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Nuclear organisation and division

Nuclear organisation and division

DEPARTMENT

Development and stem cells

TEAM LEADER

Manuel MENDOZA

Living cells have a remarkable ability to organize their internal components in a precise and dynamic manner. This is especially evident during cell division, when cells rapidly reorganize, duplicate their contents, and split into two daughters that often adopt distinct fates. These complex transformations must be tightly coordinated in space and time.

Our lab studies the molecular mechanisms that ensure this coordination, with a focus on three interconnected areas:

First, we investigate how chromosome segregation and cytokinesis are coupled, particularly through the Aurora B-dependent NoCut checkpoint, which prevents abscission in the presence of chromatin bridges. 

Second, we explore how nuclear organization influences cell identity. We found that nuclear pore complexes (NPCs) are differentially acetylated in mother and daughter cells in budding yeast, and that this modification regulates gene expression and mRNA export. We are now investigating how NPC acetylation contributes to transcriptional and post-transcriptional control, and whether similar regulatory principles apply in mouse embryonic stem (ES) cells. In this context, we focus on the role of non-histone protein acetylation in controlling mRNA processing, export, and stability during cell fate transitions.

Third, we study how cells maintain nuclear homeostasis during aging. In budding yeast, DNA damage in the ribosomal DNA (rDNA) region leads to the formation of extra-chromosomal rDNA circles (ERCs), which accumulate in aging mother cells. We are developing a proximity-labeling proteomics approach to identify proteins that associate with the rDNA during damage and ERC formation. This project, which combines mass spectrometry with live-cell imaging and microfluidics, aims to uncover how rDNA instability impacts nuclear function and how ERCs contribute to aging-related decline in nuclear organization.

Together, our work aims to uncover how cells preserve nuclear integrity and regulate gene expression through dynamic changes in nuclear architecture, with implications for understanding both development and aging.

Members

Researchers

Post-doctoral fellows

PhD students

Engineers

Current projects

1. Checkpoint control of cytokinesis in response to chromatin bridges

2. Regulation of gene expression and mRNA export by nuclear pore acetylation

3. Mechanisms of rDNA instability and extra-chromosomal rDNA circle accumulation during aging

Funding and partners

  • French National Research Agency (ANR), Coordinator of Collaborative Research Project, 2022-2025
  • ARC Foundation for Cancer Research, « Programme Labellisé », 2022-2025
  • FRM Medical Research Foundation, “Equipe Labellisée”, 2021-2024

 

 

 

Awards and recognitions

European Research Council, Starting Grant (2011-2017)

Publications

Development and stem cells - Cancer research