ED Mathématiques et Informatique
Mathematical modeling of cardiac tissue response after Pulsed Field Ablation
by Simone NATI POLTRI (IMB - Institut de Mathématiques de Bordeaux)
The defense will take place at 13h30 - Salle de conférences Institut de Mathématiques de Bordeaux Université de Bordeaux, 351, cours de la Libération - F 33 405 TALENCE
in front of the jury composed of
- Clair POIGNARD - Directeur de recherche - Centre Inria de l'Université de Rennes - Directeur de these
- Muriel BOULAKIA - Professeure des universités - Université de Versailles Saint-Quentin en Yvelines - Rapporteur
- Grégory VIAL - Professeur des universités - École Centrale de Lyon - Rapporteur
- Marcela SZOPOS - Professeur des universités - Université Paris Cité - Examinateur
- Annabelle COLLIN - Professeure des universités - Nantes Université - Directeur de these
- Lisl WEYNANS - Professeur des universités - Université de Bordeaux - Examinateur
Cardiac arrhythmias are irregularities in the normal rhythm of the heart, caused by anomalies in the electrical activity of the myocardium. Among the many ablation strategies used to isolate these pathologies, Pulsed electric Field Ablation (PFA) has emerged as a novel non-thermal technique that takes advantage of short and high-voltage electrical pulses to kill cardiac cells, by ensuring the precise targeting of the abnormal tissue and the preservation of the tissue scaffold. The aim of this thesis is to propose a mathematical model to study the long-term effects of PFA on the cardiac tissue, in the context of two different pathologies: Atrial Fibrillation (AF) - a common atrial arrhythmia that mostly starts from pulmonary veins - and Ventricular Tachycardia (VT), a rapid and irregular heartbeat that originates from tissue heterogeneity in the ventricles. While for AF the ablated area is thin compared to the left atrium domain, for VT the ablated region is not negligible. To describe the electrical activity of the heart we start from the bidomain model - a standard parabolic degenerate semilinear model that describes the electrophysiology of the heart - and we modify it depending on the pathology of interest. In the context of AF we introduce inside the ablated area a small parameter $varepsilon$ - proportional to the thickness of the region - that also rescales the intracellular conductivity. We analyze the static version of the modified bidomain system in the semilinear context, and we perform a formal asymptotic analysis to determine the approximate transmission conditions at the interface between the ablated area and the healthy region, as $varepsilon$ approaches zero. The asymptotic expansion at any order is proven and numerically validated. We also propose numerical simulations (obtained using FreeFem++, a finite element library) in a dynamic context. By considering a synthetic geometry of a left atrium, we simulate the isolation of a pulmonary vein from which AF is supposed to trigger. Non-overlapping Schwarz methods are studied and adopted to numerically impose well-designed conditions at the interface. The results are compared with another technique, radio-frequency ablation (RFA), known to burn cardiac tissue through heat transfer and then to destroy the tissue scaffold. Our objective is to numerically predict the success or failure of the two ablation procedures. Then, we validate our approaches in a real heart data from sheep. Our collaborators at IHU Liryc first induced VT in different sheep by creating two cardiac scars separated by a slow conduction channel, and then performed a PFA procedure to treat the induced VT. In the context of VT, our model proposed for AF is not applicable, since the hypothesis regarding the small size of the ablated region is no longer valid. Moreover, VT is a more complex pathology to model as it is caused by tissue heterogeneity. We modify the bidomain model by introducing a parameter $varepsilon$ - that in this case stands for the ablation level - inside the ablated area and we use it to rescale the intracellular conductivity. Simulations are performed to reproduce VT in a sheep ventricle geometry thanks to a signal reentry placed nearby the channel and validated with the activation endocardium map built before the PFA intervention. We also propose simulations of PFA and we compare them with RFA to numerically predict the success or failure of the two ablation procedures. To conclude, this work provides a first numerical study of the mathematical descriptions of PFA in both AF and VT context, opening perspectives towards clinical applications.
