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Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

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ANR-Funded PhD Position in Neurosciences

Our lab has obtained a 3 year-financial support for a PhD student to work on the role of tubulin (de)tyrosination on neuronal differentiation and synaptic maturation.

A better understanding of the molecular and cellular mechanisms of synaptic plasticity is important for our understanding of the development and functions of the brain. On the postsynaptic side, dendritic spines are plastic and this plasticity depends on actin and microtubule cytoskeletons. Our project aims to understand the biological mechanisms that link the dynamics of microtubules to the functions of dendritic spines.

Microtubule dynamics are modulated by tubulin post-translational modifications such as the detyrosination/re-tyrosination cycle. In this cycle, the C-terminal tyrosine of tubulin is removed by carboxypeptidases (TCPs) and re-added by a ligase (TTL). Our group demonstrated that tyrosinated-tubulin is vital, as shown by the deleterious brain disorganization of TTL KO mice (Erck C, Peris L et al PNAS 2005). We also recently identified TCP enzymes (VASH-SVBP), which had remained elusive for 40 years, and developed VASH-SVBP KO mice (Aillaud C et al, Science 2017). We documented brain abnormalities with microcephaly and cognitive impairments in SVBP KO mice (Pagnamenta et al., Human molecular genetics 2019).




Figure. The deTyr/Tyr cycle and their enzymes (MJ Moutin et al, Developmental Neurobiology. 2020). DeTyr/Tyr microtubule distribution in mature hippocampal neurons.

We hypothesize that the activity of dendritic spines depends on the tyrosination status of their microtubules, established by the enzymes TCP (detyrosination) and TTL (re-tyrosination). The PhD student will unravel the role of deTyr/Tyr microtubules in the synaptic compartment, decipher the nanoscale context of microtubule entry in dendritic spines and the consequences of the deTyr/Tyr cycle modulation in synaptic compartment.

This multidisciplinary project will use molecular biology, biochemistry, neuronal cell biology, video-microscopy and super-resolution microscopy. The success of this project may provide understanding of basic mechanisms underlying the role of microtubules in synaptic transmission, and lead to a new therapeutic concept targeting detyrosination enzymes to improve synapses of degenerating neurons.

We are seeking a highly motivated student with solid training in cell biology. Knowledge of French is not required. This ANR-funded position is open as of 1st of January 2021.
The laboratory is part of the Grenoble Institute of Neurosciences (https://neurosciences.univ-grenoble-alpes.fr/). Grenoble is a lively city with a large university and world-class research, located in the French Alps, close to numerous hiking trails and ski resorts, three hours from Paris by train and a three-hour drive from the Mediterranean coast. Candidates should apply by sending a CV, a brief outline of scientific experience, scientific interests and career goals, as well as the name and contact details of at least two academic references to Leticia Peris (leticia.peris@inserm.fr) and Marie-Jo Moutin (marie-jose.moutin@univ-grenoble-alpes.fr).


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Mise à jour le 26 octobre 2020

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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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