Mots-Clés

Epigenetics DNA methylation gene networks neuroscience drug addiction

Description

DNA methylation is a major epigenetic mark that contributes to the regulation of genomic expression. Its role has been extensively investigated in the determination of cellular identity, in particular in the context of embryological development and pathological processes such as cancer. More recently, an important role for DNA methylation has started to be uncovered in neuronal cells, the primary cell type in mammalian brains. While neurons are post-mitotic cells, their DNA methylation landscape retains a significant degree of plasticity that is increasingly thought to contribute to brain disorders, in particular drug addiction.

The present internship represents a first step towards a PhD project that will seek to investigate the role of DNA methylation in drug addiction. To do so, we plan to characterize DNA methylation changes that associate with addiction in the human brain, thanks to our established collaboration with the Douglas Bell Canada Brain Bank. We will also conduct similar analyses in mouse models of addiction, to confirm and further decipher the molecular mechanisms that underlie drug-induced epigenetic plasticity.

In this long-term perspective, the goal of the present internship will to be acquire hands-on experience with bioinformatic approaches and tools necessary to conduct the proposed PhD studies. This notably includes a variety of strategies to identify changes in DNA methylation differences as a function of exposure to drugs of abuse. You will learn to use approaches for the identification of differentially methylated regions (dmrseq, MethylSig, DSS), more recent algorithms that analyse DNA methylation patterns at the level of individual sequencing reads (CluBCpG), as well as multiomic integration and network modelling strategies (MEGENA). The intership will take place at INCI and/or IGBMC, in a friendly and international environment, under supervision by Drs Anaïs Bardet (bioinformatics) and Pierre-Eric Lutz (neurobiology). Funding for the proposed PhD work has already been secured (IReSP-INCa AAP Addictions 2022).