ED Sciences Chimiques
Role of the lipid membrane environment on antipsychotic-membrane interaction and on D2 dopamine receptor's conformation
by Ana GORSE (Institut de Chimie & de Biologie des Membranes & des Nano-objets)
The defense will take place at 13h30 - Amphithéâtre IECB, 2 Rue Robert Escarpit, 33600 Pessac
in front of the jury composed of
- Mikayel AZNAURYAN - Directeur de recherche - Université de Bordeaux - Examinateur
- Erick DUFOURC - Directeur de recherche émérite - Université de Bordeaux - Examinateur
- Julie DAM - Directrice de recherche - Université Paris-Saclay - Rapporteur
- Sara GARCIA-LINARES - Professeure - Universidad Complutense de Madrid - Rapporteur
Schizophrenia represents a severe psychiatric disorder affecting approximately 1 % of the population. Since dopaminergic pathways are disrupted in schizophrenic patients, treatment primarily involves antipsychotic medication that acts on multiple neuronal pathways, where dopamine D2 receptor (D2R) represents the primary target. Significant alterations in lipid content have been found in schizophrenic patients, including increased levels of phosphatidylserine and a decrease in omega-3 fatty acids. These modifications may impact physicochemical properties of the cell bilayer that could impact the conformation and activity (ligand binding and signaling) of membrane-embedded receptors, including D2R. High lipophilicity of antipsychotics leads them to accumulate within synaptic membranes, which signifies that: (i) the altered bilayer properties could impact their membrane partitioning, and (ii) the presence of antipsychotics could modify bilayer properties and indirectly impact receptors within the membrane. This work, therefore, aims to understand the impact of lipid abnormalities patient treatment by studying the impact of lipids on: (1) antipsychotic interaction with membranes and (2) conformational changes of D2R. (1) The first part of this work is focused on antipsychotics, with the aim of elucidating the role of key lipids: negatively charged lipids, cholesterol, sphingomyeline and polyunsaturated fatty acid-phospholipids on antipsychotic-lipid interaction, by investigating the impact of antipsychotics on membrane properties and their bilayer partitioning. (2) The second project focuses on the receptor with the ultimate aim to elucidate the role of omega-3 polyunsaturated fatty acids on D2R conformational changes. The influence of lipid unsaturation on ligand binding to D2R and β-arrestin recruitment has been demonstrated previously, and computational studies have further suggested its effect on D2R conformation. This work employs a complementary experimental approach to further investigate these conformational changes using single-molecule Förster resonance energy transfer. It provides information about D2R construct design, purification and the initial measurements, and discusses the challenges encountered during the study along with solutions proposed to address them.
Novel electrochromic materials and devices for visible – near-infrared dual-band modulation
by Suraj NAYAK (ICMCB - Institut de Chimie de la Matière Condensée de Bordeaux)
The defense will take place at 13h30 - Amphithéâtre Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), 87, Avenue du Docteur Schweitzer, 33608 PESSAC cedex
in front of the jury composed of
- Aline ROUGIER - Directrice de recherche - Université de Bordeaux - Directeur de these
- Anthony MAHO - Assistant professor - Université de Bordeaux - CoDirecteur de these
- Michael LOBET - Professeur - Université de Namur & Associate Professeur – Harvard University - Examinateur
- Delia MILLIRON - Professeure - Dpt. of Chemical Engineering; University of Michigan - Examinateur
- Sophie CASSAIGNON - Professeure - LCMCP - Rapporteur
- Nicolas STEIN - Professeur - IJL - Rapporteur
- Cyril AYMONIER - Directeur de recherche - Universié de Bordeaux - Examinateur
Dual-band electrochromic materials will allow for the design of a next generation of solar-control fenestration units providing additional energy savings in terms of lighting, cooling and heating requirements through their unique ability to selectively filter and independently modulate the visible and infrared wavelengths. In order to impart such selective control over these wavelength regions of interest, chosen compositions of metal oxides or doped metal oxides are utilised. In these, reversible electrochemical mechanisms take place, such as capacitive charging as well as faradaic ion insertion coupled to redox reactions. Such electrochemical mechanisms are accompanied by simultaneous optical property changes. This research work focuses firstly on synthesizing “self-doped” version of one of the widely studied electrochromic metal oxide i.e. sub-stoichiometric tungsten oxide (WO3-δ). Superior selective control is promoted in obtaining monoclinic (m-WO3-x) and hexagonal (h-WO3-y) phases accompanied with distinct nanocrystal morphologies, using a refined colloidal synthesis protocol. Furthermore, the influence of each crystal phase on ion-transfer kinetics, and the effect of their distinct morphologies on plasmonic near-infrared light absorption, are discussed. Meanwhile, the capability of dual-band modulation for the novel h-WO3-y phase is demonstrated, along with the existing m-WO3-x phase. Additionally, a novel class of electrochromic materials composed of niobium and tungsten bimetallic oxides (Nb,W)Ox is synthesized via both a facile hydrothermal methodology and an original colloidal synthesis procedure, and the influence of the Nb:W ratio on crystal structure, morphology, electrochemical and electrochromic response are studied. Importantly, two novel formulations of (Nb,W)Ox at Nb:W mol ratios of 0.78 and 1.00 are identified, and highlighted for their efficient dual-band modulation capabilities. Lastly, this work opens perspectives towards developing more optically functional electrochromic devices, towards the fabrication of novel smart windows of increased energy efficiency.
