ED Mathématiques et Informatique
Characterization of the retinal vascular network using a deep learning approach
by Idris DULAU (LaBRI - Laboratoire Bordelais de Recherche en Informatique)
The defense will take place at 14h00 - Amphithéâtre du LaBRI Domaine universitaire, 351, cours de la Libération, 33405 Talence, A30
in front of the jury composed of
- Marie BEURTON AIMAR - Maîtresse de conférences - Université de Bordeaux - Campus Talence - Directeur de these
- Catherine HELMER - Directrice de recherche - Université de Bordeaux - Campus Carreire - CoDirecteur de these
- David HELBERT - Professeur - UFR SFA - Université de Poitiers - Rapporteur
- Gwenolé QUELLEC - Directeur de recherche - UBO - Université de Bretagne Occidentale - Rapporteur
- Pascal BALLET - Maître de conférences - UBO - Université de Bretagne Occidentale - Examinateur
- Akka ZEMMARI - Professeur - Université de Bordeaux - Campus Talence - Examinateur
- Louis ARNOULD - Praticien hospitalier - CHU Dijon Bourgogne - Examinateur
- Benoit RECUR - Cadre scientifique - SOQUT IMAGING - Examinateur
This thesis focuses on the development of automated methods for artery-vein (AV) segmentation in retinal fundus images, a critical step toward enabling non-invasive, early detection of systemic and neurodegenerative diseases. The retina offers a unique window into neural and vascular health, with its vasculature closely reflecting changes in both the brain and cardiovascular system. As a result, accurate AV segmentation plays a key role in extracting vascular biomarkers with diagnostic and prognostic value. Despite its importance, AV segmentation remains a technically challenging task. Arteries and veins exhibit highly similar visual and structural features, leading to ambiguity even among expert annotators. This difficulty is compounded by the scarcity of high-quality, pixel-wise labeled datasets needed to train reliable models. The goal of this thesis is to address these challenges by developing automated methods to provide reliable, reproducible, and scalable AV segmentation, allowing vascular measurements from retinal fundus images.
ED Sciences de la Vie et de la Santé
Methodological developments in quantitative T1 MRI: Applications to contrast agent concentration measurement and to neuroimaging.
by Audrey LAVIELLE (Institut des Sciences Moléculaires)
The defense will take place at 14h00 - Salle Module 2.6 Bâtiment CROUS 146 rue Léo Saignat Université de Bordeaux 33076 Bordeaux Cedex
in front of the jury composed of
- Yannick CREMILLIEUX - Directeur de recherche - ISM, Institut des Sciences Moléculaires - Directeur de these
- Marlène WIART - Directrice de recherche - CARMEN, Cardiovasculaire Métabolisme Diabète et Nutrition - Rapporteur
- Virginie CALLOT - Directrice de recherche - CRMBM, Centre de Résonance Magnétique Biologique et Médicale - Rapporteur
- Francois LUX - Maître de conférences - ILM, Institut Lumière Matière - Examinateur
- Thomas TOURDIAS - Professeur des universités - praticien hospitalier - CHU de Bordeaux - Examinateur
- Valentin PREVOST - Docteur - Canon Medical Systems Corporation - Examinateur
Longitudinal T1 relaxation time is a widely used imaging biomarker for the assessment of various pathologies, including multiple sclerosis and Parkinson's disease, as well as other neurodegenerative disorders. Its value can be modulated by the administration of T1 contrast agents, which are commonly used in cancer diagnosis and follow-up. Due to its clinical importance, there is a growing interest in obtaining quantitative T1 parametric maps. Although several MRI sequences allow the generation of quantitative T1 maps, their integration into clinical practice remains limited by constraints such as restricted access to MRI scanners, the availability of specific sequences, and the acquisition time, which must often be adapted to the patient's state of health. As a result, radiologists, clinicians, and MRI specialists primarily rely on T1-weighted acquisitions, which do not directly provide quantitative T1 values. This PhD project focuses on the development of new quantitative T1 MRI approaches to generate T1 maps from T1-weighted images acquired with sequences commonly used in clinical neuroimaging. These methods have been implemented to study the biodistribution of contrast agents in the brain tissue of patients with brain tumors, providing a precise evaluation of their distribution and pharmacokinetics. They have also been applied to the study of tissue alterations in patients with multiple sclerosis, with the aim of producing T1 maps that can be used to monitor patients and evaluate therapies.
