Génétique et mécanismes moléculaires des encéphalopathies épileptogènes : migration et fonction synaptique des interneurones GABAergiques


Elsa Rossignol

Centre de recherche du Centre hospitalier universitaire Sainte-Justine


Domaine : neurosciences, santé mentale et toxicomanies

Programme chercheurs-boursiers cliniciens - Junior 2

Concours 2015-2016

Epileptic encephalopathies (EE) are severe childhood-onset epilepsies with developmental delay or intellectual deficiency. These disorders were of unknown etiology up to recently. The advent of next-generation sequencing has revolutionized our ability to identify the cause of EE in many patients and to discover new candidate EE genes in most of the other patients.

My work focuses on the identification of the genetic causes of EE and on the discovery of new candidate genes using whole-genome sequencing in a large cohort of children with unexplained EE. Furthermore, I have developed means to selectively repress or mutate these new genes of interest in developing mouse brain cells. This will enable me to study the role of these new candidate genes on neuronal development and function. I am particularly interested in the roles of these genes on the generation, migration, maturation and synaptic function of cortical GABAergic interneurons, the inhibitory cells of the cortex. Indeed, my recent work has demonstrated that altered development or function of cortical interneurons leads to severe epilepsy in mice, reminiscent of that seen in patients with EE. My preliminary results on some of the new candidate genes I identified in children with EE suggest that these genes are indeed fundamental regulators of interneurons migration or function.

My work should therefore widen our understanding of the molecular etiology underlying EE and of the cellular and network mechanisms causing the disease. A better understanding of these mechanisms will be critical to our ability to develop new and better-targeted therapies for children with EE and to improve these children's long-term neurological outcome. This personalized medicine approach will undoubtedly improve care for children with EE and their families.