Mots-Clés

Biologie computationnelle Expression des gènes RNA-Seq ChIP-Seq Topologie du chromosome Biologie systémique Chromatine Microbiologie

Description

Profile of candidate: Master/engineering student in bioinformatics, biology/biochemistry, computer science, physics, or mathematics with interest in biology and interdisciplinarity.

Context: The internship will take place in a microbiology institute with close computational-experimental collaboration and a more specific dedication to plant pathogenic bacteria.

The candidate will integrate a project dedicated to deciphering the complex relationship between the chromosome conformation (physical structure) and gene expression (biological function). The bacterial nucleoid is shaped by DNA-binding architectural proteins and DNA supercoiling, and their dynamics underpins the regulation of gene expression.

Ongoing projects involve the computational analysis of high-throughput “omics” data (RNA-Seq, ChIP-Seq) to analyze the role of specific architectural proteins (Lrp, H-NS, Fis) and variations of DNA supercoiling (by antibiotics inhibiting topoisomerases) [1,2], and biophysical simulations of transcription and DNA supercoiling [3].

Objectives: Depending on the candidate’s background, skills and preferences, the internship can be oriented towards (1) computational analysis of high-throughput data, to uncover new relations between protein binding, DNA topology and gene expression, or (2) computational modeling of transcription and DNA supercoiling, to uncover how the genome architecture underpins gene regulatory networks. An experimental part can be added to the project, depending on the candidate’s skills and motivations.

Skills required: The topic is intrinsically interdisciplinary, at the crossing of biology, informatics and physics, and we encourage applications of candidates from various backgrounds with a strong interest in understanding the fundamental processes of life. Experience with Python/R programming is required. Knowledge in biology and experience in handling biological data will be favored. Complementary experimental (wet lab) skills are encouraged. After the internship, the candidate is expected to apply for a 3-year PhD thesis with local funding.

[1] Pineau et al. (2022), NAR 50, 9149-9161, https://doi.org/10.1093/nar/gkac679

[2] Forquet et al. (2022), NAR 50, 7287-7297, https://doi.org/10.1093/nar/gkac579

[3] Reverchon et al. (2021), NAR 49, 776-790, https://doi.org/10.1093/nar/gkaa1227

[4] El Houdaigui et al. (2019), NAR 46, 5648-5657, https://doi.org/10.1093/nar/gkz300