Post-doctoral position : Species-specific mechanisms of ADAT dysfunction in cortical development (H/F) (POST-DOC)

Institut de Génétique et Biologie Moléculaire et Cellulaire; Illkirch-Graffenstaden; Sur place; EUR 33 000 - 39 000; Plein temps

Résumé du poste

The Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC) in Strasbourg, France, invites applications for a 30‑month post‑doctoral position focused on species‑specific mechanisms of ADAT dysfunction in brain development. The project uses human iPSC‑based 2D/3D models and mouse ESC derivatives to study translational control in cortical development.

Successful candidates will work in a collaborative, international environment within the SpeaDAT project; expertise in iPSC culture,

Qualifications

• PhD in Cell Biology, Molecular Biology, Developmental Biology, Neuroscience or a related field, recently obtained.
• Experience with human iPSC culture and/or 2D/3D neural differentiation protocols required.
• Proficiency in immunofluorescence, western blot, qPCR and imaging.
• Familiarity with high‑throughput sequencing approaches (RNA‑seq, ribosome profiling) is a plus.
• Strong English communication and ability to work in an interdisciplinary, international setting.

Responsabilités

• Generate and characterize human iPSC and mouse ESC‑derived 2D cortical neural cells and 3D organoids with ADAT variants.
• Assess cellular phenotypes (proliferation, cell cycle, progenitor identity, neuronal maturation) using imaging and labeling.
• Analyze and interpret sequencing data to define species‑specific translational programs.
• Present findings at team meetings and conferences; contribute to manuscript writing and project reporting.
• Collaborate with a bioinformatician and supervise students in the lab.

Connaissances

iPSC culture

neural differentiation

immunofluorescence

western blot

qPCR

imaging

RNA-seq

ribosome profiling

Formation

PhD in Cell Biology, Molecular Biology, Developmental Biology, Neuroscience or related field

Description du poste

Post-doctoral position : Species-specific mechanisms of ADAT dysfunction in cortical development (H/F)

A 30-month post-doctoral position is open at the Institute of Genetics and Molecular and Cellular Biology (IGBMC) in Strasbourg, France.
We are looking for a recently graduated PhD with experience in human iPSC-based 2D and 3D models and interest in translational control of neurodevelopment.

The recruited fellow will join the SpeaDAT project, funded by the French National Research Agency (ANR), on species-specific mechanisms of ADAT dysfunction in brain development, led by Dr. Efil Bayam (CRCN Inserm) within Dr. Juliette Godin's team “Physiological and Pathological Mechanisms of Cortical Development” (https://www.igbmc.fr/equipes/mecanismes-physiologiques-et-pathologique-du-developpement-cortical ) at IGBMC. The Godin lab is recognized for its expertise in translational control during cortical development.
Chemical modifications on different types of RNA species have emerged as critical posttranscriptional modulators of brain development and function. While transfer RNAs (tRNA) are required for translation in all cells, 77% of the pathogenic mutations in transfer RNA (tRNA) modification enzymes manifest as neurodevelopmental disorders (NDDs) suggesting that developing human brain is particularly sensitive to disrupted tRNA modifications. Recently, the team identified the NDD-associated ADAT complex (ADAT2/3), which catalyzes the conversion of Adenine (A) to Inosine (I) at position 34 of 8 ANN-tRNAs, as a regulator of cortical development and showed the pathogenicity of NDD-relevant ADAT mutations.
Surprisingly, despite the profound impact of ADAT dysfunction in humans, mouse genetic models mimicking the ADAT dysfunction displayed no detectable brain phenotype or tRNA alterations suggesting species-specific vulnerability to defects in ADAT complex.
The postdoctoral researcher will investigate species-specific ADAT functions in progenitors and neurons, and characterize the impact of ADAT dysfunction on tRNAs and translational programs, using human iPSC- and mouse ESC- derived models, including 2D cortical neural stem cells, neurons and 3D cortical organoids carrying ADAT2/ADAT3 pathogenic variants.

• Generate and characterize human iPSC and mouse ESC-derived 2D cortical neural stem cells, neurons and 3D cortical organoids carrying ADAT2/ADAT3 pathogenic variants;
• Assess cellular phenotypes (proliferation, cell cycle dynamics, progenitor identity, neuronal maturation, synaptic integration) using immunofluorescence, EdU/pulse-chase labeling and functional assays (MEA, calcium imaging);
• Analyze and interpret human mim‑tRNA‑seq and ribosome profiling data to characterize species‑specific tRNA and translational programs, in close collaboration with a bioinformatician;
• Present research findings at team and consortium meetings and at national/international conferences; contribute to manuscript writing, project reporting, and the supervision of students.
• PhD in Cell Biology, Molecular Biology, Developmental Biology, Neuroscience or a related field, recently obtained. - Experience with human iPSC culture and/or 2D/3D neural differentiation protocols is required as well as proficiency in standard molecular and cell biology techniques (immunofluorescence, western blot, qPCR, imaging).
• Familiarity with high‑throughput sequencing approaches (RNA‑seq, ribosome profiling) is a plus.
• Interest in neurodevelopment, neurodevelopmental disorders and translational control/epitranscriptomics. - Fast learner, autonomous, with strong organizational and communication skills (English, fluent, required), and the ability to work within an interdisciplinary, international consortium.
• Work environment

IGBMC is a joint research unit of Inserm (U1258), CNRS (UMR7104) and the University of Strasbourg, located in Illkirch, Strasbourg. The institute benefits from an outstanding scientific environment with four departments dedicated to genetics, developmental and structural biology, and translational medicine.
The recruited fellow will join Dr. Juliette Godin's team within the Translational Medicine and Neurogenetics department working alongside Dr. Efil Bayam. The team currently comprises four permanent researchers, three postdoctoral researchers, one PhD student, three engineers and two technicians, offering a stimulating and international working environment. The fellow will have access to IGBMC's state‑of‑the‑art technology platforms, including next‑generation sequencing (GenomEast), advanced imaging (Imaging Center of IGBMC), proteomics.

• Salary and benefits

According to the Inserm salary scale for postdoctoral researchers based on experience (€2,940 brut / month for <2 years of experience); full health and social coverage included.

As soon as possible / 30 months

- Del‑Pozo‑Rodriguez et al. ADAT3 variants disrupt the activity of the ADAT tRNA deaminase complex and impair neuronal migration. Brain (2025).
- Ramos‑Morales et al. The structure of the mouse ADAT2/ADAT3 complex reveals the molecular basis for mammalian tRNA wobble adenosine‑to‑inosine deamination. Nucleic Acids Res 49, 6529-6548 (2021).