PhD: Development of Model Extracellular Matrices from DNA (M/F).

Job Description

Thesis Subject

Osteosarcoma, the most common primary malignant bone tumor in children and young adults, is characterized, like many other pathologies (inflammation, fibrosis), by dysregulation of the extracellular matrix (ECM). Mechanical signals from the ECM directly influence cellular behavior (proliferation, migration, differentiation) and play a key role in tumor progression. Invasive cancer cells must adapt to a mechanically heterogeneous environment to form metastases, the leading cause of mortality. Preliminary data reveal a fundamental difference between invasive and non-invasive cells in their ability to sense and migrate on viscoelastic substrates, suggesting a link between ECM viscoelasticity and metastatic potential. However, most studies use linearly elastic hydrogels, overlooking this major property of biological tissues, despite recent work demonstrating its strong impact on cellular behavior, including in cancer. Moreover, measuring cellular forces in viscoelastic environments, where deformation combines elastic and viscous components, remains a challenge.
Our preliminary work has demonstrated the feasibility of preparing mechanofluorescent hydrogels and hydrogels with controlled viscoelasticity based on DNA. [1,2] We have also developed methods to protect gels from cellular degradation and to functionalize them for cell anchoring.

The primary goal of this PhD thesis is to develop a DNA-based model extracellular matrix that mimics the mechanical properties (stiffness, viscoelasticity) of healthy and tumoral ECM, allows variation of the biochemical characteristics of the cellular environment (ligand structure and density), and deciphers the impact of viscoelasticity on mechanotransduction pathways (YAP, MRTF) and cellular invasion.
References:
[1] P. Le Bourdonnec, C. Ferkous, L. Comunale, L. Cipelletti, R. Merindol, Adv. Mat. 2026, e16741.
[2] R. Merindol, G. Delechiave, L. Heinen, L. H. Catalani, A. Walther, Nat. Commun. 2019, 10, 528.

Your Work Environment

The PhD will take place in two Montpellier-based laboratories: the Soft Matter team at the Laboratoire Charles Coulomb (L2C), dedicated to the synthesis and characterization of DNA-based hydrogels, and the Tumor Signaling team at the Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM), where cellular behavior on these materials will be studied. The PhD student will work in a collaborative environment, in close interaction with another PhD student developing mechanorescent hydrogels, as part of a joint ANR-funded project between the two laboratories.

Constraints and risks

Laboratory work in physical chemistry and cell biology. Strict adherence to safety protocols is essential to prevent accidents and ensure the protection of the operator and the environment.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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