SETTREND

"Schistosoma Epigenetics - Targets, Regulation, New Drugs"

Coordinatore	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)    more  Organization address address: 101 Rue de Tolbiac city: PARIS postcode: 75654 contact info Titolo: Ms. Nome: Rofigua Cognome: Hakem Email: send email Telefono: +33 3 20 29 93 73 Fax: +33 3 20 49 01 38
Nazionalità Coordinatore	France [FR]
Totale costo	4˙326˙503 €
EC contributo	3˙299˙998 €
Programma	FP7-HEALTH Specific Programme "Cooperation": Health
Code Call	FP7-HEALTH-2009-single-stage
Funding Scheme	CP-FP-SICA
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-01-01   -   2012-12-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)  Organization address address: 101 Rue de Tolbiac city: PARIS postcode: 75654 contact info Titolo: Ms. Nome: Rofigua Cognome: Hakem Email: send email Telefono: +33 3 20 29 93 73 Fax: +33 3 20 49 01 38	FR (PARIS)	coordinator	623˙400.00
2	INOVACIA AB  Organization address address: BANVAKTSVAGEN KAROLINSKA INSTITUTET SCIENCE PARK 22 city: SOLNA postcode: 171 48 contact info Titolo: Dr. Nome: Johan Cognome: Schultz Email: send email Telefono: +46 7 35 20 40 27 Fax: +46 8 50 10 30 44	SE (SOLNA)	participant	603˙900.00
3	UNIVERSIDADE DE SAO PAULO  Organization address address: RUA DA REITORIA 109 BUTANTA city: SAO PAULO SP postcode: 05508 900 contact info Titolo: Prof. Nome: Hans Cognome: Viertler Email: send email Telefono: +55 11 3091 3839 Fax: +55 11 3815 5579	BR (SAO PAULO SP)	participant	424˙380.00
4	FUNDACAO OSWALDO CRUZ  Organization address address: AVENIDA BRASIL 4365 city: RIO DE JANEIRO postcode: 21040 900 contact info Titolo: Dr. Nome: Guilherme Cognome: Oliveira Email: send email Telefono: +55 31 3349 7785 Fax: +55 31 3295 3115	BR (RIO DE JANEIRO)	participant	385˙296.00
5	ALBERT-LUDWIGS-UNIVERSITAET FREIBURG  Organization address address: FAHNENBERGPLATZ city: FREIBURG postcode: 79085 contact info Titolo: Prof. Nome: Manfred Cognome: Jung Email: send email Telefono: +49 7612034896 Fax: +49 7612036321	DE (FREIBURG)	participant	350˙995.00
6	CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE  Organization address address: Rue Laurent Fries 1 city: ILLKIRCH GRAFFENSTADEN postcode: 67404 contact info Titolo: Dr. Nome: Steve Cognome: Brooks Email: send email Telefono: +33 3 88 65 33 94 Fax: +33 3 88 65 32 03	FR (ILLKIRCH GRAFFENSTADEN)	participant	350˙916.00
7	UNIVERSIDADE FEDERAL DO RIO DE JANEIRO  Organization address address: AV BRIGADEIRO TROMPOWSKI SN 2 city: RIO DE JANEIRO postcode: 21941 590 contact info Titolo: Prof. Nome: Maria Helena Cognome: Lacorte Email: send email Telefono: +55 21 3034 5800 Fax: +55 21 2542 3146	BR (RIO DE JANEIRO)	participant	261˙378.00
8	MARTIN-LUTHER-UNIVERSITAET HALLE-WITTENBERG  Organization address address: UNIVERSITAETSPLATZ 10 city: HALLE (Saale) postcode: 6099 contact info Titolo: Dr. Nome: Sigrid Cognome: Köhne Email: send email Telefono: +49 345 5521303 Fax: +49 345 5527225	DE (HALLE (Saale))	participant	245˙028.00
9	INSERM - TRANSFERT SA  Organization address address: Rue Watt 7 city: PARIS postcode: 75013 contact info Titolo: Mr. Nome: Louis Cognome: Jammayrac Email: send email Telefono: +33 1 55 03 01 01 Fax: +33 1 55 03 01 60	FR (PARIS)	participant	54˙705.00

Mappa

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 Obiettivo del progetto (Objective)

'We propose to develop novel drug leads for the therapy of the major human parasitic disease, schistosomiasis, using a holistic approach that will enable us to progress from the cloned target protein to the lead compound and from epigenetic inhibitors to crucial targets. For this, we have chosen to target the histone modifying enzymes (HME); histone deacetylases (HDAC), histone acetyltransferases (HAT), histone methyltransferases (HMT) and histone demethylases (HDM) of Schistosoma mansoni. In the course of the project the members of HDAC classes I, II and III (sirtuins) HAT, HMT and HDM encoded in the genome will be identified. In parallel, a reverse chemical genetics approach using generic inhibitors of HME subclasses available within the consortium in cultures of schistosome larvae will identify those classes that are bona fide drug targets. These enzymes will be validated as therapeutic targets individually or collectively using RNAi to invalidate the corresponding genes. Potential inhibitors (HDACi, HATi, HMTi, HDMi) will be screened by in silico docking to the modelled catalytic domains of the enzymes and collections of analogues will be tested for their ability to inhibit the activity of the corresponding recombinant proteins in high-throughput assays. We will also establish gene expression profiles corresponding to HME invalidation (by RNAi) and inhibition (using drug candidates in cultured larval stages (schistosomula) that will enable the determination of the specificity of action of the drugs. Finally, in vivo testing of the best candidates will be done in infected mice. In this way, during the study period we aim to develop a series of candidate molecules that can progress to clinical trials.'