Postdoctoral position - epigenetic regulation of neuronal fate specification (m/f)

About us

Premier pôle européen de recherche, de soins et d’enseignement sur les maladies génétiques créé en 2007 au cœur du campus de l’Hôpital Necker-Enfants malades. Sa mission ? Mieux comprendre les maladies génétiques pour mieux les guérir.

L’Institut Imagine est un endroit unique au monde qui rassemble chercheurs, patients, médecins et personnels de santé dans une architecture créatrice de synergies au service d’une même ambition : changer la vie des familles touchées par les maladies génétiques.


Mission

Host institution: Developmental Brain Disorders laboratory (team V. Cantagrel), Institut Imagine, Hôpital Necker-Enfants Malades, Paris, France

Contact: Marion Coolen

Funding: ANR (Agence Nationale de la Recherche)

Position type: Full-time postdoctoral fellowship Duration: 2 years

Application deadline: Open until filled

Starting date: To be defined (Summer-Fall 2026)




Scientific context :

The proper functioning of the human nervous system relies on the precise generation of diverse neuronal types during development. Disruptions in this tightly regulated process are linked to neurodevelopmental disorders (NDDs). Neuronal fate specification is orchestrated by networks of transcriptional regulators that not only activate lineage-specific programs but also actively repress alternative cell fates. While activation mechanisms have been extensively studied, the molecular basis of transcriptional repression remains comparatively poorly understood, particularly how multiple layers of epigenetic regulation, including DNA and histone modifications and chromatin accessibility, interact and cross-talk.

To tackle this question, the project focuses on PRDM13, a repressor of alternative neuronal fates, whose mutations cause Pontocerebellar Hypoplasia type 17 (PCH17), a rare and severe NDD1. PRDM13 belongs to the PRDM family of chromatin regulators, known to function as sequence-specific chromatin remodelers either directly or via interactions with other epigenetic modifiers. Previous studies have shown that PRDM13 is essential for the commitment of progenitor cells to a GABAergic fate by repressing glutamatergic programs in the cerebellum and spinal cord2,3. These findings suggest that PRDM13 functions as a sequence-specific epigenetic gatekeeper of cell fate decisions. By combining genomics and interactomics approaches in developmentally relevant human iPSC-derived organoid models of the cerebellum and spinal cord4,5, the project aims to uncover the chromatin-modulating activity of PRDM13, define its DNA-binding specificity, and understand how its function is tuned across cellular contexts.

1. Coolen, M. et al. Recessive PRDM13 mutations cause fatal perinatal brainstem dysfunction with cerebellar hypoplasia and disrupt Purkinje cell differentiation. Am. J. Hum. Genet. 109, 909–927 (2022).

2. Mona, B. et al. Repression by PRDM13 is critical for generating precision in neuronal identity. eLife 6, e25787 (2017).

3. Ma, Z. Z., Hale, M. A., Mona, B., Uruena, A. & Johnson, J. E. PRDM13 is required for specification of PAX2 lineage inhibitory neurons in the developing cerebellum. Dev. Biol. 527, 17–25 (2025).

4. Duval, N. et al. BMP4 patterns Smad activity and generates stereotyped cell fate organization in spinal organoids. Dev. Camb. Engl. 146, dev175430 (2019).

5. Rondon, R. et al. Dual transcriptional activities of PAX3 and PAX7 spatially encode spinal cell fates through distinct gene networks. PLoS Biol. 23, e3003448 (2025).




Project & Missions :

The recruited postdoc researcher will be a central role in the project and will be involved in the following activities:

* Develop and characterize human iPSC-derived cerebellar and spinal cord organoid models (wild-type and mutant) ;

* Design and perform multi-omics experiments (scRNA-seq, scATAC-seq, CUT&RUN/CUT&TAG or ChIP-seq) ;

* Analyze transcriptomic and epigenomic datasets to map PRDM13 chromatin binding and activity ;

* Integrate multi-omics datasets to uncover the epigenetic mechanisms downstream of PRDM13 and their impact on cell fate specification ;

* Contribute to the dissemination of results through publications in peer-reviewed journals and presentations at international conferences.


Profile


Required qualifications :

* PhD in neuroscience, epigenetics, developmental biology, or a related field (obtained or to be obtained before the start date) ;

* Solid background in epigenetics and/or neural development ;

* Hands-on experience with transcriptomic and/or epigenomic approaches (e.g., RNA-seq, ChIP-seq, ATAC-seq, CUT&TAG) ;

* Proficiency in bioinformatic analysis of high-throughput sequencing data ;

* Experience with iPSC-derived cellular models (neural differentiation, organoids) is a plus ;

* Strong motivation and proactive attitude ;

* Excellent collaborative and communication skills, with an ability to work in an inter-laboratory environment ;

* Proficiency in English (written and oral); French is not required.




Work environment :

Institut Imagine is one of Europe's leading research institutes dedicated to genetic diseases, embedded within the Hôpital Necker-Enfants Malades campus in Paris. The successful applicant will benefit from:

* Access to cutting-edge genomics, single-cell and imaging platforms ;

* Close interactions with clinical teams specialized in rare neurodevelopmental disorders ;

* Integration within the active young researchers community at Imagine ;

* An active collaborative network within the vibrant scientific community in the heart of Paris.

The project is developed in close collaboration with Vanessa Ribes and Stéphane Nédélec’s team at Institut Jacques Monod, providing complementary expertise in spinal cord development, functional genomics and cell fate regulation, as well as with Souhila Medjkane’s group (Epigenetics and Cell Fate Unit, EDC), contributing expertise in epigenetics and biochemical approaches.




Application :

Please send the following documents (merged into a single PDF) :

* A cover letter describing your motivation and how your background fits the project (max. 1 page) ;

* A detailed CV including a list of publications ;

* Contact details of 2–3 references (referees may be contacted directly).

Institut Imagine is committed to equal opportunity and diversity in its recruitment processes. We strongly encourage applications from all qualified candidates regardless of gender, nationality, or background.