Obiettivo The Wnt pathway is a key regulatory pathway in development and carcinogenesis. Many of the components of the pathway connecting Wnt to the transcription factor TCF4 have been identified. However, our knowledge of the regulation of TCF4 promoter and enhancer elements in response to the Wnt signal, resulting in development from a stem cell to a differentiated cell, is limited. Largely due to technical constrains it has not been possible to identify TCF4 bound DNA enhancer elements or protein complexes associated with them which dictate specificity of the Wnt signal in the developing tissue. The mouse intestinal epithelium is a rapidly renewing tissue under the control of the canonical Wnt pathway, and therefore ideal to study the above mentioned questions. The proposed project combines state of the art ChIP on chip Genome wide Agilent DNA arrays, Mass Spectrometry, Flow Cytometry, as well as conventional Biochemistry and Molecular Biology to examine Wnt/TCF4 controlled intestinal development in mice. Using these techniques I will identify distal TCF4 regulatory elements, the associated promoters and the protein complexes responsible. Study of the associated complexes and epigenetic marks will help to identify mechanism of activation and repression of the Wnt pathway resulting in the differentiation from a stem cell to a differentiated cell. Stem cells and their development or the misregulation resulting in tumor growth are of major interest to the academic as well pharmaceutical world for their potential use in treatment (stem cells) or the need for a cure (cancer). Therefore it is important to understand how these processes are regulated in vivo. Research in this ever expanding field is very important to maintain Europe’s scientific excellence in the future. Campo scientifico natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologynatural scienceschemical sciencesanalytical chemistrymass spectrometry Parole chiave TCF4 differentiation intestine stem cell Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) PEOPLE-2007-4-2.IIF - Marie Curie Action: "International Incoming Fellowships" Invito a presentare proposte FP7-PEOPLE-2007-4-2-IIF Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IIF - International Incoming Fellowships (IIF) Coordinatore ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM Contributo UE Nessun dato Indirizzo DR MOLEWATERPLEIN 40 3015 GD Rotterdam Paesi Bassi Mostra sulla mappa Regione West-Nederland Zuid-Holland Groot-Rijnmond Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Riet Van Zeijl (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Partecipanti (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto KONINKLIJKE NEDERLANDSE AKADEMIE VAN WETENSCHAPPEN - KNAW Partecipazione conclusa Paesi Bassi Contributo UE € 227 373,86 Indirizzo KLOVENIERSBURGWAL 29 HET TRIPPENHUIS 1011 JV AMSTERDAM Mostra sulla mappa Regione West-Nederland Noord-Holland Groot-Amsterdam Tipo di attività Research Organisations Contatto amministrativo Don Van Velzen (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato