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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Impact of Alzheimer’s disease-related tau mutations on the cytoskeleton homeostasis

Objectifs

Our objective is to characterize how pathological mutants of tau, a major neuronal microtubule-associated protein, affect the dynamic properties of microtubules and actin filaments.
 

Résumé

Tau is a microtubule-associated protein abundant in neurons, where it promotes microtubule assembly and bundling, and contributes to axonal transport and synaptic function. Tau dysfunction and aggregation are main hallmarks of neurodegenerative diseases called tauopathies, Alzheimer’s disease being the most emblematic one. In pathological conditions, tau undergoes modifications, including abnormal phosphorylation, truncation and/or mutations, eventually leading to its aggregation. Tau aggregation has long been considered as one major cause of neurodegeneration. However, soluble modified forms of tau appear to be toxic species still being able to bind microtubules and impairing neuronal function, albeit mechanisms of this toxicity remain poorly explored. During internship, student will study the effect of toxic species of tau on MT and actin organization and behavior using biomimetic assays and advanced-light microscopy techniques.
 

Méthodes

Protein expression and purification; in vitro biomimetic assays; TIRF (Total Internal Reflection Fluorescence) microscopy
 

Références

  • Stoppin-Mellet V, Bagdadi N, Saoudi Y, Arnal I(2020) Studying Tau-Microtubule Interaction Using Single-Molecule TIRF Microscopy. Methods Mol Biol. 2101:77.
  • Prezel E, Elie A, Delaroche J, Stoppin-Mellet V, Bosc C, Serre L, Fourest-Lieuvin A, Andrieux A, Vantard M and Arnal I (2018) Tau can switch microtubule network organizations: from random networks to dynamic and stable bundles Mol Biol Cell 29(2): 154.
  • Elie A, Prezel E, Guérin C, Denarier E, Ramirez-Rios S, Serre L, Andrieux A, Fourest-Lieuvin A, Blanchoin L, Arnal I (2015) Tau co-organizes dynamic microtubule and actin networks Sci Rep. 5:9964.

Domaines d'expertise requis

Biology of the neuron; fundamentals of the cytoskeleton; fundamentals of biochemistry; fluorescence microscopy

Contacts

V. Stoppin-Mellet, MCU UGA
Email : virginie.stoppin-mellet@univ-grenoble-alpes.fr
Tél : 04 56 52 06 89
 

Mise à jour le 26 juin 2020

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.

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