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DTSTART;TZID=Europe/Paris:20251001T093000
DTEND;TZID=Europe/Paris:20251001T093000
DTSTAMP:20260511T191419
CREATED:20250428T073914Z
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SUMMARY:Thesis defense - Violeta Milanovic
DESCRIPTION:Venue : CARF \nVideoconference link: https://u-bordeaux-fr.zoom.us/j/83185319457 \nDefense in English \n\nVioleta Milanovic\nTeam : Mechano-biology of motile and neuronal structures\nIINS \nThesis supervisor : Olivier Rossier \nTitle\nStudying cellular mechanotransduction in living cells using single molecule fluorescence polarization microscopy \nAbstract\nMechanotransduction\, the process by which mechanical forces are converted into biochemical signals\, is fundamental to cellular adhesion\, migration\, and the spatial organization and integrity of tissues. Integrin adhesion sites (IAS) serve as the mechanical interface between the extracellular matrix and the cytoskeleton\, and host a complex network of force-sensitive proteins such as talin. Key protein in integrin adhesive structure\, talin establishes the physical linkage that transmits cell mechanical forces to its surroundings. Far from being a rigid structural element\, talin is a large multimodular protein carrying multiple domains with binding sites which are exposed when talin is stretched by force. This complex mechanical response led to propose the interesting hypothesis of a talin code in which both the shape of talin scaffolds and the set of partners bound to talin could serve as a readout for the mechanical information encoded by cells.\nWhile the force-induced conformational changes of talin have been extensively studied in vitro\, how talin conformation is changing within the native architecture of living cells still remain poorly resolved\, particularly in terms of spatial orientation.\nThis thesis focuses primarily on talin molecular orientation in focal adhesions (FAs) using single-molecule fluorescence polarization microscopy. To probe distinct mechanical segments along talin\, we engineered a panel of talin constructs fused to mEos3.2 at specific domains – neck\, R3\, R12\, and the C-terminus. Using an optimized live-cell imaging pipeline\, we successfully extracted mEos3.2 in-plane (ρ)\, out-of-plane (η)\, and wobbling (δ) angles used as proxies for talin domain orientation. The orientation distributions of talin domains were consistent with their known mechanical context: domains closer to integrins\, such as the neck and R3\, exhibited strong directional alignment along the focal adhesion axis\, while R12 and C-terminal tags showed more isotropic behavior. These results in living cells recapitulated those we obtained in fixed samples\, confirming the robustness and reproducibility of the approach under basal contractile conditions.\nThis thesis demonstrates that molecular orientation serves as a powerful and previously underused live-cell readout of mechanical state. Beyond talin\, the molecular tools\, methods and insights developed here provide a framework to study how proteins such as integrins\, vinculin\, or actin reorganize under force in their native environment. With continued technological development\, orientation-resolved single-molecule microscopy holds strong potential to decode the mechanical logic of adhesion and signaling in both physiological and pathological contexts. \nKeywords\nmechanotransduction\, cell adhesion\, single protein tracking\, fluorescence polarization \nPublication\nCarla Silva Martins\, Cyntia Taveneau\, Gerard Castro-Linares\, Mikhail Baibakov\, Nicolas Buzhinsky\, Mar Eroles\, Violeta Milanović\, Shizue Omi\, Jean-Denis Pedelacq\, Francois Iv\, Léa Bouillard\, Alexander Llewellyn\, Maxime Gomes\, Mayssa Belhabib\, Mira Kuzmić\, Pascal Verdier-Pinard\, Stacey Lee\, Ali Badache\, Sanjay Kumar\, Cristel Chandre\, Sophie Brasselet\, Felix Rico\, Olivier Rossier\, Gijsje H. Koenderink\, Jerome Wenger\, Stéphanie Cabantous\, Manos Mavrakis; Human septins organize as octamer-based filaments and mediate actin-membrane anchoring in cells. J Cell Biol 6 March 2023; 222 (3): e202203016. doi: https://doi.org/10.1083/jcb.202203016.