Phd Subject

**PHD SUBJECT : Contribution of topographical constraints to kidney pathophysiological organization**:

- Réf **ABG-123537**
- Sujet de Thèse- 30/04/2024- Autre financement public- Centre de Recherche en Biologie cellulaire de Montpellier (CRBM)- Lieu de travail- Montpellier - Occitanie - France- Intitulé du sujet- PHD SUBJECT : Contribution of topographical constraints to kidney pathophysiological organization- Champs scientifiques- Biologie
- Mots clés- Cell division, tissue morphogenesis, renal epithelial tubule, tissue curvature, imaging, 3D micro-fabrication, biophysics**Description du sujet**:
**Interdisciplinary thesis project.** Despite lots of efforts to identify the origin of kidney diseases, the contribution of tissue topographical properties to renal pathophysiological organization remains poorly explored. Animal models are widely used, but remain complex systems that do not allow the dynamic study of tissues at the cellular scale in modular et standardized topographies. As for cellular studies on flat substrates, they do not take into account the naturally curved shape of the renal epithelial tubule. The thesis project proposed here combines cell biology and bioengineering. It consists in developing micro-fabricated 3D substrates that mimic the dynamic topographical constraints of the renal tubule, compatible with cell culture (renal MDCK cells and zebrafish renal tubule cells ex-vivo). These systems will be used to study how static or dynamic changes in tissue curvature influence the organization and integrity of the renal epithelium. High-resolution live microscopy will allow to focus on the organization and geometry of cell divisions. This project will lead to the implementation of a new device for ex vivo study of zebrafish renal tubules, and will allow to tackle, from a biophysical angle, the question of renal pathophysiology.

**Role of the PhD student**. He/she will be trained in 3D micro-fabrication (Team C. Tomba, Lyon) and will use these substrates to characterize the impact of curvature on cell division in the Delaval team (CRBM, Montpellier). He/she will be in charge of MDCK cell culture, microscopy, quantification and biophysical analyses. He/she will also set up ex vivo cultures of zebrafish cells on structured 3D substrates and will participate in the optimization of micro-fabrication devices.

**Funding and work context.** This thesis project is funded for 3 years by the CNRS through the MITI interdisciplinary programs. It will be carried out in Montpellier in Bénedicte DELAVAL's team at the _Centre de Recherche en Biologie cellulaire de Montpellier_ (CRBM), in close collaboration with Caterina TOMBA (_Institut des Nanotechnologies de Lyon_). The PhD student will have access to laboratory equipment, microscopy facility (MRI) and aquatic models for research (ZEFIX) in Montpellier, as well as clean room and L2 (Nanolyon). Travel to Lyon will be required for the PhD student's training in micro-fabrication, as well as for consortium meetings

**Prise de fonction**:

- 01/10/2024**Nature du financement**:

- Autre financement public**Précisions sur le financement**:

- Funded for 3 years by the CNRS through the MITI interdisciplinary programs**Présentation établissement et labo d'accueil**:

- Centre de Recherche en Biologie cellulaire de Montpellier (CRBM)The DELAVAL Team, Centrosome Cilia and Pathologies addresses emerging questions in the field of cell biology and epithelial tissue morphogenesis focusing on the contribution of highly dynamic cellular processes such as cell division. More specifically, we are studying, from the molecular to the tissue scale how intracellular transport complexes (proteins of the IntraFlagellar Transport machinery, IFT) involved in kidney pathologies control the geometry of cell division. We also focus our interest on understanding how cell division contributes to kidney tubule morphogenesis under normal and pathological conditions. To address these questions we combine in the team cell biology and microscopy approaches on complementary systems going from single molecules in vitro and 2D/3D cell culture to zebrafish as an in vivo model.

**Site web**:
**Intitulé du doctorat**:

- Biologie**Pays d'obtention du doctorat**:

- France**Etablissement délivrant le doctorat**:

- Université de Montpellier**Ecole doctorale**:

- Sciences Chimiques et Biologiques pour la Santé (CBS2)-
- 17/05/2024