Obiettivo Recent progress in constructing small artificial gene networks has allowed the engineering of predictable logical switches, or system behaviours, by harnessing feedback loops (Becskei, A. & Serrano, L. Nature 405, 590-3 (2000)). It should be possible to apply our growing knowledge of such networks to construct multi-component sensors and effectors to react to particular metabolic states in a cell, especially the aberrant states associated with disease. In this project, we aim to design modular gene n etworks of increasing complexity, that will sense errors at multiple levels in cellular pathways and will respond to repair the affected genes selectively. As a primary target, we have selected the p53 pathway; p53 itself is altered in ~50% of all cancers, while the other 50% of tumors carry alterations either in direct regulators of p53 (such as MDM2, p14ARF, E6 from HPV), or in pathways activating the p53 checkpoint (such as ATM, ATR, Brca1). Therefore we can consider that the p53 pathway is altered in v irtually every cancer. The global idea of the project involves designing a network that will detect 3 or more steps in the pathway, identify the step that is not working properly and then selectively respond, either by killing the cell or by repairing the affected gene through double-strand induced recombination. Thus, we aim to combine expertise from a systems biology and protein design group (Serrano), a cell biology group with experience in p53 pathways (Carnero), a company specialising in meganuclease-induced recombination (Cellectis) and a group specialising in viral vector delivery to cells and cancer therapeutics (Kühnel). By integrating the experience of these different groups, we expect to develop robust cancer sensors with therapeutic potential. F urthermore, by exploring which network topologies and effector systems function best, we intend to provide a generally applicable framework to build synthetic networks to react to aberrant cellular pathways Campo scientifico natural sciencesbiological sciencescell biologyengineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensorsmedical and health sciencesclinical medicineoncologyengineering and technologyelectrical engineering, electronic engineering, information engineeringinformation engineeringtelecommunicationstelecommunications networksmedical and health scienceshealth sciencesinfectious diseasesDNA viruses Programma(i) FP6-POLICIES - Policy support: Specific activities covering wider field of research under the Focusing and Integrating Community Research programme 2002-2006. Argomento(i) NEST-2003-1 - Adventure activities Invito a presentare proposte FP6-2003-NEST-PATH Vedi altri progetti per questo bando Meccanismo di finanziamento STREP - Specific Targeted Research Project Coordinatore FUNDACIO CENTRE DE REGULACIO GENOMICA Contributo UE Nessun dato Indirizzo Passeig Maritim 37-49 BARCELONA Spagna Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato Partecipanti (4) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto CELLECTIS S.A Francia Contributo UE Nessun dato Indirizzo 102, Route de Noisy ROMAINVILLE Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS Spagna Contributo UE Nessun dato Indirizzo C/ Melchor Fernandes Almagro, 3 MADRID Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato EUROPEAN MOLECULAR BIOLOGY LABORATORY Germania Contributo UE Nessun dato Indirizzo Passeig Maritim 37-49 BARCELONA Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato MEDIZINISCHE HOCHSCHULE HANNOVER Germania Contributo UE Nessun dato Indirizzo Carl-Neuberg-Strasse 1 HANNOVER Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato
