Description du sujet de thèse

The faithful transmission of genetic material during cell division is essential for all living organisms. Errors in chromosome segregation can lead to irreversible abnormalities in chromosome structure and/or number, resulting in various genetic diseases and cancers. Understanding the mechanisms that ensure accurate chromosome segregation is therefore a major goal in biological and biomedical research.
In eukaryotes, chromosome segregation depends on the bipolar attachment of chromosomes to the mitotic spindle via their centromeres, as well as the separation of sister chromatids toward opposite spindle poles. Over the past century, significant efforts have been made to understand spindle assembly and centromere-microtubule attachment. In parallel, several studies have reported that telomeres and the integrity of telomeric heterochromatin also play an important role in the accurate segregation of chromosome arms. However, the mechanisms—whether active or passive—by which telomeres contribute to chromosome segregation remain poorly understood.
We have identified a novel cascade of events at telomeres, involving the condensin complex and Aurora B kinase, which facilitates the efficient separation of chromosome ends.
Using innovative approaches such as live-cell imaging and genetics in fission yeast, the objective of this PhD is to further investigate the molecular mechanisms by which this telomeric pathway promotes accurate chromosome segregation.
References related to the project:
• Tong Li, Yannick Gachet, Sylvie Tournier. MAARS software for automatic and quantitative analysis of mitotic progression. Methods in Molecular Biology, 2024. Book: Cell Cycle Control. DOI: 10.1007/978-1-0716-3557-5
• Léonard Colin, Céline Reyes, Julien Berthezene, et al. Condensin positioning at telomeres by Shelterin proteins promotes telomere disjunction in anaphase. eLife, 2023. DOI: https://doi.org/10.7554/eLife.89812.1
• Berthezene J., Reyes C., Li T., et al. Aurora B and condensin are dispensable for chromosome arm and telomere separation during meiosis II. Mol Biol Cell, 2020; 31(9): 889-905
• Maestroni L., Reyes C., Vaurs M., et al. Nuclear envelope attachment of telomeres limits TERRA and telomeric rearrangements in quiescent fission yeast cells. Nucleic Acids Res, 2020; 48(6): 3029–3041
• Gachet Y., Reyes C., Tournier S. Aurora B kinase controls the separation of centromeric and telomeric heterochromatin. Mol Cell Oncol, 2015; 3(2): e1043039
• Audry J., Maestroni L., Delagoutte E., et al. RPA prevents G-rich structure formation at lagging strand telomeres to allow maintenance of chromosome ends. EMBO J, 2015; 34(14): 1942–1958
• Reyes C., Serrurier C., Gauthier T., et al. Aurora B prevents chromosome arm separation defects by promoting telomere dispersion and disjunction. J Cell Biol, 2015; 208(6): 713–727

Contexte de travail

The PhD will be conducted at the Centre for Integrative Biology (CBI) in Toulouse. The CBI develops multidisciplinary and multi-scale approaches using model organisms ranging from bacteria to humans. The center includes over 400 researchers across three units:
(i) Microbiology
(ii) Molecular, Cellular and Developmental Biology
(iii) Animal Cognition
The CBI offers a state-of-the-art technological environment through eight platforms equipped with innovative tools, particularly for live imaging, electron microscopy, image analysis, and bioinformatics.
The thesis will be supervised by Sylvie Tournier (Research Director, CNRS), whose team is affiliated with the Toulouse Doctoral School "Biology, Health, Biotechnology" (BSB). The co-supervisor will be Yannick Gachet (Research Director, CNRS).
We are looking to recruit a student with prior experience in fission yeast cell biology, trained in genetic manipulation techniques in yeast, live-cell imaging, and the use of image and data analysis software such as ImageJ.
This PhD project is funded by the French National Research Agency (ANR), as part of the TeloMito 2025 project.

Contraintes et risques

None