Obiettivo During mitosis the genetic material of the mother cell is separated and distributed between two daughter cells. Responsible for this coordinated segregation is an assembly of polymers, molecular motors and adapter proteins– the mitotic spindle. This super-molecular machine moves the chromosome halves in opposite directions over impressive cellular scales (tens of µm) within a relatively short time (minutes). The regulatory biochemical pathways responsible for timing and error-control of mitosis have been extensively studied and the key factors have been identified. The major mechanical determinants are thought to be a combination of polymerization dynamics and molecular motor activity but what remains elusive is how such individual processes lead to directed movement in a large cytoskeletal assembly, and how active force generation is balanced to prevent structural collapse. Understanding the mechanical properties responsible for pulling chromosomes is at the heart of spindle function, which is critical to the life cycle of a cell. This knowledge is pivotal in developing biomedical applications. Here, I propose to investigate the mechanical basis leading to directed movement of chromosomes during segregation and how mechanical load is distributed in the spindle throughout mitosis. I plan to unravel the molecular nature of force leading to nuclear migration following segregation, an essential process in large egg cells. The experimental foundation for my studies is a recently developed cell-free assay using the genetically tractable Drosophila, providing complete accessibility to every mitotic event with time-lapse imaging and mechanical manipulation. This project lies at the interdisciplinary interface between mechanical engineering, microscopy, biochemistry and fly genetics. The basic concepts for the planned experiments are speckle microscopy, spatial constraining, mechanical relaxation and compression in combination with genetic and pharmaceutical perturbation. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural scienceschemical sciencespolymer sciencesnatural sciencesphysical sciencesopticsmicroscopyengineering and technologymechanical engineeringnatural sciencesbiological sciencesgeneticschromosomes 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) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Invito a presentare proposte FP7-PEOPLE-2013-CIG Vedi altri progetti per questo bando Meccanismo di finanziamento MC-CIG - Support for training and career development of researcher (CIG) Coordinatore FUNDACAO CALOUSTE GULBENKIAN Contributo UE € 100 000,00 Indirizzo AVENIDA BERNA 45A 1067-001 LISBOA Portogallo Mostra sulla mappa Regione Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa Tipo di attività Research Organisations Contatto amministrativo Jose Mario Leite (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
