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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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Abnormal cytoskeleton organizations in Alzheimer’s disease

Objectifs

The student will work on primary cultured neurons to investigate how pathological tau mutants alter microtubules and actin in mature neurons and how these alterations affect neuronal architecture and functions, specifically synaptic architecture and plasticity.

Résumé

Alzheimer’s disease (AD) and related dementias are characterized by the accumulation in neurons of fibrillary tangles composed of the microtubule-associated protein tau. Defects of microtubule and actin cytoskeletons are main hallmarks of these diseases. Microtubules and actin are central to neuronal architecture and functions: they form highly specific structures required for the maintenance of axons, dendrites and synapses. Though disorganization of these cytoskeletal structures are linked to AD, we still lack a clear molecular picture of how tau mutants alter microtubules and actin and how these alterations affect neuronal architecture and functions. During this internship, pathological conditions will be induced by toxic variants of tau known to be involved in AD and related dementias. Consequences of cytoskeleton alterations will be then assessed on neuronal architecture and activity in primary neurons.

Méthodes

Cell culture (primary mouse neurons), transfection, transduction with lentiviral vectors, immunofluorescence, confocal microscopy, live-cell imaging and molecular biology.

Références

  • Prezel E., A. Elie, J. Delaroche, V. Stoppin-Mellet, C. Bosc, L. Serre, A. Fourest-Lieuvin, A. Andrieux, M. Vantard and I. Arnal. 2018. Tau can switch microtubule network organizations: from random networks to dynamic and stable bundles. Mol biol cell. 29(2): 154–165
  • Ramirez-Rios, S., E. Denarier, A. Vinit, E. Prezel, V. Stoppin-Mellet, L. Peris, A. Andrieux, L. Serre, A. Fourest-Lieuvin, and I. Arnal. 2016. Tau antagonizes EB tracking at microtubule ends through a phosphorylation-dependent mechanism. Mol biol cell. 27:2924-34.
  • Elie, A., E. Prezel, C. Guerin, E. Denarier, S. Ramirez-Rios, L. Serre, A. Andrieux, A. Fourest-Lieuvin, L. Blanchoin, and I. Arnal. 2015. Tau co-organizes dynamic microtubule and actin networks. Scientific reports. 5:9964.

Domaines d'expertise requis

Cellular and molecular biology, optical microscopy, English

Contacts

Anne Fourest-Lieuvin, PhD
Email : anne.fourest-lieuvin@univ-grenoble-alpes.fr
Tél: 04 56 52 06 89

Mise à jour le 6 juin 2019

Contacts

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