Information
Team’s presentation:
The group gathers clinicians and scientists in a friendly and collaborative spirit and studies various aspects of movement disorders, such as dystonias, in patients, cells and mouse models. The group is part of the productive and international Mov’it team, working on highly transversal and innovative projects focused on movement disorders. The team is hosted in the Paris Brain Institute, located in the heart of the Pitié-Salpêtrière Hospital in the center of Paris. The ICM is an international leading-edge brain research center providing access to state-of-the-art facilities, including animal and data analysis facilities handling current needs and future developments.
Project:
The project examines the genetics, pathogenesis and therapeutic options of a rare mixed movement disorder linked to the ADCY5 gene (ADCY5-MxMD). This pathology is characterized by generalized hyperkinetic movements (Menon et al., 2023). The most frequent variant responsible for ADCY5-MxMD is a dominant p.R418W missense variant in the ADCY5 gene (Ferrini et al., 2021), resulting in a gain-of-function of the adenylate cyclase 5 (AC5) encoded by this gene (Doyle et al., 2019). We generated a mouse model of ADCY5-MxMD, by inserting the equivalent p.R419W variant in the mouse genome. The Adcy5R419W mice show motor deficits and anxiety-like behaviors, consistent with the human phenotype. The widely used treatment of ADCY5-MxMD – caffeine – (Méneret et al., 2019) restores the motor deficits of these mice. We also demonstrate an increased activation of the striatal cAMP pathway in line with hyperactivity of the mutant AC5.
Mission:
The postdoctoral project aims at refining and completing the study of this ADCY5-MxMD mouse model, as well as investigating new therapeutic options. The team would like to investigate reward learning in these mice, since AC5 is largely expressed in the striatum, a key region for both motor and reward learning behaviors. We want to carry on the characterization of their motor phenotype, beyond the classical behavioral tests already performed. Those behavioral tests will then allow to test pharmacological agents modulating the cAMP pathway, alone or in combination with caffeine, to rescue the motor, and possibly non-motor, deficits of the Adcy5R419W mice.
The position lasts 18 months with possibility for extension.
Profile
- Highly motivated post-doctoral fellow with skills and experience in mouse behavioral study.
- Doctoral degree.
- Proficiency in English.
When / How to apply?
To apply, please send a CV, a motivation letter, and the names of two references to: flamand.roze.75012@gmail.com, caroline.dubaq@sorbonne-universite.fr. The position is open until the candidate is identified.
Recent papers:
Menon PJ, et al. (2023) Scoping Review on ADCY5‐Related Movement Disorders. Mov Disord Clin Pract 10:1048–1059.
Méneret A et al. (2022) Efficacy of Caffeine in ADCY5-Related Dyskinesia: A Retrospective Study. Movement Disorders 37:1294–1298.