NOACRONYM

Equipe(s)
Etat
Titre du projet
Deciphering the signature of mutational processes and their impact in cancer development
Nom de l'appel d'offre
ITMO Cancer - PCSI: Interdisciplinary approaches to oncogenic processes and therapeutic perspectives: Contributions to oncology of physics, chemistry and engineering sciences
DĂ©fi/axe ANR
New concepts for the study of quantum or classical phenomena involved in the initiation of oncogenesis
Coordinateur.trice
Julie Soutourina (I2BC - Institut Joliot - CEA)
Participants de MaIAGE
G. Kon Kam King, C. Guérin, P. Nicolas
Partenaires (hors MaIAGE)
Julie Soutourina (I2BC - Institut Joliot - CEA), Florent Mallogi (LIONS - IRAMIS - CEA)
Année de démarrage - Année de fin de projet
2021-2024
Date de fin du projet
Résumé
The understanding of the mechanisms of somatic mutation accumulation is essential for cancer research. Global sequencing initiatives of thousands of human cancer genomes led to identification of distinct mutational signatures. However, mutational processes in many cancers remain poorly understood. Indeed, a wide range of mechanisms from dysfunctions in cellular processes including DNA repair and transcription to exogenous or endogenous mutagen exposures may lead to somatic mutations in cancer genomes. As a contribution to the understanding of complex mechanisms linking transcription and DNA repair, we recently discovered a novel function in transcription-coupled repair for Mediator, a conserved multiprotein coactivator playing a crucial role in all eukaryotes. In this interdisciplinary project, we aim to improve our understanding of the mutational processes at the origin of cancers by deciphering the contribution of genetic background and mutagen exposure to mutational signatures observed in cancer cells, using a combination of genetic, genomic (J. Soutourina), microfluidic (F. Malloggi) and computational approaches (P. Nicolas).

We will use an innovative microfluidic system to considerably accelerate mutation accumulation in yeast for the analysis of transcription-coupled repair and transcription-associated mutagenesis involving Mediator. By combining our new genomic and microfluidic-based approach with computational methods, we will study the mutational signatures of transcription/DNA repair interplay and their impact on carcinogenesis. A computational framework based on experimental data will be applied to available catalogs of human cancer somatic mutations. This work may allow us to propose targets for the development of anticancer therapeutic approaches or modifications of chemotherapeutic treatments by combination of targets in cancers directly involving Mediator and its partners in DNA repair.
Année de soumission
2020