Lipidomique des cils primaires : rôle des lipides de la membrane ciliaire dans la modulation des cancers Hedgehog dépendants. // Lipidomics of primary cilia: role of ciliary membrane lipids in modulating Hedgehog-dependent cancers.
ABG-125289
ADUM-58492 |
Thesis topic | |
2024-07-25 |
Université d'Orléans
ORLEANS - France
Lipidomique des cils primaires : rôle des lipides de la membrane ciliaire dans la modulation des cancers Hedgehog dépendants. // Lipidomics of primary cilia: role of ciliary membrane lipids in modulating Hedgehog-dependent cancers.
- Biology
Cils primaires, lipidomique, voie Sonic Hedeghog, metabolomique
pimary cilia, lipidomic, Hedeghog pathway, metabolomic
pimary cilia, lipidomic, Hedeghog pathway, metabolomic
Topic description
Le cil primaire est un organite construit à partir du centriole père du centrosome. Il est considéré comme une antenne cellulaire qui permet de coordonner certaines voies de signalisation dont la voie Hedgehog qui lui est inféodée. Certaines dérégulations de la voie Hedgehog conduisent à l'apparition de cancers comme les carcinomes basocellulaires ou les médulloblastomes, un cancer pédiatrique fréquent. Dans une précédente étude nous avons montré que la modulation des différents stérols de la membrane ciliaire, comme dans certaines erreurs innées du métabolisme du cholestérol, étaient à l'origine d'une diminution du fonctionnement de la voie Hedeghog. Ce projet de thèse a donc pour but de d'explorer la lipidomique du cil en poursuivant trois axes. 1) Mieux comprendre les spécificités de la signature lipidique de la membrane des cils primaires et son impact sur les voies de signalisation ciliaire. 2) Etudier l'établissement et le maintien de cette spécificité en essayant de comprendre les mécanismes qui sous-tendent l'homéostasie de la membrane. 3) Utiliser les cibles découvertes pour faire la preuve de concept que l'utilisation des ARN thérapeutiques pourrait permettre de moduler la signalisation des cancers Hedgehog dépendants.
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The primary cilium is an organelle formed from the centriole, the parent of the centrosome. It is considered to be a cellular antenna which coordinates certain signalling pathways, including the Hedgehog pathway, which is dependent on it. Certain deregulations of the Hedgehog pathway lead to the development of cancers such as basal cell carcinomas or medulloblastomas, a common paediatric cancer. In a previous study, we showed that modulation of the various sterols in the ciliary membrane, as in certain inborn errors of cholesterol metabolism, were responsible for a reduction in the functioning of the Hedeghog pathway. The aim of this thesis project is therefore to explore the lipidomics of the cilium in three areas. 1) To gain a better understanding of the specific lipid signature of the membrane of primary cilia and its impact on ciliary signalling pathways. 2) To study the establishment and maintenance of this specificity by trying to understand the mechanisms underlying membrane homeostasis. 3) Use the targets discovered to demonstrate that the use of RNA therapeutics could modulate signalling in Hedgehog-dependent cancers.
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Début de la thèse : 01/11/2024
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The primary cilium is an organelle formed from the centriole, the parent of the centrosome. It is considered to be a cellular antenna which coordinates certain signalling pathways, including the Hedgehog pathway, which is dependent on it. Certain deregulations of the Hedgehog pathway lead to the development of cancers such as basal cell carcinomas or medulloblastomas, a common paediatric cancer. In a previous study, we showed that modulation of the various sterols in the ciliary membrane, as in certain inborn errors of cholesterol metabolism, were responsible for a reduction in the functioning of the Hedeghog pathway. The aim of this thesis project is therefore to explore the lipidomics of the cilium in three areas. 1) To gain a better understanding of the specific lipid signature of the membrane of primary cilia and its impact on ciliary signalling pathways. 2) To study the establishment and maintenance of this specificity by trying to understand the mechanisms underlying membrane homeostasis. 3) Use the targets discovered to demonstrate that the use of RNA therapeutics could modulate signalling in Hedgehog-dependent cancers.
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Début de la thèse : 01/11/2024
Funding category
Funding further details
Financement d'une collectivité locale ou territoriale
Presentation of host institution and host laboratory
Université d'Orléans
Institution awarding doctoral degree
Université d'Orléans
Graduate school
549 Santé, Sciences Biologiques et Chimie du Vivant - SSBCV
Candidate's profile
Compétence en biologie moléculaire et chimie analytique
Skills in molecular biology and analytical chemistry
Skills in molecular biology and analytical chemistry
2024-08-18
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