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1. The WAK-like protein RFO1 acts as a sensor of the pectin methylation status in Arabidopsis cell walls to modulate root growth and defense

Author: Huerta, Apolonio I., Sancho Andrés, Gloria, Montesinos Lopez, Juan Carlos, Silva-Navas, Javier, Bassard, Solène, Pau-Roblot, Corinne, Kesten, Christopher, Schlechter, Rudolf, Dora, Susanne, Ayupov, Temurkhan, Pelloux, Jérôme, Santiago, Julia, Sanchez-Rodriguez, Clara, Departement Erdwissenschaften [ETH Zürich] (D-ERDW), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Department of Biology [ETH Zürich] (D-BIOL), Université de Lausanne = University of Lausanne (UNIL), Transfrontalière BioEcoAgro - UMR 1158 (BioEcoAgro), Université d'Artois (UA)-Université de Liège-Université de Picardie Jules Verne (UPJV)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Biologie des Plantes et Innovation - UR UPJV 3900 (BIOPI), Université de Picardie Jules Verne (UPJV)-Transfrontalière BioEcoAgro - UMR 1158 (BioEcoAgro), and Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Université d'Artois (UA)-Université de Liège-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA)
Subjects: [SDV]Life Sciences [q-bio], General Medicine
Abstract: Most organisms adjust their development according to the environmental conditions. For the majority, this implies the sensing of alterations to cell walls caused by different cues. Despite the relevance of this process, few molecular players involved in cell wall sensing are known and characterized. Here, we show that the wall-associated kinase-like protein RESISTANCE TO FUSARIUM OXYSPORUM 1 (RFO1) is required for plant growth and early defense against Fusarium oxysporum and functions by sensing changes in the pectin methylation levels in the cell wall. The RFO1 dwell time at the plasma membrane is affected by the pectin methylation status at the cell wall, regulating MITOGEN-ACTIVATED PROTEIN KINASE and gene expression. We show that the extracellular domain of RFO1 binds de-methylated pectin in vitro, whose distribution in the cell wall is altered during F. oxysporum infection. Further analyses also indicate that RFO1 is required for the BR-dependent plant growth alteration in response to inhibition of pectin de-methyl-esterase activity at the cell wall. Collectively, our work demonstrates that RFO1 is a sensor of the pectin methylation status that plays a unique dual role in plant growth and defense against vascular pathogens., Molecular Plant, 16 (5), ISSN:1752-9867, ISSN:1674-2052
Published: 2023
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2. Characterisation of a split gradient coil design induced systemic imaging artefact on 0.35 T MR-linac systems

Author: Louis Marage, Paul-Michael Walker, Julien Boudet, Pierre Fau, Pierre Debuire, Emmanuelle Clausse, Aurélie Petitfils, Léone Aubignac, Stanislas Rapacchi, Igor Bessieres, CHU Pontchaillou [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Equipe IFTIM [ImViA - EA7535], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Imagerie et Vision Artificielle [Dijon] (ImViA), Université de Bourgogne (UB)-Université de Bourgogne (UB), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), and Qualimedis
Subjects: imaging artefact, Radiological and Ultrasound Technology, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Split gradient coil, Radiology, Nuclear Medicine and imaging, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], MR-linac, MRI imaging artefact MR-linac Split gradient coil, MRI
Abstract: Objective. The aim of this work was to highlight and characterize a systemic ‘star-like’ artefact inherent to the low field 0.35 T MRIdian MR-linac system, a magnetic resonance guided radiotherapy device. This artefact is induced by the original split gradients coils design. This design causes a surjection of the intensity gradient in Z (or head-feet) direction. This artefact appears on every sequence with phase encoding in the head-feet direction. Approach. Basic gradient echo sequence and clinical mandatory bSSFP sequence were used. Three setups using manufacturer provided QA phantoms were designed: two including the linearity control grid used for the characterisation and a third including two homogeneity control spheres dedicated to the artefact management in a more clinical like situation. The presence of the artefact was checked in four different MRidian sites. The tested parameters based on the literature were: phase encoding orientation, slab selectivity, excitation bandwidth (BWRF), acceleration factor (R) and phase/slab oversampling (PO/SO). Main results. The position of this artefact is constant and reproducible over the tested MRIdian sites. The typical singularity saturated dot or star is visible even with the 3D slab-selection enabled. A management is proposed by decreasing the BWRF, the R in head-feet direction and increasing the PO/SO. The oversampling can be optimized using a formula to anticipate the location of artefact in the field of view. Significance. The star-like artefact has been well characterised. A manageable solution comes at the cost of acquisition time. Observed in clinical cases, the artefact may degrade the images used for the RT planning and repositioning during the treatment unless corrected.
Published: 2022
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3. Peripheral membrane proteins modulate stress tolerance by safeguarding cellulose synthases

Author: Christopher Kesten, Álvaro García-Moreno, Vítor Amorim-Silva, Alexandra Menna, Araceli G. Castillo, Francisco Percio, Laia Armengot, Noemi Ruiz-Lopez, Yvon Jaillais, Clara Sánchez-Rodríguez, Miguel A. Botella, Instituto de Hortofruticultura Subtropical y Mediterranea 'La Mayora' (IHSM), Universidad de Málaga [Málaga] = University of Málaga [Málaga]-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Reproduction et développement des plantes (RDP), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Biology [ETH Zürich] (D-BIOL), and Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)
Subjects: Multidisciplinary, Arabidopsis Proteins, [SDV]Life Sciences [q-bio], Cell Membrane, Arabidopsis, Membrane Proteins, Cellulose, Microtubules
Abstract: Controlled primary cell wall remodeling allows plant growth under stressful conditions, but how these changes are conveyed to adjust cellulose synthesis is not understood. Here, we identify the TETRATRICOPEPTIDE THIOREDOXIN-LIKE (TTL) proteins as new members of the cellulose synthase complex (CSC) and describe their unique and hitherto unknown dynamic association with the CSC under cellulose-deficient conditions. We find that TTLs are essential for maintaining cellulose synthesis under high-salinity conditions, establishing a stress-resilient cortical microtubule array, and stabilizing CSCs at the plasma membrane. To fulfill these functions, TTLs interact with CELLULOSE SYNTHASE 1 (CESA1) and engage with cortical microtubules to promote their polymerization. We propose that TTLs function as bridges connecting stress perception with dynamic regulation of cellulose biosynthesis at the plasma membrane., Science Advances, 8 (46), ISSN:2375-2548
Published: 2022
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4. Fitness advantage of Bacteroides thetaiotaomicron capsular polysaccharide is dependent on the resident microbiota

Author: Daniel Hoces, Giorgia Greter, Markus Arnoldini, Claudia Moresi, Sara Berent, Isabel Kolinko, Florence Bansept, Aurore Woller, Janine Häfliger, Eric Martens, Wolf-Dietrich Hardt, Claude Loverdo, Emma Slack, Department of Health Sciences and Technology [ETH Zürich] (D-HEST), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Laboratoire Jean Perrin (LJP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Biology [ETH Zürich] (D-BIOL), and Loverdo, Claude
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: SummaryMany microbiota-based therapeutics rely on our ability to introduce a microbe of choice into an already-colonized intestine. However, we remain largely blind to the quantitative effects of processes determining colonization success. In this study, we used genetically-barcoded Bacteroides thetaiotaomicron (B.theta) strains in combination with mathematical modeling to quantify population bottlenecks experienced by B.theta during gut colonization. Integrating population bottlenecks sizes with careful quantification of net growth rates in vivo and in vitro allows us to build models describing the events during intestinal colonization in the context of gnotobiotic and complex microbiotas. Using these models, we estimated the decrease in niche size for B.theta colonization with increasing microbiota complexity. In addition, our system can be applied to mechanistically dissect colonization defects of mutant strains. As a proof of concept, we demonstrated that the competitive disadvantage of a B.theta mutant lacking capsular polysaccharide is due to a combination of an increased lag-phase before growth initiation in the gut, combined with an increased clearance rate. Crucially, the requirement for the B.theta capsule depended strongly on microbiota composition, suggesting that the dominant role may be protection from bacterial or phage aggression rather than from host-induced bactericidal mechanisms.
Published: 2022
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5. Global relationships in tree functional traits

Author: Daniel S. Maynard, Lalasia Bialic-Murphy, Constantin M. Zohner, Colin Averill, Johan van den Hoogen, Haozhi Ma, Lidong Mo, Gabriel Reuben Smith, Alicia T. R. Acosta, Isabelle Aubin, Erika Berenguer, Coline C. F. Boonman, Jane A. Catford, Bruno E. L. Cerabolini, Arildo S. Dias, Andrés González-Melo, Peter Hietz, Christopher H. Lusk, Akira S. Mori, Ülo Niinemets, Valério D. Pillar, Bruno X. Pinho, Julieta A. Rosell, Frank M. Schurr, Serge N. Sheremetev, Ana Carolina da Silva, Ênio Sosinski, Peter M. van Bodegom, Evan Weiher, Gerhard Bönisch, Jens Kattge, Thomas W. Crowther, Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Estonian University of Life Sciences (EMU), Botanique et Modélisation de l'Architecture des Plantes et des Végétations (UMR AMAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université de Montpellier (UM), Universidade Federal de Pernambuco [Recife] (UFPE), Max Planck Institute for Biogeochemistry (MPI-BGC), Max-Planck-Gesellschaft, DANIEL S. MAYNARD, LALASIA BIALIC-MURPHY, CONSTANTIN M. ZOHNER, COLIN AVERILL, JOHAN VAN DEN HOOGEN, HAOZHI MA, LIDONG MO, GABRIEL REUBEN SMITH, ALICIA T. R. ACOSTA, ISABELLE AUBIN, ERIKA BERENGUER, COLINE C. F. BOONMAN, JANE A. CATFORD, BRUNO E. L. CERABOLINI, ARILDO S. DIAS, Goethe University, ANDRÉS GONZÁLEZ-MELO, PETER HIETZ, CHRISTOPHER H. LUSK, AKIRA S. MORI, ÜLO NIINEMETS, VALÉRIO D. PILLAR, BRUNO X. PINHO, JULIETA A. ROSELL, FRANK M. SCHURR, SERGE N. SHEREMETEV, ANA CAROLINA DA SILVA, ENIO EGON SOSINSKI JUNIOR, CPACT, PETER M. VAN BODEGOM, EVAN WEIHER, GERHARD BÖNISCH, JENS KATTGE, THOMAS W. CROWTHER., Maynard, Daniel S, Bialic-Murphy, Lalasia, Zohner, Constantin M, Averill, Colin, van den Hoogen, Johan, Ma, Haozhi, Mo, Lidong, Smith, Gabriel Reuben, Acosta, A. T. R., Aubin, Isabelle, Berenguer, Erika, Boonman, Coline C F, Catford, Jane A, Cerabolini, Bruno E L, Dias, Arildo S, González-Melo, André, Hietz, Peter, Lusk, Christopher H, Mori, Akira S, Niinemets, Ülo, Pillar, Valério D, Pinho, Bruno X, Rosell, Julieta A, Schurr, Frank M, Sheremetev, Serge N, da Silva, Ana Carolina, Sosinski, Ênio, van Bodegom, Peter M, Weiher, Evan, Bönisch, Gerhard, Kattge, Jen, and Crowther, Thomas W
Subjects: Multidisciplinary, Ecology, Ecophysiology, Biodiversidade, General Physics and Astronomy, Aquatic Ecology, Floresta, General Chemistry, Árvore, Biodiversity, Forests, [SDV.BV.BOT]Life Sciences [q-bio]/Vegetal Biology/Botanics, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Plant Roots, Wood, General Biochemistry, Genetics and Molecular Biology, Trees, Plant Leaves, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Biogeography, Seeds, Plant Bark, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: Due to massive energetic investments in woody support structures, trees are subject to unique physiological, mechanical, and ecological pressures not experienced by herbaceous plants. Despite a wealth of studies exploring trait relationships across the entire plant kingdom, the dominant traits underpinning these unique aspects of tree form and function remain unclear. Here, by considering 18 functional traits, encompassing leaf, seed, bark, wood, crown, and root characteristics, we quantify the multidimensional relationships in tree trait expression. We find that nearly half of trait variation is captured by two axes: one reflecting leaf economics, the other reflecting tree size and competition for light. Yet these orthogonal axes reveal strong environmental convergence, exhibiting correlated responses to temperature, moisture, and elevation. By subsequently exploring multidimensional trait relationships, we show that the full dimensionality of trait space is captured by eight distinct clusters, each reflecting a unique aspect of tree form and function. Collectively, this work identifies a core set of traits needed to quantify global patterns in functional biodiversity, and it contributes to our fundamental understanding of the functioning of forests worldwide.Understanding patterns in woody plant trait relationships and trade-offs is challenging. Here, by applying machine learning and data imputation methods to a global database of georeferenced trait measurements, the authors unravel key relationships in tree functional traits at the global scale.
Published: 2022
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6. Activating Silent Glycolysis Bypasses in Escherichia coli