ED Sciences Chimiques
Role and assembly mechanims of Remorin
by Zeren XU (Institut de Chimie & de Biologie des Membranes & des Nano-objets)
The defense will take place at 14h00 - Amphitheater 2 Rue Robert Escarpit, 33600 Pessac
in front of the jury composed of
- Birgit HABENSTEIN - Chargée de recherche - Université de Bordeaux - Directeur de these
- Douglas Vinson LAURENTS - Professeur - Instituto de Química Física - Rapporteur
- Sophie SACQUIN-MORA - Directeur de recherche - IBPC - CNRS (Institut de Biologie Physico-Chimique - CNRS) - Rapporteur
- Sébastien MONGRAND - Directeur de recherche - CNRS, Laboratoire de Biogenèse Membranaire, UMR 5200 - Examinateur
- Matthieu CHAVENT - Chargé de recherche - Institut de Pharmacologie et de Biologie Structurale (IPBS), CNRS, Université de Toulouse - Examinateur
- Isabel ALVES - Directeur de recherche - Institut de Chimie et Biologie des Membranes et des Nano-objets (CBMN), CNRS/Université de Bordeaux - Examinateur
- Yvon JAILLAIS - Directeur de recherche - ENS de Lyon, Reproduction et Développement des Plantes (RDP), CNRS UMR 5667 - Examinateur
Remorins are multifunctional proteins regulating immunity, development, and symbiosis in plants. Remorins sequester specific lipids into functional membrane nanodomains when associating with the membrane. The multigenic protein family contains six groups, classified by their protein-domain composition. Membrane targeting of remorins occurs independently from the secretory pathway. Instead, they are directed into different nanodomains depending on their phylogenetic group. All family members contain a C-terminal membrane anchor and a homo-oligomerization domain, flanked by an intrinsically disordered region of variable length at the N-terminal end. We here combined molecular imaging, Nuclear Magnetic Resonance spectroscopy, protein structure calculations, and advanced molecular dynamics simulation to unveil a stable pre-structuration of coiled-coil dimers as tunable nanodomain-targeting units containing a tunable fuzzy coat and a barcode-like positive surface charge before membrane association. These protein characteristics and the differences in structures and dynamics between C-terminal lipid anchors of the remorin groups provide a selective platform for phospholipid binding when encountering the membrane surface. Our data suggest that remorins fold in the cytosol with the N-terminal disordered region as a fuzzy structural ensemble around a dimeric anti-parallel coiled-coil core containing a symmetric interface motif reminiscent of a hydrophobic Leucine zipper. The charge distribution, the intrinsic curvature in dimeric coiled-coil remorins, and their domain geometry would confer distinctive membrane association profiles. The lipid-binding of the C-terminal creates avidity through multivalent electrostatic interactions between anionic lipid headgroups and the positively charged dimer surface, suggesting a clip-and-divide mechanism to segregate lipid-protein nanodomains selectively.
ED Droit
Competition law in the face of national and international anti competitive agreements: analysis of Moroccan law in light of French law
by Aziza AHLE LARBI (INSTITUT DE RECHERCHE EN DROIT DES AFFAIRES ET DU PATRIMOINE)
The defense will take place at 10h00 - Salle 10 Faculté des sciences juridiques, économiques et sociales de Tanger Tanger 90000, Maroc
in front of the jury composed of
- Marianne LECENE-VILLEMONTEIX - Maîtresse de conférences - Université de Bordeaux - Directeur de these
- Pierre GARELLO - Professeur des universités - Université Aix Marseille - Rapporteur
- Jaouad EL MALHOUF - Professeur des universités - Université de Tanger - CoDirecteur de these
- Mohammed JARRARI - Professeur agrégé - Faculté des sciences juridiques économiques et sociales de Salé - Rapporteur
This study aims to analyze the response of Moroccan competition law to anti-competitive agreements, both at the national and international levels. The objective is to understand the reasons behind the limited response of the Moroccan legislator to these practices, which pose a serious threat to competition, especially when they take on an international dimension. This threat is even more significant for developing countries like Morocco, which are often vulnerable due to the lack of a unified international legal framework on competition that could effectively combat such agreements. Research Problem.Anti-competitive agreements, whether domestic or international, are a major obstacle to free competition, particularly in developing economies like Morocco. Although the country has adopted competition legislation in line with international standards, notably those of the European Union, the effectiveness of its implementation remains limited. This gap creates a favorable environment for the development of agreements, including international ones, which exacerbate economic challenges and hinder the development of a competitive and fair market. In this context, a central question arises: What are the barriers to the effective enforcement of legal mechanisms intended to combat these anti-competitive practices in Morocco? From this main question, several related issues emerge. Why does Moroccan competition law, despite being inspired by European standards, struggle to curb these practices, while other countries, such as France, achieve better results? What are the main obstacles—whether institutional, legal, or structural—to the rigorous implementation of these rules in Morocco? Furthermore, how can the country draw on European best practices, particularly from France's experience, to strengthen its legislative and institutional framework for a more effective fight against anti-competitive agreements? Finally, in the face of the globalization of anti-competitive agreements, particularly in international contexts, a final question arises: How can developing countries, such as Morocco, effectively respond to these practices that transcend borders and harm their economies?
