Post Doc - D.Metzger Team
Reference : IGBMC / POST DOC
Offer publication : Dec. 18, 2020
Post-doctoral position at the Institute of Genetics and Molecular and Cellular Biology (Illkirch, France) in the laboratory of Daniel Metzger
Project: “Characterization of Lsd1 function
in glucocorticoid-induced muscle atrophy”
Aim of the project. Glucocorticoids are the most prescribed compounds for inflammatory diseases, including asthma and arthritis. However, long-term treatments are limited by adverse effects, such as diabetes and muscle wasting. Glucocorticoids effects are mediated by the glucocorticoids receptor (GR), a member of the ligand-dependent nuclear receptor superfamily. Recent data obtained in the lab show that levels of the histone demethylase Lsd1 increase upon glucocorticoid-induced muscle wasting, and that Lsd1 interacts with GR in skeletal muscle, indicating that Lsd1 acts as a coactivator of GR to promote muscle catabolism. In line with this hypothesis, we found that myofiber Lsd1 is required for the induction of proteolysis-related genes upon starvation. Therefore, the current project aims at determining whether GR activity can be modulated by targeting its tissue-specific co-regulators. The fellow’s tasks will be to identify the role of Lsd1 in muscle fibers in basal conditions and in glucocorticoid-induced muscle atrophy, and to determine whether an Lsd1 inhibitor can reduce muscle wasting. He/she will also characterize the associated epigenetic landscape using cutting-edge technics. Our team has recently developed several projects based on genome-wide characterization of transcription factor cistromes and transcriptomes in various tissues of genetically modified mice, thereby providing the unique opportunity to decipher the in vivo mode of action of nuclear receptors. Overall, this study should clarify the role of Lsd1 in muscle fibers and open new avenues to counteract glucocorticoid-induced side effects.
The project is funded by an ANR grant awarded to Dr. Duteil, and will be developed at the Institute of Genetics and Molecular and Cellular Biology (IGBMC), the largest French academic research unit, involving INSERM, CNRS and Strasbourg University. The institute develops interdisciplinary research at the interface of biology, biochemistry, physics and medicine, hosts state-of-the art scientific services and technological platforms, and attracts fellows from around the world by offering high-level education in biomedical sciences. IGBMC is located at the “Parc d’Innovation d’Illkirch”, an exceptional scientific, academic and industrial environment next to Strasbourg.
We offer a 2-year contract, starting 1st quarter 2021, with the possibility of extension. Remuneration and social benefits will be based on the CNRS agreement for public-sector employees. The applicant will be involved in a multidisciplinary group including basic scientists, pathologists and bioinformaticians, integrated in international collaborations. She/he will have access to various technologies to perform this scientific project with high clinical relevance.
Requirements. Applicants should have a PhD in biological science, a strong background in molecular biology with a sound knowledge in transcriptional regulation and chromatin remodeling.
Your responsibilities will include:
Molecular biological assays on tissues of genetically modified mice (ChIP-seq, Atac-seq, imaging, …)
Establishment of genome-wide technics, such as Hi-C and Rapid Immunoprecipitation Mass Spectrometry (RIME), in mouse tissues.
Selected publications of the team:
• Chambon C, et al. 2010. Myocytic androgen receptor controls the strength but not the mass of limb muscles. Proc Natl Acad Sci U S A 107: 14327-14332.
• Duteil D, et al. 2010. The transcriptional coregulators TIF2 and SRC-1 regulate energy homeostasis by modulating mitochondrial respiration in skeletal muscles. Cell Metab 12: 496-508.
• Duteil, D. et al. 2014. LSD1 promotes oxidative metabolism of white adipose tissue. Nat Commun 5, 4093.
• Gali Ramamoorthy T, et al. 2015. The transcriptional coregulator PGC-1beta controls mitochondrial function and anti-oxidant defence in skeletal muscles. Nat Commun 6: 10210.
• Huet T, et al. 2015. A vitamin D receptor selectively activated by gemini analogs reveals ligand dependent and independent effects. Cell Rep 10: 516-526.
• Duteil, D. et al. 2016. Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue. Cell Rep 17, 1008-1021.
• Duteil, D. et al. 2017. Lsd1 prevents age-programed loss of beige adipocytes. Proc Natl Acad Sci U S A 114, 5265-5270.
• Parisotto M, et al. 2018. PTEN deletion in luminal cells of mature prostate induces replication stress and senescence in vivo. J Exp Med 215: 1749-1763.
• Rovito D, et al. 2020. Cytosolic sequestration of the Vitamin D Receptor as a therapeutic option for vitamin D–induced hypercalcemia. Nat Commun 11: 6249.
• Rovito, D. et al. Myofiber transcriptional repertoire driven by collaboration of glucocorticoid receptor, Nrf1 and Myod. Nuclei Acid Research, in revision.
Candidates should send a curriculum vitae with a publication list, a short summary of research achievements and mastered techniques, as well as contact information of at least two references to firstname.lastname@example.org.