Mots-Clés

Bioinformatics Genomics

Description

Multicellular organisms establish and maintain different transcriptional states in disparate cell types through complex and specific regulation of gene expression. This regulation is mediated by the cooperative binding of transcription factors (TFs) to regulatory elements through the recognition of specific DNA sequence motifs. Additionally, the physical access of transcription factors to DNA can be modulated by epigenetic regulation, such as DNA methylation, nucleosome positioning and histone modifications. Failure to maintain this tight regulation of gene expression results in developmental defects and various diseases including cancer.

During this internship that could be extended into a PhD project, you will integrate genomic data (e.g. TF binding by ChIP-seq, gene expression by RNA-seq, chromatin accessibility by ATAC-seq, DNA methylation by WGBS) and sequence data (e.g. TF motifs) to study the sensitivity of transcription factors to DNA methylation. You will also develop deep learning approaches to better predict transcription factor binding sites in the context of DNA methylation.

You will work in an international environment at the IGBMC, a leading European institute. We are a team of computational and experimental biologists and you will benefit from our expertise in genomic data analysis (Anaïs Bardet) and modeling (Nacho Molina) for the success of the project.

Skills:
• Bioinformatics background with experience working in a linux environment
• Good level in a scripting language (e.g. bash, python, perl) and R as well as data analysis techniques and statistics
• Previous experience working with NGS datasets is a plus
• Good knowledge of biology and interest in genomics and gene regulation
• Ability to work in a team with both computational and experimental biologists
• Good level in spoken and written english

References
- Detilleux D, Spill YG, Balaramane D, Weber M, Bardet AF. Focal DNA hypo-methylation in cancer is mediated by transcription factors binding. (2021) Epigenetics & Chromatin 15:10
- Leporcq C, Spill Y, Balaramane D, Toussaint C, Weber M, Bardet AF. TFmotifView: a webserver for the visualization of transcription factor motifs in genomic regions. (2020) Nucleic Acid Research 48:W208-W217
- Domcke S*, Bardet AF*, Ginno P, Hartl D, Burger L, Schübeler D. Competition between DNA methylation and transcription factors determines binding of NRF1. (2015) Nature 528(7583):575-9 *co-first author
- Riba A, Oravecz A, Durik M, Jiménez S, Alunni V, Cerciat M, Jung M, Keime C, Keyes WM, Molina N. Cell cycle gene regulation dynamics revealed by RNA velocity and deep- learning. (2022) Nature Communications 13(1):2865