ALK7

Metabolic control by the TGF-² superfamily receptor ALK7: A novel regulator of insulin secretion, fat accumulation and energy balance

Coordinatore	KAROLINSKA INSTITUTET    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Sweden [SE]
Totale costo	2˙462˙154 €
EC contributo	2˙462˙154 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2008-AdG
Funding Scheme	ERC-AG
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-04-01   -   2014-03-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	KAROLINSKA INSTITUTET  Organization address address: Nobels Vag 5 city: STOCKHOLM postcode: 17177 contact info Titolo: Ms. Nome: åsa Cognome: Garmager Email: send email Telefono: +46 8 524 878 55 Fax: +46 8 31 03 43	SE (STOCKHOLM)	hostInstitution	2˙462˙154.00
2	KAROLINSKA INSTITUTET  Organization address address: Nobels Vag 5 city: STOCKHOLM postcode: 17177 contact info Titolo: Prof. Nome: Carlos Cognome: Ibanez Email: send email Telefono: +46 8 5248 7660 Fax: +46 8 33 9548	SE (STOCKHOLM)	hostInstitution	2˙462˙154.00

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 Obiettivo del progetto (Objective)

The aim of this proposal is to understand a novel regulatory signaling network controlling insulin secretion, fat accumulation and energy balance centered around selected components of the TGF-² signaling system, including Activins A and B, GDF-3 and their receptors ALK7 and ALK4. Recent results from my laboratory indicate that these molecules are part of paracrine signaling networks that control important functions in pancreatic islets and adipose tissue through feedback inhibition and feed-forward regulation. These discoveries have open up a new research area with important implications for the understanding of metabolic networks and the treatment of human metabolic syndromes, such as diabetes and obesity.

To drive progress in this new research area beyond the state-of-the-art it is proposed to: i) Elucidate the molecular mechanisms by which Activins regulate Ca2 influx and insulin secretion in pancreatic ²-cells; ii) Elucidate the molecular mechanisms underlying the effects of GDF-3 on adipocyte metabolism, turnover and fat accumulation; iii) Investigate the interplay between insulin levels and fat deposition in the development of insulin resistance using mutant mice lacking Activin B and GDF-3; iv) Investigate tissue-specific contributions of ALK7 and ALK4 signaling to metabolic control by generating and characterizing conditional mutant mice; v) Investigate the effects of specific and reversible inactivation of ALK7 and ALK4 on metabolic regulation using a novel chemical-genetic approach based on analog-sensitive alleles.

This is research of a high-gain/high-risk nature. It is posed to open unique opportunities for further exploration of complex metabolic networks. The development of drugs capable of enhancing insulin secretion, limiting fat accumulation and ameliorating diet-induced obesity by targeting components of the ALK7 signaling network will find a strong rationale in the results of the proposed work.