Author: Camillo Iacometti, Katharina Marx, Maria Hönick, Viktoria Biletskaia, Helena Schulz-Mirbach, Beau Dronsella, Ari Satanowski, Valérie A. Delmas, Anne Berger, Ivan Dubois, Madeleine Bouzon, Volker Döring, Elad Noor, Arren Bar-Even, Steffen N. Lindner, Max Planck Institute of Molecular Plant Physiology (MPI-MP), Max-Planck-Gesellschaft, Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Department of Plant and Environmental Science, Weizmann Institute of Science, Rehovot, 76100 Israe, Max Planck Institute of Molecular Physiology, and Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
Subjects: [SDV]Life Sciences [q-bio], General Medicine
Abstract: All living organisms share similar reactions within their central metabolism to provide precursors for all essential building blocks and reducing power. To identify whether alternative metabolic routes of glycolysis can operate in E. coli , we complementarily employed in silico design, rational engineering, and adaptive laboratory evolution. First, we used a genome-scale model and identified two potential pathways within the metabolic network of this organism replacing canonical Embden-Meyerhof-Parnas (EMP) glycolysis to convert phosphosugars into organic acids. One of these glycolytic routes proceeds via methylglyoxal and the other via serine biosynthesis and degradation. Then, we implemented both pathways in E. coli strains harboring defective EMP glycolysis. Surprisingly, the pathway via methylglyoxal seemed to immediately operate in a triosephosphate isomerase deletion strain cultivated on glycerol. By contrast, in a phosphoglycerate kinase deletion strain, the overexpression of methylglyoxal synthase was necessary to restore growth of the strain. Furthermore, we engineered the “serine shunt” which converts 3-phosphoglycerate via serine biosynthesis and degradation to pyruvate, bypassing an enolase deletion. Finally, to explore which of these alternatives would emerge by natural selection, we performed an adaptive laboratory evolution study using an enolase deletion strain. Our experiments suggest that the evolved mutants use the serine shunt. Our study reveals the flexible repurposing of metabolic pathways to create new metabolite links and rewire central metabolism.
Published: 2022
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7. Cryptic and abundant marine viruses at the evolutionary origins of Earth's RNA virome

Author: Ahmed A, Zayed, James M, Wainaina, Guillermo, Dominguez-Huerta, Eric, Pelletier, Jiarong, Guo, Mohamed, Mohssen, Funing, Tian, Akbar Adjie, Pratama, Benjamin, Bolduc, Olivier, Zablocki, Dylan, Cronin, Lindsey, Solden, Erwan, Delage, Adriana, Alberti, Jean-Marc, Aury, Quentin, Carradec, Corinne, da Silva, Karine, Labadie, Julie, Poulain, Hans-Joachim, Ruscheweyh, Guillem, Salazar, Elan, Shatoff, Ralf, Bundschuh, Kurt, Fredrick, Laura S, Kubatko, Samuel, Chaffron, Alexander I, Culley, Shinichi, Sunagawa, Jens H, Kuhn, Patrick, Wincker, Matthew B, Sullivan, Silvia G, Acinas, Marcel, Babin, Peer, Bork, Emmanuel, Boss, Chris, Bowler, Guy, Cochrane, Colomban, de Vargas, Gabriel, Gorsky, Lionel, Guidi, Nigel, Grimsley, Pascal, Hingamp, Daniele, Iudicone, Olivier, Jaillon, Stefanie, Kandels, Lee, Karp-Boss, Eric, Karsenti, Fabrice, Not, Hiroyuki, Ogata, Nicole, Poulton, Stéphane, Pesant, Christian, Sardet, Sabrinia, Speich, Lars, Stemmann, Shinichi, Sungawa, Department of Microbiology [Columbus], Ohio State University [Columbus] (OSU), Global Oceans Systems Ecology & Evolution - Tara Oceans (GOSEE), Université de Perpignan Via Domitia (UPVD)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Aix Marseille Université (AMU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Université de Toulon (UTLN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche pour le Développement (IRD [France-Nord])-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-European Molecular Biology Laboratory (EMBL)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université australe du Chili, Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Laboratoire des Sciences du Numérique de Nantes (LS2N), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Combinatoire et Bioinformatique (LS2N - équipe COMBI), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Department of Physics, The Ohio State University, Department of Statistics, the Ohio State University Columbus, Département de Biochimie, de Microbiologie et de Bio-informatique, Université Laval, Université Laval [Québec] (ULaval), Institute of Microbiology, Department of Biology, ETH Zurich, Institute of Microbiology, Department of Microbiology, The Ohio state university, Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, and Nantes Université (Nantes Univ)
Subjects: Multidisciplinary, Virome, Oceans and Seas, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Genome, Viral, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Biological Evolution, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDE]Environmental Sciences, Viruses, RNA, RNA Viruses, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Ecosystem, Phylogeny, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Whereas DNA viruses are known to be abundant, diverse, and commonly key ecosystem players, RNA viruses are insufficiently studied outside disease settings. In this study, we analyzed ≈28 terabases of Global Ocean RNA sequences to expand Earth’s RNA virus catalogs and their taxonomy, investigate their evolutionary origins, and assess their marine biogeography from pole to pole. Using new approaches to optimize discovery and classification, we identified RNA viruses that necessitate substantive revisions of taxonomy (doubling phyla and adding >50% new classes) and evolutionary understanding. “Species”-rank abundance determination revealed that viruses of the new phyla “ Taraviricota ,” a missing link in early RNA virus evolution, and “ Arctiviricota ” are widespread and dominant in the oceans. These efforts provide foundational knowledge critical to integrating RNA viruses into ecological and epidemiological models.
Published: 2022
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8. Critical Assessment of Metagenome Interpretation: the second round of challenges

Author: Fernando Meyer, Adrian Fritz, Zhi-Luo Deng, David Koslicki, Till Robin Lesker, Alexey Gurevich, Gary Robertson, Mohammed Alser, Dmitry Antipov, Francesco Beghini, Denis Bertrand, Jaqueline J. Brito, C. Titus Brown, Jan Buchmann, Aydin Buluç, Bo Chen, Rayan Chikhi, Philip T. L. C. Clausen, Alexandru Cristian, Piotr Wojciech Dabrowski, Aaron E. Darling, Rob Egan, Eleazar Eskin, Evangelos Georganas, Eugene Goltsman, Melissa A. Gray, Lars Hestbjerg Hansen, Steven Hofmeyr, Pingqin Huang, Luiz Irber, Huijue Jia, Tue Sparholt Jørgensen, Silas D. Kieser, Terje Klemetsen, Axel Kola, Mikhail Kolmogorov, Anton Korobeynikov, Jason Kwan, Nathan LaPierre, Claire Lemaitre, Chenhao Li, Antoine Limasset, Fabio Malcher-Miranda, Serghei Mangul, Vanessa R. Marcelino, Camille Marchet, Pierre Marijon, Dmitry Meleshko, Daniel R. Mende, Alessio Milanese, Niranjan Nagarajan, Jakob Nissen, Sergey Nurk, Leonid Oliker, Lucas Paoli, Pierre Peterlongo, Vitor C. Piro, Jacob S. Porter, Simon Rasmussen, Evan R. Rees, Knut Reinert, Bernhard Renard, Espen Mikal Robertsen, Gail L. Rosen, Hans-Joachim Ruscheweyh, Varuni Sarwal, Nicola Segata, Enrico Seiler, Lizhen Shi, Fengzhu Sun, Shinichi Sunagawa, Søren Johannes Sørensen, Ashleigh Thomas, Chengxuan Tong, Mirko Trajkovski, Julien Tremblay, Gherman Uritskiy, Riccardo Vicedomini, Zhengyang Wang, Ziye Wang, Zhong Wang, Andrew Warren, Nils Peder Willassen, Katherine Yelick, Ronghui You, Georg Zeller, Zhengqiao Zhao, Shanfeng Zhu, Jie Zhu, Ruben Garrido-Oter, Petra Gastmeier, Stephane Hacquard, Susanne Häußler, Ariane Khaledi, Friederike Maechler, Fantin Mesny, Simona Radutoiu, Paul Schulze-Lefert, Nathiana Smit, Till Strowig, Andreas Bremges, Alexander Sczyrba, Alice Carolyn McHardy, Braunschweig Integrated Centre of Systems Biology [Braunschweig] (BRICS), Technische Universität Braunschweig = Technical University of Braunschweig [Braunschweig]-Helmholtz Centre for Infection Research (HZI), Pennsylvania State University (Penn State), Penn State System, German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Saint Petersburg State University (SPBU), Department of Information Technology and Electrical Engineering [Zürich] (D-ITET), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Center for Algorithmic Biotechnology [Saint Petersburg], Institute of Translational Biomedicine [Saint-Petersburg], Saint Petersburg University (SPBU)-Saint Petersburg University (SPBU), Centre for Integrative Biology (CIBIO), University of Trento (CIBIO), University of Trento [Trento], Genome Institute of Singapore (GIS), University of Southern California (USC), University of California [Davis] (UC Davis), University of California (UC), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Institut Pasteur [Paris] (IP), National Food Institute [Lyngby] (Forside), Drexel University, Robert Koch Institute [Berlin] (RKI), University of Technology Sydney (UTS), DOE Joint Genome Institute [Walnut Creek], University of California [Los Angeles] (UCLA), Intel Corporation [Santa Clara], Intel Corporation [USA], Department of Plant and Environmental Sciences [Frederiksberg], University of Copenhagen = Københavns Universitet (UCPH), Fudan University [Shanghai], Beijing Genomics Institute [Shenzhen] (BGI), Novo Nordisk Foundation Center for Biosustainability, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Université de Genève = University of Geneva (UNIGE), The Arctic University of Norway [Tromsø, Norway] (UiT), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], University of California [San Diego] (UC San Diego), University of Wisconsin-Madison, Scalable, Optimized and Parallel Algorithms for Genomics (GenScale), Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hasso Plattner Institute [Potsdam, Germany], The University of Sydney, Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria), Amsterdam UMC - Amsterdam University Medical Center, Structural and Computational Biology, European Molecular Biology Laboratory [Heidelberg] (EMBL), DTU Electrical Engineering [Lyngby], National Institutes of Health [Bethesda] (NIH), Department of Biology [ETH Zürich] (D-BIOL), University of Virginia, IT University of Copenhagen (ITU), Freie Universität Berlin, University of Potsdam = Universität Potsdam, Florida International University [Miami] (FIU), National Research Council of Canada (NRC), Phase Genomics [Seattle], Max Planck Institute for Plant Breeding Research (MPIPZ), Helmholtz Centre for Infection Research (HZI), Aarhus University [Aarhus], Center for Biotechnology (CeBiTec), Universität Bielefeld = Bielefeld University, Open access funding provided by Helmholtz-Zentrum für Infektionsforschung GmbH (HZI), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), and Medical Microbiology and Infection Prevention
Subjects: 06 Biological Sciences, 10 Technology, 11 Medical and Health Sciences, Reproducibility of Results, Cell Biology, DNA, Sequence Analysis, DNA, Biochemistry, Archaea, Software, Metagenome, Metagenomics, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Molecular Biology, Sequence Analysis, Biotechnology, Developmental Biology
Abstract: Evaluating metagenomic software is key for optimizing metagenome interpretation and focus of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI). The CAMI II challenge engaged the community to assess methods on realistic and complex datasets with long- and short-read sequences, created computationally from around 1,700 new and known genomes, as well as 600 new plasmids and viruses. Here we analyze 5,002 results by 76 program versions. Substantial improvements were seen in assembly, some due to long-read data. Related strains still were challenging for assembly and genome recovery through binning, as was assembly quality for the latter. Profilers markedly matured, with taxon profilers and binners excelling at higher bacterial ranks, but underperforming for viruses and Archaea. Clinical pathogen detection results revealed a need to improve reproducibility. Runtime and memory usage analyses identified efficient programs, including top performers with other metrics. The results identify challenges and guide researchers in selecting methods for analyses., Nature Methods, 19 (8), ISSN:1548-7105, ISSN:1548-7091
Published: 2022
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9. Posttranscriptional Regulation of the Human LDL Receptor by the U2-Spliceosome

