Mots-Clés

Transcriptomics gene networks neuroscience psychiatry

Description

Chronic pain is a major risk factor for the emergence of emotional dysfunction, in particular anxiety and depressive disorders. Understanding molecular mechanisms that contribute to this relationship is therefore a public health issue. Over the last few years, our group has developed a robust mouse model in which the induction of a sustained neuropathic pain leads to anxiodepressive-like behaviours. Building on this model, we now seek to better characterize the brain-wide molecular changes that mediate these behaviours.

To do so, we opted for a massive next-generation sequencing strategy, whereby gene expression changes that occur following the induction of chronic pain will be systematically characterized in 7 brain regions known to process nociceptive information and regulate emotions. Importantly, we will characterize the kinetics of these changes by analysing 3 successive time-points (TP): when pain only (TP1), pain and emotional dysfunction (TP2), or emotional dysfunction only (TP3), are present. This is expected to provide deeper understanding of the molecular mechanisms that differentially contribute to pain and its emotional consequences.

In this context, the goal of the present internship will to be acquire hands-on experience with bioinformatic approaches and tools necessary to analyse and integrate large gene expression datasets.  This notably includes a variety of strategies to: i) conduct threshold-free Gene Ontology analyses (GSEA), ii) compare genome-wide changes in expression across brain regions and time-points (e.g. Rank-Rank Hypergeometric Overlay, RRHO), as well as iii) construct gene networks and characterize their disorganization by chronic pain (MEGENA, WGCNA).

The intership will take place at INCI, in a friendly and international environment, under supervision by Drs Ipek Yalcin (neurobiology) and Pierre-Eric Lutz (bioinformatics). It is expected to be prolonged by a Study Engineer position (IE) in our group, for a duration of at least 6-month. Funding for this position has already been secured (FRM équipe).