JobPostdoctoral researcher (M/F), pathological mechanisms and therapies in murine models of epileptic encephalopathies: in vivo electrophysiology, silicon probes, neuropixels, behavior, pharmacology

About

Job title: Postdoc(M/F), pathological mechanisms and therapies of murine models of epileptic encephalopathies: in vivo electrophysiology, silicon probes neuropixels, behavior, pharmacology.
Reference: UMR7275-MASMAN-017
Number of Positions: 1
Workplace: VALBONNE
Publication date: Tuesday, December 17, 2024
Contract type: Researcher on a fixed-term contract
Contract duration: 12 months
Expected start date: March 1, 2025
Workload: Full
Salary: Between €3,021 and €4,208 gross per month depending on experience
Desired level of study: Doctorate
Desired experience: 1 to 4 years
CN Section(s): 25 – Molecular and Cellular Neurobiology, Neurophysiology

Missions

Postdoctoral researcher (initial 1-year contract renewable up to 4 years) responsible for the design, execution, and analysis of experiments within the framework of research projects on models of developmental and epileptic encephalopathies (DEEs). DEEs are serious conditions characterized by drug-resistant epileptic seizures, cognitive/behavioral deficits, movement disorders, and mortality, often due to sudden unexpected death in epilepsy (SUDEP). The team is expert in the study of murine models of these pathologies (Capitano et al. 2024 PNAS https://doi.org/10.1073/pnas.2316364121; Guerrini et al 2023 Physiological Reviews 103(1):433) https://doi.org/10.1152/physrev.00063.2021; Rusina et al. 2023 J.Neurochemistry https://onlinelibrary.wiley.com/doi/10.1111/jnc.15947; Mantegazza et al., 2021, Physiological Reviews, 101(4):1633 https://doi.org/10.1152/physrev.00025.2020).
The general objectives of the research project are to study knock-out and knock-in mouse models of genetic variants that cause different DEEs in patients (Kcna2, Kcnb1 and Scn1a genes) for:
1) Characterize the epileptic and behavioral phenotypes of mice (a line will be generated for the project) with ECoG/LFP electrophysiological recordings and behavioral tests.
2) Gain a better understanding of pathological mechanisms at the level of neural networks using chronic recordings with Neuropixels silicon probes (https://www.neuropixels.org/): large-scale neuronal recordings in multiple brain regions (up to 5126 electrodes) with single-cell resolution. This technique allows for the characterization of the activity of hundreds of individual neurons during normal or pathological behaviors (behavioral tests, epileptic seizures, etc.). The results will be integrated into a computational model developed by collaborators to reconstruct brain activity from that of individual neurons.
3) Testing the effect of pre-clinical treatments on epileptic activity, single-unit neuronal activity (see point 2) and on cognitive/behavioral deficits in mice: we will test small molecules and antisense oligonucleotides (ASOs) selected by collaborators using zebrafish models and human neurons differentiated from iPSCs.
The project is part of the RHU Innov4ePiK network, which brings together 11 academic and industrial partners (https://www.institutimagine.org/fr/innov4-epik-approches-diagnostiques-et-therapeutiques-innovantes-dans-les-encephalopathies-1679). The postdoc will work within a multidisciplinary team and in a scientifically stimulating environment, interacting with project collaborators (computer modelers, clinicians, pharmacologists). They will be able to use the numerous techniques available within the team and the institute and will also contribute to the development of new techniques.

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