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Team 3: Functions and mecanisms of thyroid hormones receptors (Sachs)

by Administrateur - published on , updated on

In all multicellular organisms, homeostasis relies on the integration of all physiological functions. Thyroid hormones are an essential component of these regulatory systems and control a very diverse set of cellular processes, ranging from mitosis and apoptosis, to metabolism, growth and development. We use amphibian metamorphosis, which is controlled by thyroid hormones, to decipher the corresponding regulatory programs and describe the complexity of their interaction/integration with other signals. Indeed, metamorphosis also integrate environmental factors, which can be linked to stress and are mediated in part by glucocorticoids.

Our scientific objectives are:

  1. Characterize the genomic action of thyroid hormones and glucocorticoids (at the transcriptome, interactome and epigenome levels),
  2. Compare the diversity of regulatory networks induced by thyroid hormones during different modes of post-embryonic development through comparative molecular approaches in amphibians (Anurians, netotenic amphibians and direct developer).

To this end, we heavily rely on the combined use of physiology, molecular biology and functional genomics. The integration of these complementary datasets is at the corner piece of modern physiology and is the methodological and conceptual framework of our approach. The characterization of the transcriptional regulation programs induced by thyroid hormones and glucocorticoids and the molecular mechanisms controlling them will provide new light on how these two endocrine systems control cell fate (and thus morphogenesis) during metamorphosis.

Given the ancestral origin of the post-embryonic remodeling controlled by thyroid hormones and glucocorticoids in chordates, the impact of our results is not limited to Xenopus biology but are also of interest in medical biology and ecology:

  • amphibian metamorphosis is a model to understand the functional impact of interference between signaling pathways, in response to environmental signals or exposure to exogenous compounds (clinical treatments/pharmacology, toxicology),
  • amphibian metamorphosis also allows us to probe the role of thyroid hormones at different scale, through their action on gene expression regulation, adaptation and biodiversity.

Methodologies: in vivo gene transfer, real time PCR, functional genomics (RNA-Seq, RNA-PET, PE-RNA-Seq, ChIP-Seq, ChIA-PET), structural genomic (DNA-PET), Bioinformatic.



Staff:
Team leader
Laurent Sachs, DR CNRS
laurent.sachs@mnhn.fr
01.40.79.36.04

Permanent staff
Assistant professor
Nicolas Buisine, MC MNHN

Temporay staff
Researchers, Engineers
Vincent Jonchère, IR CNRS
Gwenneg Kervidel, post-doc MNHN