Job ID: 121516

Pathological mechanisms and therapies of mouse models of epileptic encephalopathies: in vivo electrophysiology, silicon probes neuropixels, behaviour, pharmacology.

Position: Post-doctoral Position

Deadline: 26 January 2025

Employment Start Date: 1 March 2025

Contract Length: 1 Year renewable up to 4 years

City: Valbonne

Country: France

Institution: Centre National de la Recherche Scientifique (CNRS)

Department: Institute of Molecular and Cellular Pharmacology (IPMC)

Description:

Applications have to be submitted through the CNRS job market web site:

https://emploi.cnrs.fr/Offres/CDD/UMR7275-MASMAN-017/Default.aspx

Post-doctoral researcher (initial contract 1 year, renewable up to 4 years) in charge of the development, conduct and analysis of experiments in the framework of research projects on models of developmental and epileptic encephalopathies (DEEs). DEEs are severe 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 studying mouse 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 overall objectives of the research project are to study knockout and knock-in mouse models of genetic variants that cause different DEEs in patients (Kcna2, Kcnb1 and Scn1a genes) for:
1) The characterization of epileptic and behavioral phenotypes in mice (a line will be generated for the project) with ECoG/LFP electrophysiological recordings and behavioral tests.
2) Better understanding pathological mechanisms at the level of neural networks through chronic recordings with silicon probes Neuropixels (https://www.neuropixels.org/): large-scale neuronal recordings in several brain regions (up to 5126 electrodes) with individual cell resolutions. The technique allows to characterize 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, unitary neuronal activity (see point 2) and on cognitive/behavioral deficits in mice: we will test small molecules and anti-sense oligonucleotides (ASOs) selected by collaborators using zebrafish models and human neurons differentiated from iPSCs.
The project is integrated into the RHU Innov4ePiK network which brings together 11 academic and industrial partners. The postdoc will work in a multidisciplinary team and in a scientifically stimulating environment, interact with project collaborators (computational neuroscientists, clinicians, pharmacologists). He/she will be able to use the many techniques available within the team and the institute, and will also contribute to the development of new techniques.

Activities

– Chronic electrophysiological recordings in mice (video-ECoG/LFP, Neuropixels) and signal analysis.
– Behavioral tests on mice to quantify cognitive functions, motor skills, social interactions, etc
– Perform experiments with mice such as: stereotactic brain surgery, injections, sampling, labeling, etc.
– Results formatting and statistical analysis.
– Follow-up of the literature and improvement/adaptation of techniques and analyses according to research projects.
– Writing scientific articles.

Skills

– Electrophysiology in vivo (experience with silicon probes is a plus).
– Brain surgery, ideally stereotaxic, placement of electrodes in the mouse brain.
– Know how to perform chronic in vivo experiments in mice.
– Know how to analyze data: statistical analysis, electrophysiological signal analysis.
– Histology, immunohistochemistry.
– Training in animal experimentation and surgery.
– Organizational skills, rigor and method, motivation, autonomy, team player.
– Knowledge of written and oral English.

Work Context

The position is at the Institute of Molecular and Cellular Pharmacology in Valbonne – Sophia Antipolis, France. The IPMC is a joint research unit established between CNRS, Inserm and University Côte d’Azur (250 people, 8000 m2 of buildings). Its 20 research teams benefit from a high-level technological environment in integrative biology, electrophysiology, molecular and cellular biology, imaging, cytometry, biomolecular analysis, functional genomics. In particular, the common technical platforms for animal experiments and the team’s own equipment allow detailed phenotyping of mice. The postdoc will work in the team «Physiopathology of Na+ channels and neuronal excitability» (www.ipmc.cnrs.fr/?page=mantegazza&lang=uk) under the direction of Massimo Mantegazza and Fabrizio Capitano.