Mots-Clés
disease severity
disease progression.
pipeline
Multiple sclerosis
Progression
GWAS
HLA
Description
Master 2 Research Internship: “From MS genetics to remyelination: investigating the RARβ locus” ( Bioinformatics, Genetic Immunoepidemiology, Public Health)
Scientific context: Recent genome-wide association studies have identified genetic variants associated not only with susceptibility to multiple sclerosis (MS), but also with substantial inter-individual differences in disease severity and progression. Among the most compelling signals, variants within the RARβ (RARB, Retinoic Acid Receptor Beta) locus have been associated with MS severity in European populations and, more recently, with MS susceptibility in multi-ancestry genetic studies.
However, the biological mechanisms linking these variants to MS remain unknown. Genetic variation within RARB may affect gene expression, alternative splicing or isoform-specific transcription, potentially influencing oligodendrocyte biology and remyelination.
Resource : This project will leverage a unique French and international research environment combining complementary genetic and clinical resources from REFGENSEP, the International Multiple Sclerosis Genetics Consortium (IMSGC) and the French Multiple Sclerosis Registry–High Definition (OFSEP-HD).
OFSEP-HD provides access to deeply characterised MS patients with longitudinal clinical, biological and imaging data, together with genome-wide genetic information generated using the Affymetrix Precision Medicine Research Array and subsequent genotype imputation.
The Master 2 project : The objective is to develop a bioinformatic pipeline to investigate populational evidence; whether genetic variation within the RARβ locus (as a paradigmatic example) and biologically related pathways contributes to differences in:
The student will perform targeted bioinformatics and statistical genetic analyses of biologically selected SNPs, building upon previously published genome-wide association results and multivariate genotype–phenotype association models. Particular attention will be given to the integration of: clinical severity and progression phenotypes; patient-specific characteristics; genetic and ancestral background; functional annotation of candidate variants.
Deliverable :The project will result in the prioritisation of candidate genetic variants and genetic profiles/load for subsequent functional investigations. These analyses will provide the foundation for future genetically stratified studies using patient-derived cellular models, including iPSC-based approaches, to investigate the effects of selected variants on RARβ expression, alternative splicing and oligodendrocyte/remyelination biology.
Training environment and supervision : The student will be embedded within a multidisciplinary environment at the interface of: statistical genetics · bioinformatics · multiple sclerosis research · precision medicine · clinical data science
The project will benefit from access to established French and international MS genetics networks and large-scale genomic and clinical datasets.
Supervision: Prof. Pierre-Antoine Gourraud; Dr Nicolas Vince
Dr Sonia Bourguiba; Dr Wojciech Krezel (IGBMC) in collaboration with the French and international MS genetics research networks, including REFGENSEP, OFSEP-HD and IMSGC.
Candidate profile: We are looking for a highly motivated Master 2 student with a background in bioinformatics, statistical genetics, computational biology, genomics or data science applied to biomedical research. Experience with R/Python, genetic association analyses or large biomedical datasets would be an advantage.
Expected start: 2026–2027 academic year Location: CR2TI research Unit Nantes, France