“Data integration from intracellular phospho-signaling to gene expression re-programming”
Extracellular stimuli are perceived by cells and converted into signaling cascades relayed by dynamic phosphorylations of proteins. These cascades finally reach the chromatin, made up of histones and DNA, and impact it, in part by changing the modification pattern of its histone constituents. Ultimately, the gene expression program is revisited, to allow the cells to develop an adequate response to the stimulus. We wish to decipher these iterative steps upon uptake by endothelial cells of extracellular vesicles produced by cancer cells: these vesicles contain microRNAs and proteins, including oncogenes, which can have combined impacts on the recipient cells. The obtained data should allow better understanding how cancer tumors manipulate their environment to ensure their survival, in particular by stimulating angiogenesis.
Analyses of the phosphoproteome and of histone post-translational modifications (PTMs) by mass spectrometry, of chromatin re-organization by ATAC-sequencing, and of mRNA by RNA-sequencing will be performed on endothelial cells at different time points after application of extracellular vesicles produced by a cancer cell line.
First, the recruited person will carry out bioinformatics analysis of each omics data independently. In proteomics, given the wealth of PTMs modifying histones described over the past ten years (including several acylations, e.g. propionylation, butyrylation, etc, on Lys residues), a particular challenge consists of the interpretation of mass spectrometry (MS/MS) spectra by the establishment of a dedicated bioinformatics method. Transcriptomic data will be processed to quantify expression and to detect differentially expressed / spliced transcripts. Epigenomic data will be used to identify differentially accessible chromatin regions.
Then, the recruited person will work on the integrated analysis of these multi-omics processed data to decipher target cell perturbations undergone after internalization of extracellular vesicles secreted by cancer cells. We expect to identify connections between alterations of signaling pathways, remodeling of chromatin and gene expression reprogramming associated with the complex stimulus applied to endothelial cells.
The recruited person will be supervised by Delphine Pflieger and Christophe Bruley, experts in proteomics from the biochemical sample preparation to the bioinformatic analysis of data, and by Christophe Battail, expert in the bioinformatic analysis of NGS data.
The applicant should be familiar with Linux environment and have experience in computer programming (mainly R, Python, Shell) dedicated to the analysis of omics data. The successful candidate will be collaborative and have good communicating skills. Practical knowledge of basic statistics would be appreciated.
We encourage bioinformaticians with previous experience in proteomics and/or NGS (RNAseq and ChIPseq) data analysis to submit a cover letter outlining motivations with a brief statement about career goals, a CV, and at least one reference letter.
Duration: guaranteed till end of March 2019.
Salary: between 2000 and 2800 Euros netto per month, depending on experience.
Contact: Delphine Pflieger (email@example.com)