Regulation, maturation, and functions of mitochondrial ferredoxins

The mitochondrial ferredoxin FDX2 is an electron transporter containing a [2Fe-2S] cluster and plays a central role in the biogenesis of all Fe-S cluster proteins. These proteins are essential for numerous fundamental cellular processes, including respiration, mRNA translation, and DNA replication and repair. Mutations in FDX2 disrupt the formation of the Fe-S clusters and lead to severe mitochondrial disorders. In addition, FDX2 and the ferredoxin FDX1, which is involved in steroidogenesis and various redox processes, exhibit tumour suppressor functions and regulate ferroptosis and cuproptosis, two forms of non-apoptotic cell death that have gained a strong interest in cancer research. Despite their importance, the mechanisms governing their regulation, maturation (Fe-S cluster insertion into the apo-protein), and certain of their functional roles remain poorly understood. This project aims to elucidate these mechanisms using diverse approaches in human cell lines, including breast cancer models, as well as in the eukaryotic model Saccharomyces cerevisiae. First, the protein network of the ferredoxins will be mapped using proteomics, genomics, and chemoproteomics approaches. This mapping will allow the identification of factors involved in their regulation and maturation, as well as new functional partners. These candidates will then be studied in details using cell biology, molecular biology, biochemical and biophysical techniques to precisely define these processes. 

The ICSN is the chemistry center of the CNRS campus in Gif sur Yvette. The Institute belongs to the Paris-Saclay University Campus, which will incorporate 10% of the French research. The ICSN develops research activities at the boundary between chemistry and biology, that draw inspiration from natural substances. ICSN is organised in four research departments and has important analytical platforms.

The 'oxidative stress, iron-sulphur proteins and cancer' group (part of the Chemical Biology department) focuses on the large field of 'Redox Biology', notably on iron-sulphur (Fe-S) proteins, redox signaling, and regulation of reactive oxygen and nitrogen species (ROS/RNS) production in non-pathological and pathological contexts, using molecular and cellular approaches, as well as different model organisms.

We are looking for a rigorous and curious candidate, motivated by experimental research and able to work effectively in a team. Laboratory experience and a solid practical and theoretical background in molecular biology, genetics, and biochemistry are required. A good level of English is necessary to read scientific literature and communicate with international colleagues. Experience in mitochondrial biology, the yeast model, or bioinformatics will be considered an additional asset.