IJM News since 2010

  • New insights into the polarization of multicellular epithelia

    Multi-ciliated epithelia play an important role in respiratory function. In humans, multi-ciliated cells are particularly needed for respiratory clearance, a mechanism that allows renewing the protective mucus barrier protecting the lungs from pathogens and dust. Disturbances in the function of these cells caused by certain genetic mutations can thus be at the origin of severe respiratory diseases. An international collaboration between two teams form the IJM and the Max Planck Institute in Dresden has highlighted a novel mechanism for controlling the direction of ciliary beat in a multicellular epithelium. Using an invertebrate model, the planarian Schmidtea mediterranea, researchers have shown that the joint action of two conserved signaling pathways can generate a ciliary pattern that reflects the bilateral symmetry of the animal itself. However, the elements of the cytoskeleton on which the polarity signals act to orient the cilia exhibit chiral asymmetry. This work thus allowed to identify new molecular actors in the polarization of multi-ciliated epithelia, but also to understand how the so-called Bilaterian animals, of which we are part, can generate a bilateral symmetry from chiral molecules or structures.

  • Des pincettes en ADN pour étudier l’interaction entre une médicament et sa cible à l’échelle molécule-unique

    L’efficacité d’un médicament est fortement liée au temps que la molécule médicamenteuse passe accolée à sa cible, typiquement une protéine. Bien souvent si l’interaction est de longue durée la drogue aura un effet plus fort que si l’interaction est de courte durée. Une équipe pluridisciplinaire vient de décrire dans la revue Nature Nanotechnology une nouvelle approche à très haute résolution permettant d’observer, en temps réel, l’interaction d’une seule molécule médicamenteuse avec une seule molécule de cible. Cette observation du « quantum » d’interaction moléculaire ouvre de nouvelles perspectives dans le développement des médicaments mais aussi des anticorps thérapeutiques et de la science des matériaux.

  • News from the third branch of humanity, the Denisovans

    A tiny fragment of a finger bone from Denisova cave in Siberia containing exceptionally well preserved DNA led in 2010, through the analysis of its genome, to the discovery of a previously unknown human population, the Denisovans, a sister-group of Neandertals. Denisovans have been documented living in the Middle and Upper Pleistocene (at least between 50,000 and 195,000 years ago) in southern Siberia and Tibet, but have left traces in the genomes of present-day populations in Melanesia and, to a lesser extent, in some populations in Asia. Yet, due to the scarcity of identified skeletal remains, almost nothing is known about their physical appearance. In the framework of an international, interdisciplinary collaboration coordinated by Eva-Maria Geigl, the Epigenome & Paleogenome group of the Institut Jacques Monod measured and photographed another fragment of the phalanx, analyzed its mitochondrial genome and demonstrated that it as the larger part of the famous phalanx that had yielded the first Denisovan genome. Paleoanthropologists from PACEA, University of Bordeaux, and from the Department of Anthropology, University of Toronto, Canada, reconstructed the image of the complete phalanx (Figure) and performed careful morphometric analyses of the measurements and pictures of the phalanx and comparison with finger phalanges of Neandertals and anatomically modern humans. This analysis shows that the finger phalanx of the Denisovan woman is close in shape to that of anatomically modern humans, in contrast to the molars and a recently identified mandible from Tibet. Thus, Denisovans seem to have mosaic characters that may challenge paleoanthropologists searching for Denisovan skeletal remains to better characterize morphologically this “third” branch of humanity.

  • Une stratégie de résistance à un inhibiteur métabolique découverte grâce à la levure

    Les cellules cancéreuses prolifèrent de manière incontrôlée. Ceci s’accompagne d’une capacité accrue à importer les nutriments et à les métaboliser. Le dérivé toxique d’un sucre, le 2-désoxyglucose (2DG), est préférentiellement importé par les cellules cancéreuses et inhibe leur croissance. En utilisant la levure de boulanger comme organisme modèle, les chercheurs ont précisé les effets cellulaires de cette drogue et les mécanismes de résistance associés. Ces résultats sont publiés dans la revue Science Signaling.

  • A multi-faceted enzyme silences repeats in the genome

    In plants and animals, histone proteins bind to DNA and carry different chemical modifications, which can repress the expression of genes or of mobile genetic elements. Sandra Duharcourt’s team characterized the properties of an unconventional enzyme in the unicellular eukaryote Paramecium, which catalyses two distinct silent histone modifications and silences genomic repeats. This work published in Nature Communications reveals that these two modifications share a common ancestral role in keeping silent transposable elements.

