Objetivo Equal partition of the genetic material to the daughter cells in mitosis requires the accurate anchorage of the mother cell s chromosomes to spindle microtubules. This process takes place at kinetochores, complex scaffolds containing ~100 different proteins. Conceptually, kinetochores can be viewed as performing four distinct but highly integrated functions: 1) they bind centromeric chromatin at a specialized protein-DNA interface; 2) they build a dynamic microtubule-binding interface that is tightly linked to the centromere-binding interface; 3) they correct erroneous microtubule attachments; 4) they synchronize the progression of the cell cycle oscillator with the progression of the microtubule-kinetochore attachment process. In mammals, all four functions are essential, and their abrogation has untenable consequences for normal cell life. Conversely, their partial impairment has been implicated in chromosome instability and in the development of cancer and an array of genetic diseases. Our goal is to be able to map the kinetochore functions schematized above to the as yet largely uncharacterized architecture of the kinetochore and to unravel the elements of feedback control that allow their integration. By using a combination of structural and functional methods, we have made several recent important contributions to the field of kinetochore biology. In this application, we propose to take our efforts to a new level of complexity that will allow us to gain an integrated view of how kinetochores bind microtubules, how they correct improper attachment, and how they coordinate microtubule attachment with cell cycle progression. Our approach rests on strong experience in biochemical reconstitution and structural analysis, and is complemented by the introduction of methods to assess and model the dynamic responses of kinetochores to their variable environment. Ámbito científico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologynatural sciencesbiological scienceszoologymammalogynatural sciencesbiological sciencesgeneticschromosomes Palabras clave aneuploidy cancer kinetochores single-molecule Programa(s) 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) Tema(s) ERC-AG-LS1 - ERC Advanced Grant - Molecular and Structural Biology and Biochemistry Convocatoria de propuestas ERC-2008-AdG Consulte otros proyectos de esta convocatoria Régimen de financiación ERC-AG - ERC Advanced Grant Institución de acogida MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Aportación de la UE € 1 336 201,41 Dirección HOFGARTENSTRASSE 8 80539 Munchen Alemania Ver en el mapa Región Bayern Oberbayern München, Kreisfreie Stadt Tipo de actividad Research Organisations Contacto administrativo Barbara Dobruchowski Investigador principal Andrea Musacchio (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos Beneficiarios (2) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Alemania Aportación de la UE € 1 336 201,41 Dirección HOFGARTENSTRASSE 8 80539 Munchen Ver en el mapa Región Bayern Oberbayern München, Kreisfreie Stadt Tipo de actividad Research Organisations Contacto administrativo Barbara Dobruchowski Investigador principal Andrea Musacchio (Prof.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos ISTITUTO EUROPEO DI ONCOLOGIA SRL La participación finalizó Italia Aportación de la UE € 1 163 798,59 Dirección VIA FILODRAMMATICI 10 20121 Milano Ver en el mapa Región Nord-Ovest Lombardia Milano Tipo de actividad Private for-profit entities (excluding Higher or Secondary Education Establishments) Contacto administrativo Ilaria Foti (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
