ENS - Départment de biologie

Blind cavefish retain functional connectivity in the tectum despite loss of retinal input

Frédérique Godfroid — 2023-01-05T09:42:29Z

Abstract

Sensory systems display remarkable plasticity and are under strong evolutionary selection. The Mexican cavefish, Astyanax mexicanus, consists of eyed river-dwelling surface populations and multiple independent cave populations that have converged on eye loss, providing the opportunity to examine the evolution of sensory circuits in response to environmental perturbation. Functional analysis across multiple transgenic populations expressing GCaMP6s showed that functional connectivity of the optic tectum largely did not differ between populations, except for the selective loss of negatively correlated activity within the cavefish tectum, suggesting positively correlated neural activity is resistant to an evolved loss of input from the retina. Furthermore, analysis of surface-cave hybrid fish reveals that changes in the tectum are genetically distinct from those encoding eye loss. Together, these findings uncover the independent evolution of multiple components of the visual system and establish the use of functional imaging in A. mexicanus to study neural circuit evolution.

More information

Curr Biol. 2022 Sep 12 ;32(17):3720-3730.e3. doi : 10.1016/j.cub.2022.07.015. Epub 2022 Aug 4.

Microglial TNFα orchestrates protein phosphorylation in the cortex during the sleep period and controls homeostatic sleep

Frédérique Godfroid — 2023-01-04T15:16:06Z

Authors
Maria J Pinto, Léa Cottin, Florent Dingli, Victor Laigle, Luís F Ribeiro, Antoine Triller, Fiona Henderson, Damarys Loew, Véronique Fabre, Alain Bessis

Abstract

Sleep intensity is adjusted by the length of previous awake time, and under tight homeostatic control by protein phosphorylation. Here, we establish microglia as a new cellular component of the sleep homeostasis circuit. Using quantitative phosphoproteomics of the mouse frontal cortex, we demonstrate that microglia-specific deletion of TNFα perturbs thousands of phosphorylation sites during the sleep period. Substrates of microglial TNFα comprise sleep-related kinases such as MAPKs and MARKs, and numerous synaptic proteins, including a subset whose phosphorylation status encodes sleep need and determines sleep duration. As a result, microglial TNFα loss attenuates the build-up of sleep need, as measured by electroencephalogram slow-wave activity and prevents immediate compensation for loss of sleep. Our data suggest that microglia control sleep homeostasis by releasing TNFα which acts on neuronal circuitry through dynamic control of phosphorylation.

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EMBO J. 2022 Nov 16 ;e111485. doi : 10.15252/embj.2022111485.

Laura Cantini, lauréate du Prix Claude Paoletti 2022

Frédérique Godfroid — 2023-01-04T08:02:53Z

Le prix Claude Paoletti est une distinction décernée par le CNRS à destination de jeunes chercheurs s'étant distingués durant leur doctorat ou leur post-doctorat pour leurs travaux portant sur les sciences de la vie.

Après une thèse sur l'intégration de données multi-omiques obtenue en 2016 à l'Université de Turin, Laura Cantini a effectué un postdoc sur le même sujet dans l'équipe d'Emmanuel Barillot à l'Institut Curie. En 2018, Laura a rejoint le CNRS et l'IBENS en tant que Chargée de Recherche. Depuis, elle a obtenu la bourse L'Oréal-UNESCO pour les femmes et la science, des multiples financements (ANR JCJC, Sanofi iTech Award) et un poste de chaire à l'institut PRAIRIE. À partir de 2023, Laura dirigera une équipe axée sur les méthodes d'apprentissage automatique pour l'analyse de données à l'échelle de la cellule unique à l'Institut Pasteur.

Le séquençage à haut débit de cellules uniques permet dorénavant de caractériser les profils moléculaires de milliers de cellules. Cette abondance de données offre des possibilités de dévoiler des mécanismes encore totalement inconnus. Néanmoins, les données en cellule unique sont si massives et complexes qu'il est difficile d'en extraire les informations sur les processus biologiques sous-jacents. Laura et son équipe travaillent à la croisée de l'apprentissage automatique et de la génomique, en développant des méthodes qui exploitent toute la richesse et la complémentarité des données en cellule unique, pour en tirer des connaissances biologiques exploitables.

