Description Inserm is the only French public organization entirely dedicated to biological, medical, and population health research. It has research laboratories throughout the country, organized into 12 Regional Delegations. Our institute brings together 15,000 researchers, engineers, technicians, and administrative staff, all with a common goal: to improve everyone’s health through advances in knowledge about living organisms and diseases, innovation in treatments, and public health research. Joining Inserm means becoming part of an institute committed to gender equality and professional equality, diversity, and supporting its employees with disabilities, from recruitment and throughout their careers. To promote well-being at work, Inserm pursues an active policy regarding working conditions, based in particular on a fair work-life balance. In 2016, Inserm received the European HR Excellence in Research label and has committed to evolving its recruitment and evaluation practices for researchers. The Position: We are recruiting an experienced postdoctoral researcher (2-3 years post-PhD) to study the cellular and molecular determinants of impaired epithelial regeneration and barrier dysfunction in chronic inflammatory bowel diseases (IBD: Crohn’s disease, ulcerative colitis) and metabolic disorders, with a particular focus on obesity. The central objective is to develop and validate a microphysiological human gut-on-a-chip system, derived from patient material and environmentally controlled, enabling direct functional interrogation of human tissues. Beyond modeling a pathophysiology relevant to the disease, the platform will enable quantitative and patient-specific phenotyping of epithelial alterations (e.g., stem/progenitor cell dynamics, differentiation trajectories, junctional integrity, permeability, wound closure/repair) and will support functional stratification for personalized medicine. Ultimately, the gut-on-a-chip will provide an ex vivo framework for (i) characterizing patient-specific intestinal functional alterations and (ii) evaluating individual responses to drug candidates, in order to prioritize personalized therapeutic strategies aimed at restoring epithelial integrity and promoting mucosal healing. The work integrates complementary human approaches, including patient-derived intestinal and colorectal organoids, our patented gut-on-a-chip microfluidic platform, functional genome editing, and high-content 3D imaging. Research project: We invite applications for an experienced Postdoctoral Fellow (2–3 years post-PhD) to investigate the cellular and molecular determinants of impaired epithelial regeneration and barrier dysfunction in inflammatory bowel diseases (IBD; Crohn’s disease, ulcerative colitis) and metabolic disorders, with a specific focus on obesity.The central objective is to engineer and validate an environment-controlled, patient-derived intestine-on-chip (gut-on-chip) microphysiological system enabling direct functional interrogation of human patient material. Beyond modeling disease-relevant physiology, the platform will deliver quantitative, patient-specific phenotyping of epithelial alterations (eg, stem/progenitor dynamics, differentiation trajectories, junctional integrity, permeability, wound closure/repair) and support functional stratification for personalized medicine. Ultimately, the intestine-on-chip will serve as an ex vivo framework to (i) characterize individual patient alterations and (ii) evaluate patient-specific responses to candidate interventions, enabling priority of personalized therapeutic strategies aimed at restoring epithelial integrity and promoting mucosal healing.The work integrates complementary human-relevant approaches, including patient-derived intestinal and colorectal organoids, our in-house microfluidic intestine-on-chip platform, functional genome editing, and high-content 3D imaging.The successful candidate will combine quantitative phenotyping with mechanistic disturbance to resolve the cellular events and signaling networks underlying defective regeneration and barrier failure in IBD and obesity. Expected outcomes include mechanistically grounded biomarkers and actionable targets, as well as a validated experimental pipeline for patient-centric testing of barrier-restoring and pro-regenerative strategies. Fixed-term contract of 12 months, renewable twice, full-time (38.5 hours per week). Host institution: Institute of Metabolic and Cardiovascular Diseases – U1297 – Occitanie Pyrénées Regional Delegation, 1 avenue Jean Poulhès – 31432 Toulouse Cedex 4. Unit Director: Dominique Langin. Reporting CSS (Centre de Soins Sociales – Social Security Centre): 3. Team Leader: Anne Bouloumie ProfileWork on an integrated experimental program investigating barrier dysfunction and impaired regeneration in IBD and obesity: study design, hypothesis prioritization, implementation, interpretation, and reporting. Establish, culture, and maintain human intestinal and colorectal organoids and fibroblasts derived from patients (healthy controls, IBD, obese patients), ensuring rigorous quality control, traceability, and reproducibility (donors, cell lines, passages, lots/batches). Develop and implement quantitative functional assays of epithelial regeneration and barrier function (e.g., wound healing, proliferation/differentiation dynamics, cell adhesion, permeability, and/or TEER when applicable), with appropriate hierarchical experimental designs (donor/cell line/batch). Perform functional genetic perturbations to investigate candidate pathways (CRISPR/Cas9 editing; CRISPRi/a as appropriate; gene delivery via viral and non-viral systems), including construct design, validation, and phenotypic readouts. Integrate organoid and fibroblast models into the gut-on-a-chip platform, contributing to the setup and operation of the microphysiological system (seeding strategies, flow/shear and environmental control, sampling workflows), in close collaboration with a PhD student and engineering partners, and adapting readouts for patient-specific phenotyping and intervention testing. Acquire and analyze high-content 3D imaging data (confocal and light-sheet microscopy), including sample preparation/clarification as needed, quantitative image analysis, and the development/maintenance of robust pipelines for structural and functional metrics. Conduct multi-level molecular and cellular profiling of tissues and organoids (histology/immunostaining, transcriptomic/protein analyses, and single-cell approaches depending on implementation) and integrate these profiles with functional phenotypes. Collaborate within the PEPR MED-OOC/ENVie consortium to integrate imaging, functional, and multi-omics data for patient stratification and mechanistic inference. Ensure rigorous documentation and reproducibility (SOPs, electronic lab notebooks, metadata, QC reports, data management/curation). Present results at internal meetings and international conferences. Contribute substantially to the preparation of manuscripts and, where applicable, to project/funding deliverables. Apply high standards of good scientific practice, biosafety, and compliance with institutional quality procedures for human samples (traceability, consent/ethical constraints, data protection where applicable). Mentor and support junior researchers/students as needed (e.g., PhD students, Master’s students). Expertise: Advanced culture of intestinal/colorectal organoids and quality control: traceability, batch management, reproducibility, standardization. Development and implementation of functional barrier/regeneration assays: permeability, tight junctions, repair/healing; TEER (Team Energy Evaluation) is an asset where applicable. Robust experimental designs adapted to nested/hierarchical data (donor/line/batch) and management of batch effects. Molecular and cellular biology: immunostaining, qPCR, protein analyses; interest/experience with multi-level approaches (multi-omics/single-cell as needed). Genome editing and functional genetics: CRISPR/Cas9, CRISPRi/a as appropriate; viral and non-viral gene delivery; associated phenotypic readouts. High-resolution 3D imaging (confocal, light-sheet) and quantitative image analysis workflows (standard tools; scripts preferred). Interest in organ-on-a-chip/microfluidics and the ability to integrate readouts into MPS systems in collaboration with engineers and PhD students. Documentation and reproducibility: lab notebook,