Mots-Clés

Bioinformatics DNA replication Computational biology epigenomics Artificial intelligence

Description

We look for a motivated young scientist interested in the integration of different layers of genomic data with the aim to reach a rigorous, quantitative description of the regulation of the human genome replication program.

The successful researcher will join the Sisyph team at Laboratoire de Physique de l'ENS de Lyon (LPENSL, CNRS UMR5672, project supervisors: B. Audit).

The identification of human (and other metazoan) DNA replication origins has given rise to controversies, due to variable results between techniques and laboratories (Hyrien 2015). Integration of original in-house maps of DNA replication obtained by high-throughput sequencing (OK-seq; Petryk 2016; Wu 2018) and single molecule techniques (FORK-seq; Hennion 2020) with other publicly available maps, will be pursued in order to establish a definitive picture of replication initiation.

Further integration with chromatin profiles will aim at dissecting the cis- and trans-acting determinants of replication initiation in human cells. This step will benefit from our previous experience in replication maps analysis (Audit 2013; Kirstein 2021) and mathematical modelling of genome replication kinetics (Arbona 2018; Goldar 2016), in relation to epigenetic data and chromatin structure.

Arbona JM et al (2018) eLife, 7, e35192. doi: 10.7554/eLife.35192
Audit B et al (2013) Nature Protocols 8, 98-110. doi: 10.1038/nprot.2012.145
Goldar A et al (2016) Scientific Reports 6, 22469. doi: 10.1038/srep22469
Hennion M et al (2020). Genome Biology 21, 125. doi: 10.1186/s13059-020-02013-3
Hyrien, O (2015) Journal of Cell Biology, 208, 147-160. doi: 10.1083/jcb.201407004
Kirstein N et al (2021) Elife 10, e62161. doi: 10.7554/eLife.62161
Petryk, N et al (2016) Nature communications, 7, 10208. doi: 10.1038/ncomms10208
Wu X et al (2018) Nucleic Acids Research 46, 10157-10172. doi: 10.1093/nar/gky797

Knowhow

The candidate should have:
- a PhD or equivalent experience in computational biology or bioinformatics.
- previous experience with next generation sequencing data.
- the willingness to work in an interdisciplinary context.

We would also appreciate applicants with:
- background knowledge of DNA replication mechanisms.
- experience with nanopore sequencing.
- interest for the application of artificial intelligence to genomic data.

Work context:

The researcher will integrate a long-lasting interdisciplinary collaboration between the host computational group at LPENSL and the experimental group of Olivier Hyrien (Eukaryotic Chromosome Replication team, Institut de Biologie, de l'ENS, Paris), funded by Agence National de la Recherche (ANR projects NanoPoRep and Hudror).

The researcher will benefit from the rich and stimulating scientific environment of ENS de Lyon, including the access to the knowhow and computing resources of Pôle Scientifique de Modélisation Numérique de l'ENS de Lyon (PSMN).