MECHANICUS

The mechanics of nuclear division and positioning

Coordinatore	FUNDACAO CALOUSTE GULBENKIAN    more  Organization address address: AVENIDA DE BERNA 45A city: LISBOA postcode: 1000 contact info Titolo: Mr. Nome: Jose Mario Cognome: Leite Email: send email Telefono: 351214000000 Fax: 351214000000
Nazionalità Coordinatore	Portugal [PT]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-CIG
Funding Scheme	MC-CIG
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-01-01   -   2017-12-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FUNDACAO CALOUSTE GULBENKIAN  Organization address address: AVENIDA DE BERNA 45A city: LISBOA postcode: 1000 contact info Titolo: Mr. Nome: Jose Mario Cognome: Leite Email: send email Telefono: 351214000000 Fax: 351214000000	PT (LISBOA)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'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.'