ENS - MemoLife

Adel AL JORD

Godfroid — 2022-09-07T08:16:40Z

Adel Al Jord, Gaëlle Letort, Soline Chanet, Feng-Ching Tsai, Christophe Antoniewski, Adrien Eichmuller, Christelle Da Silva, Jean-René Huynh, Nir S. Gov, Raphaël Voituriez, Marie-Émilie Terret & Marie-Hélène Verlhac

Abstract

Cells remodel their cytoplasm with force-generating cytoskeletal motors. Their activity generates random forces that stir the cytoplasm, agitating and displacing membrane-bound organelles like the nucleus in somatic and germ cells. These forces are transmitted inside the nucleus, yet their consequences on liquid-like biomolecular condensates residing in the nucleus remain unexplored. Here, we probe experimentally and computationally diverse nuclear condensates, that include nuclear speckles, Cajal bodies, and nucleoli, during cytoplasmic remodeling of female germ cells named oocytes. We discover that growing mammalian oocytes deploy cytoplasmic forces to timely impose multiscale reorganization of nuclear condensates for the success of meiotic divisions. These cytoplasmic forces accelerate nuclear condensate collision-coalescence and molecular kinetics within condensates. Disrupting the forces decelerates nuclear condensate reorganization on both scales, which correlates with compromised condensate-associated mRNA processing and hindered oocyte divisions that drive female fertility. We establish that cytoplasmic forces can reorganize nuclear condensates in an evolutionary conserved fashion in insects. Our work implies that cells evolved a mechanism, based on cytoplasmic force tuning, to functionally regulate a broad range of nuclear condensates across scales. This finding opens new perspectives when studying condensate-associated pathologies like cancer, neurodegeneration and viral infections.

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Nat Commun. 2022 Aug 29 ;13(1):5070. doi : 10.1038/s41467-022-32675-5

Ioana GENESCU

Godfroid — 2022-04-15T12:24:18Z

Authors : I Genescu, M Aníbal-Martínez, V Kouskoff, N Chenouard, C Mailhes-Hamon, H Cartonnet, L Lokmane, F M. Rijli, G López-Bendito, F Gambino, S Garel

Summary

Cortical wiring relies on guidepost cells and activity-dependent processes that are thought to act sequentially. Here, we show that the construction of layer 1 (L1), a main site of top-down integration, is regulated by crosstalk between transient Cajal-Retzius cells (CRc) and spontaneous activity of the thalamus, a main driver of bottom-up information. While activity was known to regulate CRc migration and elimination, we found that prenatal spontaneous thalamic activity and NMDA receptors selectively control CRc early density, without affecting their demise. CRc density, in turn, regulates the distribution of upper layer interneurons and excitatory synapses, thereby drastically impairing the apical dendrite activity of output pyramidal neurons. In contrast, postnatal sensory-evoked activity had a limited impact on L1 and selectively perturbed basal dendrites synaptogenesis. Collectively, our study highlights a remarkable interplay between thalamic activity and CRc in L1 functional wiring, with major implications for our understanding of cortical development.

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Cell Reports Vol. 39, Issue 2, 110667, April 12, 2022. doi : 10.1016/j.celrep.2022.110667

Espace emploi

Godfroid — 2022-01-26T10:33:43Z

Post-doc or Engineer in Neuroscience | optical imaging

Development of novel calcium imaging methods to record
neuronal activity
Equipes : Cathie Ventalon (IBENS) & Michael Zugaro (CIRB, Collège de France)
Contacts : Cathie Ventalon & Michael Zugaro

Détails de l'offre d'emploi

Guilhem SOMMERIA-KLEIN

Godfroid — 2021-11-18T18:10:03Z

Guilhem Sommeria-Klein, Romain Watteaux, Federico M. Ibarbalz, Juan José Pierella Karlusich, Daniele Iudicone, Chris Bowler, Hélène Morlon

