Job ID: 111621

Gene therapy and pathological mechanisms of SCN2A mouse models of neurodevelopmental disorders.

Position: Post-doctoral Position

Deadline: 25 June 2023

Employment Start Date: 28 August 2023

Contract Length: 1 year renewable (up to 3 years)

City: Valbonne

Country: France

Institution: CNRS

Department: Institute of Molecular and Cellular Pharmacology

Description:

Research project on neurodevelopmental disorders and epilepsy linked to mutations of the SCN2A gene. Voltage-dependent sodium channel mutations have been implicated in different types of severe neurodevelopmental disorders, including developmental and epileptic encephalopathies (DEEs) (Mantegazza et al., 2021, Physiological Reviews, 101(4):1633; Guerrini et al 2023 Physiological Reviews 103(1):433. Mutations in the SCN2A gene cause a particularly broad phenotypic spectrum. In particular, mutations “loss of function” can cause either DEE or Autism Spectrum Disorder (ASD) without epilepsy, and their differential mechanism is not yet clear. We characterized a murine knock-out model (Lena et al 2019 Scientific Rep. 9:12886), which models «loss of function» mutations. Importantly, our more recent studies have allowed us to identify in vitro a new specific mechanism of SCN2A ASD mutations, and we have generated a knock-in mouse model of one of these mutations that we characterize.
The general objectives of the research project are: 1) to develop treatments by directly targeting the new mechanism that we have identified (including with gene therapy approaches) or by targeting the loss of function more generally; 2) test the effects of treatments on mouse phenotype, comparing knock-in and knock-out models.

Activities

– Gene therapy in mice: intracerebral injections of AAV viral vectors
– Pharmacological treatments in mice.
– Mouse behavioural tests to quantify cognitive functions, motor skills, social interactions (including Live Mouse Tracker), etc.
– Perform interventions in mice such as: cerebral stereotactic surgery, injections, sampling, marking.
– Chronic video-EEG recordings in mice and signal analysis.
– Formatting of results and statistical analysis.
– Literature monitoring and improvement/adaptation of techniques and analyses according to research projects.

Skills

– Behavioral experiments in mice.
– Brain surgery, including stereotactic surgery and virus injection in mice.
– Data analysis: statistical analysis, signal analysis (EEG).
– Training in animal experimentation and surgery.
– Organizational skills, rigor and method, motivation, autonomy.
– Knowledge of written and oral English

Applications must be sent via the official CNRS Work Market web site:

https://emploi.cnrs.fr/Offres/CDD/UMR7275-MASMAN-011/Default.aspx?lang=EN