M2 internship: Cortical organoids, cortex atlas and trisomy 21: a single-cell multiome study

SFBI; Paris; On-site; EUR 7,800 - 12,000; Part time

Job summary

SFBI is offering an M2 internship in Paris to study cortical organoids, cortex atlas and trisomy 21 using a single-cell multiome approach. The project aims to build an eRegulon-level map of organoid transcriptional regulation and compare with in vivo cortex datasets.

You will integrate data, assess organoid fidelity, and explore regulatory alterations linked to chromosome 21 TFs. The role requires a motivated M2 student in bioinformatics or related field, with strong statistics, programming in R

Qualifications

• M2 student in bioinformatics, computational biology, data science or a related field.
• Strong background in statistics and data analysis.
• Proficiency in R or Python in a Linux environment.
• Experience with single-cell data analysis (Seurat/Signac/Scanpy/ArchR) is a plus.

Responsibilities

• Integrate single-cell multiome data with a cortex atlas and map organoid cells to atlas types and stages.
• Evaluate organoid fidelity by TF expression, enhancer accessibility and target gene expression.
• Characterise trisomy 21-associated regulatory alterations in in vivo datasets and relate to organoid data.
• Contribute to design of future genome-editing and disease-modeling experiments.

Skills

Statistics

R or Python

Linux environment

Single-cell analysis

Gene regulation

Education

M2 in bioinformatics / computational biology / data science or related field

Tools

Seurat

Signac

Scanpy

ArchR

Git

Conda/Docker

Snakemake

Jupyter notebooks

Job description

M2 internship: Cortical organoids, cortex atlas and trisomy 21: a single-cell multiome study

Stage·Stage M2·6 moisBac+5 / Master NeuroDiderot ·Paris (France)internship stipend (gratification)

Description

CONTEXT
The team studies how genetic variation disrupts gene regulatory networks in neurological and neurodevelopmental disorders ( Delahaye-Duriez et al., 2016 Genome Biol ; Dufour et al., 2024 Brain Behav Immun ). Building on open-source datasets, it has assembled a consensus single-cell multiome atlas of the human cortex. The atlas covers 8 public studies, 144 donors from 6 post-conception weeks to 60 years, and more than 1 million nuclei. It is summarised as eRegulons: a transcription factor (TF), its enhancers and its target genes, per cell type and developmental stage. In the CORTEXSCOPE project, the atlas is used to interpret non-coding variants in neurodevelopmental disorders, and the best candidates will be validated by genome editing in iPSC-derived cortical organoids. However, organoid fidelity has mostly been assessed on the transcriptome, not on gene regulation. Before editing an enhancer, one must know whether the organoid reproduces the relevant cell type, stage and eRegulon.
Trisomy 21, the leading genetic cause of intellectual disability, provides a benchmark. It increases the dosage of several chromosome 21 TFs (OLIG2, RUNX1, ERG, ETS2, GABPA, BACH1, SIM2), and should therefore shift identifiable regulatory programmes, both in vivo ( Lattke et al., 2026 Nature Medicine ) and possibly in organoids (GEO GSE305145 ).

OBJECTIVES

This internship will establish an eRegulon-level map of what cortical organoids capture of human cortical gene regulation, and use it to assess which trisomy 21-associated alterations observed in vivo can be studied in organoids. The student will:

1. Integrate single-cell multiome data (RNA and chromatin accessibility from the same nucleus) of cortical organoids, from public and/or in-house datasets, with the reference atlas, and map organoid cells onto atlas cell types and developmental stages.
2. Evaluate the fidelity of each eRegulon in organoids (TF expression, accessibility of its enhancers, expression of its target genes) and produce a map of the cell types, stages and regulatory programmes that organoids faithfully reproduce.
3. Characterise trisomy 21-associated regulatory alterations in two in vivo datasets: fetal cortex between 10 and 20 PCW (15 trisomic fetuses, 15 controls) and postnatal prefrontal cortex between 0 and 3 years (5 matched pairs, about 221,000 nuclei), with a focus on eRegulons driven by chromosome 21 TFs.
4. Determine which of these alterations fall within the regulatory space that organoids reproduce, in order to guide the design of future genome-editing and disease-modelling experiments.

PROFILE

M2 student in bioinformatics, computational biology, data science or a related field.

• Interest in biological data analysis and solid background in statistics.
• Proficiency in R or Python in a Linux environment.
• Prior experience in single-cell analysis (Seurat, Signac, Scanpy, ArchR) is a plus.
• Interest in gene regulation and neurodevelopment.
• Knowledge of reproducible-research tools (Git, Conda/Docker, Snakemake, Jupyter notebooks) desired.