Plus d'information
Plus d'information sur le Prix Claude Paoletti 2022

Genome-wide mapping of individual replication fork velocities using nanopore sequencing

Frédérique Godfroid — 2023-01-03T16:17:07Z

Authors
Bertrand Theulot ^#, Laurent Lacroix^#, Jean-Michel Arbona, Gael A Millot, Etienne Jean, Corinne Cruaud, Jade Pellet, Florence Proux, Magali Hennion, Stefan Engelen, Arnaud Lemainque, Benjamin Audit, Olivier Hyrien, Benoît Le Tallec

Abstract

Little is known about replication fork velocity variations along eukaryotic genomes, since reference techniques to determine fork speed either provide no sequence information or suffer from low throughput. Here we present NanoForkSpeed, a nanopore sequencing-based method to map and extract the velocity of individual forks detected as tracks of the thymidine analogue bromodeoxyuridine incorporated during a brief pulse-labelling of asynchronously growing cells. NanoForkSpeed retrieves previous Saccharomyces cerevisiae mean fork speed estimates (≈2 kb/min) in the BT1 strain exhibiting highly efficient bromodeoxyuridine incorporation and wild-type growth, and precisely quantifies speed changes in cells with altered replisome progression or exposed to hydroxyurea. The positioning of >125,000 fork velocities provides a genome-wide map of fork progression based on individual fork rates, showing a uniform fork speed across yeast chromosomes except for a marked slowdown at known pausing sites.

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Nat Commun. 2022 Jun 8 ;13(1):3295. doi : 10.1038/s41467-022-31012-0.

Functional abnormalities in the cerebello-thalamic pathways in a mouse model of DYT25 dystonia.

Frédérique Godfroid — 2022-12-21T17:11:13Z

Abstract

Dystonia is often associated with functional alterations in the cerebello-thalamic pathways, which have been proposed to contribute to the disorder by propagating pathological firing patterns to the forebrain. Here, we examined the function of the cerebello-thalamic pathways in a model of DYT25 dystonia. DYT25 (Gnal+/-) mice carry a heterozygous knockout mutation of the Gnal gene, which notably disrupts striatal function, and systemic or striatal administration of oxotremorine to these mice triggers dystonic symptoms. Our results reveal an increased cerebello-thalamic excitability in the presymptomatic state. Following the first dystonic episode, Gnal+/- mice in the asymptomatic state exhibit a further increase of the cerebello-thalamo-cortical excitability, which is maintained after θ-burst stimulations of the cerebellum. When administered in the symptomatic state induced by a cholinergic activation, these stimulations decreased the cerebello-thalamic excitability and reduced dystonic symptoms. In agreement with dystonia being a multiregional circuit disorder, our results suggest that the increased cerebello-thalamic excitability constitutes an early endophenotype, and that the cerebellum is a gateway for corrective therapies via the depression of cerebello-thalamic pathways.

More information

Elife. 2022 Jun 14 ;11:e79135. doi:10.7554/eLife.79135.

Cerebellar stimulation prevents Levodopa-induced dyskinesia in mice and normalizes activity in a motor network.

Frédérique Godfroid — 2022-12-20T10:53:56Z

Authors
Bérénice Coutant, Jimena Laura Frontera^#, Elodie Perrin^#, Adèle Combes^#, Thibault Tarpin, Fabien Menardy, Caroline Mailhes-Hamon, Sylvie Perez, Bertrand Degos, Laurent Venance, Clément Léna, Daniela Popa

Abstract

Chronic Levodopa therapy, the gold-standard treatment for Parkinson's Disease (PD), leads to the emergence of involuntary movements, called levodopa-induced dyskinesia (LID). Cerebellar stimulation has been shown to decrease LID severity in PD patients. Here, in order to determine how cerebellar stimulation induces LID alleviation, we performed daily short trains of optogenetic stimulations of Purkinje cells (PC) in freely moving LID mice. We demonstrated that these stimulations are sufficient to suppress LID or even prevent their development. This symptomatic relief is accompanied by the normalization of aberrant neuronal discharge in the cerebellar nuclei, the motor cortex and the parafascicular thalamus. Inhibition of the cerebello-parafascicular pathway counteracted the beneficial effects of cerebellar stimulation. Moreover, cerebellar stimulation reversed plasticity in D1 striatal neurons and normalized the overexpression of FosB, a transcription factor causally linked to LID. These findings demonstrate LID alleviation and prevention by daily PC stimulations, which restore the function of a wide motor network, and may be valuable for LID treatment.

