Date Limite Candidature : mardi 9 juillet 2024 23:59:00 heure de Paris
Informations générales
Intitulé de l’offre : Doctorant en biochimie et biologie cellulaire – Cryo-EM (H/F)
Référence : UMR9198-CECSAU-016
Nombre de Postes : 1
Lieu de travail : GIF SUR YVETTE
Date de publication : mardi 18 juin 2024
Type de contrat : CDD Doctorant/Contrat doctoral
Durée du contrat : 36 mois
Date de début de la thèse : 1 octobre 2024
Quotité de travail : Temps complet
Rémunération : La rémunération est d’un minimum de 2135,00 € mensuel
Section(s) CN : Biologie moléculaire et structurale, biochimie
Description du sujet de thèse
Etude du complexe Miro/Trak responsable du transport mitochondrial
Les mitochondries sont des organites extrêmement dynamiques qui fusionnent, se divisent et se déplacent constamment. Les mouvements des mitochondries sont bidirectionnels, soit antérogrades en suivant la polarité des microtubules du noyau vers la membrane plasmique, soit rétrogrades de l’extrémité de la cellule vers le centre. La compréhension de ce mécanisme est particulièrement importante dans les neurones, cellules hautement spécialisées dont l’architecture complexe peut s’étendre sur plusieurs micromètres et jusqu’à un mètre pour les neurones moteurs. En effet, le positionnement et la fonction des mitochondries sont essentiels pour maintenir le bon fonctionnement des neurones. De plus, les principales maladies neurodégénératives telles que les maladies d’Alzheimer et de Parkinson ont été liées à un dysfonctionnement ou à une mauvaise localisation des mitochondries. Il est donc fondamental de comprendre comment les mitochondries sont positionnées dans l’espace pour élucider la physiopathologie des maladies neurodégénératives.
C’est plus précisément à la relation entre le cytosquelette de microtubules ou de l’actine et le complexe MIRO/TRAK présent à la surface des mitochondries et responsable de leur mouvement que l’équipe s’intéresse. En particulier, nous nous s’intéressons à la régulation de ce transport par le complexe MIRO/TRAK et souhaitons déchiffrer les mécanismes mis en place par la cellule pour déterminer quand, comment et où les mitochondries doivent être transportées.
Pour mener à bien ce projet, nous recherchons un étudiant qui participera à l’étude structurelle et fonctionnelle du complexe MIRO/TRAK. L’étudiant utilisera différentes approches méthodologiques innovantes afin de caractériser ces protéines et leur régulation lors du transport mitochondrial. La caractérisation structurelle du complexe MIRO/TRAK nécessitera l’utilisation d’approches de biochimie, biophysique ainsi que leur analyse par cryo-microscopie électronique. L’étude de la régulation de ces protéines passera par la reconstitution in vitro du transport mitochondrial via des approches de biologie cellulaire et de biochimie. Cette étude sera couplée à la cryo-microscopie électronique et en particulier à la cryo-tomographie pour élucider les réarrangements conformationnels requis pour le transport des mitochondries.
Ce projet nous permettra de comprendre les mécanismes régissant l’organisation et la régulation de la motilité des mitochondries dans les cellules neuronales et de déchiffrer les mécanismes liés aux maladies neurodégénératives.
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