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Chromosome Architecture and the Fidelity of Mitosis during Development

Project description

Active chromosomes during cell division

During cell division, chromosomes segregate to ensure equal distribution of the genomic materials into daughter cells. For years, chromosomes were considered as passive structures during cell division, but accumulating evidence suggests a more active role. Funded by the European Research Council, the ChromoCellDev project will focus on the condensin and cohesin protein complexes which are implicated in chromosome architecture. Researchers will investigate the process of chromosome assembly and examine how chromosome condensation and cohesion affect chromosome movement and surveillance mechanisms. Results will provide novel insight into the role of chromatin in cell division.


Genome stability relies on accurate partition of the genome during nuclear division. Proper mitosis, in turn, depends on changes in chromosome organization, such as chromosome condensation and sister chromatid cohesion. Despite the importance of these structural changes, chromatin itself has been long assumed to play a rather passive role during mitosis and chromosomes are usually compared to a “corpse at a funeral: they provide the reason for the proceedings but do not take an active part in them.” (Mazia, 1961). Recent evidence, however, suggests that chromosomes play a more active role in the process of their own segregation. The present proposal tests the “active chromosome” hypothesis by investigating how chromosome morphology influences the fidelity of mitosis. I will use innovative methods for acute protein inactivation, developed during my postdoctoral studies, to evaluate the role of two key protein complexes involved in mitotic chromosome architecture - Condensins and Cohesins. Using a multidisciplinary approach, combining acute protein inactivation, 3D-live cell imaging and quantitative methods, I propose to investigate the role of mitotic chromosomes in the fidelity of mitosis at three different levels. The first one will use novel approaches to uncover the process of mitotic chromosome assembly, which is still largely unknown. The second will explore how mitotic chromosomes take an active part in mitosis by examining how chromosome condensation and cohesion influence chromosome movement and the signalling of the surveillance mechanisms that control nuclear division. Lastly we will evaluate how mitotic errors arising from abnormal chromosome structure impact on development. We aim to evaluate, at the cellular and organism level, how the cell perceives such errors and how (indeed if) they tolerate mitotic abnormalities. By conceptually challenging the passive chromosome view this project has the potential to redefine the role of chromatin during mitosis.


Net EU contribution
€ 1 492 000,00
Avenida berna 45a
1067-001 Lisboa

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Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa
Activity type
Research Organisations
Other funding
€ 0,00

Beneficiaries (1)