Deciphering The Structural Mechanisms of Raf Kinase Regulation

il y a 5 jours

Bordeaux, France Laboratoire de Chimie et Biologie des Membranes et des Nano Objets (CBMN) Temps plein

**Deciphering the structural mechanisms of RAF kinase regulation**:

- Réf **ABG-134003**
- Stage master 2 / Ingénieur
- Durée 6 mois
- Salaire net mensuel 650 euros
- 23/10/2025
- Laboratoire de Chimie et Biologie des Membranes et des Nano Objets (CBMN)
- Lieu de travail- Bordeaux Nouvelle Aquitaine France
- Champs scientifiques- Biochimie
- Mots clés- Protein biochemistry, Structural biology, Kinase, cryo-EM- 21/11/2025

**Établissement recruteur**:
**Site web**:
You will join a dynamic, multidisciplinary team with on-site access to cutting-edge facilities in cryo-EM, X-ray crystallography, NMR, biochemistry, biophysics, molecular biology and cell biology. The project is part of an international collaboration in which the student will take part.

**Description**:
**Mission**:

- We are looking for a**motivated**M2 student in protein biochemistry and structural biology to decipher the molecular mechanisms of RAF kinase signalling associated with human cancer.

**Project**:

- The RAF kinase family is a key component of the RAS-ERK signalling pathway controlling cell growth and proliferation. Hyperactivation of this pathway is a hallmark of cancer, with RAF mutated in ~8% of tumors. Although the RAS-ERK pathway is heavily targeted in the clinic, resistance mechanisms limit drug efficacy. Improving our understanding of the RAS-ERK pathway regulation is therefore crucial to develop new treatments.
- We previously showed how RAF kinases are regulated by KSR pseudokinases (Lavoie*, Sahmi*, Maisonneuve* et al. _Nature_ 2018) and by the scaffolding proteins CNK and HYP (Maisonneuve*, Sahmi* et al. _Nature Structural & Molecular Biology _2024). More recently, we obtained strong preliminary results showing that RAF activation is controlled by additional regulatory proteins whose mechanisms of action remain poorly understood. Our aim is to characterize the structural mechanisms by which these novel regulatory proteins modulate RAF activation.

**Methodology**:

- Molecular biology (site-directed mutagenesis of expression plasmids).
- Protein expression in bacteria and insect cells (established in the lab).
- Protein purification by affinity, ion exchange and gel filtration chromatography (established in the lab).
- Structural characterization of protein complexes by single particle cryo-EM.
- In vitro functional/biophysical assays of protein-protein interactions (NMR, BLI, SPR or fluorescent polarization, etc).

**Profil**:

- Master 2 or 5th year engineering student
- Previous experience in protein expression and purification is strongly preferred.
- Good background in biophysics (BLI, SPR, FP) and structural biology is encouraged

**Prise de fonction**:

- 05/01/2026

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