\nJury\nM. WEHRLE-HALLER Bernhard; Professor\, UNIGE; Rapporteur \nM. HYTÖNEN Vesa; Professor\, TAU; Rapporteur \nMme. ALBIGES-RIZO Corinne; Directrice de recherche (CNRS)\, IAB; Examinatrice \nM. NASSOY Pierre; Directeur de recherche (CNRS)\, LP2N; Examinateur \nMme. BRASSELET Sophie;Directrice de recherche (CNRS)\, IF; Membre invitée \nM. ROSSIER Olivier; Chargé de recherche (INSERM)\, IINS; Directeur de thèse \n
URL:https://www.bordeaux-neurocampus.fr/en/event/thesis-defense-violeta-milanovic/
CATEGORIES:Thesis
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DTSTART;TZID=Europe/Paris:20251001T133000
DTEND;TZID=Europe/Paris:20251001T133000
DTSTAMP:20260511T191419
CREATED:20250725T085719Z
LAST-MODIFIED:20250725T090655Z
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SUMMARY: Thesis defense -  Juliette Montet
DESCRIPTION:Venue : BBS conference room \nThesis defended in French \n\nJuliette Montet \nNutrition and Neuropsychiatric Symptom Dimensions (NutriPsy)\nNutrineuro \nTitle\nRole of early-life adversity in inflammation-related neuropsychiatric comorbidities in obesity:  Implication of GTP-CH1 enzymatic pathway and dopamine metabolism \nAbstract\nNeuropsychiatric comorbidities are common in obesity\, and numerous studies highlight the involvement of adiposity-related chronic low-grade inflammation in this effect. Cytokines alter dopamine metabolism by modulating the activity of the enzyme GTP cyclohydrolase 1 (GTP-CH1). This mechanism could contribute to the onset of several key symptoms\, such as fatigue\, decreased motivation\, anhedonia\, and psychomotor slowing in vulnerable individuals. Various data suggest that early life adversity (ELA) is an important factor in vulnerability to the neuropsychiatric effects of inflammation. Interestingly\, ELA\, like inflammation\, can disrupt the activity of the GTP-CH1 pathway. The objective of this thesis is i) to evaluate the combined effect of ELA and obesity-related inflammation in neuropsychiatric comorbidities associated with obesity\, and ii) to determine whether this effect is based on modulation of dopaminergic metabolism. The methodology used combines neuropsychiatric assessments\, peripheral measurements of GTP-CH1 activity and inflammation\, and [18F]DOPA PET brain imaging in a cohort of obese subjects. This work could contribute to the definition of new treatment perspectives for neuropsychiatric symptoms occurring in inflammatory contexts\, which are known for their frequent resistance to conventional antidepressants. \nKeywords\nObesity\, inflammation\, neuropsychiatric symptoms\, early life adversity\, dopamine \nSelected publication\nMontet J\, Dexpert S\, Darnaudéry M\, Beau C\, Forestier D\, Ledaguenel P\, Magne E\, Aouizerate B\, Capuron L. Role of early life adversities in inflammation-related neuropsychiatric comorbidity in obesity. Brain Behav Immun. 2025 Aug;128:612-619. doi: 10.1016/j.bbi.2025.04.039. Epub 2025 Apr 30. PMID: 40316033. \nJury\n\nPr Philippe Fossati\, PU-PH\, APHP\, Sorbonne Université\, Rapporteur\nPr Christine Poitou-Bernert\, PU-PH\, APHP\, Sorbonne Université\, Rapportrice\nDr Raphaële Castagné\, Chargée de recherche\, Université Toulouse III Paul Sabatier\, Examinatrice\nDr Lucile Capuron\, Directrice de recherche\, Université de Bordeaux\, Directrice de Thèse\nPr Bruno Aouizerate\, PU-PH\, CH Charles Perrens\, Univerité de Bordeaux\, Examinateur invité\nDr Eric Magne\, Chirurgien\, Clinique Tivoli\, Bordeaux\, Examinateur invité\n\n
URL:https://www.bordeaux-neurocampus.fr/en/event/thesis-defense-juliette-montet/
CATEGORIES:Thesis
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