More information

Nat Commun. 2022 Jun 9 ;13(1):3211.doi : 10.1038/s41467-022-30844-0

An atlas of fish genome evolution reveals delayed rediploidization following the teleost whole-genome duplication

Frédérique Godfroid — 2022-12-20T09:30:59Z

Abstract

Teleost fishes are ancient tetraploids descended from an ancestral whole-genome duplication that may have contributed to the impressive diversification of this clade. Whole-genome duplications can occur via self-doubling (autopolyploidy) or via hybridization between different species (allopolyploidy). The mode of tetraploidization conditions evolutionary processes by which duplicated genomes return to diploid meiotic pairing, and subsequent genetic divergence of duplicated genes (cytological and genetic rediploidization). How teleosts became tetraploid remains unresolved, leaving a fundamental gap in the interpretation of their functional evolution. As a result of the whole-genome duplication, identifying orthologous and paralogous genomic regions across teleosts is challenging, hindering genome-wide investigations into their polyploid history. Here, we combine tailored gene phylogeny methodology together with a state-of-the-art ancestral karyotype reconstruction to establish the first high-resolution comparative atlas of paleopolyploid regions across 74 teleost genomes.
We then leverage this atlas to investigate how rediploidization occurred in teleosts at the genome-wide level. We uncover that some duplicated regions maintained tetraploidy for more than 60 million years, with three chromosome pairs diverging genetically only after the separation of major teleost families. This evidence suggests that the teleost ancestor was an autopolyploid. Further, we find evidence for biased gene retention along several duplicated chromosomes, contradicting current paradigms that asymmetrical evolution is specific to allopolyploids. Altogether, our results offer novel insights into genome evolutionary dynamics following ancient polyploidizations in vertebrates.

More information

Genome Res. 2022 Aug 12 ;32(9):1685-1697. doi : 10.1101/gr.276953.122

Early Mars habitability and global cooling by H2-based methanogens

Frédérique Godfroid — 2022-12-20T09:11:01Z

Abstract

During the Noachian, Mars' crust may have provided a favourable environment for microbial life. The porous brine-saturated regolith would have created a physical space sheltered from ultraviolet and cosmic radiation and provided a solvent, whereas the below-ground temperature and diffusion of a dense, reduced atmosphere may have supported simple microbial organisms that consumed H2 and CO2 as energy and carbon sources and produced methane as a waste. On Earth, hydrogenotrophic methanogenesis was among the earliest metabolisms, but its viability on early Mars has never been quantitatively evaluated. Here we present a probabilistic assessment of Mars' Noachian habitability to H2-based methanogens and quantify their biological feedback on Mars' atmosphere and climate. We find that subsurface habitability was very likely, and limited mainly by the extent of surface ice coverage. Biomass productivity could have been as high as in the early Earth's ocean. However, the predicted atmospheric composition shift caused by methanogenesis would have triggered a global cooling event, ending potential early warm conditions, compromising surface habitability and forcing the biosphere deep into the Martian crust. Spatial projections of our predictions point to lowland sites at low-to-medium latitudes as good candidates to uncover traces of this early life at or near the surface.

More information

Nature Astronomy volume 6, pages 1263–1271 (2022)

Hiring new teams at IBENS in Computational Biology and Plant Sciences

Frédérique Godfroid — 2022-11-04T15:53:08Z

The Institute of Biology of the École Normale Supérieure, IBENS is seeking to recruit new group leaders in Computational Biology and Plant Sciences.
IBENS is a prime Life Sciences research institute located in the heart of Paris. Its overarching goal is to make fundamental contributions to our understanding of the basic mechanisms and principles that underlie biological processes. IBENS is part of the Department of Biology of the École Normale Supérieure (ENS), and is affiliated to CNRS and INSERM. It hosts 29 research teams organized into four research axes : Functional Genomics, Developmental Biology, Neuroscience, and Ecology & Evolution. Research performed at IBENS is highly collaborative and multiscale, and combines experimental and theoretical approaches. Multidisciplinarity is reinforced by local collaborations with other ENS departments as well as with several nearby top research institutions (Curie Institute, Collège de France, ESPCI ParisTech...). As part of ENS and PSL University, IBENS scientists have strong links with higher-education teaching and training both at undergraduate and graduate levels, and have access to top-level students.

Applications should include a CV and a summary of scientific achievements (max 2 pages) and proposed research program (max 2 pages). In addition, three letters of recommendation should be emailed directly to the same address. IBENS is committed to a transparent, open and merit-based recruitment policy and actively seeks to achieve gender equality.

