiological ligands that link the receptor to a physiological system, tool compounds for pharmacological characterisation, and G protein inhibitors for effective dissection of the intracellular signalling pathways.

The main results are:
1. Discovery of physiological peptide hormones for five GPCRs (Foster et al., Cell 2019).
2. Tool compounds for three receptors that can be used to uncover their pharmacology and function.
3. Unique data and webserver tools in our open access database GPCRdb serving >4,000 users/mon.

So far, the project has led to 20 peer-reviewed articles, 15 invited conference talks by the PI and 4 workshops.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The identified physiological and surrogate ligands open up for characterisation of these important receptors in terms of their function and therapeutic relevance/area. The open access GPCRdb resources is a unique dissemination of data and tools of relevance not only for this project, but the wide receptor community. In all, the results will allow the research field to advance into studies of receptor functions and exploitation of druggable targets, ligands and mechanisms.

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