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Understanding the role of CyclinB1-NuMA interaction in spindle orientation and epithelial morphogenesis

Project description

Molecular regulation of spindle formation in cell division

During cell division, chromosomes attach to and migrate on the so-called mitotic spindle, a protein-based net which spans the cell and ensures correct chromosomal segregation. Disruption of the mitotic spindle has detrimental consequences such as genetic instability and cancer. The EU-funded NuMA_CyclinB1_EM project focuses on the importance of mitotic spindle regulation with respect to orientation and timing. Researchers aim to provide fundamental knowledge on the regulatory factors that drive spindle orientation and thus play a central role in tissue morphogenesis, homeostasis and regeneration. Moreover, NuMA_CyclinB1_EM is expected to shed light on the pathogenic mechanisms of carcinogenesis.

Objective

In multicellular organisms, oriented cell divisions sustain tissue morphogenesis, tissue architecture and homeostasis by ensuring the correct positioning of daughter cell after mitosis. Accurate execution of oriented divisions and chromosome segregation relies on the positioning of an essential actor, the mitotic spindle. The consequence of spindle misorientation is drastic. Disruption of any of the spindle orientation factors could lead to genetic instability, tissue disorganization and tumorigenesis. However, cell division is controlled not only in orientation, but also in time. Indeed, spindle orientation is also very important for a wide range of developmental processes, ranging from germline stem cell division to epithelial tissue homeostasis and regeneration. A more complete understanding of how spindles are oriented will therefore require more extensive research, e.g. using CRISPR-based strategies to interrogate the proposed interactions in vivo, into how the spindle-orienting machinery is localized and regulated in multiple systems. The aim of this project is to advance knowledge on how cell cycle regulates spindle positioning and its contribution in epithelial morphogenesis in the intestinal tissues. This advance knowledge will serve to better understand the pathogenic mechanisms of important human diseases such as cancer.

Coordinator

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Net EU contribution
€ 160 932,48
Address
CALLE SERRANO 117
28006 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
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Total cost
€ 160 932,48