ED Sciences de la Vie et de la Santé
Studying cellular mechanotransduction in living cells using single molecule fluorescence polarization microscopy
by Violeta MILANOVIC (Institut Interdisciplinaire de Neurosciences)
The defense will take place at 9h30 - Salle de conférence CGFB Building 146 Rue Léo Saignat, 33000 Bordeaux CGFB Building
in front of the jury composed of
- Olivier ROSSIER - Chargé de recherche - Université de Bordeaux - Directeur de these
- Bernhard WEHRLE-HALLER - Professeur des universités - Universite de Geneve - Rapporteur
- Vesa HYTONEN - Professeur des universités - Faculty of Medicine and Health Technology, Tampere University - Rapporteur
- Corinne ALBIGES-RIZO - Directrice de recherche - Institut pour l'Avancée des Biosciences (IAB) – Grenoble - Examinateur
- Pierre NASSOY - Directeur de recherche - Laboratoire Photonique Numérique et Nanosciences (Institut d'Optique Graduate School, CNRS et Université de Bordeaux) - Examinateur
Integrin-dependent adhesion sites (IAS) are large macromolecular assemblies that mediate cell-extracellular matrix (ECM) interactions. Knowledge of the spatial organization of AS proteins, their connectivity, and dynamics is required to decipher how these macromolecular complexes perform their biological functions. One of them, integrin mechanotransduction, converts mechanical forces and cues arising from the ECM into biochemical signals and is critically involved during stem cell differentiation, migration, as well as cancer metastasis. At the molecular level, in vitro approaches showed that force regulates the conformation of proteins present in cell adhesion sites. Yet, how force changes the conformation of proteins directly in IAS is still unknown, due to the lack of techniques able to quantify the conformational states and mechanical responses of individual proteins in living cells. My PhD project primarily aims to assess the orientation of single proteins in IAS, in collaboration with S. Brasselet and her team (Institut Fresnel, Marseille), using single-molecule fluorescence polarization microscopy. Additionally, due to the importance of 3D spatial localization of proteins, we also explored different techniques to reach 3D tracking of individual proteins in living cells.
Role of early-life adversity in inflammation-related neuropsychiatric comorbidities in obesity: Implication of GTP-CH1 enzymatic pathway and dopamine metabolism
by Juliette MONTET (Nutrition et Neurobiologie Intégrée)
The defense will take place at 13h30 - Amphithéâtre du BBS Bâtiment Bordeaux Biologie Santé (BBS) 2, rue du Dr Hoffmann Martinot 33076 Bordeaux cedex. France
in front of the jury composed of
- Lucile CAPURON - Directrice de recherche - Université de Bordeaux/ Laboratoire NutriNeuro, UMR 1286, INRAE - Directeur de these
- Philippe FOSSATI - Professeur des universités - praticien hospitalier - Inserm/CNRS/AP-HP/Sorbonne Université - Rapporteur
- Christine POITOU-BERNERT - Professeure des universités - praticienne hospitalière - INSERM/Sorbonne Universités/AP-HP - Rapporteur
- Raphaële CASTAGNé - Chargée de recherche - Université de Toulouse Inserm - Examinateur
Neuropsychiatric comorbidities are common in obesity, and numerous studies highlight the involvement of adiposity-related 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, reduced motivation, anhedonia and psychomotor slowing in vulnerable subjects. Various data suggest that early life adversity (ELA) represents an important factor of vulnerability to the neuropsychiatric effects of inflammation. Interestingly, ELA, like inflammation, may disrupt the activity of the GTP-CH1 pathway. The aim of this thesis is i) to assess the combined effect of ELA and adiposity-related inflammation in the neuropsychiatric comorbidities associated with obesity, and ii) to determine whether this effect relies on a modulation of dopaminergic metabolism. The methodology employed combines neuropsychiatric assessments, peripheral measurements of GTP-CH1 activity and inflammation, together with [18F]DOPA PET brain imaging in a cohort of obese individuals. This work could contribute to the definition of new perspectives for the treatment of neuropsychiatric symptoms occurring in inflammatory contexts, known for their frequent resistance to conventional antidepressants.