DEADLINE FOR APPLICATIONS : 31^st December, 2022

Applications and information requests should be sent to
ibens.newresearchgroups chez biologie.ens.fr

Shortlisted applicants will be notified in the first quarter of 2023 and interviews will be conducted shortly after.

__________________________

Group leader in Computational Biology at IBENS

The Functional Genomics section aims to understand genome expression, organization, evolution and regulation. Projects range from the study of genome evolution, programmed rearrangements and replication to how molecules or bacterial infection modifies gene expression and its translation into cell phenotypes and functions. The IBENS currently hosts several teams in computational biology that develop mathematical and machine learning models as well as bioinformatics tools to perform measurement on, represent or explain biological systems.
We are looking for an outstanding candidate developing an ambitious research program in computational biology with the potential to interact with and complement the existing strengths of IBENS. Junior as well as senior applications will be considered. Applications can span the whole spectrum of computational biology.
IBENS hosts state-of-the-art facilities, including advanced imaging, genomics, and protein production platforms, as well as a high-performance computing cluster, efficient IT support, and several plant and animal housing facilities.
Download pdf "Call for a new team leader in Computational Biology"

__________________________

Group leader(s) in Plant Sciences at IBENS

We are looking for outstanding candidates developing ambitious research programs in the broad field of plant sciences and that complement the existing strengths of IBENS in Ecology & Evolutionary Biology. We are particularly interested in candidates who aim to investigate the mechanisms of signalling, adaptation, diversification, and/or species interactions, using approaches such as biochemistry, genetics, genomics, and computational biology. At least one of the selected teams will develop research benefiting from the in-house facilities for performing molecular genetics on model plants, notably Arabidopsis or other emerging models for evolutionary studies. Programs that can benefit from our ECOTRON facility for ecological research will be appreciated, although not mandatory. We aim to recruit one or two group leaders at junior and/or mid-career levels.
IBENS hosts state-of-the-art facilities, including advanced imaging, genomics, bioinformatics and protein production platforms, as well as several plant and animal house facilities.
Download pdf "Call for a new team leader in Plant Sciences"

Philippe Ascher

Frédérique Godfroid — 2022-10-10T12:35:07Z

Ses travaux sont des ‘classiques' et figurent dans tous les ‘text books' de neurosciences modernes. Philippe Ascher a marqué, influencé et inspiré des générations entières d'étudiants et de collègues de tous horizons. Il était un point de repère, qu'on venait consulter pour son érudition hors norme, sa clairvoyance, son ouverture et sa générosité. Il avait une capacité exceptionnelle à transmettre sa passion, notamment aux plus jeunes collègues. Fondateur du Laboratoire de Neurobiologie de l'ENS dans les années 70 et directeur du Département de Biologie pendant deux décennies (1981-2001), Philippe Ascher a radicalement transformé la recherche et l'enseignement en biologie à l'Ecole Normale Supérieure. Il a notamment œuvré sans relâche pour aider les jeunes à développer leurs propres recherches et pour hisser nos laboratoires et formations au tout meilleur niveau. Il a joué un rôle déterminant dans le développement et la reconnaissance de l'école de neurobiologie française et plus généralement de la recherche scientifique française. Son aura dépassait très largement les frontières de l'Hexagone et il suscitait l'admiration de tous. Nous lui devons beaucoup. Notre communauté perd un grand savant et un grand humaniste. Toutes nos pensées vont à sa famille et ses proches.

ENS - Départment de biologie

Blind cavefish retain functional connectivity in the tectum despite loss of retinal input

Abstract

Microglial TNFα orchestrates protein phosphorylation in the cortex during the sleep period and controls homeostatic sleep

Abstract

Laura Cantini, lauréate du Prix Claude Paoletti 2022

Genome-wide mapping of individual replication fork velocities using nanopore sequencing

Abstract

Functional abnormalities in the cerebello-thalamic pathways in a mouse model of DYT25 dystonia.

Abstract

Cerebellar stimulation prevents Levodopa-induced dyskinesia in mice and normalizes activity in a motor network.

Abstract

An atlas of fish genome evolution reveals delayed rediploidization following the teleost whole-genome duplication

Abstract

Early Mars habitability and global cooling by H2-based methanogens

Abstract

Hiring new teams at IBENS in Computational Biology and Plant Sciences

DEADLINE FOR APPLICATIONS : 31st December, 2022

__________________________

Group leader in Computational Biology at IBENS

__________________________

Group leader(s) in Plant Sciences at IBENS

Philippe Ascher

DEADLINE FOR APPLICATIONS : 31^st December, 2022