PhD in Biochemistry of Metaloproteins, mechanisms and functions (M/F)

Job Description

Thesis Subject

Iron-sulfur (Fe-S) clusters are prosthetic groups of proteins found in virtually all living organisms. They constitute the active sites of a vast number of enzymes and proteins involved in electron transfer, catalysis, protein and DNA synthesis, and signaling. They are biosynthesized on assembly platforms by multiprotein machinery in the [2Fe-2S], [3Fe-4S], and [4Fe-4S] forms and are subsequently transferred to target proteins. Because Fe-S clusters play key roles in numerous processes, defects in their biosynthesis lead to severe human pathologies (neurodegenerative diseases, cardiomyopathies, cancers). Therefore, understanding the biosynthesis and transfer mechanisms of Fe-S clusters is of fundamental importance in the biomedical field. The laboratory has made significant progress in recent years on the assembly process of [2Fe-2S] clusters, which are the building blocks for [4Fe-4S] cluster assembly, by identifying several intermediates and uncovering a new regulatory pathway for cluster synthesis by the ISC machinery. However, several questions remain regarding the assembly and transfer mechanisms of [2Fe-2S] clusters. This thesis project aims to elucidate these mechanisms. To this end, the human ISC machinery will be reconstituted in vitro with recombinant proteins. We will study the assembly and transfer processes step by step using various biochemical, biophysical, and structural techniques (native mass spectrometry, NMR, EPR, ITC, FIDA, BLI, cryo-EM, crystallography, modeling, etc.). The PhD student will be responsible for protein purification and protein complex reconstitution, as well as analysis, in collaboration with our internal partners at I2BC and external partners (IPHC Strasbourg, BIP Marseille, ICSN Saclay).

References

1. Cross-regulation of [2Fe–2S] cluster synthesis by ferredoxin-2 and frataxin. Want K., Gorny H., Turki E., Noiray M., Monfort B., Mor-Gautier R., Tubiana T., Jullian E., Monnier V., D'Autréaux B., Nature (2026), 649, 721–728. doi: s41586-025-09822-1

2. The ISC machinery assembles [2Fe–2S] clusters by formation and fusion of [1Fe–1S] precursors. Gervason S., Dutkiewicz R., Want K., Benazza R., Mor-Gautier R., Grabinska-Rogala A., Sizun C., Hernandez-Alba O., Cianferani S., Guigliarelli B., Burlat B., D'Autréaux, B., Nat. Chem. Biol. (2025), 21, 767–778. doi: 10.1038/s41589-024-01818-8

3. Mechanism of mitochondrial [2Fe2S] cluster biosynthesis. K. Want, B. D'Autréaux, Biochim. Biophys. Acta Mol. Cell Res. (2024), 1871(8), 119811. doi: 10.1016/j.bbamcr.2024.119811

Your Work Environment

The Institute for Integrative Biology of the Cell (I2BC) is a joint research unit of the CNRS, Université Paris-Saclay, and CEA, at the forefront of biology, biochemistry, and biophysics, with nearly 600 researchers located on the Gif-sur-Yvette campus and a wide range of platforms, notably for mass spectrometry, protein-protein interaction, NMR, EPR, and cryo-EM (Glacios and Titan at the SOLEIL Synchrotron). The Biochemistry of Metalloproteins and Associated Diseases team is an internationally recognized group for the study of the biosynthesis mechanisms of Fe-S clusters and associated human pathologies.

Candidate profile: a strong background in biochemistry, biophysics, enzymology, and molecular biology; specific skills in protein and metalloprotein purification, structural methods, and spectroscopy would be an asset.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

The research professions