Régulation post-transcriptionnelle et division cellulaire asymmétrique dans l'embryon de C. elegans // Post-transcriptional regulation and asymmetric cell division in the C. elegans embryo

La Division Cellulaire Asymétrique est un mécanisme essentiel pour spécifier l'identité cellulaire au cours du développement, engendrant l'apparition de la diversité de types cellulaires. Les cellules se divisant asymétriquement deviennent polarisées avant la mitose, la division a lieu le long de l'axe de polarité assurant une ségrégation inégale des déterminants d'identité cellulaire entre les cellules filles. Le développement embryonnaire précoce de C. elegans implique une série de division asymétriques, qui se déroulent en absence de transcription, comme chez tous les animaux. La spécification des identités et lignages cellulaires repose en grande partie sur la régulation post-transcrioptionnelle de l'expression d'ARNm maternels. Particulièrement il a été montré que le gène spn-4 régule des processus fondamentaux au cours des premières étapes du développement comme l'expression asymétrique de certains facteurs de transcription ou l'orientation du fuseau mitotique, ce qui est le point de départ de ce projet. SPN-4 est une protéine de liaison à l'ARN, régulant au niveau post-transcriptionnel des ARNm au cours des premières étapes du développement embryonnaire en aval de la division asymétrique.
L'embryon précoce de C. elegans constitue un modèle d'exception pour étudier la division asymétrique et la régulation posttranscriptionnelle en combinant des approches de Génétique, de Biologie Cellulaire, de Biologie Moléculaire et de Biochimie. Ce projet a pour objectif d'identifier les cibles pertinentes de la protéine SPN-4 impliquées dans la spécification de l'identité cellulaire et
l'orientation du fuseau mitotique, et établir les mécanismes moléculaires impliqués dans leur régulation afin de comprendre leur rôle dans la division cellulaire asymétrique.
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Stem cells are essential for integrity and renewal of human tissues. It has been established that many, if not most types of cancer arise from defects in stem cell division. Often the stem cells vs differentiation fate relies on asymmetric cell division. Asymmetric Cell Division is an essential mechanism to specify cell fate during development as well as in adult stem cells, ensuring the generation of cell type diversity and cell renewal. Asymmetrically dividing cells become polarized before mitosis, and subsequent division along the axis of polarity ensures the unequal segregation of cell fate determinants between the daughter cells. There is now ample evidence for abnormal asymmetric cell division being a cause of cancer, and contributing to cancer progression. The C. elegans early embryo provides an excellent model system to investigate the fundamental mechanisms of asymmetric cell division. In C. elegans, early development proceeds through a series of asymmetric divisions. It has been shown, by the supervisor and others, that spn-4 gene plays an essential role in these early asymmetric divisions. Specifically spn-4 regulates the asymmetric expression of cell fate determinants, and mitotic spindle orientation. SPN-4 is an RNA-binding protein, regulating post-transcriptionally mRNAs during the early steps of embryonic development. However, the relevant mRNA target involved in mitotic spindle orientation remains to be identified.
The C. elegans embryo is exceptionally amenable to study asymmetric cell division and post-transcriptional regulation combining Genetics, Cell Biology, Molecular Biology and Biochemistry approaches.
Stem cells are essential for integrity and renewal of human tissues. It has been established that many, if not most types of cancer arise from defects in stem cell division. Often the stem cells vs differentiation fate relies on asymmetric cell division. Asymmetric Cell Division is an essential mechanism to specify cell fate during development as well as in adult stem cells, ensuring the generation of cell type diversity and cell renewal. Asymmetrically dividing cells become polarized before mitosis, and subsequent division along the axis of polarity ensures the unequal segregation of cell fate determinants between the daughter cells. There is now ample evidence for abnormal asymmetric cell division being a cause of cancer, and contributing to cancer progression. The C. elegans early embryo provides an excellent model system to investigate the fundamental mechanisms of asymmetric cell division. In C. elegans, early development proceeds through a series of asymmetric divisions. It has been shown, by the supervisor and others, that spn-4 gene plays an essential role in these early asymmetric divisions. Specifically spn-4 regulates the asymmetric expression of cell fate determinants, and mitotic spindle orientation. SPN-4 is an RNA-binding protein, regulating post-transcriptionally mRNAs during the early steps of embryonic development. However, the relevant mRNA target involved in mitotic spindle orientation remains to be identified.
The C. elegans embryo is exceptionally amenable to study asymmetric cell division and post-transcriptional regulation combining Genetics, Cell Biology, Molecular Biology and Biochemistry approaches.
This project's goal is to identify and characterize the relevant targets of the SPN-4 protein involved in cell fate specification and mitotic spindle orientation, and establish the molecular mechanisms involved in their regulation in order to understand their role in asymmetric cell division. This should allow to better understand the fundamental mechanisms controlling asymmetric cell division, including stem cells, and potentially contribute to understand the link between asymmetric cell division and cancer.
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Début de la thèse : 01/10/2025

Appel à projets - UB PhD Scholarships

Université de Bordeaux

154 Sciences de la Vie et de la Santé

- Rigueur, esprit critique et créativité développés. - Solides connaissances en Génétique, Biologie Cellulaire et Moléculaire, et Biochimie. - Expérience avec des modèles génétiques animaux (C. elegans, Drosophile, etc...) est souhaitable, mais pas obligatoire. - Curiosité développée, intérêt pour la recherche fondamentale et motivation solide. Sont éligibles uniquement des candidatures internationales, à savoir : - des candidates ou candidats ayant obtenu (ou en cours d'obtention de) leur diplôme d'accès au doctorat (Master ou équivalent) dans un établissement à l'étranger - des candidates ou candidats actuellement dans un Graduate Program de l'université de Bordeaux, inscrits en deuxième année de Master et ayant obtenu leur diplôme d'accès au Master dans un établissement à l'étranger Seront prises en compte uniquement les candidatures soumises sur la plateforme suivante : https://aap.u-bordeaux.fr/ et avant le 17 mars à 23h59 (GMT Paris). Un guide de candidature ainsi que la liste des documents à soumettre sont disponibles sur la plateforme. Pour toute question, veuillez contacter : internationalisation.doctorat@u-bordeaux.fr
- Strong sense of rigor, a critical thinking skills and creativity. - Solid knowledge in Genetics, Molecular and Cell Biology, and Biochemistry. - Experience with animal genetic models (C. elegans, Drosophila, etc...) is desirable, but not mandatory. - Genuine curiosity, interest for basic science and unwavering motivation. The UB PhD scholarship program is open to international candidates only, which means: - candidates holding (or currently enrolled in) a national level master's degree or another degree conferring master's status from a foreign institution - candidates currently in a Graduate Program, enrolled in second year of Master at the University of Bordeaux, and holding a degree from a foreign institution We will only consider applications submitted on the following platform: https://aap.u-bordeaux.fr/ and prior March 17, at 11:59pm (GMT Paris). A guide on how to apply as well as the list of documents to submit are available on the platform. For any question, please contact: internationalisation.doctorat@u-bordeaux.fr