The Marie S. Curie Postdoctoral Fellowship (MSCA-PF) programme is a highly prestigious renowned EU-funded scheme. It offers talented scientists a unique chance to set up 2-year research and training projects with the support of a supervising team. Besides providing an attractive grant, it represents a major opportunity to boost the career of promising researchers. 

Research laboratories in Brittany are thus looking for excellent postdoctoral researchers with an international profile to write a persuasive proposal to apply for a Marie S. Curie Postdoctoral Fellowship in 2025 (deadline of the EU call is set for 10th September 2025). The topic and research team presented below have been identified in this regard.

Main Research Field

Life Sciences (LIF)

Research sub-fields

Cell biology ; Biophysics.

Keywords

Cell division, Chromosome segregation, Microtubule flexural rigidity, Doublecortin-domain proteins, Fluorescence microscopy.

Research project description

Context: Our lab recently uncovered the key role of microtubule rigidity in spindle orientation during cell division in Caenorhabditis elegans zygote [1]. We perturbed microtubule flexural rigidity by targeting ZYG-8, the only protein of the Doublecortin family in nematodes. This family is known to regulate microtubule rigidity in neuronal cells. We demonstrated that ZYG-8 controls microtubule rigidity during zygote division, showing larger curvatures upon ZYG-8 depletion and even greater curvatures in zyg-8(or484ts) mutants, where ZYG-8 binding to microtubules is impaired. We found that overly soft microtubules in zyg-8(or484ts) mutants led to defects in the final orientation of the mitotic spindle due to a reduced cortical pushing force. Our results indicate that sufficient microtubule rigidity is essential for effective cortical pushing during mitosis, ensuring accurate spindle orientation and correct daughter cell fates.

Interestingly, we observed chromosomal defects (e.g. chromosomal bridge or lagging chromosome) during anaphase, as well as impaired chromosome congression on the metaphase plate in zyg-8(or484ts) mutants. We also found that chromosome congression was perturbed upon zyg-8(RNAi). Previous studies on cell division, targeting proteins from the Doublecortin and Tau families (the latter also known to regulate microtubule rigidity), have revealed defects in the formation and integrity of meiotic or mitotic spindles, as well as aneuploidy and chromosome misalignment. However, the underlying mechanisms remain unclear. Proposed explanations include perturbations in microtubule stability, or in molecular motor activity and recruitment. Whether microtubule rigidity plays a role in these mechanisms remains to be investigated in dedicated studies.

Hypothesis: Microtubule flexural rigidity contributes to an accurate segregation of the chromosomes during cell division. In particular, microtubules must be mechanically stiff under compressive load to withstand forces permitting chromosome segregation, for which tension sensing at the kinetochore interface is critical. An optimal microtubule-rigidity range may exist and permit cell division adapting, especially to chromosomal attachment defects. 

Objectives:

(1) To characterize the shape of spindle microtubules and the morphology of the mitotic spindle in response to perturbations of proteins known to regulate microtubule rigidity. (2) To investigate the roles of microtubule rigidity in chromosome segregation (e.g., does a reduced microtubule rigidity decrease the pushing force exerted on chromosomes, potentially impairing chromosome congression?).  (3) To uncover the mechanisms regulating microtubule-rigidity (e.g., protofilament coupling, bundling, post-translational modifications, repaired lattice defects, coupling with an elastic environment).

Approaches:

We are seeking a motivated post-doctoral fellow to help advance on this topic. Depending on his/her expertise, the candidate is encouraged to propose new and original approaches to achieve the objectives.

We will use the C. elegans zygote as model for asymmetric division with holocentric chromosomes. Studying human cell division with monocentric chromosomes may also serve as a complementary model. The candidate will manipulate the expression levels (via RNAi or overexpression) of proteins from the Tau or Doublecortin families or use mutants from these families to perturb microtubule rigidity. Using fluorescent reporters and fluorescence microscopy, he/she will track the key components of cell division (e.g. microtubules, centrosomes, chromosomes) throughout mitosis. He/she will also have access to advanced, in-house biophysical tools, which provide unique insights into the regulation of spindle external forces and internal mechanics [2,3]. This will provide the candidate with the opportunity to develop new skills in a multi-disciplinary research environment. Besides, the proposed secondment in the lab of Stefanie Redemann, an expert in electron microscopy for studying mitotic and meiotic spindles, will allow the use of this technique as a complementary method to investigate how microtubule rigidity contributes to chromosome segregation.