Author: Joel T. Haas, Jan Albert Kuivenhoven, Justina C. Wolters, Andrzej J. Rzepiela, Mathilde Varret, Ann Verhaegen, Valérie Carreau, Szymon Stoma, Anne Philippi, Alaa Othman, Jerome Robert, N. Dalila, Belle V. van Rosmalen, An Verrijken, Arnold von Eckardstein, Bart van de Sluis, Silvija Radosavljevic, Paolo Zanoni, Simon F. Norrelykke, Roger Meier, M. Yalcinkaya, Bart Staels, Andreas Geier, Lucia Rohrer, Michael Stebler, Michele Visentin, Antoine Rimbert, Catherine Boileau, Antonio Gallo, Melinde Wijers, Nicolette C. A. Huijkman, Steve E. Humphries, Jonas Weyler, Freerk van Dijk, Michaela Keel, Srividya Velagapudi, Jean-Pierre Rabès, Marieke Smit, Anne Tybjærg-Hansen, Adriaan van der Graaf, Luisa Vonghia, Yara Abou-Khalil, Sven Francque, Grigorios Panteloglou, Marta Futema, Luc Van Gaal, University hospital of Zurich [Zurich], Universität Zürich [Zürich] = University of Zurich (UZH), Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Scientific Center for Optical and Electron Microscopy (ScopeM), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), University of Groningen [Groningen], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), St George's, University of London, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Saint-Joseph de Beyrouth (USJ), University of Copenhagen = Københavns Universitet (UCPH), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP. Université Paris Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Antwerp University Hospital [Edegem] (UZA), University of Antwerp (UA), University of Amsterdam [Amsterdam] (UvA), Columbia University [New York], University Hospital of Würzburg, University College of London [London] (UCL), 603091, ANR-10-LABX-46, 2015T068, CVON2017-2020, AOM06024, 2014/267, Pfizer: 24052829, European Molecular Biology Organization, EMBO: ALTF277-2014, Seventh Framework Programme, FP7, Sixth Framework Programme, FP6: LSHM-CT-2005-018734, Fondation Maladies Rares, FMR, International Atherosclerosis Society, IAS, British Heart Foundation, BHF, European Commission, EC, European Research Council, ERC: 694717, ANR 16-RHUS-0006, Agence Nationale de la Recherche, ANR: ANR-16-RHUS-0007, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNF: 310030-185109, 31003A-160126, Fonds De La Recherche Scientifique - FNRS, FNRS, Fonds Wetenschappelijk Onderzoek, FWO: 1802154 N, PG008/08, RG3008, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, NWO: 184.021.007, Universität Zürich, UZH: FK-20-037, We acknowledge the use of data from BIOS-consortium ( http://wiki.bbmri.nl/wiki/BIOS_bios ) which is funded by BBMRI-NL (NWO project 184.021.007). Flow cytometry was performed with equipment of the flow cytometry facility, University of Zurich., This work was conducted as part of the TransCard project of the seventh Framework Program (FP7) granted by the European Commission, to J. Albert Kuivenhoven, A. Tybjaerg-Hansen, and A. von Eckardstein (number 603091) as well as partially the FP7 RESOLVE project (to J.T. Haas, B. Staels, A. Verhaegen, S. Francque, L. Van Gaal, and A. von Eckardstein) and the European Genomic Institute for Diabetes (EGID, ANR-10-LABX-46 to B. Staels). Additional work by A. von Eckardstein’s team was funded by the Swiss National Science Foundation (31003A-160126, 310030-185109) and the Swiss Systems X program (2014/267 [Medical Research and Development (MRD)] HDL-X). P. Zanoni received funding awards from the Swiss Atherosclerosis Society (Arbeitsgruppe Lipide und Atherosklerose [AGLA] and the DACH Society for Prevention of Cardiovascular Diseases). G. Panteloglou received funding from the University of Zurich (Forschungskredit, grant no. FK-20-037). J. Albert Kuivenhoven is an Established Investigator from the Dutch Heart Foundation (2015T068). J. Albert Kuivenhoven was also supported by GeniusII (CVON2017-2020). The Laboratory for Vascular Translational Science (L.V.T.S.) team is supported by Fondation Maladies Rares, Programme Hospitalier de Recherche Clinique (PHRC) (AOM06024), and the national project CHOPIN (CHolesterol Personalized Innovation), granted by the Agence Nationale de la Recherche (ANR-16-RHUS-0007). Y. Abou Khalil is supported by a grant from Ministère de l’Education Nationale et de la Technologie (France). J.T. Haas was supported by an EMBO Long Term Fellowship (ALTF277-2014). B. Staels is a recipient of an ERC Advanced Grant (no. 694717). Both are also supported by PreciNASH (ANR 16-RHUS-0006). Research at the Antwerp University Hospital was supported by the European Union: FP6 (HEPADIP Contract LSHM-CT-2005-018734). S. Francque has a senior clinical research fellowship from the Fund for Scientific Research (FWO) Flanders (1802154 N). S.E. Humphries received grants RG3008 and PG008/08 from the British Heart Foundation, and the support of the UCLH NIHR BRC. S.E. Humphries directs the UK Children’s FH Register which has been supported by a grant from Pfizer (24052829) given by the International Atherosclerosis Society., This work was conducted as part of the TransCard project of the seventh Framework Program (FP7) granted by the European Commission, to J. Albert Kuivenhoven, A. Tybjaerg-Hansen, and A. von Eckardstein (number 603091) as well as partially the FP7 RESOLVE project (to J.T. Haas, B. Staels, A. Verhaegen, S. Francque, L. Van Gaal, and A. von Eckardstein) and the European Genomic Institute for Diabetes (EGID, ANR-10-LABX-46 to B. Staels). Additional work by A. von Eckardstein's team was funded by the Swiss National Science Foundation (31003A-160126, 310030-185109) and the Swiss Systems X program (2014/267 [Medical Research and Development (MRD)] HDL-X). P. Zanoni received funding awards from the Swiss Atherosclerosis Society (Arbeitsgruppe Lipide und Atherosklerose [AGLA] and the DACH Society for Prevention of Cardiovascular Diseases). G. Panteloglou received funding from the University of Zurich (Forschungskredit, grant no. FK-20-037). J. Albert Kuivenhoven is an Established Investigator from the Dutch Heart Foundation (2015T068). J. Albert Kuivenhoven was also supported by GeniusII (CVON2017-2020). The Laboratory for Vascular Translational Science (L.V.T.S.) team is supported by Fondation Maladies Rares, Programme Hospitalier de Recherche Clinique (PHRC) (AOM06024), and the national project CHOPIN (CHolesterol Personalized Innovation), granted by the Agence Nationale de la Recherche (ANR-16-RHUS-0007). Y. Abou Khalil is supported by a grant from Minist?re de l'Education Nationale et de la Technologie (France). J.T. Haas was supported by an EMBO Long Term Fellowship (ALTF277-2014). B. Staels is a recipient of an ERC Advanced Grant (no. 694717). Both are also supported by PreciNASH (ANR 16-RHUS-0006). Research at the Antwerp University Hospital was supported by the European Union: FP6 (HEPADIP Contract LSHMCT- 2005-018734). S. Francque has a senior clinical research fellowship from the Fund for Scientific Research (FWO) Flanders (1802154 N). S.E. Humphries received grants RG3008 and PG008/08 from the British Heart Foundation, and the support of the UCLH NIHR BRC. S.E. Humphries directs the UK Children's FH Register which has been supported by a grant from Pfizer (24052829) given by the International Atherosclerosis Society., ANR-16-RHUS-0006,PreciNASH,PreciNASH(2016), ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016), Center for Liver, Digestive and Metabolic Diseases (CLDM), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), HAL UVSQ, Équipe, Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires (RNMCD - U1011), Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Spliceosome, Physiology, RNA Splicing, Population, Hypercholesterolemia, Familial hypercholesterolemia, 030204 cardiovascular system & hematology, Biology, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Gene expression, medicine, Humans, education, Gene, 030304 developmental biology, 0303 health sciences, Gene knockdown, education.field_of_study, Intron, Nuclear Proteins, Hep G2 Cells, medicine.disease, Molecular biology, Endocytosis, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Lipoproteins, LDL, Cholesterol, HEK293 Cells, Cardiovascular diseases, Liver, Receptors, LDL, Mutation, LDL receptor, Hepatocytes, Spliceosomes, lipids (amino acids, peptides, and proteins), Human medicine, Cardiology and Cardiovascular Medicine
Abstract: Background: The LDLR (low-density lipoprotein receptor) in the liver is the major determinant of LDL-cholesterol levels in human plasma. The discovery of genes that regulate the activity of LDLR helps to identify pathomechanisms of hypercholesterolemia and novel therapeutic targets against atherosclerotic cardiovascular disease. Methods: We performed a genome-wide RNA interference screen for genes limiting the uptake of fluorescent LDL into Huh-7 hepatocarcinoma cells. Top hit genes were validated by in vitro experiments as well as analyses of data sets on gene expression and variants in human populations. Results: The knockdown of 54 genes significantly inhibited LDL uptake. Fifteen of them encode for components or interactors of the U2-spliceosome. Knocking down any one of 11 out of 15 genes resulted in the selective retention of intron 3 of LDLR . The translated LDLR fragment lacks 88% of the full length LDLR and is detectable neither in nontransfected cells nor in human plasma. The hepatic expression of the intron 3 retention transcript is increased in nonalcoholic fatty liver disease as well as after bariatric surgery. Its expression in blood cells correlates with LDL-cholesterol and age. Single nucleotide polymorphisms and 3 rare variants of one spliceosome gene, RBM25 , are associated with LDL-cholesterol in the population and familial hypercholesterolemia, respectively. Compared with overexpression of wild-type RBM25 , overexpression of the 3 rare RBM25 mutants in Huh-7 cells led to lower LDL uptake. Conclusions: We identified a novel mechanism of posttranscriptional regulation of LDLR activity in humans and associations of genetic variants of RBM25 with LDL-cholesterol levels.
Published: 2022
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10. Integrative omics framework for characterization of coral reef ecosystems from the Tara Pacific expedition