ED Sciences de la Vie et de la Santé
Barth syndrome and the search for therapeutic approaches
by Claire ALMYRE (Institut de Biochimie et Génétique Cellulaires)
The defense will take place at 14h00 - Salle de conférence Institut de Biochimie et Génétique Cellulaires (IBGC) - UMR5095 CNRS 1, Rue Camille Saint Saëns, CS61390 33077 Bordeaux cedex, France
in front of the jury composed of
- Giovanni BéNARD - Directeur de recherche - Inserm U1211 - Université de Bordeaux - Examinateur
- David BENOIST - Maître de conférences - Inserm U1045 - Université de Bordeaux - Examinateur
- Inge KUHL - Chargée de recherche - CNRS UMR9198 - Université Paris-Saclay - Rapporteur
- Julie STEFFANN - Professeure des universités - praticienne hospitalière - Université de Paris - Rapporteur
Mitochondrial diseases are diverse and pleiotropic, severe and largely untreatable. To help the discovery of candidate therapeutic molecules, we developed a screening method using yeast Saccharomyces cerevisiae models of mitochondrial disorders. Among these is the Barth syndrome (BTHS), a rare X-linked cardiomyopathy caused by mutations in a nuclear gene (TAZ) that encodes an acyltransferase (called Tafazzin) involved in the maturation of Cardiolipin (CL). This is a phospholipid with multiple functions in mitochondria that optimize oxidative phosphorylation (OXPHOS)-dependant production of the energy-rich ATP molecule. We isolated several FDA-approved compounds able to improve mitochondrial function in a yeast model of BTHS. Remarkably, we found that these drug candidates has the capacity to rescue a large panel of other yeast and human cellular models of mitochondrial disorders.
What molecular mechanisms allow the strawberry axillary bud to make the decision to become a stolon or a branch that end in an inflorescence?
by Kilian DEHLOUZ (BFP - Biologie du Fruit et Pathologie)
The defense will take place at 9h30 - Amphithéatre INRAE 71 Av. Edouard Bourlaux, Amphithéatre INRAE, 33140 Villenave-d'Ornon
in front of the jury composed of
- Amélia GASTON - Chargée de recherche - Université de Bordeaux - Directeur de these
- Valérie SCHURDI-LEVRAUD - Professeur des universités - Université de Bordeaux - Examinateur
- Sandra CORTIJO - Chargée de recherche - Institut des Sciences des Plantes de Montpellier - Rapporteur
- Soulaiman SAKR - Professeur des universités - Institut Agro Rennes-Angers - Rapporteur
Strawberries reproduce both sexually (flowering) and asexually (stolons). These two methods, although antagonistic, are agronomically important: flowering influences fruit yield, while stolons enable the propagation of varieties. This competition takes place in particular at the level of axillary buds (AxB), which develop either into branches that can end in an inflorescence, or into stolons. Understanding the genetic network controlling AxB development is crucial, as it affects both fruit and plant yield in strawberry. The aim of my thesis is to elucidate the molecular mechanisms involved in the balance between sexual and asexual reproduction in diploid strawberry through three main questions: 1. What are the molecular actors involved in the development of axillary buds into stolons or branches? A comparative transcriptomics approach on morphologically undifferentiated AxB has enabled us to identify biological processes and a shortlist of genes potentially involved in this balance. 2. What are the molecular actors involved in the differentiation of AxB into stolons or branches, and can we associate a molecular signature of AxB according to differentiation stage and fate? Comparative and predictive transcriptomic analyses of AxB taken from different genotypes, at different stages of development and in different positions on the plant, have revealed key players and signature genes for AxB fate and differentiation status. 3. Do changes in the expression of candidate genes alter the balance between sexual and asexual reproduction? Genome-editing approaches via CRISPR were used on two genes of interest to assess the impact of loss-of-function of these genes on the balance between sexual and asexual reproduction. This thesis enabled us to complete the regulatory network that controls AxB fate and differentiation, and thus the balance between sexual and asexual reproduction in strawberry, and to highlight potential targets for the improvement of cultivated strawberry.