ED Sciences de la Vie et de la Santé
Exogenous paracrine effects of Dental Pulp Stem Cells on glia and neuronal circuits: a new therapeutic strategy for neuroprotection
by Irene MANERO ROIG (Institut Interdisciplinaire de Neurosciences)
The defense will take place at 10h00 - Sala de Grados Medicina Facultad de Medicina y Enfermería Barrio Sarriena s/n CP- 48940 Leioa
in front of the jury composed of
- Stéphane MARTIN - Directeur de recherche - IPMC - Institut de Pharmacologie Moléculaire et Cellulaire - Rapporteur
- Fekrije SELIMI - Directrice de recherche - Centre for Interdisciplinary Research in Biology (CIRB) - Rapporteur
- Tony HEURTAUX - Associate Professor - University of Luxembourg - Examinateur
- Ana María ZUBIAGA ELORDIETA - Professeure des universités - University of the Basque Country (UPV/EHU) - Examinateur
- Jean-Christophe DELPECH - Chargé de recherche - Université de Bordeaux - Examinateur
Stem cell–based neuroprotective therapies depend on the availability of large numbers of viable cells, minimal host immune rejection, and proper integration into neural circuits, all while avoiding uncontrolled proliferation. These stringent requirements, together with the technical and biological challenges they present, substantially increase treatment costs and reduce the likelihood of clinical success. As a result, recent therapeutic strategies have shifted toward the use of subcellular products, such as the stem cell secretome. This shift is supported by extensive evidence indicating that many stem cell–mediated benefits arise primarily from paracrine signaling rather than from direct cell replacement. Within this framework, human dental pulp stem cells (hDPSCs) have emerged as a particularly promising source for brain-oriented therapies, especially those aimed at neuroimmunomodulation. Both hDPSCs and their secretome display a broad set of beneficial biological activities, including neurotrophic and angiogenic effects, anti-inflammatory and anti-apoptotic properties, and the ability to enhance cell migration, neurite extension, and immune regulation. Despite these advantages, it remains unclear to what extent the stem cell secretome can regulate synaptic function or modulate inflammatory and immune responses. It is also unknown whether its application could become a viable therapeutic strategy to improve synaptic function in cognitive disorders, which impose a considerable social and economic burden on patients and their families. The present work demonstrates that the DPSC-derived secretome—particularly its soluble fraction—can modulate microglial state in vitro following an inflammatory challenge. Specifically, it promotes a shift from a reactive microglial phenotype toward a more homeostatic one. Although astrocytes did not respond directly to treatment with the DPSC secretome, their strong dependence on microglial signaling suggests that indirect modulation via microglial regulation is plausible and warrants further investigation. Additionally, extracellular vesicles (EVs) isolated from the secretome were found to modulate synaptic function under inflammatory conditions. EV treatment prevented early synaptic plasticity deficits occurring within the first 24 hours after an inflammatory event. This protective effect was confirmed through ex vivo assessment of long-term potentiation (LTP) in the CA1 region, indicating that EVs help preserve synaptic responsiveness during acute inflammatory stress. Finally, attempts to enhance the therapeutic potential of the secretome by preconditioning DPSCs under various stress-related culture conditions did not lead to improvements beyond the effects observed under standard basal conditions. This suggests that the intrinsic properties of the DPSC secretome may already represent an optimal balance of beneficial factors without requiring additional manipulation.
ED Sociétés, Politique, Santé Publique
Collaborative design of spaces for debate on work as a tool for learning and organizational development
by Latifa BENREZKALLAH (Laboratoire de l'Intégration du Matériau au Système)
The defense will take place at 14h00 - Amphi Bât E Campus de la Victoire Collège Sciences de l'homme 3 ter place de la Victoire 33076 Bordeaux Cedex
in front of the jury composed of
- Flore BARCELLINI - Professeure des universités - CNAM-Paris - Rapporteur
- Justine ARNOUD - Professeure - Université Paris-Est Créteil - Rapporteur
- Vincent BOCCARA - Maître de conférences - Université Paris Saclay, Faculté des sciences - Examinateur
- Sandrine CAROLY - Professeure des universités - INP Grenoble Alpes - CoDirecteur de these
- Bernard N'KAOUA - Professeur des universités - Université de Bordeaux - Examinateur
- Johann PETIT - Maître de conférences - Université de Bordeaux - Directeur de these
The main objective of this research is to show that work discussion spaces (WDS) are designed. This research is based on an intervention in an Algerian pension fund in response to a request from its director, focusing on production efficiency and the skills development of its staff. The author highlights that production is marked by anomalies due to a lack of coordination between the different staff and departments of the fund. Discussion spaces on work have been implemented and progressively designed, focusing on production anomalies and their determinants. The research findings highlight those spaces for discussion about work initially facilitate learning for liquidators, and that this learning is intensified by the revitalization of prescribed collective work. Furthermore, as collective work evolves into work collectives, it accelerates learning and extends it to all professional categories. This process leads operational staff to act on the organization's structure by (re)developing new rules. Pending validation, these rules lead operational staff, particularly frontline managers, to create two additional spaces for discussion to support the first, activating a subsidiary logic to further activate cooperation processes and the creation of new tasks. The author then shows the possibilities for the ergonomist to develop a collaborative process for designing timetables within the framework of organizational change management. This process consists of two stages. This process consists of two phases. The first phase involves strategic analysis and diagnosis, which serves as a means to populate the actors' representations of the situation, take into account the work and structure their participation in order to debate the diagnosis as a resource for decision-making and learning. A second phase of support and experimentation with the EDTs (Economic Development Teams) enabled the development of both operator and decision-maker activities. This iterative process, comprised of sequences and bifurcations, required us to utilize process analysis of interventions and project trajectories, both taking into account elements of the intervention context and the situation, with configurations varying from one moment to the next.