Mots-Clés

single cell RNA-seq immunology autoimmune encephalitis translational research

Description

Context

Our group investigates the clinical and immunological aspects of autoimmune encephalitis (AE) and paraneoplastic neurological syndromes (PNS) to uncover and exploit novel therapeutic targets. AE and PNS, which often lead to long-term neurological impairments, are rare neurological diseases associated with autoantibodies targeting intracellular and cell-surface neuronal antigens in serum and cerebrospinal fluid (CSF). Although recent clinical studies have improved our understanding of the natural history and long-term outcomes of AE/PNS, therapeutic options remain scarce. Very little is known about their neurobiology and immunopathology, hindering the development of innovative therapies.
To address this, we aim to characterize the immune cell populations present in patients’ peripheral blood mononuclear cells (PBMCs) and CSF, and to compare their transcriptome profile to controls and other PNS. We have already generated single-cell RNA-seq data from patient samples, together with T-cell and B-cell receptor sequencing (TCR-seq and BCR-seq) to study immune cell clonotypes. Building on our previous work comparing CSF and PBMCs in anti-Yo PNS, we now aim to extend our investigation to anti-NMDAR AE, which affects mostly young women and children and is one of the most frequent subtypes of AE.

Mission

We have generated single-cell RNA-seq, TCR-seq, and BCR-seq datasets from CSF and PBMCs of five anti-NMDAr patients, and the analysis is already underway.
The student will:

• Become familiar with the initial steps of single-cell RNA-seq and repertoire analysis.
• Take responsibility for advancing and completing the analyses.
• Perform comparative analyses with our previously published anti-Yo dataset.

A bioinformatician and a biologist, with additional input from a clinician, will directly supervise the student. The starting date can be changed.
This internship could lead to a PhD project.

Profile

We are seeking a Master 2 bioinformatics student, ideally with experience in:

• R programming
• Linux environment
• High-performance computing environments (Slurm preferred but not required)

Location

The project will take place at the French Reference Centre on Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes, based at the Pierre Wertheimer Hospital in Lyon. We combine genomic, transcriptomic, and epigenetic high-throughput approaches (e.g., DNA-seq, RNA-seq, and related methods) in collaboration with partner teams in the BETPSY project (https://www.rhu-betpsy.fr/).

Bibliography

• Dalmau J, et al. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Lancet Neurol. 2008;7(12):1091-1098.
• Schafflick D, et al. Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis. Nat Commun 11, 247 (2020).
• Cantoni C, et al. A single-cell compendium of human cerebrospinal fluid identifies disease-associated immune cell populations. J Clin Invest. 2025 Jan 2;135(1):e177793.