Mots-Clés

DNA Replication Genome Instability Mutational Signatures Cancers Transcription-Replication Conflicts

Description

Subject: Analysis of replication stress associated mutational signatures in cancers

Team:     Replication program and genome instability

               Intitut Curie, UMR3244 – Dynamics of Genetic Information

Group leader: CHEN Chunlong (chunlong.chen@curie.fr)

Website: https://science.institut-curie.org/team-chen 

Project description: DNA replication must adapt to changes in chromatin organization associated with cell differentiation and development, whose deregulation can challenge genome stability and leads to mutations, cancer and many other genetic diseases. Our team focuses on developing cutting-edge high-throughput genomic approaches and using genome-wide data analyses to study the spatio-temporal replication program of the human genome, and how its deregulation causes genome instability and leads to human diseases. Recently, we have published several pioneer papers showing how gene transcription shapes the replication landscape of human cells and how transcription-replication conflicts lead to genome instability, which is amongst the key factors playing an important role in cancer development.

We are looking for a motivated bioinformatics master student, who likes teamwork and interaction with both experimental and computational biologists. The candidate will develop the bioinformatic tools and perform the analysis on the high-throughput genome-wide data of the human replication, gene transcription and genome instability, and then compare with the mutational data (both point mutations and structure variations) obtained from cancer genomics projects, in order to gain better insight in understanding the replication stress associated mutational signatures in cancers. The student will be placed in an excellent multidisciplinary environment of the Institut Curie. He/she will work in close collaboration with the worldwide experimental and computational biology experts and tightly interact with the bioinformatics/sequencing platform of Institut Curie.

Key publications in recent years:

- Wang W, et al., Chen CL# (# co-last authors), Gilbert DM# and Rhind N# (2021) Genome-Wide Mapping of Human DNA Replication by Optical Replication Mapping Supports a Stochastic Model of Eukaryotic Replication. Mol. Cell. 81:2975-2988.e6.

- Shi MJ, Meng XY, Chen CL, Radvanyi F and Prokunina-Olsson L (2020) Identification of new driver and passenger mutations within APOBEC-induced hotspot mutations in bladder cancer. Genome Medicine. 12:85

- Promonet A*, Padioleau I*, Liu Y* (*co-first authors), et al., Chen CL# (# co-last authors), Lin YL # and Pasero P# (2020) Topoisomerase 1 prevents replication stress at R-loop-enriched transcription termination sites. Nat. Commun. 11:3940.

- Brison O*, EL-Hilali S*, et al., Chen CL (2019) Transcription-Mediated Organization of the Replication Initiation Program Across Large Genes Sets Common Fragile Sites Genome-Wide. Nat. Commun. 10:5693

- Petryk N, et al., Chen CL* and Hyrien O* (*co-last authors). (2016) Replication landscape of the human genome. Nat. Commun. 7:10208.

- Van Dijk EL*, Chen CL* (co-first authors), et al. (2011) XUT, a novel class of antisense regulatory ncRNA in yeast. Nature 475:114-7.

- Chen CL, et al. (2011) Replication-associated mutational asymmetry in the human genome. Mol. Bio. Evol. 28: 2327-2337.

- Chen CL, et al. (2010) Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes. Genome. Res. 20:447-457.