Job: Postdoctoral fellow M/F: Inhibition of the potassium channel TREK-1 by S6 kinases: a mechanism for aberrant neuronal excitability in mTORopathies

About

Missions

A post-doctoral position (for two years) is currently available for a collaborative project (co-PIs: Dr. Mario Pende, Institut Imagine, Paris and Dr. Massimo Mantegazza, IPMC, Valbonne), focusing on the role of the potassium channel TREK-1 in epilepsy. Candidates should have a keen interest in integrating and understanding ion channels biophysical properties and physiology. A strong backround in patch clamp (single channel recordings) and calcium imaging (Fura-2) is required.

Activities

The mammalian Target Of Rapamycin (mTOR) kinase is a master regulator of cell growth present in every eukaryotic cell, from unicellular organisms to humans. Genetic diseases, such as Tuberous Sclerosis Complex (TSC), leading to the up-regulation of mTOR activity predispose to altered cortical development, now classified as mTORopathies, which are associated with epilepsy as well as intellectual disability and autism. Our preliminary data identified one mTOR substrate, S6 kinases 1 (S6K1), as an essential factor for cortical malformations and seizures in a mouse model of TSC. In collaboration between the three partner teams, by phospho-proteomics and electrophysiological studies, we observed that S6K1 phosphorylates and inhibits the K+ channel TREK-1. Since TREK-1 influences neuronal excitability, we hypothesized that its down-regulation by S6K1-mediated phosphorylation may contribute to epileptic seizures in Tuberous Sclerosis. This model will be tested by original pharmacological, nutritional, biophysical and genetic approaches. Our project combines expertise in mTOR signaling and animal models of genetic diseases, as well as skills in electrophysiology of K+ channels and epileptogenesis, with the aim of exploring TREK1 contribution as a novel therapeutic target in epilepsy associated with mTORopathies.

Skills

1) Electrophysiology
2) Calcium Imaging

Work Context

Our laboratory is part of the CNRS Institute of Molecular and Cellular Pharmacology located in the City of Nice-Sophia Antipolis (South East of France). This is a leading center in biology research with state of the art equipment. The city of Nice offers an international dynamic cultural experience combined with a magnificent scenery and easy access to air travel.

The position is located in a sector under the protection of scientific and technical potential (PPST), and therefore requires, in accordance with the regulations, that your arrival is authorized by the competent authority of the MESR.

The position is located in a sector under the protection of scientific and technical potential (PPST), and therefore requires, in accordance with the regulations, that your arrival is authorized by the competent authority of the MESR.

Additional Information

Interested candidates should apply using the following link:

https://emploi.cnrs.fr/Offres/CDD/UMR7275-MALARH-016/Default.aspx?Lang=EN

And e-mail a letter of application, including a CV and the names and addresses of at least two referees to: Eric HONORE (honore@ipmc.cnrs.fr)