Le plancton eucaryote est une composante essentielle et extrêmement diversifiée des écosystèmes marins, dont la distribution géographique (la « biogéographie ») reste pourtant mal connue. Dans une étude parue fin octobre dans la revue Science, une équipe de chercheurs de l'Institut de Biologie de l'École Normale Supérieure de Paris (IBENS, CNRS / ENS Paris / Inserm) et de Naples (Station Zoologique Anton Dohrn) ont étudié sa biogéographie à l'échelle mondiale à partir de données ADN récoltées par la goélette d'exploration océanique Tara. A l'aide d'un modèle probabiliste, ils ont établi que la biogéographie variait considérablement d'un groupe planctonique à l'autre, et que ces variations suivaient deux axes principaux : d'une part, les groupes les plus diversifiés sont davantage spatialement structurés ; d'autre part, les zooplanctons de grande taille (plusieurs millimètres) sont structurés par bassin océanique et à grande échelle spatiale, principalement sous l'influence des courants marins, tandis que les producteurs primaires de petite taille (quelques micromètres) sont structurés par latitude et à plus petite échelle spatiale, du fait d'une sensibilité accrue aux variations environnementales locales.

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Science. Vol 374, Issue 6567, pp. 594-599, 10.1126/science.abb3717

Odile MALIET

Godfroid — 2021-10-08T11:09:14Z

Abstract

Diversification rates vary across species as a response to various factors, including environmental conditions and species-specific features. Phylogenetic models that allow accounting for and quantifying this heterogeneity in diversification rates have proven particularly useful for understanding clades diversification. Recently, we introduced the cladogenetic diversification rate shift model, which allows inferring multiple rate changes of small magnitude across lineages. Here, we present a new inference technique for this model that considerably reduces computation time through the use of data augmentation and provide an implementation of this method in Julia. In addition to drastically reducing computation time, this new inference approach provides a posterior distribution of the augmented data, that is the tree with extinct and unsampled lineages as well as associated diversification rates. In particular, this allows extracting the distribution through time of both the mean rate and the number of lineages. We assess the statistical performances of our approach using simulations and illustrate its application on the entire bird radiation.[Birth–death model ; data augmentation ; diversification ; macroevolution.]

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Syst Biol. 2021 Jul 6 ;syab055.

Odile MALIET

Godfroid — 2020-12-22T08:31:49Z

Abstract

How ecological interaction networks emerge on evolutionary time scales remains unclear. Here we build an individual‐based eco‐evolutionary model for the emergence of mutualistic, antagonistic and neutral bipartite interaction networks. Exploring networks evolved under these scenarios, we find three main results. First, antagonistic interactions tend to foster species and trait diversity, while mutualistic interactions reduce diversity. Second, antagonistic interactors evolve higher specialisation, which results in networks that are often more modular than neutral ones ; resource species in these networks often display phylogenetic conservatism in interaction partners. Third, mutualistic interactions lead to networks that are more nested than neutral ones, with low phylogenetic conservatism in interaction partners. These results tend to match overall empirical trends, demonstrating that structures of empirical networks that have most often been explained by ecological processes can result from an evolutionary emergence. Our model contributes to the ongoing effort of better integrating ecological interactions and macroevolution.

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Ecol Lett. 2020 Sep 4. doi : 10.1111/ele.13592

Hélène Morlon | IBENSAmaury Lambert | CIRB

Godfroid — 2020-09-08T10:52:47Z

Abstract

In standard models of molecular evolution, DNA sequences evolve through asynchronous substitutions according to Poisson processes with a constant rate (called the molecular clock) or a rate that can vary (relaxed clock). However, DNA sequences can also undergo episodes of fast divergence that will appear as synchronous substitutions affecting several sites simultaneously at the macroevolutionary time scale. Here, we develop a model, that we call the Relaxed Clock with Spikes model (RCS), combining basal, clock-like molecular substitutions with episodes of fast divergence called spikes arising at speciation events. Given a multiple sequence alignment and its time-calibrated species phylogeny, our model is able to detect speciation events (including hidden ones) co-occurring with spike events and to estimate the probability and amplitude of these spikes on the phylogeny. We identify the conditions under which spikes can be distinguished from the natural variance of the clock-like component of molecular substitutions and from variations of the clock. We apply the method to genes underlying snake venom proteins and identify several spikes at gene-specific locations in the phylogeny. This work should pave the way for analyses relying on whole genomes to inform on modes of species diversification.