Characterization of the txpA/RatA and hok/Sok type I toxin-antitoxin systems: from regulation to function
by Adriana MESSINEO (Acides nucléiques : Régulations Naturelles et Artificielles)
The defense will take place at 14h00 - BBS Auditorium 2 rue Docteur Hoffmann Martinot Bâtiment BBS, 33000 Bordeaux
in front of the jury composed of
- Ciarán CONDON - Directeur de recherche - UMR8261, CNRS - Institut de Biologie Physico-Chimique - Université de Paris - Rapporteur
- Charlotte MICHAUX - Chargée de recherche - Inserm 1230 - Bacterial Regulatory RNAs & Medicine, BRM- Université de Rennes - Rapporteur
- Pascal SIRAND-PUGNET - Professeur des universités - UMR 1332 – Biologie du Fruit et Pathologie (BFP) - Université de Bordeaux - Examinateur
- Patricia BORDES - Chargée de recherche - CNRS, UPS - Laboratoire de Microbiologie et de Génétique Moléculaires, Centre de Biologie Intégrative -Université de Toulouse - Rapporteur
Toxin-Antitoxin systems (TAs) are widespread in bacterial genomes. Due to their capacity to trigger bacterial cell death, they are considered promising targets for antibiotic development. In Type I toxin- antitoxin systems (T1TAs), the antitoxin is a small RNA regulating the toxin mRNA expression at the post-transcriptional level by impeding its translation. Additional mechanisms of regulation are present, and defined by secondary structure determinants of the toxin mRNAs. These mechanisms, described for only few families T1TAs, vary depending on the toxin family and whether they are encoded by Gram-negative or Gram-positive bacteria . The biological function of T1TAs include maintenance of mobile genetic elements, defence against phages and bacterial persistence. Although numerous T1TA families have been described, most studies have focused on a single representative per family, leaving the toxic potential and functional diversity of other loci within the same family largely unexplored. This manuscript is structured into four chapters addressing the translational regulation mechanisms of two T1TAs: txpA/RatA from Bacillus subtilis and hok/Sok from Escherichia coli (Chapter 1 and 2), the toxic activity of hok/Sok homologs (Chapter 3) and the role of the hok/Sok system in mediating phage defence (Chapter 4). In Chapter 1, we aimed at identify loss-of-function (LoF) mutation within the txpA mRNA by using a life/death genetic selection followed by Next Generation Sequencing (NGS), a method named FASTBAC-Seq. However, generating enough transformants for NGS was not possible. Nonetheless, the project was redirected toward the study of txpA mRNA expression in E. coli where we showed that, contrary to what was previously described, the TxpA toxin was lethal to E. coli and that its expression was regulated by its 5′ untranslated region (UTR). In Chapter 2, we focused on the identification of LoF mutants impacting the hok mRNA translation. Specifically, we aimed at generating individual strains harboring single LoF substitutions for further characterization followed by a comprehensive identification of all possible LoF affecting hok expression. We successfully generated 44 hok LoF strains and identified 112 LoF mutations in the hok 5′ UTR impairing hok mRNA translation. However, their mode of action could not be elucidated based on current knowledge, highlighting the presence of uncharacterized regulatory mechanisms governing hok expression. In Chapter 3, we aimed at exploring the toxic ability of hok homologs. We selected 35 diverse Hok homologs and assessed their toxic activity in Salmonella Typhimurium under overexpression from an inducible promoter. Hok coding sequences grouped into two distinct categories, toxic and non-toxic, regardless of their sequence conservation or localization (chromosome versus mobile genetic elements). Finally, in Chapter 4, we aimed at understanding the mechanistic detail of the hok/Sok phage defense function. We monitored optical density at 600 nm (OD) of E. coli cell harboring a hok/Sok vector upon T4 phage infection. In contrast with previous reports, we did not observe any protection conferred by the hok/Sok system against T4 bacteriophage infection under our experimental conditions. Altogether, these findings offer new insights into the translational regulation, activity, and function of T1TAs.