PRECISE

Spatiotemporal regulation of chromosome segregation fidelity

 Coordinatore INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR - IBMC 

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 Nazionalità Coordinatore Portugal [PT]
 Totale costo 1˙485˙097 €
 EC contributo 1˙485˙097 €
 Programma 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)
 Code Call ERC-2010-StG_20091118
 Funding Scheme ERC-SG
 Anno di inizio 2011
 Periodo (anno-mese-giorno) 2011-01-01   -   2015-12-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR - IBMC

 Organization address address: RUA DO CAMPO ALEGRE 823
city: PORTO
postcode: 4150 180

contact info
Titolo: Prof.
Nome: Claudio
Cognome: Sunkel
Email: send email
Telefono: +351 22 6074900
Fax: +351 22 6099157

PT (PORTO) hostInstitution 1˙485˙097.00
2    INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR - IBMC

 Organization address address: RUA DO CAMPO ALEGRE 823
city: PORTO
postcode: 4150 180

contact info
Titolo: Prof.
Nome: Helder Jose
Cognome: Martins Maiato
Email: send email
Telefono: +351 22 6074900
Fax: +351 22 6099157

PT (PORTO) hostInstitution 1˙485˙097.00

Mappa


 Word cloud

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mitosis    chromosomes    segregation    human    fidelity    spindle    molecular    kt    cells    mitotic    chromosome    mts    errors   

 Obiettivo del progetto (Objective)

'At any given moment, 250 million cells are dividing in the human body through an essential process known as mitosis. Inaccuracy of mitosis leads directly to aneuploidy (gain or loss of chromosomes), a hallmark of several cancers and birth defects. Mitotic fidelity is controlled by the spindle assembly checkpoint (SAC), a signaling pathway that delays the progression of mitosis to ensure that all chromosomes are attached to mitotic spindle microtubules (MTs). Central to this activity, the kinetochore (KT), a minute structure on each replicated sister-chromatid, promotes the rapid turnover of MTs to correct potential attachment errors during early mitotic stages. Upon anaphase onset, the KT then switches to bind MTs with higher affinity, so that the energy derived from their depolymerizing plus ends helps driving chromosome motion to the poles. While the molecular basis of the KT-MT interface is only now starting to be elucidated, how the multiple KT activities are regulated throughout mitosis remains unknown. Here we propose to dissect from a molecular perspective how the interaction between spindle MTs and KTs controls chromosome segregation fidelity in space and time. For this purpose we will combine the power of biochemical analysis and genome-wide RNAi screens with the detailed functional investigation of already identified candidate genes using state-of-the-art live cell microscopy and pilot laser microsurgery tools in animal cells. Additionally, we have in place all the necessary conditions to investigate the physiological significance of chromosome segregation errors and evaluate respective outcomes using unique mammalian model systems. With this synergistic approach we aim to unveil the molecular routes of aneuploidygenesis and their implications to human health.'

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