The DYSCLO project, recently funded by ANR jc-jc aims at unraveling the mechanisms underlying epileptogenicity in pediatric focal cortical dysplasia (FCD).
By studying ex vivo surgical specimens our team recently showed a paradoxical GABAergic depolarization, secondary to chloride cotransporters deregulation in FCD.
How this functional disorder is related to the genomic defect in the mTOR pathway is still to decipher and is the milestone of this project.
We will address this by the combination of in vitro electrophysiology with multiomics approaches. First, a precise mapping of epileptic activities on the cortical slice with micro electrode arrays will allow us to delineate the epileptic focus and to perform microdissections of the tissue. Ex vivo pharmacological studies will dissect the modulation of neural activity in response to the manipulation of the WNK-SPAK/OSR1 pathway that regulate chloride cotransporters. Second unbiased comparison of epileptic areas to non-epileptic areas through proteomics and single cell transcriptomics have the potential to reveal molecular networks dysregulated in response to the PI3K/AKT/MTOR mutations. Eventually, these newly identified druggable targets will be tested in vitro on the cortical slices from operated patients.
Altogether translation of this research project onto clinical practice paves the way to personalized medicine in epilepsy surgery in the coming years.
The “Translational Research for Neurological Disorders laboratory focuses on neuronal excitability ranging from Amyotrophic Lateral Sclerosis research headed by Dr Kabashi to epileptic encephalopathies led by Pr. Nabbout and has an expertise in modelling the diseases and experimenting new drugs. Pr. Blauwblomme a neurosurgeon and a scientist is the PI of the DYSCLO project on human postoperative cortical tissues.
The lab hosts an electrophysiology platform and provides close collaboration within IHU Imagine with the proteomic, single cell and imaging platforms.
We are looking for a highly motivated post-doctoral scientist, capable of independence and initiative, yet fully integrated in a teamwork.
The candidate has a track record of research in invitro neurophysiology, ideally in epileptic disorders. Candidates with a background in molecular biology and multiomics approaches are encouraged to apply.
Length of contract
Applications in English including a letter of motivation, a detailed CV, and contacts of referees should be sent to Pr. Thomas Blauwblomme