Author: Caroline Belser, Julie Poulain, Karine Labadie, Frederick Gavory, Adriana Alberti, Julie Guy, Quentin Carradec, Corinne Cruaud, Corinne da Silva, Stefan Engelen, Paul Mielle, Aude Perdereau, Gaelle Samson, Shahinaz Gas, Genoscope Technical Team, Voolstra, Christian R., Galand, Pierre E., Michel Flores, J., Benjamin Cc Hume, Gabriela Perna, Maren Ziegler, Hans-Joachim Ruscheweyh, Emilie Boissin, Sarah Romac, Guillaume Bourdin, Guillaume Iwankow, Clémentine Moulin, Paz García, David A., Sylvain Agostini, Bernard Banaigs, Emmanuel Boss, Chris Bowler, Colomban de Vargas, Éric Douville, Didier Forcioli, Paola Furla, Éric Gilson, Fabien Lombard, Stephane Pesant, Stéphanie Reynaud, Shinichi Sunagawa, Olivier Thomas, Romain Troublé, Rebecca Vega Thurber, Didier Zoccola, Claude Scarpelli, Krame Jacoby, E., Oliveira, Pedro H., Jean-Marc Aury, Denis Allemand, Serge Planes, Patrick Wincker, Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universität Konstanz, Laboratoire d'Ecogéochimie des environnements benthiques (LECOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Weizmann Institute of Science [Rehovot, Israël], Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Centre de recherches insulaires et observatoire de l'environnement (CRIOBE), Université de Perpignan Via Domitia (UPVD)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Maine, Tara Expéditions, Centro de Investigaciones Biologicas del Noroeste [Mexico] (CONACYT-CIBNOR), Consejo Nacional de Ciencia y Tecnología [Mexico] (CONACYT), Université de Tsukuba = University of Tsukuba, Laboratoire d'Excellence CORAIL (LabEX CORAIL), Institut de Recherche pour le Développement (IRD)-Université des Antilles et de la Guyane (UAG)-École des hautes études en sciences sociales (EHESS)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de La Réunion (UR)-Université de la Polynésie Française (UPF)-Université de la Nouvelle-Calédonie (UNC)-Institut d'écologie et environnement-Université des Antilles (UA), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Géochrononologie Traceurs Archéométrie (GEOTRAC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA), Laboratoire d'océanographie de Villefranche (LOV), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), European Molecular Biology Laboratory (EMBL), Centre Scientifique de Monaco (CSM), National University of Ireland [Galway] (NUI Galway), Oregon State University (OSU), Menguy, Caroline, Université de Perpignan Via Domitia (UPVD)-École pratique des hautes études (EPHE), and Institut de Recherche pour le Développement (IRD)-Université des Antilles et de la Guyane (UAG)-École des hautes études en sciences sociales (EHESS)-École pratique des hautes études (EPHE)
Subjects: FOS: Biological sciences, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Quantitative Biology - Quantitative Methods, Quantitative Methods (q-bio.QM), [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract: Coral reef science is a fast-growing field propelled by the need to better understand coral health and resilience to devise strategies to slow reef loss resulting from environmental stresses. Key to coral resilience are the symbiotic interactions established within a complex holobiont, i.e. the multipartite assemblages comprising the host coral organism, endosymbiotic dinoflagellates, bacteria, archaea, fungi, and viruses. Tara Pacific is an ambitious project built upon the experience of previous Tara Oceans expeditions, and leveraging state-of-the-art sequencing technologies and analyses to dissect the biodiversity and biocomplexity of the coral holobiont screened across most archipelagos spread throughout the entire Pacific Ocean. Here we detail the Tara Pacific workflow for multi-omics data generation, from sample handling to nucleotide sequence data generation and deposition. This unique multidimensional framework also includes a large amount of concomitant metadata collected side-by-side that provide new assessments of coral reef biodiversity including micro-biodiversity and shape future investigations of coral reef dynamics and their fate in the Anthropocene.
Published: 2022
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11. CD44v6 Defines a New Population of Circulating Tumor Cells Not Expressing EpCAM

Author: Zeinab Homayed, Gérald Lossaint, Thibault Mazard, Sophie Bravo, Jérôme Solassol, Emilie Mamessier, Jai Smith, Julie A. Vendrell, Olivia Villeronce, Marc Ychou, Emmanuelle Samalin, Guillaume Belthier, Fanny Grillet, Frédéric Hollande, Jihane Vitre-Boubaker, Matthieu Merlot, Julie Pannequin, Nicola Aceto, Jean-Marc Pascussi, Françoise Macari-Fine, François Bertucci, Diana Heaug-Wane, Fabienne Portales, Ilona Krol, Christophe Duperray, Jean-Christophe Boyer, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), MRI-Cytométrie-IRB [CHU Montpellier] (Montpellier RIO Imaging), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), University of Melbourne, Victorian Comprehensive Cancer Centre [Melbourne, Australia] (V3C), Institut du Cancer de Montpellier (ICM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), BioCampus (BCM), Guerineau, Nathalie C., CHU Montpellier, Department of Biology [ETH Zürich] (D-BIOL), Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)
Subjects: Cancer Research, circulating tumor cells, colorectal cancer, breast cancer, biomarker, patient blood samples, EMT, Colorectal cancer, [SDV]Life Sciences [q-bio], Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, 0302 clinical medicine, Circulating tumor cell, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, RC254-282, 030304 developmental biology, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, business.industry, CD44, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, New population, 3. Good health, Biomarker (cell), [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Oncology, Cell culture, 030220 oncology & carcinogenesis, Cancer research, biology.protein, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Simple Summary In the present work, we describe (for the first time) the use of the transmembrane protein, CD44v6, to detect CTCs from blood samples of several patients with colorectal or breast cancer. We used CD44v6 antibodies to demonstrate that live CTCs can be specifically purified from CRC patient blood samples via magnetic bead- or FACS-based isolation techniques. Finally, we demonstrated that CD44v6-positive CTCs rarely expressed EpCam, which is currently the gold standard to enumerate CTCs, suggesting the need to use a combination of markers for a more comprehensive view of CTC heterogeneity. Abstract Circulating tumor cells (CTCs) are promising diagnostic and prognostic tools for clinical use. In several cancers, including colorectal and breast, the CTC load has been associated with a therapeutic response as well as progression-free and overall survival. However, counting and isolating CTCs remains sub-optimal because they are currently largely identified by epithelial markers such as EpCAM. New, complementary CTC surface markers are therefore urgently needed. We previously demonstrated that a splice variant of CD44, CD44 variable alternative exon 6 (CD44v6), is highly and specifically expressed by CTC cell lines derived from blood samples in colorectal cancer (CRC) patients. Two different approaches—immune detection coupled with magnetic beads and fluorescence-activated cell sorting—were optimized to purify CTCs from patient blood samples based on high expressions of CD44v6. We revealed the potential of the CD44v6 as a complementary marker to EpCAM to detect and purify CTCs in colorectal cancer blood samples. Furthermore, this marker is not restricted to colorectal cancer since CD44v6 is also expressed on CTCs from breast cancer patients. Overall, these results strongly suggest that CD44v6 could be useful to enumerate and purify CTCs from cancers of different origins, paving the way to more efficacious combined markers that encompass CTC heterogeneity.
Published: 2021
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12. Bradyrhizobium diazoefficiens Requires Chemical Chaperones To Cope with Osmotic Stress during Soybean Infection

Author: Raphael Ledermann, Barbara Emmenegger, Jean-Malo Couzigou, Nicola Zamboni, Patrick Kiefer, Julia A. Vorholt, Hans-Martin Fischer, ETH Zurich, Institute of Microbiology, Zurich, Switzerland, Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Department of Biology [ETH Zürich] (D-BIOL), and Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)
Subjects: compatible solutes, [SDV]Life Sciences [q-bio], Bradyrhizobium diazoefficiens, general stress response, nitrogen fixation, symbiosis, trehalose, food and beverages, Amino Acids, Diamino, Trehalose, Plant Root Nodulation, Microbiology, QR1-502, Betaine, Bacterial Proteins, Osmotic Pressure, Bradyrhizobium, Soybeans, Root Nodules, Plant, Research Article
Abstract: When engaging in symbiosis with legume hosts, rhizobia are confronted with environmental changes, including nutrient availability and stress exposure. Genetic circuits allow responding to these environmental stimuli to optimize physiological adaptations during the switch from the free-living to the symbiotic life style. A pivotal regulatory system of the nitrogen-fixing soybean endosymbiont Bradyrhizobium diazoefficiens for efficient symbiosis is the general stress response (GSR), which relies on the alternative sigma factor σEcfG. However, the GSR-controlled process required for symbiosis has not been identified. Here, we demonstrate that biosynthesis of trehalose is under GSR control, and mutants lacking the respective biosynthetic genes otsA and/or otsB phenocopy GSR-deficient mutants under symbiotic and selected free-living stress conditions. The role of trehalose as a cytoplasmic chemical chaperone and stress protectant can be functionally replaced in an otsA or otsB mutant by introducing heterologous genetic pathways for biosynthesis of the chemically unrelated compatible solutes glycine betaine and (hydroxy)ectoine. Alternatively, uptake of exogenously provided trehalose also restores efficient symbiosis and tolerance to hyperosmotic and hyperionic stress of otsA mutants. Hence, elevated cytoplasmic trehalose levels resulting from GSR-controlled biosynthesis are crucial for B. diazoefficiens cells to overcome adverse conditions during early stages of host infection and ensure synchronization with root nodule development. IMPORTANCE The Bradyrhizobium-soybean symbiosis is of great agricultural significance and serves as a model system for fundamental research in bacterium-plant interactions. While detailed molecular insight is available about mutual recognition and early nodule organogenesis, our understanding of the host-imposed conditions and the physiology of infecting rhizobia during the transition from a free-living state in the rhizosphere to endosymbiotic bacteroids is currently limited. In this study, we show that the requirement of the rhizobial general stress response (GSR) during host infection is attributable to GSR-controlled biosynthesis of trehalose. Specifically, trehalose is crucial for an efficient symbiosis by acting as a chemical chaperone to protect rhizobia from osmostress during host infection., mBio, 12 (2), ISSN:2150-7511, ISSN:2161-2129
Published: 2021
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13. A lamin A/C variant causing striated muscle disease provides insights into filament organization

