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. Fields of science natural sciencesbiological sciencesgeneticsepigenetics Programme(s) FP7-HEALTH - Specific Programme "Cooperation": Health Topic(s) HEALTH-2009-4.3.1-1 - Discovery and development of new vaccines or drugs for helminth infections (SICA) Call for proposal FP7-HEALTH-2009-single-stage See other projects for this call Funding Scheme CP-FP-SICA - Small/medium-scale focused research project for specific cooperation actions dedicated to international cooperation partner countries(SICA) Coordinator INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE EU contribution € 623 400,00 Address RUE DE TOLBIAC 101 75654 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Administrative Contact Rofigua Hakem (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Participants (8) Sort alphabetically Sort by EU Contribution Expand all Collapse all CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET MEDECINE France EU contribution € 350 916,00 Address Rue Laurent Fries 1 67404 Illkirch Graffenstaden See on map Region Grand Est Alsace Bas-Rhin Activity type Research Organisations Administrative Contact Steve Brooks (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data MARTIN-LUTHER-UNIVERSITAT HALLE-WITTENBERG Germany EU contribution € 245 028,00 Address UNIVERSITATSPLATZ 10 6108 Halle See on map Region Baden-Württemberg Stuttgart Stuttgart, Stadtkreis Activity type Higher or Secondary Education Establishments Administrative Contact Sigrid Köhne (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data UNIVERSIDADE FEDERAL DO RIO DE JANEIRO Brazil EU contribution € 261 378,00 Address AV BRIGADEIRO TROMPOWSKI SN 2 21941 590 Rio De Janeiro See on map Activity type Higher or Secondary Education Establishments Administrative Contact Maria Helena Lacorte (Prof.) Links Contact the organisation Opens in new window Total cost No data ALBERT-LUDWIGS-UNIVERSITAET FREIBURG Germany EU contribution € 350 995,00 Address FAHNENBERGPLATZ 79098 Freiburg See on map Region Baden-Württemberg Freiburg Freiburg im Breisgau, Stadtkreis Activity type Higher or Secondary Education Establishments Administrative Contact Manfred Jung (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data FUNDACAO OSWALDO CRUZ Brazil EU contribution € 385 296,00 Address AVENIDA BRASIL 4365 21040 900 Rio De Janeiro See on map Activity type Research Organisations Administrative Contact Guilherme Oliveira (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data INSERM TRANSFERT SA France EU contribution € 54 705,00 Address 10 RUE D'ORADOUR-SUR-GLANE - PARISANTE CAMPUS 75015 PARIS See on map Region Ile-de-France Ile-de-France Paris Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Administrative Contact Louis Jammayrac (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data INOVACIA AB Sweden EU contribution € 603 900,00 Address BANVAKTSVAGEN KAROLINSKA INSTITUTET SCIENCE PARK 22 171 48 SOLNA See on map Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Administrative Contact Johan Schultz (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data UNIVERSIDADE DE SAO PAULO Brazil EU contribution € 424 380,00 Address RUA DA REITORIA 109 BUTANTA 05508 900 Sao Paulo Sp See on map Activity type Higher or Secondary Education Establishments Administrative Contact Hans Viertler (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
