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 

Among the mTORC1 targets, S6 kinases 1 and 2 (S6K1 and S6K2) are exquisitely sensitive to nutrient availability and rapamycin inhibition. Of note, in vivo analysis of mutant mice reveals that S6K1 regulates cell size in a predominant way as compared to S6K2. Mutant animals also mimic a caloric restriction phenotype with decreased adiposity and increased lifespan. S6K1 may be therefore be key at the interconnection between cell size, regenerative and ageing responses. The doctoral candidate will perform structure-function studies and phospho-proteomics to reveal (1) the selective targets of S6K1 vs. S6K2 mediating cell size control; (2) the structural changes of key substrates upon phosphorylation; (3) the suitable residues for the design of covalent S6K1/S6K2 inhibitors. Molecular biology and genome editing tools will be used to produce mutant kinases and swap relevant domains in S6K1 and S6K2. Phosphoproteomics will broaden the list of S6K1 specific substrates that may be involved in cell size control. Protein modeling will clarify the kinase-substrate as well as inhibitor-kinase interactions in collaboration with EKUT-Gehringer. The molecular understanding of cell size control by mTOR/S6K1 should open new therapeutic perspectives for mTORopathy in which giant cells are prominent pathological feature. The doctoral candidate will define the molecular landscape for cell size regulation by the mTOR/S6K pathway and open pharmacological strategies for specific targeting in 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 website, before 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).