Job ID: 118115
PhD project: Multimodal profiling of epilepsy onset and progression in preclinical models of cortical malformations
Position: Ph.D. Student
Deadline: 14 April 2024
Employment Start Date: 1 October 2024
Contract Length: 3 years
City: Marseille
Country: France
Institution: Aix-Marseille Université
Department: INMED
Description:
The NeuroSchool PhD Program of Aix-Marseille University (France) has launched its annual calls for PhD contracts for students with a master’s degree in a non-French university. This project is one of the 13 proposed projects. Not all proposed projects will be funded, check our website for details.
State of the art
Brain malformations are a major cause of drug-resistant epilepsy in children and adolescents. Studying the pathophysiological mechanisms that lead to these epilepsies is challenging because malformations are typically diagnosed only after the first seizure. In addition, it is impossible to directly study the pathological changes that occur in the brains of patients and contribute to the onset and progression of epilepsy. Preclinical models are therefore essential for a better understanding of the disease, its onset and progression, and ultimately for improved therapy.
This project will combine electrophysiology to study brain activity and transcriptomics to measure gene expression changes in preclinical models of brain malformations. By correlating epilepsy-associated electrophysiological properties of anatomically identified brain regions with their underlying, spatially resolved, molecular changes, the project aims to 1) gain new insights into the onset and progression of epilepsy and 2) precisely delineate key pathophysiological mechanisms underlying circuit alterations in cortical malformations.
Methods
in vivo and in vitro electrophysiology; transcriptomics; in vivo genetic manipulations to induce MCDs (in utero electroporation); in vivo stereotactic injection of viral vectors to express candidate genes; histology
Expected results
Identification of circuit and molecular changes detectable at different stages of disease progression that may serve as biomarkers or predictors of epilepsy outcome and as potential targets for therapy (some will be tested).
Feasibility
3 murine models with cortical malformations; equipped in vivo setups for head-fixed and freely moving recordings; in-house in vivo imaging facility; project authorization for animal research; ongoing local and international collaborations, including with human epileptologists and geneticists
Expected candidate profile Prior experience with rodent handling and surgeries; in vivo recordings including electrode preparation and stereotactic implantation; histology and microscopy; data analysis; prior experience with bioinformatics and transcriptomics is a plus
Bibliography
Petit, Jalabert et al Ann Neurol 2014; Sahu et al Epilepsia 2019; Plantier et al Cereb Cortex 2019; Hardy, Buhler, Suchkov et al Neurobiol Dis 2023; Vermoyal, Hardy et al Brain 2023 ; Roig-Puiggros et al bioRxiv 2024