The Team
  • Researchers

    Nicolas CHARLET BERGUERAND

    Chantal SELLIER

  • PhD Students

    Manon BOIVIN

    Camille CORBIER

  • Engineers & Technicians

    Véronique PFISTER

  • Master

    Nacima CHILA

Translational medicine and neurogenetics

RNA diseases

Studies in our group are focused on how expanded repeats located in the “non-coding” parts (5’UTR, introns, 3’UTR, etc.) of the genome lead to human genetic diseases. We are mainly interested in three genetic diseases:

  • Myotonic Dystrophies (DM), the most common muscular dystrophy in adults is caused by expanded CTG repeats located in the 3’UTR of the DMPK gene.
  • Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) is a rare neurodegenerative disorder due to expanded CGG repeats in the 5’UTR of the FMR1 gene.
  • Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (ALS-FTD) is the third neurodegenerative disease worldwide. The most common genetic cause of ALS-FTD is an expansion of GGGGCC repeats in the first intron of the C9ORF72 gene.

These expanded repeats (CTG, CGG, GGGGCC, etc.), located in the “non-coding” parts of the genes, are pathogenic by diverse mechanisms, such as expression of pathogenic RNA repeats that sequester specific RNA binding proteins and/ or non-canonical translation of the expanded repeats in absence of any ATG start codon.

 

Our goals are to (1) elucidate the molecular causes of these diseases, (2) establish relevant cellular (iPS, neurons, muscle cells, etc.) and rodent (mouse and rat) models of these diseases and (3) identify drugs able to correct pathogenicity in these models. To achieve these goals, we developed a wide range of technique and approaches from biochemistry with protein purification and functional analysis, Omics and bioinformatics (large scale transcriptomic, splicing, genomic and proteomic analyzes), cell biology (primary human muscle cell culture, iPS from patients, primary mouse neuronal cultures, etc.) and transgenic or knockout mouse and rat animal models.

 

Our most recent achievement are the identification of the molecular causes of skeletal muscle and cardiac dysfunctions in individuals with Myotonic Dystrophies (Fugier et al., Nature Medicine, 2011; Rau et al., Nature Structural and Molecular Biology, 2011; Freyermuth et al., Nature Communication, 2016), the clarification of the mechanisms underlying FXTAS and translation of CGG repeats translation in absence of any ATG codon (Sellier et al., EMBO J. 2010; Sellier et al., Cell reports, 2013; Sellier et al., Neuron, 2017) and the study of the molecular and cellular functions of the C9ORF72 protein complex in the regulation of autophagy (Sellier et al., EMBO J. 2016).

 

Overall, our work clarified the molecular and cellular causes of neuronal and muscular cell dysfunctions in these inherited disorders, but also provides novel cell and animal model to develop innovative therapeutic approaches for these devastating diseases.  

Imprimer Envoyer

Université de Strasbourg
INSERM
CNRS

IGBMC - CNRS UMR 7104 - Inserm U 1258
1 rue Laurent Fries / BP 10142 / 67404 Illkirch CEDEX / France Tél +33 (0)3 88 65 32 00 / Fax +33 (0)3 88 65 32 01 / directeur.igbmc@igbmc.fr