Contenu

x

Moteur de recherche interne

Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

  • Youtube
  • Linkedin
  • Twitter

Accueil > Nous rejoindre > Sujets de thèse

Accéder au plan complet du site

Contribution of MAP6 protein as a Microtubule Inner Protein in neuronal growth under normal, constrained and regenerative conditions

Summary of the project

Microtubules, major components of the eukaryotic cytoskeleton, are hollow cylinders composed of alpha and beta-tubulin heterodimers. Microtubules are able to alternate between phases of growth and shrinkage through gain and loss of tubulin at their extremities. In neurons, such dynamic microtubules co-exist with long-lived stable microtubules characterized by a reduced tubulin turnover, which are crucial for neuronal architecture and functions. How neurons generate stable microtubules is a long-standing question in the cytoskeleton field. Strikingly, protein densities called MIPs (for Microtubule Inner Proteins) have been observed for long inside neuronal microtubules and proposed to confer them their high stability. The identity of neuronal MIPs remained totally unknown until we recently identified the first as the neuronal protein MAP6 (Cuveillier, Delaroche, Seggio et al, 2020). MAP6 can localize in the lumen of MTs to generate highly stable polymers with novel properties including their helical growth and the formation of persistent holes in their lattice.
We hypothesise that MAP6-containing MTs (1) contribute to the ability of neurons to grow and maintain their shape in constrained conditions; and (2) are crucial during neuronal regeneration, where axons must re-grow in unfavourable contexts. The goal of the PhD thesis is to investigate these possibilities.
To assay the the role of MAP6-containing MTs in neuronal resistance to external constraints, the ability of WT and MAP6-KO neurons to grow in unconstrained (normal) and constrained conditions by varying the stiffness of substrates in 2D and in 3D cultures will be monitored (Collab S. Gabriele, U. Mons, Belgium). Various parameters of the neuronal morphology (number and length of neurites, axon/dendrite branching, synapses morphology and density) will be analysed by confocal microscopy, after differentiation. To assay the role of MAP6-containing MTs in pathological contexts the ability of WT and MAP6 KO neurons to regrow after injury in the peripheral system using the sciatic nerve crush model will be monitored (Collab H Nawabi, Grenoble).

Required skills

We are seeking a highly motivated student with background in cellular biology. Additional knowledge in molecular biology, imaging technologies and neurosciences would be appreciated. The student will perform primary neuronal cell culture, immunolabelling, image acquisitions using super resolution imaging and images processing (PIC-GIN, Imaging facility at Grenoble Institute of Neuroscience). He/she will also perform the in vivo analysis of post-injury axonal regeneration.

Reference

Cuveillier C, Delaroche J, Seggio M, Gory-Fauré S, Bosc C, Denarier E, Bacia M, Schoehn G, Mohrbach H, Kulic I, Andrieux A, Arnal I, Delphin C, MAP6 is an intraluminal protein that induces neuronal microtubules to coil. Sci. Adv. 6, eaaz4344 (2020)

Contact

Candidates should send their CV, as well as the name and contact details of two academic references, to sylvie.gory-faure@univ-grenoble-alpes.fr and annie.andrieux@univ-grenoble-alpes.fr
 

Mise à jour le 5 mars 2021

Contacts

Pour les stages (master, licence, 3ème), envoyer directement un email au responsable de l'équipe que vous avez identifiée.

Pour une candidature spontanée pour un emploi et uniquement pour cela, envoyez un email à gincomm[at]univ-grenoble-alpes.fr ou utilisez le formulaire de contact.

Membres
Associés renforcés
Associés simples