Author: Wei Wu, Gisèle Bonne, Matthias Eibauer, Ji-Yeon Shin, Refael Kronenberg-Tenga, Howard J. Worman, Meltem Tatli, Ohad Medalia, University of Zurich, Medalia, Ohad, Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Monsanto Company, Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Columbia University [New York], Gestionnaire, HAL Sorbonne Université 5, and Centre de recherche en Myologie – U974 SU-INSERM
Subjects: [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], congenital, hereditary, and neonatal diseases and abnormalities, Heterochromatin, Lamin binding, 610 Medicine & health, macromolecular substances, Biology, LMNA, Protein filament, 1307 Cell Biology, 03 medical and health sciences, Mice, 0302 clinical medicine, Myosin, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], 10019 Department of Biochemistry, Animals, Muscular dystrophy, Intermediate filament, Cytoskeleton, 030304 developmental biology, 0303 health sciences, Nuclear Lamina, integumentary system, Lamin Type B, Chemistry, Cell Biology, medicine.disease, Lamin Type A, Muscle, Striated, Chromatin, Cell biology, embryonic structures, Mutation, Nuclear lamina, 570 Life sciences, biology, 030217 neurology & neurosurgery, Lamin, Research Article
Abstract: TheLMNAgene encodes the A-type lamins that polymerize into ~3.5 nm thick filaments, and together with B-type lamins and lamin binding proteins form the nuclear lamina. Mutations inLMNAare associated with a wide variety of pathologies. In this study, we analyzed the nuclear lamina of embryonic fibroblasts fromLmnaH222P/H222Pmice, which develop cardiomyopathy and muscular dystrophy. Although the organization of the lamina appeared unaltered, there were changes in chromatin and B-type lamin expression. An increase in nuclear size and consequently a relative reduction in heterochromatin near the lamina allowed for a higher resolution structural analysis of lamin filaments using cryo-electron tomography. This was most apparent when visualizing lamin filamentsin situ, and using a nuclear extraction protocol. Averaging of individual segments of filaments inLmnaH222P/H222Pmouse fibroblasts resolved two-polymers that constitute the mature filaments. Our findings provide better views of the organization of lamin filaments and the effect of a striated muscle disease-causing mutation on nuclear structure.
Published: 2021

14. Morphological bases of phytoplankton energy management and physiological responses unveiled by 3D subcellular imaging

Author: Guy Schoehn, Clarisse Uwizeye, Gilles Curien, Rachel Templin, Samuel C. Zeeman, Yannick Schwab, Davide Dal Bo, Denis Falconet, Fabien Chevalier, Serena Flori, Christine Moriscot, Florence Courtois, Claire Seydoux, Jean-Baptiste Keck, Benoit Gallet, Johan Decelle, Nicole L. Schieber, Pierre-Henri Jouneau, Giovanni Finazzi, Guillaume Allorent, LIPID, Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Photosymbiose, Modélisation et Exploration des Matériaux (MEM), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Light Photosynthesis & Metabolism (Photosynthesis), Institut de biologie structurale (IBS - UMR 5075), Calcul des Variations, Géométrie, Image (CVGI), Laboratoire Jean Kuntzmann (LJK), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Cell Biology and Cell Biophysics Unit, European Molecular Biology Laboratory, European Molecular Biology Laboratory [Grenoble] (EMBL), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Défi X-Life grant from CNRS, CEA DRFimpulsion FIB-Bioprogram, Auvergne-Rhône-Alpes Region, Fondation Recherche Medicale (FRM), FEDER and the GIS-Infrastructures en Biologie Santé et Agronomie (IBiSA), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-17-CE05-0029,MoMix,Modélisation de la Mixotrophie chez l'algue extrêmophile Galdieria sulphuraria(2017), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-15-IDEX-0002,UGA,IDEX UGA(2015), European Project: 833184, ChloroMito, and European Project: 654248,H2020,H2020-INFRADEV-1-2014-1,CORBEL(2015)
Subjects: 0106 biological sciences, 0301 basic medicine, Cell biology, Light, Bioenergetics, MESH: Mitochondria, Acclimatization, Science, General Physics and Astronomy, MESH: Acclimatization, MESH: Imaging, Three-Dimensional, Cellular imaging, Photosynthesis, 01 natural sciences, Article, General Biochemistry, Genetics and Molecular Biology, Pyrenoid, MESH: Microalgae, 03 medical and health sciences, Imaging, Three-Dimensional, Phytoplankton, Microalgae, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Plastids, Plastid, Cellular microbiology, Trophic level, Biomass (ecology), Multidisciplinary, biology, Ecology, MESH: Energy Metabolism, fungi, MESH: Plastids, General Chemistry, biology.organism_classification, MESH: Light, Mitochondria, 030104 developmental biology, Diatom, MESH: Subcellular Fractions, Energy Metabolism, Subcellular Fractions, MESH: Phytoplankton, 010606 plant biology & botany
Abstract: Eukaryotic phytoplankton have a small global biomass but play major roles in primary production and climate. Despite improved understanding of phytoplankton diversity and evolution, we largely ignore the cellular bases of their environmental plasticity. By comparative 3D morphometric analysis across seven distant phytoplankton taxa, we observe constant volume occupancy by the main organelles and preserved volumetric ratios between plastids and mitochondria. We hypothesise that phytoplankton subcellular topology is modulated by energy-management constraints. Consistent with this, shifting the diatom Phaeodactylum from low to high light enhances photosynthesis and respiration, increases cell-volume occupancy by mitochondria and the plastid CO2-fixing pyrenoid, and boosts plastid-mitochondria contacts. Changes in organelle architectures and interactions also accompany Nannochloropsis acclimation to different trophic lifestyles, along with respiratory and photosynthetic responses. By revealing evolutionarily-conserved topologies of energy-managing organelles, and their role in phytoplankton acclimation, this work deciphers phytoplankton responses at subcellular scales., Nature Communications, 12 (1), ISSN:2041-1723
Published: 2021
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15. A wheat cysteine-rich receptor-like kinase confers broad-spectrum resistance against Septoria tritici blotch

Author: Bruno Favery, Seyed Mahmoud Tabib Ghaffary, Cyrille Saintenac, Lamia Aouini, Julien Alassimone, Gert H. J. Kema, Oliver Robert, Andrea Sánchez-Vallet, Florence Cambon, Justin D. Faris, Thierry Langin, Théo Poucet, Hélène Berges, E.C.P. Verstappen, Maëlle Jaouannet, William Marande, Steven S. Xu, Génétique Diversité et Ecophysiologie des Céréales (GDEC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Wageningen University and Research [Wageningen] (WUR), Department of agronomy and Earth and Atmospheric Sciences [West Lafayette], Purdue University [West Lafayette], Seed and Plant Improvement Research Department, Agricultural Research, Education and Extension Organisation (AREEO ), Department of Plant Biology and Ecology (Bilbao, Spain), Universidad del Pais Vasco / Euskal Herriko Unibertsitatea [Espagne] (UPV/EHU), Université de Bordeaux Ségalen [Bordeaux 2], Centre National de Ressources Génomiques Végétales (CNRGV), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 1.Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, U.S.A., Cereal Crops Research Unit, USDA-ARS : Agricultural Research Service, Institut Sophia Agrobiotech (ISA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Côte d'Azur (UCA), Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Centro de Biotecnologia y Genomica de Plantas (CBGP), Laboratory of Phytopathology, Florimond Desprez, ETH Zurich Career Seed Grant (SEED-58 16-1)Fond de Soutien à l’Obtention Végétale, ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), Université Nice Sophia Antipolis (... - 2019) (UNS), Institut National de la Recherche Agronomique (France), ETH Zurich, Saintenac, Cyrille [0000-0002-3791-301X], Aouini, Lamia [0000-0001-6605-3488], Ghaffary, Seyed Mahmoud Tabib [0000-0001-7372-4163], Poucet, Théo [0000-0001-8910-9245], Berges, Hélène [0000-0002-5492-1062], Jaouannet, Maëlle [0000-0001-6635-5363], Favery, Bruno [0000-0003-3323-1852], Alassimone, Julien [0000-0002-8118-2605], Sánchez-Vallet, Andrea [0000-0002-3668-9503], Faris, Justin [0000-0002-9653-3287], Kema, Gert [0000-0002-2732-6911], Langin, Thierry [0000-0003-4955-4277], Saintenac, Cyrille, Aouini, Lamia, Ghaffary, Seyed Mahmoud Tabib, Poucet, Théo, Berges, Hélène, Jaouannet, Maëlle, Favery, Bruno, Alassimone, Julien, Sánchez-Vallet, Andrea, Faris, Justin, Kema, Gert, and Langin, Thierry
Subjects: 0106 biological sciences, 0301 basic medicine, Unclassified drug, [SDV]Life Sciences [q-bio], General Physics and Astronomy, secreted protein, avirulence, 01 natural sciences, Plant breeding, Septoria, Pathogen, Triticum, Disease Resistance, Plant Proteins, aegilops-tauschii, 2. Zero hunger, Genetics, region, Multidisciplinary, Phosphotransferase, 1. No poverty, food and beverages, Complementary DNA, Plants, Genetically Modified, 3. Good health, Complementation, rotein serine threonine kinase, Seeds, reveals, Crops, Agricultural, Science, Mutagenesis (molecular biology technique), Virulence, Protein Serine-Threonine Kinases, Plant disease resistance, Biology, Genes, Plant, Article, General Biochemistry, Genetics and Molecular Biology, Plant protein, Biointeractions and Plant Health, 03 medical and health sciences, Plant immunity, Ascomycota, zymoseptoria-tritici, cultivars, Life Science, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Cysteine, genome, Gene, Cysteine rich receptor like kinase, Alleles, Comparative genomics, disease, Cell Membrane, General Chemistry, biology.organism_classification, Laboratorium voor Phytopathologie, 030104 developmental biology, Laboratory of Phytopathology, identification, EPS, 010606 plant biology & botany
Abstract: 10 Pág. Centro de Biotecnología y Genómica de Plantas (CBGP), The poverty of disease resistance gene reservoirs limits the breeding of crops for durable resistance against evolutionary dynamic pathogens. Zymoseptoria tritici which causes Septoria tritici blotch (STB), represents one of the most genetically diverse and devastating wheat pathogens worldwide. No fully virulent Z. tritici isolates against synthetic wheats carrying the major resistant gene Stb16q have been identified. Here, we use comparative genomics, mutagenesis and complementation to identify Stb16q, which confers broad-spectrum resistance against Z. tritici. The Stb16q gene encodes a plasma membrane cysteine-rich receptor-like kinase that was recently introduced into cultivated wheat and which considerably slows penetration and intercellular growth of the pathogen., Our works was supported by the “Fond de Soutien à l’Obtention Vegetale” (FSOV), the French National Institute for Agricultural Research (INRA), and the ETH Zurich Career Seed Grant (SEED-58 16-1). We thank Sreedhar Kilaru and Gero Steinberg for providing the strain 3D7 expressing eGFP. Confocal laser scanning microscopy experiments were performed in the Scientific Center for Optical and Electron Microscopy (ScopeM), ETH Zurich and at the SPIBOC imaging facility of the Institut Sophia Agrobiotech. B.F. was supported by INRA and the French Government (National Research Agency, ANR) through the ‘Investments for the Future’ LabEx SIGNALIFE: program reference #ANR-11-LABX-0028-01.
Published: 2021
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16. Two distinct phases of chloroplast biogenesis during de-etiolation in Arabidopsis thaliana

