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PhD in Deciphering mTOR-S6K1 Signaling in Epilepsy and Cortical Malformations in Tuberous Sclerosis - Pende Lab

Institut Necker Enfants Malades (INEM) is a leading biomedical research center located on the Hôpital Necker-Enfants Malades campus in Paris. It benefits from state-of-the-art core facilities and is situated in a vibrant research environment with a strong history of scientific excellence and medical breakthroughs, including transplantation, biotherapy, and gene therapy.

The host laboratory

The Cell Growth Control by Nutrients team, led by Mario Pende, investigates molecular programs regulating cell growth and metabolic responses. The lab focuses on two key nutrient signaling pathways: mTOR and the Vps15/Vps34 complex, which play fundamental roles in coordinating metabolic adaptation across all eukaryotic cells.

About the project 

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. However, why aberrant mTOR activity alters neuronal excitability remains unknown. By genetic epistasis experiments in mouse models of the disease, 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. By phospho-proteomics and electrophysiological studies, we observed that S6K1 phosphorylates key determinants of neuronal excitability. We hypothesized that their regulation by S6K1-mediated phosphorylation may contribute to epileptic seizures in Tuberous Sclerosis. Doctoral candidate will test this model by original pharmacological, nutritional, biophysical and genetic approaches. Our project combines expertise in mTOR signaling and animal models of genetic diseases, allowing to explore the contribution of key determinants of neuronal excitability as novel putative therapeutic targets in epilepsy associated with mTORopathies.

Your profile
We are looking for a highly motivated and independent researcher who thrives in an interdisciplinary and international environment. Requirements:

- Master’s degree (or equivalent) before the start date and International mobility.
- Background in molecular/cell biology, biochemistry, or a related field. 
- Strong commitment to scientific research.
- Proficiency in English.
- Mobility requirement: The candidate must not have spent more than 12 months in France in the last 3 years. 


The position is funded for 3 years.

How to apply

Submit the following documents via the project’s websitebefore March 28, 2025:

  • Completed application form
  • CV
  • Two recommendation letters from previous mentors
  • Master’s degree certificate + transcripts (If not yet completed, upload a BSc degree + current Master’s transcript with expected graduation date).