Thèses

Jeudi 4 Septembre 2025 à 12h00.

Characterization of the genic response to hypoxia and identification of molecular factors involved in aerotaxis in Dictyostelium discoideum

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Directeur de thèse / thesis director :
Anjard Christophe

Membres du jury / jury members :
Pierre Cosson
Ascel Regis Samba Laouka
Violaine See
Wei Liu
Aurélien Dumètre
Christophe Anjard

Résumé / Abstract :
Aerobic eukaryotes use oxygen (O₂) to oxidize metabolites and generate ATP. This thesis focuses on two adaptive strategies to hypoxia in the social amoeba Dictyostelium discoideum. The first part of my work aimed to identify the molecular mechanisms driving the directed migration toward favorable O2 environments (aerotaxis). To do so, I performed a motility assay, in which cells were confined to generate an O₂ gradient due to cellular oxygen consumption. In response to this gradient, Dictyostelium cells exhibited collective migration forming an expanding ring of cells, characteristic of their aerotactic response. Using mutants and various cellular inhibitors, I demonstrated that aerotaxis does not depend on prolyl hydroxylase activity, oxidative stress, nitrosative stress, or mitochondrial activity. I also studied the respiratory capacity of Dictyostelium cells, which showed a global affinity for O₂ of approximately 2.5 μM. My second objective was to identify the genic response to hypoxia. To do so, I characterized transcriptomic alterations in cells exposed to 1% O₂ under nutrient-rich conditions for 24 h, followed by a 5 h reoxygenation period. Remarkably, 32% of quantified transcripts were differentially expressed, with the greatest changes occurring in the early (1 h) and late (24 h) phases. Changes were observed in various metabolic, anabolic, and catabolic pathways. Interestingly, transcripts associated with the cAMP signaling pathway, generally triggered by nutrient deprivation, were also induced during chronic hypoxia. Furthermore, I investigated the molecular mechanisms underlying the transcriptomic response, which seem to rely on several induction mechanisms.

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