Selected publications of the team relevant to the proposal:

[1]  Cueff L. et al., “Microtubule stiffening by doublecortin-domain protein ZYG-8 contributes to spindle orientation during C. elegans zygote division.” bioRxiv, 2024.11.29.624795. 

[2] Bouvrais H. et al., “The coordination of spindle-positioning forces during the asymmetric division of the C. elegans zygote is revealed by distinct microtubule dynamics at the cortex.” EMBO Reports, 2021.

[3] Pécréaux J. et al., “The mitotic spindle in the one-cell C. elegans embryo is positioned with high precision and stability.” Biophysical Journal, 2016.

Supervisor

The Postdoctoral Fellow will be supervised by Hélène Bouvrais, CNRS researcher.

Short CV of Dr Hélène Bouvrais:

Dr. Hélène BOUVRAIS conducts interdisciplinary research to investigate how microtubules contribute to the robustness of cell division. She leads her project team in the lab of Dr. Jacques Pécréaux at the Institute of Genetics and Development of Rennes (IGDR). Her project-team includes a biological assistant engineer, a PhD student in informatics, a PhD student in biology who will join the lab in autumn 2025, and a post-doctoral researcher with expertise in deep learning who will join in spring 2025. In 2022, she was awarded ANR JCJC funding to study how microtubule mechanics contribute to accurate cell division, and the current project will benefit from this funding.

Hélène's research journey began with model systems in biology and evolved toward the modelling of living systems, always within a multidisciplinary environment. She completed a joint PhD between a Danish lab (MEMPHYS – Center for Biomembrane Physics) and a French lab (ENSCR) in lipid biochemistry and membrane biophysics, publishing six peer-reviewed papers and receiving the Bretagne Young Researcher Prize. Her first postdoctoral position in Denmark involved applying membrane model systems to the field of ecotoxicology, resulting in collaborative work and four peer-reviewed publications. She then moved to France for her second postdoctoral position, focusing on quantifying and modelling living systems, which laid the foundation for her current research project. This work was supported by a competitive EMBO post-doctoral long-term fellowship. While this funding was ongoing, Dr. Hélène Bouvrais was awarded a permanent CNRS position in January 2016.

Three most significant publications:

• Bouvrais H. et al., “Microtubule feedback and LET-99-dependent control of pulling forces ensure robust spindle position”, Biophysical J., 115(11): 2189-2205, 2018.
• Bouvrais H. et al., “The coordination of spindle-positioning forces during the asymmetric division of the Caenorhabditis elegans zygote”, EMBO report, 22, e50770, 2021.
• Cueff L. et al., “Microtubule stiffening by doublecortin-domain protein ZYG-8 contributes to spindle orientation during C. elegans zygote division.” bioRxiv, 2024.11.29.624795. Submitted to EMBO J.

Webpage:

https://igdr.univ-rennes.fr/helene-bouvrais

Department/ Research 

Lab of Jacques Pécréaux:

The research team, led by Dr Jacques Pécréaux, is interested in the robustness of cell division to internal (e.g. chromosomal aberrations) and external (e.g. mechanical deformations) perturbations. This robustness is ambivalent. On the one hand, this property of cell division allows, from a unicellular embryo, the correct development of a complex and multicellular organism, such as Humans. On the other hand, this robustness allows the division of cancerous cells despite the accumulated defects (e.g. abnormal number of chromosomes) and leads to the resistance of cancer cells to anti-cancer treatments. Understanding the mechanisms of this robustness is therefore one of the research challenges in cell biology. This robustness emerges from the mechanistic interactions between many molecular players, which are the microtubules, the motors and their regulators. A study of this robustness by the biophysical tools seems relevant, as it considers the complex network of these multiple interactions.

To address these questions, the Pécréaux lab performs multi-disciplinarily research (cell biology, biophysics, bioinformatics), combines investigations at the cellular and microscopic scales and develops original methods based on advanced image and data analysis, to access unique data, such as the DiLiPop assay. Besides, our lab, together with the Tramier lab (same institute) and Inscoper, SAS (a spin-off of the labs), contributes to developing an automated microscope that feeds back image on-the-fly classification to the driving unit (roboscope). The roboscope will be particularly relevant to study human cell division, since it will permit an automated acquisition of dividing cells, avoiding chemical cell synchronizing that may affect cell division robustness mechanisms.

