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DTSTART;TZID=Europe/Paris:20250919T140000
DTEND;TZID=Europe/Paris:20250919T140000
DTSTAMP:20260511T203049
CREATED:20250428T072503Z
LAST-MODIFIED:20250731T080424Z
UID:183455-1758290400-1758290400@www.bordeaux-neurocampus.fr
SUMMARY:Thesis defense - Ænora Letourneur
DESCRIPTION:Venue : CARF \n \nOn zoom: https://u-bordeaux-fr.zoom.us/j/83810704899 \nThèse défendue en français \n\nÆnora Letourneur \nTeam : SynTeam\nIMN \nTitle\nThe chaperone DNAJB6 as a regulator of alpha-synuclein aggregation in neuronal models of induced synucleinopathy \nAbstract\nThe protein α-synuclein self-assembles into amyloid fibrils\, found in the neuronal or glial inclusion observed in synucleinopathies. In vitro studies have characterized the aggregation mechanisms of the protein\, but the processes that the cell can use to modulate this aggregation are still under investigation. We chose to work in models of induced synucleinopathy\, both primary cultures and in adult mice brains. \nWe first look at a panel of molecular chaperones\, which have been shown to be involved in this regulation\, before focusing of DNAJB6. Indeed\, we observed\, with this protein\, a specific relocalization of DNAJB6\, condensed as punctae\, to the neo-formed aggregates. This observation\, combined with the studies showing DNAJB6 to have an affinity for amyloid structures\, made us hypothesize that DNAJB6 had a functional role in the regulation of the induced synucleinopathy. \nIndeed\, functional studies then allowed us to observe an inhibition of the aggregation of α-syn when DNAJB6 is overexpressed\, both in primary cultures and in mice brains. We deduced that this effect was due to a selective interaction of DNAJB6 with the fibrillar α-syn\, and not the monomeric one. Furthermore\, we were able to show that this inhibition of the aggregation was due to the activity of DNAJB6 alone and not\, as we thought in the beginning\, due to its involvement in a system also containing Hsp110 and Hsc70\, for which DNAJB6 is a co-chaperone. Indeed\, the mutated H31Q DNAJB6\, which cannot interact with Hsc70\, showed the same inhibitory effect as the wild-type DNAJB6. We confirmed this point by reconstituting in vitro the system and seeing that\, in contrast with DNAJB1\, DNAJB6 does not induce a disaggregase activity of the system on the α-syn fibrils. \nKey words\nalpha-synuclein ; synucleinopathy ; molecular chaperones ; DNAJB6 ; neurons \nPublication\nDe Giorgi\, F.\, Letourneur\, A.\, Kashyrina\, M.\, Zinghirino F.\, Dovero\, S.\, Dutheil\, N.\, Largitten L.\, Arotçarena\, M.\, Bezard\, E.\, Canron\, M.\, Meissner\, W.\, De Nuccio\, F.\, Ichas\, F.\, 2024. Reconsidering α-Synuclein inclusion pathology in neurons\, mice\, and humans with an antibody sensing NAC engagement during α-Synuclein amyloid conversion. (preprint)\nJury\nDr. Nocca Smet\, Université de Lille – Rapportrice\nDr. Genevaux Pierre\, Université Toulouse 3 – Rapporteur\nDr. Angot Elodie\, ROCHE – Examinatrice\nDr. Baron Thierry\, Anses Lyon – Examinateur\n
URL:https://www.bordeaux-neurocampus.fr/en/event/thesis-defense-aenora-letourneur/
CATEGORIES:IMN,Thesis
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DTSTART;TZID=Europe/Paris:20250919T143000
DTEND;TZID=Europe/Paris:20250919T143000
DTSTAMP:20260511T203049
CREATED:20250827T115015Z
LAST-MODIFIED:20250911T095506Z
UID:187284-1758292200-1758292200@www.bordeaux-neurocampus.fr
SUMMARY:Thesis defense - Christer Lohk
DESCRIPTION:Venue: IBGC \n\nChrister Lohk\nTeam: Quantitative imaging of the cell \nIINS \nThesis supervised by Jean-Baptiste Sibarita (IINS) & Macha Nikolski (IBGC) \nTitle\n“Artificial intelligence for the characterization of 3D cultures in high content fluorescence microscopy” \nAbstract\nOver the recent years\, 3D cell cultures have become the gold standard in cell biology\, with applications ranging from fundamental research to high-content drug screening and biomedicine. Among them\, organoids oVer a major advantage over traditional two-dimensional cell cultures as they accurately replicate the cellular architecture and function of a tissue of interest. 3D cell cultures have\, therefore\, become irreplaceable as biological models for studying disease mechanisms\, normal tissue development\, and screening drug responses. \nThe main focus of this thesis project was the development of computational tools for the analysis of 3D cell culture images obtained with the light sheet microscopy-based high- content screening platform developed in our lab. This acquisition system employs disposable microfabricated chips\, containing arrays of small pyramidal wells enabling the cultivation and parallel three-dimensional imaging of individual organoids. With this approach\, imaging data can be acquired simultaneously from over a hundred single organoids using two complementary modalities: i) fluorescence single-objective Selective Plane Illumination Microscopy (soSPIM)\, which captures three-dimensional multi-channel image stacks\, and ii) transmission light modality\, allowing for rapid\, label-free acquisition of two-dimensional images of the samples. When used in conjunction with an integrated well detection algorithm\, the image acquisition process can be fully automated and run over extended periods of time. \nThis thesis presents a toolkit of computational workflows for monitoring and quantification of drug-induced changes in spheroid and organoid cell cultures. Our proposed methods include i) a deep learning-based real-time segmentation model to rapidly localize organoid boundaries in transmission light images\, ii) foundation model- based approach for volumetric segmentation of organoids in three-dimensional images\, and iii) a feature extraction pipeline that integrates classical image features with deep representations from vision transformer and variational autoencoder networks to quantify morphological diVerences across conditions. The feature extraction strategy supports both quality control during acquisition workflow and comprehensive toolset for phenotypic profiling of organoids in fluorescence and brightfield images. Combined with the soSPIM-based culturing and imaging capabilities\, these established methods provide a foundation for future large-scale\, fully automated experimental pipelines targeted at predicting the response of 3D cell cultures to chemical and biological treatments. \nKeywords\n3D cell culture\, image processing and analysis\, fluorescence microscopy\, deep learning \nJury\n\nWALTER Thomas\, Directeur de recherche\, Institut Curie\, Examinateur\nZIMMER Christophe\, Professeur\, Rudolf Virchow Center\, University of Würzburg\, Rapporteur\nDESCOMBES Xavier\, Directeur de recherche\, INRIA Sophia Antipolis\, CNRS\, Rapporteur\nSIBARITA Jean-Baptiste\, Chargé de recherche\, Université de Bordeaux\, CNRS\, Directeur de Thèse\nNIKOLSKI Macha\, Directrice de recherche\, IBGC\, CNRS\, Université de Bordeaux\, Co-Directrice de Thèse\n\n
URL:https://www.bordeaux-neurocampus.fr/en/event/thesis-defense-christer-lohk/
CATEGORIES:Thesis
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