ED Sciences de la Vie et de la Santé
Development of a toxicology assay using 3D cellular models and soSPIM-based high content screening
by Ihssane IDRISSI (Institut Interdisciplinaire de Neurosciences)
The defense will take place at 14h30 - Amphithéâtre Broca 146 Rue Léo Saignat, 33076 Bordeaux
in front of the jury composed of
- Jean-Baptiste SIBARITA - Ingénieur de recherche - Université de Bordeaux - Directeur de these
- Charlotte RIVIèRE - Directrice de recherche - L'institut Lumière Matière (iLM) - Rapporteur
- Corinne LORENZO - Ingénieure de recherche - RESTORE - Rapporteur
- Pierre NASSOY - Directeur de recherche - Laboratoire Photonique, Numérique et Nanosciences - Examinateur
Drug-induced liver injury (DILI) remains a major cause of drug withdrawal, highlighting the urgent need for predictive and physiologically relevant in vitro assays. Three-dimensional (3D) cell cultures have emerged as promising models for drug screening and toxicity testing, as they better reproduce tissue architecture and function compared to conventional two-dimensional (2D) systems. However, their integration into high-content screening (HCS) still faces important challenges, including the standardization and parallelization of culture, the minimization of handling steps between culture and imaging, and the development of imaging methods capable of capturing complete 3D volumes with high speed and minimal photobleaching and phototoxicity, while remaining fully compatible with HCS requirements. This PhD project aims to establish a dedicated HCS pipeline for hepatotoxicity assays using HepaRG liver spheroids, microfabricated JeWells culture devices, single-objective light-sheet fluorescence microscopy (soSPIM), and dedicated analysis tools. The soSPIM architecture, based on integrated 45° mirrors, enables high-speed, low-phototoxic 3D imaging. Combined with JeWells devices, arrays of truncated pyramidal-shaped cavities, it allows the parallelized culture and standardized imaging of hundreds of 3D samples within a single chip, providing quantitative morphological readouts at the single-organoid level. As a proof of concept, we modeled drug-induced cholestasis on 7-day-old HepaRG spheroids cultured in JeWell devices. Spheroids were exposed to reference compounds, including chlorpromazine and indomethacin, imaged on the soSPIM-HCS platform after immunolabelling, and analyzed for nuclear, cytoskeletal, and hepatobiliary transporter markers. We demonstrated the ability of this platform to capture both morphological disruptions and functional impairments characteristic of cholestatic injury in liver organoids. Overall, this work establishes a methodological framework integrating standardized 3D culture, advanced 3D imaging, and automated analysis into a single HCS pipeline for hepatotoxicity assessment. Beyond the case study of cholestasis, this platform paves the way for broader applications of 3D organoid-based assays in drug discovery and toxicology.
ED Sociétés, Politique, Santé Publique
Pedagogical innovation within teacher training policies. Comparative study France China.
by Sébastien MAUVE (Laboratoire Cultures, Education, Sociétés)
The defense will take place at 13h30 - Salle des thèses 3 Place de la Victoire, 33000 Bordeaux
in front of the jury composed of
- Régis MALET - Professeur des universités - Université de Bordeaux - Directeur de these
- Joël BELLASSEN - Professeur des universités - Inalco - Rapporteur
- Magdalena KOHOUT DIAZ - Professeure des universités - LACES - Examinateur
- Lijuan WANG - Full professor - Hunan University - Rapporteur
- Martine DERIVRY - Professeure des universités - Université de Bordeaux - Examinateur
- Min LIU - Professeur associé - université Normale de Pékin - Examinateur
Machiavelli argued that while "not everything is political, politics takes an interest in everything," highlighting the influence of political power across domains. He also recognized that this power tends toward a demand for totality, which cannot be fully realized without understanding reality. This pragmatic approach paradoxically applies to teacher training policies in France and China: despite numerous reforms (1975-2023) and ministerial reports (1983-2023), few significant changes have occurred. These reforms, often driven by social or educational demands, have sidelined the core objective of instruction (Rayou & Ria, 2021). Political rhetoric frequently praises pedagogical innovation as a miracle solution for reducing educational inequalities in both France and China. This study not only compares these reforms but also examines how teachers in both countries perceive these innovation mandates. Do they retain autonomy, or are they overwhelmed by competing priorities? The research is based on surveys of French teachers in China (Guangdong) and Chinese teachers in France, analyzing: -The integration of innovation into training policies; -Teachers' perceptions of innovation (via questionnaires); -Their innovative practices, with or without training (via interviews). Unlike historical studies like Zhao & Zhong's (2023) on rural-urban disparities in China, this work adopts a comparative and critical approach, examining bureaucratic and authoritarian logics in education policies. It cross-references diverse sources (political discourse, official texts, inspection reports) to reveal gaps between policy intentions and local realities. The originality of this study lies in its analysis of cultural, linguistic, and contextual dimensions of teacher training, beyond a mere chronology of reforms. It highlights contradictions between top-down institutional mandates and teachers' actual practices.