Author: Rosa Pipitone, Simona Eicke, Barbara Pfister, Gaetan Glauser, Denis Falconet, Clarisse Uwizeye, Thibaut Pralon, Samuel Zeeman, Felix Kessler, Emilie Demarsy, Physiologie Végétale, University of Neuchâtel, Université de Neuchâtel (UNINE), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Neuchâtel Platform of Analytical Chemistry (NPAC), LIPID, Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Botany and Plant Biology, University of Geneva, Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), and Université de Genève = University of Geneva (UNIGE)
Subjects: 0106 biological sciences, 0303 health sciences, 03 medical and health sciences, food and beverages, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 01 natural sciences, 030304 developmental biology, 010606 plant biology & botany
Abstract: Light triggers chloroplast differentiation whereby the etioplast transforms into a photosynthesizing chloroplast and the thylakoid rapidly emerges. However, the sequence of events during chloroplast differentiation remains poorly understood. Using Serial Block Face Scanning Electron Microscopy (SBF-SEM), we generated a series of chloroplast 3D reconstructions during differentiation, revealing chloroplast number and volume and the extent of envelope and thylakoid membrane surfaces. Furthermore, we used quantitative lipid and whole proteome data to complement the (ultra)structural data, providing a time-resolved, multi-dimensional description of chloroplast differentiation. This showed two distinct phases of chloroplast biogenesis: an initial photosynthesis-enabling ‘Structure Establishment Phase’ followed by a ‘Chloroplast Proliferation Phase’ during cell expansion. Moreover, these data detail thylakoid membrane expansion during de-etiolation at the seedling level and the relative contribution and differential regulation of proteins and lipids at each developmental stage. Altogether, we establish a roadmap for chloroplast differentiation, a critical process for plant photoautotrophic growth and survival.
Published: 2020

17. In-cell quantitative structural imaging of phytoplankton using 3D electron microscopy

Author: Nicole L. Schieber, Gilles Curien, Rachel Templin, Johan Decelle, Jean-Baptiste Keck, Samuel C. Zeeman, Denis Falconet, Pierre-Henri Jouneau, Christine Moriscot, Guy Schoehn, Fabien Chevalier, Giovanni Finazzi, Clarisse Uwizeye, Benoit Gallet, Yannick Schwab, LIPID, Physiologie cellulaire et végétale (LPCV), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Light Photosynthesis & Metabolism (Photosynthesis), Modélisation et Exploration des Matériaux (MEM), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de biologie structurale (IBS - UMR 5075), Calcul des Variations, Géométrie, Image (CVGI), Laboratoire Jean Kuntzmann (LJK), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Integrated Structural Biology Grenoble (ISBG - UMS 3518 ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), European Molecular Biology Laboratory (EMBL), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), This project received funding from the European Research Council: ERC Chloro-mito (grant no. 833184). Research was also supported by a Défi X-Life grant from CNRS, funds from the CEA DRF impulsion FIB-Bio program, the LabEx GRAL (ANR-10-LABX-49-01), financed within the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS (ANR-17-EURE-0003) and the ANR ‘Momix’ (Projet-ANR-17-CE05-0029). This project also received funds from the European Union’s Horizon 2020 research and innovation programme CORBEL under the grant agreement No 654248. This work used the platforms of the Grenoble Instruct-ERIC centre (ISBG, UMS 3518 CNRS-CEA-UGA-EMBL) within the Grenoble Partnership for Structural Biology (PSB), supported by FRISBI (ANR-10-INBS-05-02) and GRAL. The electron microscope facility is supported by the Auvergne-Rhône-Alpes Region, the Fondation Recherche Medicale (FRM), the funds FEDER and the GIS-Infrastructures en Biologie Santé et Agronomie (IBISA). J.D. was supported by ATIP-Avenir program. C.U. is supported by a joint UGA-ETH Zurich PhD grant in the framework of the 'Investissements d’avenir' programme (ANR-15-IDEX-02). The authors thank the Roscoff Culture Collection that provided phytoplankton strains and Noan Le Bescot (Ternog Design) for help in the conception and realisation of the figures of this article., ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), ANR-17-CE05-0029,MoMix,Modélisation de la Mixotrophie chez l'algue extrêmophile Galdieria sulphuraria(2017), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-15-IDEX-0002,UGA,IDEX UGA(2015), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), and Integrated Structural Biology Grenoble (ISBG)
Subjects: 0106 biological sciences, Abiotic component, 0303 health sciences, Biomass (ecology), Biotic component, Chemistry, [SDV]Life Sciences [q-bio], fungi, Genomics, 01 natural sciences, Chromatin, 03 medical and health sciences, Phytoplankton, Organelle, Biophysics, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, 030304 developmental biology, 010606 plant biology & botany, Biomineralization
Abstract: Phytoplankton is a minor fraction of the global biomass playing a major role in primary production and climate. Despite improved understanding of phytoplankton diversity and genomics, we lack nanoscale subcellular imaging approaches to understand their physiology and cell biology. Here, we present a complete Focused Ion Beam - Scanning Electron Microscopy (FIB-SEM) workflow (from sample preparation to image processing) to generate nanometric 3D phytoplankton models. Tomograms of entire cells, representatives of six ecologically-successful phytoplankton unicellular eukaryotes, were used for quantitative morphometric analysis. Besides lineage-specific cellular architectures, we observed common features related to cellular energy management: i) conserved cell-volume fractions occupied by the different organelles; ii) consistent plastid-mitochondria interactions, iii) constant volumetric ratios in these energy-producing organelles. We revealed detailed subcellular features related to chromatin organization and to biomineralization. Overall, this approach opens new perspectives to study phytoplankton acclimation responses to abiotic and biotic factors at a relevant biological scale.
Published: 2020

18. ScalaFlux: a scalable approach to quantify fluxes in metabolic subnetworks

Author: Julia A. Vorholt, Patrick Kiefer, Stéphanie Heux, Jean-Charles Portais, Uwe Schmitt, Pierre Millard, Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Scientific IT Services, Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Métabolomique et Fluxomique (MetaToul) (TBI-MetaToul), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (Inserm), ETH Zurich, ANR-16-CE11-0022,ENZINVIVO,Détermination in vivo des paramètres enzymatiques dans une voie métabolique synthétique(2016), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Department of Biology, University of Memphis, Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul FluxoMet (TBI-MetaToul), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Metabolic Analysis, 0301 basic medicine, 0106 biological sciences, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Computer science, Biochemistry, Physical Chemistry, 01 natural sciences, 0302 clinical medicine, Polyisoprenyl Phosphates, Metabolic flux analysis, Metabolites, Biology (General), Subnetwork, flux métabolique, Carbon Isotopes, 0303 health sciences, Ecology, Simulation and Modeling, Systems Biology, metabolic flux, 3. Good health, Chemistry, Bioassays and Physiological Analysis, Reaction Dynamics, Metabolic Engineering, Computational Theory and Mathematics, Modeling and Simulation, Physical Sciences, Scalability, Metabolic Labeling, Metabolic Pathways, Biological system, Network Analysis, Metabolic Networks and Pathways, Research Article, Computer and Information Sciences, QH301-705.5, Systems biology, Saccharomyces cerevisiae, Research and Analysis Methods, Biosynthesis, Models, Biological, Metabolic engineering, Metabolic Networks, Cellular and Molecular Neuroscience, 03 medical and health sciences, 010608 biotechnology, Genetics, Molecular Biology Techniques, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Terpenes, Biology and Life Sciences, Robustness (evolution), Missing data, Metabolic Flux Analysis, Metabolic pathway, Metabolism, 030104 developmental biology, Cell Labeling, Identifiability, 030217 neurology & neurosurgery
Abstract: 13C-metabolic flux analysis (13C-MFA) allows metabolic fluxes to be quantified in living organisms and is a major tool in biotechnology and systems biology. Current 13C-MFA approaches model label propagation starting from the extracellular 13C-labeled nutrient(s), which limits their applicability to the analysis of pathways close to this metabolic entry point. Here, we propose a new approach to quantify fluxes through any metabolic subnetwork of interest by modeling label propagation directly from the metabolic precursor(s) of this subnetwork. The flux calculations are thus purely based on information from within the subnetwork of interest, and no additional knowledge about the surrounding network (such as atom transitions in upstream reactions or the labeling of the extracellular nutrient) is required. This approach, termed ScalaFlux for SCALAble metabolic FLUX analysis, can be scaled up from individual reactions to pathways to sets of pathways. ScalaFlux has several benefits compared with current 13C-MFA approaches: greater network coverage, lower data requirements, independence from cell physiology, robustness to gaps in data and network information, better computational efficiency, applicability to rich media, and enhanced flux identifiability. We validated ScalaFlux using a theoretical network and simulated data. We also used the approach to quantify fluxes through the prenyl pyrophosphate pathway of Saccharomyces cerevisiae mutants engineered to produce phytoene, using a dataset for which fluxes could not be calculated using existing approaches. A broad range of metabolic systems can be targeted with minimal cost and effort, making ScalaFlux a valuable tool for the analysis of metabolic fluxes., Author summary Metabolism is a fundamental biochemical process that enables all organisms to operate and grow by converting nutrients into energy and ‘building blocks’. Metabolic flux analysis allows the quantification of metabolic fluxes in vivo, i.e. the actual rates of biochemical conversions in biological systems, and is increasingly used to probe metabolic activity in biology, biotechnology and medicine. Isotope labeling experiments coupled with mathematical models of large metabolic networks are the most commonly used approaches to quantify fluxes within cells. However, many biological questions only require flux information from a subset of reactions, not the full network. Here, we propose a new approach with three main advantages over existing methods: better scalability (fluxes can be measured through a single reaction, a metabolic pathway or a set of pathways of interest), better robustness to missing data and information gaps, and lower requirements in terms of measurements and computational resources. We validate our method both theoretically and experimentally. ScalaFlux can be used for high-throughput flux measurements in virtually any metabolic system and paves the way to the analysis of dynamic fluxome rearrangements.
Published: 2020
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19. Protein Side-Chain-DNA Contacts Probed by Fast Magic-Angle Spinning NMR

Author: Beat H. Meier, Pengzhi Wu, Thomas Wiegand, Loïc Salmon, Denis Lacabanne, Julien Boudet, Riccardo Cadalbert, Frédéric H.-T. Allain, Alexander A. Malär, Laboratory of Physical Chemistry [ETH Zürich] (LPC), Department of Chemistry and Applied Biosciences [ETH Zürich] (D-CHAB), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Department of Biochemistry [Netherlands] (DB), and Department of Biochemistry-Medical Faculty, Erasmus University Medical Centre-Erasmus University Rotterdam
Subjects: Fast magic-angle spinning, Magnetic Resonance Spectroscopy, 1 H-detection, Noncovalent interactions, Stereochemistry, 010402 general chemistry, 01 natural sciences, Article, chemistry.chemical_compound, Molecular recognition, pRN1 primase, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, 0103 physical sciences, Materials Chemistry, Magic angle spinning, Non-covalent interactions, Physical and Theoretical Chemistry, DNA binding, Nuclear Magnetic Resonance, Biomolecular, chemistry.chemical_classification, 010304 chemical physics, Hydrogen bond, Proteins, Hydrogen Bonding, Magnetic Resonance Imaging, 3. Good health, 0104 chemical sciences, Surfaces, Coatings and Films, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], chemistry, Proton NMR, Nucleic acid, Primase, Protons, DNA
Abstract: The journal of physical chemistry / B 124(49), 11089-11097 (2020). doi:10.1021/acs.jpcb.0c08150 special issue: "Hellmut Eckert Festschrift : virtual issue", Published by American Chemical Society, Washington, DC
Published: 2020
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20. The sickle cell trait affects contact dynamics and endothelial cell activation in Plasmodium falciparum-infected erythrocytes