The quality of CeDRE-team research is demonstrated by competitive grants (since 2013: 1 ANR PCR, 1 ANR PRCE, 1 ANR JCJC, a Plan Cancer, 2 charity-funded PhD fellowships, and the roboscope funding by the “pôle de compétitivité Images et Réseaux”), publications in high-profile journals, two patents, and selected oral presentations or invitations in meetings.

The institute:

The IGDR is Brittany's leading institute of cell and developmental biology, and genomics. It is a dynamic and expanding institute, which is internationally renowned and administratively supervised by CNRS, INSERM and University of Rennes. The institute includes 16 teams and covers a wide range of subjects in cell biology, using different model organisms (e.g. C. elegans nematode, Drosophila melanogaster, Xenopus species, mice, human cells). The candidate will thus benefit from the research environment from other IGDR teams on related topics and local core facilities. The institute strongly promotes interdisciplinary approaches, particularly at the interface between physics and biology. Besides, CeDRE team is strongly involved in the scientific animation of the institute, e.g. organizing shared labmeetings (MicBioPhys for Microscopy Biology & Physics, and C. elegans related ones), thematical meetings (BIS for Biology In Silico, and MT-igdr dedicated to microtubule field), and being part of the PhD program.

Research environment in Rennes:

In Rennes, the candidate will benefit from a state-of-the-art microscopy facility (MRiC). In particular, the teams of S. Huet, M. Tramier and J. Pécréaux contribute to transferring their microscopy-related developments and are thus identified as R&D teams by the France BioImaging national infrastructure. Finally, the BIOSIT facility offers a helpdesk for image analysis.

Webpage:

For the team: https://igdr.univ-rennes.fr/en/cedre-lab

For the institute: https://igdr.univ-rennes.fr/en

Location:

Campus Santé de Villejean, Faculté de Médecine

2 avenue du Professeur Léon Bernard, CS 34317

35043 Rennes Cedex, France

Suggestion for interdisciplinary / intersectoral secondments and placements

A 3 to 6-month secondment at the University of Virginia, in Stefanie Redemann’s lab, can be considered to conduct electron microscopy experiments. These experiments will focus on revealing spindle structure and microtubule shape, in particular the curvature, when perturbing microtubule rigidity. During this secondment, the candidate will develop complementary skills in electron microscopy to perform investigations at the nanoscale level. In the French lab, confocal fluorescence microscopy will be used for related studies.

Webpage of Stefanie Redemann’s lab:

https://med.virginia.edu/redemann-lab/ 

Skills Requirements  

The applicant should hold a PhD in biology. Proven experience in the field of cell biology and in fluorescence microscopy are a prerequisite. Prior experience in the study of microtubules or cell division and in image analysis will be considered favourably but is not mandatory. Some knowledge in genetics and some interests for biophysics and system biology would be a plus.

Fluency in English, both written and oral, is mandatory. French is not a prerequisite.

At least two publications in the field of cell biology, with one as first author, are expected.

Eligibility criteria for applicants

Academic qualification: By the MSCA-PF call deadline (10 September 2025), applicants must be in possession of a doctoral degree, defined as a successfully defended doctoral thesis, even if the doctoral degree has yet to be awarded.

Research experience: Applicants must have a maximum of 8 years full-time equivalent experience in research, measured from the date applicants were in possession of a doctoral degree. Years of experience outside research and career breaks (e.g. due to parental leave), will not be taken into account.

Nationality & Mobility rules: Applicants can be of any nationality but must not have resided more than 12 months in France in the 36 months immediately prior to the MSCA-PF call deadline (10 September 2025).

Application process

We encourage all motivated and eligible postdoctoral researchers to send their expressions of interest through the EU Survey application form (link here)[1], before 31st May 2025. Your application shall include:

• a CV detailing: (i) for each position you had, the exact dates and location (country) and (ii) a list of accepted publications;

• a cover letter including a research outline (up to 2 pages) identifying the research synergies with the project supervisor(s) and proposed research topics described above.

   

Estimated timetable

Deadline for sending an expression of interest: 31st May 2025

Selection of the applicant: June 2025 at the latest

Writing the MSCA-PF proposal with the support of the above-mentioned supervisor(s): June – September 2025

MSCA-PF 2025 call deadline: 10 September 2025

Publication of the MSCA-PF evaluation results: February 2026

Start of the MSCA-PF project (if funded): May 2026 (at the earliest)