Mots-Clés

Transcriptomics gene networks neuroscience psychiatry

Description

Chronic pain is a major risk factor for the emergence of emotional disorders, and understanding underlying molecular mechanisms is a public health issue. Our group has developed a mouse model in which sustained neuropathic pain leads to anxiodepressive-like behaviours, and we now seek to characterize the molecular changes that mediate these behaviours.

To do so, we used a massive 3’ RNA-Sequencing strategy to identify pain-induced gene expression changes in 6 brain regions processing pain and emotions. We also characterized 3 successive time-points defined by the presence of pain only (TP1), pain and related emotional dysfunction (TP2), or emotional dysfunction only (TP3). This analysis, already conducted in MALE mice, revealed time-dependent and brain region-specific kinetics. We now seek to conduct similar analyses in FEMALE mice, as anxiodepressive behaviors may rely on sex-specific mechanisms.

In this context, the goal of the internship will to be acquire experience in the analysis of large gene expression datasets. This will include primary analysis of raw sequencing data (QC, demultiplexing, alignment, counting), as well as strategies to: conduct threshold-free Gene Ontology analyses (GSEA); compare genome-wide changes in expression within (differential expression, DESeq2) and across brain regions or time-points (Rank-Rank Hypergeometric Overlay, RRHO2); construct gene networks and characterize their disorganization by chronic pain (MEGENA).

Overall, the internship is expected to provide deeper understanding of molecular mechanisms contributing in males and females to emotional consequences of chronic pain.