Author: Dimitris Missirlis, Christine Lansche, Marilou Tétard, Anil K. Dasanna, Benjamin Fröhlich, Benoit Gamain, Ulrich S. Schwarz, Cecilia P. Sanchez, Katharina A. Quadt, Bernd Buchholz, Motomu Tanaka, Michael Lanzer, Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), Universität Heidelberg [Heidelberg], Max-Planck-Institut für Chemische Physik fester Stoffe (CPfS), Max-Planck-Gesellschaft, Abteilung Parasitologie, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)
Subjects: 0301 basic medicine, Endothelium, [SDV]Life Sciences [q-bio], Cell, Medicine (miscellaneous), Biology, Article, General Biochemistry, Genetics and Molecular Biology, Membrane bending, 03 medical and health sciences, 0302 clinical medicine, parasitic diseases, medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, Sickle cell trait, Plasmodium falciparum, Adhesion, medicine.disease, biology.organism_classification, 3. Good health, Cell biology, Endothelial stem cell, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030104 developmental biology, medicine.anatomical_structure, Blood Disorder, lcsh:Biology (General), General Agricultural and Biological Sciences, 030217 neurology & neurosurgery
Abstract: Sickle cell trait, a common hereditary blood disorder, protects carriers from severe disease in infections with the human malaria parasite Plasmodium falciparum. Protection is associated with a reduced capacity of parasitized erythrocytes to cytoadhere to the microvascular endothelium and cause vaso-occlusive events. However, the underpinning cellular and biomechanical processes are only partly understood and the impact on endothelial cell activation is unclear. Here, we show, by combining quantitative flow chamber experiments with multiscale computer simulations of deformable cells in hydrodynamic flow, that parasitized erythrocytes containing the sickle cell haemoglobin displayed altered adhesion dynamics, resulting in restricted contact footprints on the endothelium. Main determinants were cell shape, knob density and membrane bending. As a consequence, the extent of endothelial cell activation was decreased. Our findings provide a quantitative understanding of how the sickle cell trait affects the dynamic cytoadhesion behavior of parasitized erythrocytes and, in turn, endothelial cell activation., Christine Lansche, Anil Dasanna et al. investigate the dynamic cytoadhesion behavior of erythrocytes infected with malaria parasite using quantitative flow chamber experiments and computer simulations. They find that parasitized erythrocytes have altered adhesion dynamics, mainly due to differences in cell shape, knob density and membrane bending.
Published: 2018
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21. Down-selection of the VAR2CSA DBL1-2 expressed in E. coli as a lead antigen for placental malaria vaccine development

Author: Chêne, Arnaud, Gangnard, Stéphane, Dechavanne, Célia, Dechavanne, Sebastien, Srivastava, Anand, Tétard, Marilou, Hundt, Sophia, Leroy, Odile, Havelange, Nicolas, Viebig, Nicola K., Gamain, Benoît, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), European Vaccine Initiative [Heidelberg, Germany], UniversitätsKlinikum Heidelberg, and Gamain, Benoit
Subjects: lcsh:Immunologic diseases. Allergy, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, parasitic diseases, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, lcsh:RC581-607, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Article
Abstract: Over 50 million women are exposed to the risk of malaria during pregnancy every year. Malaria during pregnancy is a leading global cause of maternal morbidity and adverse pregnancy outcomes. Adhesion of Plasmodium falciparum-infected erythrocytes to placental chondroitin-4-sulfate (CSA) has been linked to the severe disease outcome of placental malaria. Accumulated evidence strongly supports VAR2CSA as the leading placental malaria vaccine candidate. Recombinant proteins encompassing the VAR2CSA high affinity CSA binding site have been generated, and their activity as immunogens that elicit functional (inhibitory) and cross-reactive antibodies against CSA-binding parasites assessed. The expression of His-tagged proteins was compared in four different expression systems and their capacity to bind specifically to CSA was analyzed. CHO cells and E. coli SHuffle cells were the two expression systems able to express some of the recombinant proteins in reasonable amounts. Larger analytical scale production of DBL1x-2× (3D7) and DBL3x-4ε (FCR3) best expressed in CHO and E. coli SHuffle cells were performed. Purified proteins were administered to rats either alone or adjuvanted with human approved adjuvants. Analysis of the functionality and cross-reactivity of the induced antibodies allowed us to down-select the DBL1x-2(3D7) expressed in E. coli SHuffle cells as the best antigen to be transitioned to further clinical development in order to protect future pregnant women living in malaria endemic areas against the severe clinical outcomes of placental malaria., Pre-clinical studies: Finding the tools to beat placental malaria A mix of the right parasitic protein with the right production method has yielded a vaccine candidate for placental malaria. Primarily affecting first-time pregnant women, placental malaria is estimated to cause 200,000 infant deaths and 10,000 maternal deaths annually. In this study, led by Benoît Gamain, researchers from France’s INSERM and Germany’s European Vaccine Initiative assayed a combination of proteins designed to target and block a key pathogenic mechanism of parasite-infected red blood cells. Finding the highest performing protein, the researchers also used an Escherichia coli expression system able to replicate and fold the complex protein correctly. During tests, this protein/vector combination bested others in production qualities and immunogenicity. The team’s efforts laid the foundations for a scalable, low-cost vaccine that is currently undergoing clinical trials.
Published: 2018
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22. Activity of Tumor Necrosis Factor α Is Modulated by Dynamic Conformational Rearrangements

Author: Daniela Hofmann, Loïc Salmon, Gerhard Wider, Department of Biology [ETH Zürich] (D-BIOL), and Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)
Subjects: 0301 basic medicine, Chemistry, medicine.medical_treatment, Regulator, General Chemistry, Nuclear magnetic resonance spectroscopy, Ligand (biochemistry), Biochemistry, Solution structure, Catalysis, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 03 medical and health sciences, 030104 developmental biology, Colloid and Surface Chemistry, Immune system, Cytokine, medicine, Biophysics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Tumor necrosis factor alpha, Tumor necrosis factor α, ComputingMilieux_MISCELLANEOUS
Abstract: The homotrimeric ligand tumor necrosis factor α (TNFα) is a key cytokine and immune regulator; however, when deregulated, it leads to several major chronic inflammatory diseases. Perturbation of the protein-protein interface has proven to be an efficient strategy to inactivate TNFα, but the atomic-resolution mechanism of its inactivation remains poorly understood. Here, we probe the solution structure and dynamics of active and inactive TNFα using NMR spectroscopy. The data reveal that TNFα undergoes motions on different time scales. Furthermore, by site-directed mutagenesis of residues at the trimerization interface and by targeting the interface with a low molecular weight inhibitor, we show that TNFα retains its overall structure and trimeric state. However, upon perturbation, TNFα exhibits increased conformational dynamics spanning from the trimerization interface to the regions mediating receptor binding. These findings provide novel insights into the inactivation mechanism of TNFα and the basis for strategies to target TNFα activity.
Published: 2017
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23. Molecular Landscape of the Ribosome Pre-initiation Complex during mRNA Scanning: Structural Role for eIF3c and Its Control by eIF5

Author: Asokan Ananbandam, Hisashi Yoshida, Florian Stengel, Mahmoud L. Nasr, Brytteny Thompson, Takeshi Urano, Fan Zhang, Philip Gao, Haribabu Arthanari, Takashi Nagata, Riccardo Pellarin, Gerhard Wagner, Alan G. Hinnebusch, Jacob Morris, Rafael E. Luna, Katsura Asano, Evangelos Papadopoulos, Chelsea Moore, Eric Aube, Pilar Martin-Marcos, Hiroyuki Hiraishi, Eiji Obayashi, Eddie Dagraca, Jan P. Erzberger, Chingakham Ranjit Singh, Satoru Unzai, Ian Harmon, Samantha Hustak, Berkeley California Institute for Quantitative Biosciences [Berkeley], University of California (UC), University of California [San Francisco] (UC San Francisco), Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Division of Biology, Kansas State University, Kansas State University, This work was supported by a grant from the NIH (R01 GM64781), a pilot grant from University of Kansas COBRE-PSF (P30 GM 110761), NSF Research Grant (1412250), and an Innovative Award from KSU Terry Johnson Cancer Center to K.A., CA68262 and GM47467 to G.W., an intramural grant from NICHD, NIH, to A.G.H., and JSPS KAKENHI 15H01634 and 26440026 to T.N., We thank Hiroshi Matsuo and Erin Adamson for comments, Ivan Topisirovic for proofreading, and Michaela Flax and Speed Rogers for technical assistance., University of California, and University of California [San Francisco] (UCSF)
Subjects: Models, Molecular, MESH: Eukaryotic Initiation Factor-5, 0301 basic medicine, Magnetic Resonance Spectroscopy, MESH: Eukaryotic Initiation Factor-3, Eukaryotic Initiation Factor-3, ribosomal pre-initiation complex, Eukaryotic Initiation Factor-1, MESH: Amino Acid Sequence, MESH: Saccharomyces cerevisiae Proteins, Start codon, Eukaryotic initiation factor, Eukaryotic Initiation Factor-5, Peptide Chain Initiation, Translational, lcsh:QH301-705.5, Shine-Dalgarno sequence, MESH: Protein Subunits, MESH: Saccharomyces cerevisiae, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, EIF1, ribosome, eIF1, eIF3, MESH: Eukaryotic Initiation Factor-1, eIF5, MESH: Models, Molecular, Protein Binding, MESH: Peptide Chain Initiation, Translational, Saccharomyces cerevisiae Proteins, MESH: Mutation, Saccharomyces cerevisiae, Biology, start codon selection, translation initiation, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, ddc:570, MESH: Protein Binding, Initiation factor, Amino Acid Sequence, RNA, Messenger, MESH: RNA, Messenger, Binding Sites, MESH: Magnetic Resonance Spectroscopy, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Molecular biology, Ribosomal binding site, Protein Subunits, A-site, Internal ribosome entry site, 030104 developmental biology, lcsh:Biology (General), MESH: Binding Sites, Ribosomal pre-initiation complex, Ribosome, Start codon selection, Translation initiation, Mutation, Biophysics, Ribosomes, MESH: Ribosomes
Abstract: During eukaryotic translation initiation, eIF3 binds the solvent-accessible side of the 40S ribosome and recruits the gate-keeper protein eIF1 and eIF5 to the decoding center. This is largely mediated by the N-terminal domain (NTD) of eIF3c, which can be divided into three parts: 3c0, 3c1, and 3c2. The N-terminal part, 3c0, binds eIF5 strongly but only weakly to the ribosome-binding surface of eIF1, whereas 3c1 and 3c2 form a stoichiometric complex with eIF1. 3c1 contacts eIF1 through Arg-53 and Leu-96, while 3c2 faces 40S protein uS15/S13, to anchor eIF1 to the scanning pre-initiation complex (PIC). We propose that the 3c0:eIF1 interaction diminishes eIF1 binding to the 40S, whereas 3c0:eIF5 interaction stabilizes the scanning PIC by precluding this inhibitory interaction. Upon start codon recognition, interactions involving eIF5, and ultimately 3c0:eIF1 association, facilitate eIF1 release. Our results reveal intricate molecular interactions within the PIC, programmed for rapid scanning-arrest at the start codon., Cell Reports, 18 (11), ISSN:2666-3864, ISSN:2211-1247
Published: 2017
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24. Expanding Tara Oceans Protocols for Underway, Ecosystemic Sampling of the Ocean-Atmosphere Interface During Tara Pacific Expedition (2016–2018)