  • Le prix Nicloux 2019 a été attribué à Odil Porrua

    La Société Française de Biochimie et Biologie moléculaire a remis le Prix Maurice Nicloux 2019 à Odil Porrua, chargée de recherche CNRS, membre de l'Institut Jacques Monod. Odil Porrua s’intéresse depuis le début de sa carrière à différents aspects de l’expression des gènes. De 2005 à 2009, Odil a effectué sa thèse dans le laboratoire de E. Santero (Espagne) où elle a étudié la régulation de certains gènes impliqués dans la dégradation de molécules contaminantes chez la bactérie.En 2009, Odil a rejoint le laboratoire de Domenico Libri, d’abord au Centre de Génétique Moléculaire (Gif sur Yvette) puis à l’Institut Jacques Monod (Paris) à partir de 2013. D’abord comme post-doc puis comme chercheur CNRS, Odil a conduit plusieurs projets autour du métabolisme des ARN non-codants chez la levure. Notamment par des approches biochimiques et structurales, elle a pu dévoiler les mécanismes de terminaison de la transcription non-codante qui étaient alors très peu connus. Deux ans après avoir obtenu son poste de chercheur CNRS, en 2014, et grâce à un financement ANR JCJC, Odil a abordé l’étude du rôle de la terminaison de la transcription dans la régulation de l’expression de gènes.

  • June 2019 : Chromatin condensation fluctuations rather than steady-state predict chromatin accessibility

    Chromatin accessibility to protein factors is critical for genome activities. However, the dynamic properties of chromatin higher-order structures that regulate its accessibility are poorly understood. Researchers from the team “mechanotransduction: from cell surface to nucleus” took advantage of the microenvironment sensitivity of the fluorescence lifetime of EGFP-H4 histone incorporated in chromatin to map in the nucleus of live cells the dynamics of chromatin condensation and its direct interaction with a tail acetylation recognition domain (the double bromodomain module of human TAFII250, dBD). They revealed chromatin condensation fluctuations supported by mechanisms fundamentally distinct from that of condensation. Fluctuations are spontaneous, yet their amplitudes are affected by their sub-nuclear localization and by competing mechanisms dependent on histone acetylation, ATP and both. Moreover, accessibility of acetylated histone H4 to dBD is not restricted by chromatin condensation nor predicted by acetylation, rather, it is predicted by chromatin condensation fluctuations.

  • March 2019: Is the replication timing control constant through S phase?

    Before each cell division, the full genome has to be entirely and faithfully duplicated thereby each daughter cell inherits the complete genetic information. This duplication occurs under the control of a highly sophisticated replication program during the restricted time period corresponding to S phase. DNA replication is initiated at a large number of sites, known as origins of replication, on the chromosomes of eukaryotic cells. In one individual cell, only a part of the origins licensed in G1 phase are activated during S phase thus illustrating the flexible origin choice which is directly related to the stochastic nature of the eukaryotic replication program. Another particularity of the program is that origin activation is also subject to temporal regulation. Like this, some domains of hundred kilobases are replicated in early S phase, others are replicated in mid S phase and the remainders in late S phase. This temporal control is very strict. To date, the factors responsible for the establishment, regulation and maintenance of these domains throughout the cell cycle remain largely unknown. As a first step towards a better comprehension of this temporal program, the team of MN Prioleau has investigated whether the stochasticity of the timing program is changing along the S phase.

  • January 2019: when Transcription Meets Replication

    Conflicting activities necessary for the expression, the maintenance and the propagation of genomes need to be coordinated. Just like one's liberty to swing fists ends where another's nose begins, coordination is achieved through a tight control of where and when directly opposed activities take place. In a study published recently in eLife, researchers from the Libri team are now showing that replication factors generally "protect" sites where replication initiates by terminating incoming transcription, and that the low levels of transcription that enter origins of replication affect their firing efficiency.

  • January 2019 : Cell shape changes and cytoskeleton adaptation to migrate into complex environments

    Cell migration is an essential biological process that drives tissue and organ formation during embryo development, and also helps protect the body through immune response and wound healing mechanisms.

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