Studying novel histone acylations in the regulation of gene expression

Posted 01 Jun 2022

CEA Grenoble

France (Post Doc)

http://www.edyp.fr/web/2019/10/22/integrative-omic...


Project summary:

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. In the present project, we aim to study the role of various novel acylations of histone H3, to improve our understanding of their functions in the regulation of gene expression. We will explore these questions in the context of mouse spermatogenesis, a biological model perfectly adapted to the exploration of the functional role of new histone marks.

Your tasks:

  • Preparation of histone samples for their exploratory and targeted proteomic analyses; interpretation of these data to quantify lysine acylations in successive male germ cell stages.
  • Affinity-purification of crosslinked protein/DNA complexes using antibodies raised against selected histone modifications, to identify both the genomic regions bound by these histone molecules (by ChIP-seq) and the proteins preferentially binding onto them (by proteomics).
  • Opportunity to spend several months in the laboratory of Till Bartke (Helmholtz Zentrum München, Munich, Germany) to learn and apply the technique of nucleosome pulldown.
  • Be involved in the integration of the ChIP-seq data with available RNA-seq data to assess the impact on gene expression of selected histone lysine modifications.
  • The hired post-doctorate will be responsible for carrying out and orienting the project, while benefitting from regular interaction with the PIs collaborating on this project. This project will indeed be performed under the guidance of Delphine Pflieger, who is an expert in the proteomic analysis of histones, and in tight collaboration with Julie Cocquet (Institut Cochin Paris), expert in mouse spermatogenesis, and Christophe Battail (CEA Grenoble), expert in bioinformatics of genomics data.

Desired skills:

This post-doctoral project lies at the interface between biochemistry, analytical chemistry and bioinformatics to handle large-scale omics datasets. The candidate should have a solid experience in biochemistry to prepare and characterize protein complexes (immuno-purification, Western Blots, etc) and/or in proteomics (preferentially in the field of quantitative analysis of protein modifications). The candidate should also be interested in bioinformatics analysis and biological interpretation of large-scale multi-omics datasets (R language). He/she is expected to master speaking and writing in English, to be able to write articles, and to be endowed with team spirit. We are looking for a highly motivated and qualified individual holding, or shortly expecting to be awarded, a PhD degree in biochemistry or analytical chemistry. The candidate will have proven research skills in biochemistry / proteomics attested by a track record of research achievement and publications in internationally recognized peer-reviewed journals. Only applications from junior candidates (i.e. with less than 2 years of postdoctoral experience) with the above-described profile will be considered.

Location:

You will work in the EDyP team (Studying the Dynamics of Proteomes), whose main specialty lies in the use of mass-spectrometry-based proteomics to characterize complex protein samples. The lab is equipped with latest generation MS instruments and has developed software tools to help identify and quantify proteins and their post-translational modifications.

Keywords:

Histone lysine acylations, selective protein assemblies, quantitative proteomics, functional genomics, spermatogenesis, multi-omics data integration.

Relevant publications of the team:

El Kennani S, Crespo M, Govin J, Pflieger D. Proteomic analysis of histone variants and their PTMs: strategies and pitfalls. Proteomes. 2018 Jun 21;6(3). pii: E29. doi: 10.3390/proteomes6030029

Crespo M. […], Battail C., Cocquet J., Pflieger D. Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes. Nucleic Acids Res., 2020. doi:10.1093/nar/gkaa163

How to Apply

Please send a CV, a motivation letter and two letters of recommendation to Delphine Pflieger, delphine.pflieger@cea.fr