ED Sciences Physiques et de l'Ingénieur
Application development on the integrability of imaging and thickness control systems using FMCW radar in the Terahertz wave domain.
by Barnabé CARRÉ (Laboratoire de l'Intégration du Matériau au Système)
The defense will take place at 10h00 - Amphithéâtre Jean-Paul DOM Université de Bordeaux, Laboratoire IMS, 351 Cours de la Liberation, Bâtiment A31, 33405 Talence
in front of the jury composed of
- Jean-Paul GUILLET - Maître de conférences - Université de Bordeaux, Laboratoire IMS - Directeur de these
- Cyril DECROZE - Professeur des universités - XLim - Rapporteur
- Claire MIGLIACCIO - Professeure des universités - LEAT - Rapporteur
- Stéphane BLIN - Maître de conférences - Université de Montpellier & IES - Examinateur
- Thomas ZIMMER - Professeur des universités - Université de Bordeaux, Laboratoire IMS - Examinateur
In order to encourage industrial interest in terahertz systems for non-destructive testing, this manuscript features various methods and techniques for improving the imaging and thickness measurement performance of sub-THz FMCW (Frequency Modulated Continuous Wave) radar sensors. Focused imaging approaches are restricted by diffraction and involve a compromise between lateral resolution and depth of field. The SAR (Synthetic Aperture Radar) imaging technique overcomes these limitations. In this context, a new algorithmic approach is proposed, significantly improving lateral resolution by a factor of three compared with conventional focused imaging systems. In addition, the SAR technique is tested on specific objects relevant to non-destructive imaging. Point-by-point acquisition systems are often limited in measurement speed due to the constraints associated with translation vectors, which are subject to excessively high inertias. To tackle this problem, an ultra-fast imaging system has been developed. This incorporates a rotating polygonal mirror which deflects the radar beam and directs it onto a telecentric f-theta lens, which focuses the beam onto a plane. This lens, with a numerical aperture of 0.28, outperforms those reported in the literature. In addition, sub-THz FMCW radar transceivers are not limited to non-destructive imaging, but also enable precise measurement of material thickness. However, these measurements are usually limited by the longitudinal resolution of the radar unit. This study proposes an innovative algorithm, combined with a new genetic algorithm approach, which overcomes this limitation by measuring thicknesses five times thinner than the longitudinal resolution in the air of the sensor.
ED Sociétés, Politique, Santé Publique
SCIENTIFIC KNOWLEDGE AND POLITICAL DECISION-MAKING FOR ADAPTATION TO CLIMATE CHANGE: THE REGIONAL FABRIC OF PUBLIC ACTION
by Camille FRANCOIS DIT JONCHÉRES (Environnement, Territoires en Transition, Infrastructures, Sociétés)
The defense will take place at 14h00 - Denucé Université de Bordeaux - Campus Victoire, 3ter Pl. de la Victoire, 33000 Bordeaux
in front of the jury composed of
- Valérie DELDRèVE - Directrice de recherche - ETTIS - Directeur de these
- Olivier BOUBA-OLGA - Professeur des universités - Université de Poitiers - Examinateur
- Pascal RAGOUET - Professeur des universités - Université de Bordeaux - Examinateur
- Céline GRANJOU - Directrice de recherche - LESSEM - Rapporteur
- François-Mathieu POUPEAU - Directeur de recherche - LATTS - Rapporteur
Integrating and assimilating scientific expertise is a strategic issue for regional authorities to take action in the fight against climate change. This thesis shows how the Nouvelle-Aquitaine Region translates the political priority of climate change adaptation (CCA) into an operational regional policy. In particular, this work answers questions such as how do regional agents use scientific knowledge? What processes of expertise are in place? How is government action elaborated between the regional level and the more local scale to make CCA measures operational ? The thesis is based on three case studies: the observation of a declared policy of "transitions" (NéoTerra); the appropriation of CCA by the technostructure through 50 semi-structured interviews with regional agents; and the retrospective analysis of a radical adaptation leading to the erasure of a pond in Limousin. The thesis shows the implications of integrating CCA into regional policy; the political and expert work of regional agents in shaping public decision-making; and the conditions for carrying out transformative CCA action on a specific issue and territory. The aim of this research project, carried out as part of a CIFRE cooperation with the Nouvelle-Aquitaine Region, is to promote transformational and inclusive adaptation to address the challenges of anticipating climate change.