Phd On Muscle Cell Fusion (M/W)

Universities and Institutes of France
September 30, 2022
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Offerd Salary:Negotiation
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Contract Type:Temporary
Working Time:Full time
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  • Organisation/Company: CNRS
  • Research Field: Biological sciences › Biology
  • Researcher Profile: First Stage Researcher (R1)
  • Application Deadline: 30/09/2022 23:59 - Europe/Brussels
  • Location: France › LYON 08
  • Type Of Contract: Temporary
  • Job Status: Full-time
  • Hours Per Week: 35
  • Offer Starting Date: 01/11/2022
  • The doctorate degree will be pursued in the team of Fabien Le Grand within the UMR 5261 of the NeuroMyoGene Institute in Lyon (France). The laboratory is located on the 3rd floor of the Faculty of Medicine Lyon-Est. It gathers 12 research teams which have access to internal technical platforms. The research project is a collaboration with the iGReD (UMR 6293 Clermont-Ferrand) and MéLiS (UMR 5284, Lyon) laboratories. The student will have the opportunity to work in both environments.

    Skeletal muscles are composed of multinucleated myofibers formed through the fusion of muscle progenitor cells during development and postnatal growth. In the adult, cell fusion is crucial for muscle regeneration after injury, and it relies on the action of satellite cells, the adult muscle stem cells (MuSCs) that form myoblasts and differentiating myocytes. We recently demonstrated that TGFβ (SMAD2/3-dependent) signaling acts as a molecular brake on muscle fusion during mouse muscle regeneration (PMID: 33531466). The goal of the PhD prject is to identify effectors mediating the inhibitory effect of TGFβ signaling on myoblast fusion. To this aim, the applicant will undertake a multi-level, genome-wide approach on primary myocytes derived from FACS-sorted MuSCs. He/she will perform RNA-sequencing of myocytes with gain- of-function and loss-of-function for TGFβ signaling. Then, he/she will use GO and KEGG gene annotation schemes to identify significant co-clustering of genes with similar functional properties. Finally pathway enrichment analysis and visualization will be performed using g:Profiler, GSEA, Cytoscape and EnrichmentMap. The result of these approaches will provide a gene signature of muscle cells exposed to TGFβ signaling. In addition, direct targets of TGFβ signaling will be identified by CUT&TAG to analyze the binding of SMAD2/3 to DNA throughout the genome. Candidate genes that display expression patterns compatible with a role in myoblast fusion will then be functionally tested in vitro using confocal microscopy. In summary, this project will characterize novel aspects of the machinery regulating MuSC fusion through the identification of novel molecules and the characterization of their function during this process.

    Web site for additional job details

    https: // emploi.cnrs.fr/Offres/Doctorant/UMR5261-FABLEG-010/Default.aspx

    Required Research Experiences
  • RESEARCH FIELD
  • Biological sciences

  • YEARS OF RESEARCH EXPERIENCE
  • None

  • RESEARCH FIELD
  • Biological sciences › Biology

  • YEARS OF RESEARCH EXPERIENCE
  • None

    Offer Requirements
  • REQUIRED EDUCATION LEVEL
  • Biological sciences: Master Degree or equivalent

  • REQUIRED LANGUAGES
  • FRENCH: Basic

    Contact Information
  • Organisation/Company: CNRS
  • Department: Pathophysiologie et génétique du neurone et du muscle
  • Organisation Type: Public Research Institution
  • Website: https: // pgnm.inmg.fr/le-grand/
  • Country: France
  • City: LYON 08
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