Mots-Clés
multi-omics
epigenetics
chromatin regulation
regulation of gene expression
cell differentiation and development
Description
Offer: 18-month work contract of engineer in bioinformatics of multi-omics data (CEA Grenoble)
Title: Integrated bioinformatic analysis of multi-omics data to decipher the dynamics of chromatin regulatory mechanisms
Background: In the nucleus of eukaryotes, DNA wraps around octamers of histone proteins to form a structure called chromatin. Dynamic post-translational modifications (PTMs) of histones are essential to regulate gene expression. Acetylation of histone lysines is now well known to be associated with increased chromatin accessibility and active gene transcription. Lysine acetylation is classically described to mark active transcription both when localized at gene promoter regions, or when present at distant genomic regions, called distal enhancers, that regulate gene expression via long-range interactions made by chromatin looping. However, the presence of this mark alone appears insufficient to define active promoters and enhancers. In the present project, we study the role of various novel acylations of histone H3 at promoters and distal enhancers, to improve our understanding of their functions in the regulation of gene expression. We explore these questions in the context of mouse spermatogenesis, in which several new lysine acylations were discovered.
Objective: The research project consists of an integrated bioinformatic analysis of multi-omics data (epigenomics, transcriptomics and epiproteomics) to decipher the dynamics of chromatin regulatory mechanisms through the differentiation of male germ cells.
Workplan: The engineer will work on the global data cycle from experimental multi-omics data (promoter capture Hi-C, ChIP-seq, CUT&Tag, RNA-seq and histone mark proteomics) which are generated by the project partners from populations of male germ cells isolated from mice. The bioinformatics work will first consist in processing, standardizing and harmonizing the raw omics data in order to make them interoperable and allow their integration. He/she will continue with the use of multivariate statistics and machine learning models in order to integrate several omics data within the same stage of differentiation and to reveal the dynamics of chromatin regulation through cell differentiation.
Host laboratory: The engineer will be hosted in the “Genetics and Chemogenomics” lab and work in close collaboration with the EDyP proteomics lab, both from the Interdisciplinary Research Institute of Grenoble (IRIG) of the CEA Grenoble, and with the “Epigenetic & Spermiogenesis” group at the Cochin Institute. He/she will be supervised by Christophe Battail, expert in computational analysis of genomics data, and co-supervised by Delphine Pflieger, expert in epi-proteomics analysis of chromatin regulatory mechanisms, and by Julie Cocquet, expert in male germ cell differentiation. He/she will evolve in a multidisciplinary research environment composed of bioinformaticians, AI experts and biologists.
Candidate profile:
Knowledge and skills: Bioinformatics of omics data (epigenomics, transcriptomics, epiproteomics), R and Python programming, unix command line and strong interest in biology of gene expression and chromatin regulatory mechanisms.
Professional aptitude: curiosity and desire to improve their scientific and technological skills, rigor and organization, and ability to work in a team and interact with other students, engineers and researchers
Job contract:
18-month work contract of engineer in bioinformatics starting in October 2023.
Please send your CV, a cover letter and the name of a referee to delphine.pflieger@cea.fr and christophe.battail@cea.fr.