Le groupe Mitochondries et NDD est à la recherche d’un postdoctorant. Découvrez l’opportunité et postulez ici !
Postdoctoral position in the field of Neurosciences
Type of contract: temporary position (CDD)
Contract/project period: 1-2 years
Expected date of employment: 1.04.2025
Proportion of work: 100%
Workplace: Université Paris Cité, Inserm, NeuroDiderot, F-75019 Paris, France
Desired level of education: PhD
Experience required: The candidate should have knowledge in biology / health sciences / neurosciences and mitochondrial function, and good experience of working with mouse models. He/she should have expertise in setting up phenotypic evaluations using behavioral approaches for testing memory, stress, movement coordination and muscular strength in mouse models.
Contact(s) for information on the position (identity, position, e-mail address, telephone):
Marisol Corral-Debrinski (PhD, HDR)
Leader of the team: “Involvement of mitochondrial dysfunction in neurological diseases and the development of mitochondrial therapies” in the NeuroDev group of the NeuroDiderot Laboratory (https://neurodiderot.u-paris.fr/en/)
Address: Hôpital Robert Debré, 48 Boulevard Sérurier 75019, Paris
Phone: +33 (0) 1 40 03 19 45 & +33 (0) 6 60 95 12 73
Email: marisol.corral@inserm.fr
Research project
The research project has the ultimate objective of implementing a treatment, via gene therapy, which effectively and durably preserves the functional integrity of mitochondria within the neurons of preclinical models of neurological diseases. We have demonstrated that the neuroglobin protein localizes to mitochondria and that its neuroprotective properties rely on its ability to preserve mitochondrial homeostasis in the retina, optic nerve and cerebellum (Harlequin mice).
The current project has two main objectives: a) understand the mitochondrial involvement in the degeneration of the cerebellum of Atxn1154Q/2Q mice which suffer from spinocerebellar ataxia type 1, due to the introduction of 154 CAG repeats in the Atxn1 gene; b) develop an AAV2/9-mediated gene therapy, using an intravenous route to induce the overexpression of the neuroglobin gene aimed at protecting the cerebellum and thus reducing the ataxic phenotype of these mice.
Activities
Description of the research activities:
The postdoctoral fellow will have the mission to pursue the studies of Atxn1154Q/2Q mice initiated in February 2024. The research project is financed since 2020 as a strategic project by the AFM-Telethon association. The final objective is to consolidate the proof-of-principle that the neuroglobin is a promising candidate to develop clinical studies on patients suffering from spinocerebellar ataxia by operating through the International Application No. PCT/EP2023/068369.
The candidate will be responsible for conducting: (i) Intravenous administration of AAV2/9 vectors in the retro-orbital sinus of 1-month-old Atxn1154Q/2Q mice and their wild-type counterparts; (ii) behavioral studies, in a longitudinal protocol to monitor the evolution of the pathology over time in treated and untreated mice. These two aspects of the project are performed in the PHENO-ICMice Platform of the Paris Brain Institute; (iii) post-mortem studies in cerebellum and hippocampus, 6 months after gene therapy, are carried-out in the NeuroDiderot laboratory of the Robert Debré Hospital. They encompass immunohistochemistry and biochemical studies (spectrophotometry of respiratory chain enzymes). The recruited candidate will work in close collaboration with the project’s partner teams (ultrastructural and omics studies), and the study should lead to publications in high-impact international journals.
Related activities: The selected candidate will have the opportunity to participate of the overall activities of the NeuroDiderot laboratory and to work in a multi-disciplinary environment dedicated to understanding the mechanisms that disrupt brain functioning.
Skills
Qualifications/knowledge:
Ph.D. in Biology/Neurosciences
Operational skills/expertise:
– Experience with mouse models;
– Thorough evaluation of collected behavioral / biochemical / morphological data;
– Track record of research and publications in scientific journals and international conferences.
Personal qualities: Self-driven and highly motivated to work in an interdisciplinary team.
Environment and context of work
Presentation of the laboratory/unity: NeuroDiderot laboratory includes multidisciplinary teams with over of 150 researchers committed to pushing the boundaries of knowledge and making a positive impact on the lives of individuals affected by neurological conditions. The NeuroDev group, of which Dr. Corral-Debrinski is a member, combines experts in experimental and clinical research in the field of neurodevelopmental and neurodegenerative disorders. Brain formation in mammals requires a series of developmental sequences. Altering these sequences through genetic mutations or environmental insults leads to lifelong neurological and psychiatric disorders. Besides later in live, neurodegenerative diseases could also result from perturbations in developmental sequences and/or the impairment of brain maintenance. Mitochondrial integrity throughout life is essential for maintaining a healthy brain. Over the past decades, an emerging role for mitochondrial dysfunction and altered energy metabolism has been associated to the pathogenesis of an array of neurodegenerative and neurodevelopmental diseases. This can be explained by the high energy requirements of neurons, resulting in their dependence on functional mitochondria for their integrity.
In light of these facts, the main objective of Dr. Corral-Debrinski’s research project is appropriate in regards of the unsatisfied medical needs for neurological handicaps such as cerebellar ataxias. Gene therapy mediated by an AAV2/9 vector harboring the neuroglobin coding sequence will effectively and permanently preserves mitochondrial homeostasis of cerebellar neurons regardless the mutation responsible for tissue degeneration. Thus, the proof-of principle sought in Atxn1154Q/2Q mice will strengthen research hypothesis and open the way to design a clinical study with the neuroglobin.
Hierarchical relationship
The selected candidate will be part of the NeuroDev research group, under the direct supervision of Dr. Marisol Corral-Debrinski, head of the NEUROGLOBIN & NEUROPROTECTION team.
Special conditions of practice (notice attached): The team has access to the PHENO-ICMice Platform (Brain Institute), and within the NeuroDiderot lab to the imaging platform but also to the HumBO and Neuroinflammation services if the progress of the project requires it.
The recruited post-doc will collaborate with our long-established partners from: the Neonatal Research Group of the Health Research Institute La Fe (Valencia, Spain) and the Université de Paris, UMR-S 1144 Inserm, Platform of Cellular and Molecular Imaging (Paris) and since more recently with the Research Group in Alzheimer Disease, Health Research Institute La Fe (Valencia, Spain).
Recent Publications
1. H. Cwerman-Thibault, V. Malko-Baverel, G. Le Guilloux, I. Torres-Cuevas, E. Ratcliffe, D. Mouri, V. Mignon, B. Saubaméa, O. Boespflug-Tanguy, P. Gressens, M. Corral-Debrinski. Biochim Biophys Acta Mol Basis Dis (2024) 17:167272. DOI: 10.1016/j.bbadis.2024.167272.
2. H. Cwerman-Thibault, V. Malko-Baverel, G. Le Guilloux, E. Ratcliffe, D. Mouri, I. Torres-Cuevas, I. Millán, B. Saubaméa, V. Mignon, O. Boespflug-Tanguy, Pierre Gressens, Marisol Corral-Debrinski. Mol Ther. 2024: S1525-0016(24)00332-0. DOI: 10.1016/j.ymthe.2024.05.030.
3. H. Cwerman-Thibault, C. Lechauve, V. Malko-Baverel, S. Augustin, G. Le Guilloux, É. Reboussin, J. Degardin-Chicaud, M. Simonutti, T. Debeir, M. Corral-Debrinski. Neurobiol Dis. (2021) 159: 105483. DOI: 10.1016/j.nbd.2021.105483.
To apply, please send your CV and a cover letter to: marisol.corral@inserm.fr