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Mol Biol Evol. 2020 Jun 10 ; msaa144. doi : 10.1093/molbev/msaa144.

Virginia Busetto,

Godfroid — 2020-07-21T14:22:12Z

V. Busetto, I. Barbosa, J. Basquin, E. Marquenet, R. Hocq, M. Hennion, J.A. Paternina, A. Namane, E. Conti, O. Bensaude, H. Le Hir

Abstract

Human CWC27 is an uncharacterized splicing factor and mutations in its gene are linked to retinal degeneration and other developmental defects. We identify the splicing factor CWC22 as the major CWC27 partner. Both CWC27 and CWC22 are present in published Bact spliceosome structures, but no interacting domains are visible. Here, the structure of a CWC27/CWC22 heterodimer bound to the exon junction complex (EJC) core component eIF4A3 is solved at 3Å-resolution. According to spliceosomal structures, the EJC is recruited in the C complex, once CWC27 has left. Our 3D structure of the eIF4A3/CWC22/CWC27 complex is compatible with the Bact spliceosome structure but not with that of the C complex, where a CWC27 loop would clash with the EJC core subunit Y14. A CWC27/CWC22 building block might thus form an intermediate landing platform for eIF4A3 onto the Bact complex prior to its conversion into C complex. Knock-down of either CWC27 or CWC22 in immortalized retinal pigment epithelial cells affects numerous common genes, indicating that these proteins cooperate, targeting the same pathways. As the most up-regulated genes encode factors involved in inflammation, our findings suggest a possible link to the retinal degeneration associated with CWC27 deficiencies.

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Nucleic Acids Res. 2020 Jun 4 ;48(10):5670-5683. doi : 10.1093/nar/gkaa267

Isma Bennabi

Godfroid — 2020-04-07T15:01:30Z

Isma Bennabi, Flora Crozet°, Elvira Nikalayevich°, Agathe Chaigne, Gaëlle Letort, Marion Manil-Ségalen, Clément Campillo, Clotilde Cadart, Alice Othmani, Rafaele Attia, Auguste Genovesio, Marie-Hélène Verlhac* & Marie-Emilie Terret*.
(°equal contribution, *co-corresponding authors)

Abstract

Human and mouse oocytes' developmental potential can be predicted by their mechanical properties. Their development into blastocysts requires a specific stiffness window. In this study, we combine live-cell and computational imaging, laser ablation, and biophysical measurements to investigate how deregulation of cortex tension in the oocyte contributes to early developmental failure. We focus on extra-soft cells, the most common defect in a natural population. Using two independent tools to artificially decrease cortical tension, we show that chromosome alignment is impaired in extra-soft mouse oocytes, despite normal spindle morphogenesis and dynamics, inducing aneuploidy. The main cause is a cytoplasmic increase in myosin-II activity that could sterically hinder chromosome capture. We describe here an original mode of generation of aneuploidies that could be very common in oocytes and could contribute to the high aneuploidy rate observed during female meiosis, a leading cause of infertility and congenital disorders.

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Nat Commun. 2020 Apr 3 ;11(1):1649. doi : 10.1038/s41467-020-15470-y.

Dorota Kostrz

Godfroid — 2019-10-10T12:53:20Z

Abstract

The residence time of a drug on its target has been suggested as a more pertinent metric of therapeutic efficacy than the traditionally used affinity constant. Here, we introduce junctured-DNA tweezers as a generic platform that enables real-time observation, at the single-molecule level, of biomolecular interactions. This tool corresponds to a double-strand DNA scaffold that can be nanomanipulated and on which proteins of interest can be engrafted thanks to widely used genetic tagging strategies. Thus, junctured-DNA tweezers allow a straightforward and robust access to single-molecule force spectroscopy in drug discovery, and more generally in biophysics. Proof-of-principle experiments are provided for the rapamycin-mediated association between FKBP12 and FRB, a system relevant in both medicine and chemical biology. Individual interactions were monitored under a range of applied forces and temperatures, yielding after analysis the characteristic features of the energy profile along the dissociation landscape.

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CNRS press release

Nat Nanotechnol. 2019 Sep 23. doi : 10.1038/s41565-019-0542-7