ED Sciences Chimiques
Evolution of the decomposition mechanisms as a function of heating rate of a carbon fiber reinforced biosourced polymers.
by Victor ASENSIO (Laboratoire des Composites ThermoStructuraux)
The defense will take place at 9h00 - Amphithéâtre du LCTS Laboratoire des Composites ThermoStructuraux 3 allée de la Boétie 33600 Pessac
in front of the jury composed of
- Francis REBILLAT - Professeur des universités - Université de Bordeaux - Directeur de these
- Laurent GALLAIS - Professeur des universités - Institut Fresnel - Rapporteur
- Sophie DUQUESNE - Professeure des universités - Centrale Lille Institut - Rapporteur
- Emmanuel DE BILBAO - Professeur des universités - CEMHTI - Examinateur
- Alixe DEKEYREL - Ingénieure de recherche - ArianeGroup - Examinateur
- Romain LUCAS-ROPER - Professeur des universités - IRCER - Examinateur
- David DAMIANI - Directeur de recherche - CEA Le Ripault - CoDirecteur de these
- Antonio COSCULLUELA - Ingénieur de recherche - CEA CESTA - CoDirecteur de these
Atmospheric re-entry is a critical phase in the return of a space module to Earth, as it involves intense thermal and thermomechanical stresses. The modules are equipped with insulating shields that dissipate the high heat flux. This thesis focuses on understanding the physical phenomena occurring within the materials that comprise the thermal protection system. The research is conducted at the Thermo-Structural Composites Laboratory (LCTS), with the support of CEA-CESTA and CEA-Le Ripault. Composite materials with thermodegradable matrices offer a potential solution to the stringent requirements for thermal protection, including insulation, structural integrity, and optimized mass. These materials can endure extremely high heat fluxes (up to 100 MW.m-2) while maintaining low ablation rates. The composites are made of carbon fibers and a polymer matrix. During operation, the temperature rise triggers the pyrolysis of the matrix. The objective of this thesis is to identify and quantify the evolution of degradation and transfer mechanisms during the pyrolysis process of a composite with a bio-based matrix, depending on the heating rate. The first part of this research is dedicated to analyzing the physicochemical properties of the composite and its components at elevated temperatures. Thermal tests (ATG-FTIR, ATG-SM, TMA, ATD) are conducted under conditions of homogeneous heating of the sample surfaces, with heating rates ranging from 5 to 1000 K.min-1. These tests enable a kinetic analysis and a five-stage description of pyrolysis. Changes in thermal and morphological properties as a function of heating conditions are monitored at each stage. The collected data contributes to a deeper understanding of the physicochemical behavior of the material subjected to uniform pyrolysis. In the second part, a novel methodology is proposed for characterizing the behavior of materials exposed to high heat fluxes. A new laser heating technique was developed. Under controlled conditions, a heat flux of 28 MW.m-2 can be applied to the material. Heating is carried out under heterogeneous conditions, where only one side is exposed to the flux, simulating real-world application scenarios. The system is equipped with multiple instruments to monitor both the heating of the material and its pyrolysis. After a detailed characterization of the optical setup and laser flux, a numerical method is presented to identify the thermal properties of a stabilized material using inverse calculation. Once validated on a model graphite material, this method is applied to characterize the composite material of interest. Finally, an integrated understanding of the physicochemical transformations, as well as the thermal and thermomechanical phenomena, as a function of heating rate, is presented.
ED Sciences de la Vie et de la Santé
Modulation of HIV-1 replication and regulation by SARS-CoV-2: GCN2 kinase as a key restriction factor of viral infections
by Chloé TORRES (Microbiologie fondamentale et Pathogénicité)
The defense will take place at 14h30 - Amphithéâtre du BBS Bâtiment Bordeaux Biologie Santé (BBS) 2 Rue Dr Hoffmann Martinot 33000 Bordeaux
in front of the jury composed of
- Mathieu METIFIOT - Chargé de recherche - Université de Bordeaux - Directeur de these
- Hélène MUNIER-LEHMANN - Chargée de recherche - Institut Pasteur - Rapporteur
- Patrice GOUET - Professeur des universités - Université Claude Bernard Lyon 1 - Examinateur
- Charles BODET - Professeur des universités - Université de Poitiers - Rapporteur
GCN2 is a human cellular kinase involved in the integrated stress response (ISR). Once activated, it phosphorylates the translation initiation factor eIF2α, inducing a global inhibition of translation and promoting the expression of the transcription factor ATF4. The latter activates the expression of genes involved in adaptation to stress or apoptosis. GCN2 is a sensor of amino acid starvation, but an increasing number of studies reveal its involvement in the cell's antiviral response. Indeed, GCN2 is activated during infection by different viruses and its deletion enhances viral replication. Hypotheses regarding the mode of kinase activation during infection involve direct interactions with viral factors, and mechanisms linked to the translation machinery. In the case of HIV-1, GCN2 interacts with the viral integrase (IN) which is phosphorylated on its serine 255. IN catalyzes the integration of viral DNA into the genome of the infected host. Its phosphorylation by GCN2 reduces integration and therefore replication. To counteract this restrictive effect of GCN2, viruses have developed escape mechanisms. For example, GCN2 protein level reduces upon infection by HIV-1 or SARS-CoV. In this context, the aims of this thesis were (1) to develop modulators of the interaction between GCN2 and HIV-1 IN and to assess the potential impact of these molecules on viral replication, and (2) to study the role of GCN2 during SARS-CoV-2 infection. After setting up an assay to monitor the GCN2-IN interaction using AlphaLISA technology, we screened 2 different chemical libraries and identified 18 active molecules. The study of their structure-activity relationship as well as the measurement of their activity in cells allowed us to identify chemical structures that could serve as a basis for the development of inhibitors of the interaction. In parallel, we generated a cell line permissive to SARS-CoV-2 infection and detected a downregulation of the kinase upon infection. We then identified GCN2 partners in this context, including viral factors and a cellular protein of the protein degradation pathway. We showed that this pathway is not directly responsible for the regulation of GCN2, but rather that the kinase may be degraded by the SARS-CoV-2 protease. Further work will be necessary to elucidate the role of GCN2 in SARS-CoV-2 replication.