Author: Gorsky, Gabriel, Bourdin, Guillaume, Lombard, Fabien, Pedrotti, Maria Luiza, Audrain, Samuel, Bin, Nicolas, Boss, Emmanuel, Bowler, Chris, Cassar, Nicolas, Caudan, Loic, Chabot, Genevieve, Cohen, Natalie R., Cron, Daniel, De Vargas, Colomban, Dolan, John R., Douville, Eric, Elineau, Amanda, Flores, J. Michel, Ghiglione, Jean Francois, Haentjens, Nils, Hertau, Martin, John, Seth G., Kelly, Rachel L., Koren, Ilan, Lin, Yajuan, Marie, Dominique, Moulin, Clementine, Moucherie, Yohann, Pesant, Stephane, Picheral, Marc, Poulain, Julie, Pujo-pay, Mireille, Reverdin, Gilles, Romac, Sarah, Sullivan, Mathew B., Trainic, Miri, Tressol, Marc, Trouble, Romain, Vardi, Assaf, Voolstra, Christian R., Wincker, Patrick, Agostini, Sylvain, Banaigs, Bernard, Boissin, Emilie, Forcioli, Didier, Furla, Paola, Galand, Pierre E., Gilson, Eric, Reynaud, Stephanie, Sunagawa, Shinichi, Thomas, Olivier P., Thurber, Rebecca Lisette Vega, Zoccola, Didier, Planes, Serge, Allemand, Denis, Karsenti, Eric, Planes, S., Banaig, B., Boissin, E., Iwankow, G., Allemand, D., Zoccola, D., Reynaud, S., Beraud, E., Djerbi, N., Forcioli, D., Furla, P., Gilson, E., Mcmind, R., Ottaviani, A., Rottinger, E., Rouan, A., Zamoum, T., Flume, B. C. C., Pogoreutz, C., Voolstra, C. R., Rothig, T., Ziegler, M., Paoli, L., Ruscheweyh, H-j, Salazar, G., Sunagawa, S., Flores, J. M., Koren, I, Trainic, M., Lang-yona, N., Vardi, A., Conan, P., Ghiglione, J-f, Pujo-pay, M., Galand, P. E., Hochart, C., Audrain, S., Bourgois, E., Hertau, M., Lancelot, J., Monmarche, D., Moulin, C., Moucherie, Y., Trouble, R., Boss, E., Bourdin, G., Haentjens, N., Karp-boss, L., Agostini, S., Mitsuhashi, G., Kitano, Y., Da Silva, O., Dolan, J. R., Gorsky, G., Lemee, R., Lombard, F., Pedrotti, M-l, Cronin, D., Sullivan, M., Armstrong, E., Aury, J-m, Barbe, V, Belser, C., Carradec, Q., Labadie, K., Le-hoang, J., Noel, B., Poulain, J., Wincker, P., Klinges, G., Vega-thunder, R., Bonnival, E., De Vargas, C., Henry, N., Marie, D., Romac, S., Pesant, S., Miguel-gorda, M., Thomas, O. P., Bowler, C., Friedrich, R., Cassar, N., Lin, Y., John, S. G., Kelly, R. L., Cohen, N. R., Reverdin, G., Filee, J., Pedrotti, Maria Luiza, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Laboratoires d'excellence - LabexMER Marine Excellence Research: a changing ocean - - LabexMER2010 - ANR-10-LABX-0019 - LABX - OLD, Laboratoire d'océanographie de Villefranche (LOV), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Maine, Tara Expéditions, Institut de biologie de l'Ecole Normale Supérieure (IBENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Nicholas School of the Environment, Duke University [Durham], Mercator Océan, Société Civile CNRS Ifremer IRD Météo-France SHOM, Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Woods Hole Oceanographic Institution (WHOI), Evolution des Protistes et Ecosystèmes Pélagiques (EPEP), Adaptation et diversité en milieu marin (AD2M), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Géochrononologie Traceurs Archéométrie (GEOTRAC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Department of Earth and Planetary Science [Rehovot], Weizmann Institute of Science [Rehovot, Israël], Laboratoire d'Océanographie Microbienne (LOMIC), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of Southern California (USC), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Center for Marine Environmental Sciences [Bremen] (MARUM), Universität Bremen, Data Publisher for Earth and Environmental Science (PANGAEA), University of Bremen, Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Processus et interactions de fine échelle océanique (PROTEO), Laboratoire d'Océanographie et du Climat : Expérimentations et Approches Numériques (LOCEAN), Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Department of Civil, Environmental and Geodetic Engineering [Columbus], Ohio State University [Columbus] (OSU), Laboratoire d'aérologie (LAERO), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Universität Konstanz, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Shimoda Marine Research Center, Université de Tsukuba = University of Tsukuba, Laboratoire d'Excellence CORAIL (LabEX CORAIL), Institut de Recherche pour le Développement (IRD)-Université des Antilles et de la Guyane (UAG)-École des hautes études en sciences sociales (EHESS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de La Réunion (UR)-Université de la Polynésie Française (UPF)-Université de la Nouvelle-Calédonie (UNC)-Institut d'écologie et environnement-Université des Antilles (UA), Centre de recherches insulaires et observatoire de l'environnement (CRIOBE), Université de Perpignan Via Domitia (UPVD)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Symbiose Marine (SM), Evolution Paris Seine, Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Dpt génétique médicale [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratoire d'Ecogéochimie des environnements benthiques (LECOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Centre Scientifique de Monaco (CSM), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), National University of Ireland [Galway] (NUI Galway), Oregon State University (OSU), European Molecular Biology Laboratory [Heidelberg] (EMBL), TARA, ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-10-LABX-0019,LabexMER,LabexMER Marine Excellence Research: a changing ocean(2010), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire océanologique de Banyuls (OOB), Institut Pierre-Simon-Laplace (IPSL (FR_636)), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut de Recherche pour le Développement (IRD)-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut de Recherche pour le Développement (IRD)-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Université des Antilles (UA)-Institut d'écologie et environnement-Université de la Nouvelle-Calédonie (UNC)-Université de la Polynésie Française (UPF)-Université de La Réunion (UR)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Université des Antilles et de la Guyane (UAG)-Institut de Recherche pour le Développement (IRD), Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles et de la Guyane (UAG)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Nice Sophia Antipolis (... - 2019) (UNS), Université de Toulouse (UT)-Université de Toulouse (UT)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Université des Antilles et de la Guyane (UAG)-École des hautes études en sciences sociales (EHESS)-École Pratique des Hautes Études (EPHE), Université de Perpignan Via Domitia (UPVD)-École Pratique des Hautes Études (EPHE), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0106 biological sciences, 010504 meteorology & atmospheric sciences, lcsh:QH1-199.5, [SDE.MCG]Environmental Sciences/Global Changes, trace metals, Ocean Engineering, neuston, Aquatic Science, lcsh:General. Including nature conservation, geographical distribution, Oceanography, 01 natural sciences, Pacific ocean, taxonomy, neuston/plankton genomics/taxonomy/imaging, ddc:570, Ecosystem, 14. Life underwater, lcsh:Science, Reef, 0105 earth and related environmental sciences, Water Science and Technology, [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, Global and Planetary Change, geography, geography.geographical_feature_category, aerosols, NCP, IOP, microplastic, plankton genomics, [SDU.OCEAN] Sciences of the Universe [physics]/Ocean, Atmosphere, ACL, 010604 marine biology & hydrobiology, Community structure, imaging, Pelagic zone, Plankton, Inlet, neuston/plankton genomics/taxonomy/imaging, aerosols, NCP, IOP, trace metals, microplastic, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, [SDE.MCG] Environmental Sciences/Global Changes, 13. Climate action, lcsh:Q, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Neuston
Abstract: Interactions between the ocean and the atmosphere occur at the air-sea interface through the transfer of momentum, heat, gases and particulate matter, and through the impact of the upper-ocean biology on the composition and radiative properties of this boundary layer. The Tara Pacific expedition, launched in May 2016 aboard the schooner Tara, was a 29-month exploration with the dual goals to study the ecology of reef ecosystems along ecological gradients in the Pacific Ocean and to assess inter-island and open ocean surface plankton and neuston community structures. In addition, key atmospheric properties were measured to study links between the two boundary layer properties. A major challenge for the open ocean sampling was the lack of ship-time available for work at “stations”. The time constraint led us to develop new underway sampling approaches to optimize physical, chemical, optical, and genomic methods to capture the entire community structure of the surface layers, from viruses to metazoans in their oceanographic and atmospheric physicochemical context. An international scientific consortium was put together to analyze the samples, generate data, and develop datasets in coherence with the existing Tara Oceans database. Beyond adapting the extensive Tara Oceans sampling protocols for high-resolution underway sampling, the key novelties compared to Tara Oceans’ global assessment of plankton include the measurement of (i) surface plankton and neuston biogeography and functional diversity; (ii) bioactive trace metals distribution at the ocean surface and metal-dependent ecosystem structures; (iii) marine aerosols, including biological entities; (iv) geography, nature and colonization of microplastic; and (v) high-resolution underway assessment of net community production via equilibrator inlet mass spectrometry. We are committed to share the data collected during this expedition, making it an important resource important resource to address a variety of scientific questions. ISSN:2296-7745
Published: 2019
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25. Protein post-translational modifications in bacteria

Author: Ivan Mijakovic, Eilika Weber-Ban, Boris Macek, Christophe Grangeasse, Karl Forchhammer, Julie Hardouin, Tuebingen University [Germany], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and Chalmers University of Technology [Göteborg]
Subjects: 0303 health sciences, General Immunology and Microbiology, biology, Bacteria, 030306 microbiology, Microbial metabolism, Virulence, Cell cycle, biology.organism_classification, Microbiology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 03 medical and health sciences, Infectious Diseases, Biochemistry, Ubiquitin, Bacterial Proteins, Proteome, Spore germination, biology.protein, Protein biosynthesis, Protein Processing, Post-Translational, ComputingMilieux_MISCELLANEOUS
Abstract: Over the past decade the number and variety of protein post-translational modifications that have been detected and characterized in bacteria have rapidly increased. Most post-translational protein modifications occur in a relatively low number of bacterial proteins in comparison with eukaryotic proteins, and most of the modified proteins carry low, substoichiometric levels of modification; therefore, their structural and functional analysis is particularly challenging. The number of modifying enzymes differs greatly among bacterial species, and the extent of the modified proteome strongly depends on environmental conditions. Nevertheless, evidence is rapidly accumulating that protein post-translational modifications have vital roles in various cellular processes such as protein synthesis and turnover, nitrogen metabolism, the cell cycle, dormancy, sporulation, spore germination, persistence and virulence. Further research of protein post-translational modifications will fill current gaps in the understanding of bacterial physiology and open new avenues for treatment of infectious diseases.
Published: 2019
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26. The Tara Pacific expedition-A pan-ecosystemic approach of the '-omics' complexity of coral reef holobionts across the Pacific Ocean

Author: Planes, Serge, Allemand, Denis, Agostini, Sylvain, Banaigs, Bernard, Boissin, Emilie, Boss, Emmanuel, Bourdin, Guillaume, Bowler, Chris, Douville, Eric, Flores, J. Michel, Forcioli, Didier, Furla, Paola, Galand, Pierre E., Ghiglione, Jean-francois, Gilson, Eric, Lombard, Fabien, Moulin, Clementine, Pesant, Stephane, Poulain, Julie, Reynaud, Stephanie, Romac, Sarah, Sullivan, Matthew B., Sunagawa, Shinichi, Thomas, Olivier P., Trouble, Romain, De Vargas, Colomban, Thurber, Rebecca Vega, Voolstra, Christian R., Wincker, Patrick, Zoccola, Didier, Planes, S., Allemand, D., Agostini, S., Armstrong, E., Audrain, S., Aury, J-m, Banaig, B., Barbe, V, Belser, C., Beraud, E., Boissin, E., Bonnival, E., Boss, E., Bourdin, G., Bourgois, E., Bowler, C., Carradec, Q., Cassar, N., Cohen, N. R., Conan, P., Cronin, D. R., Da Silva, O., De Vargas, C., Djerbi, N., Dolan, J. R., Herta, Dominguez G., Du J, Filee, J., Flores, J. M., Forcioli, D., Friedrich, R., Furla, P., Galand, P. E., Ghiglione, J-f, Gilson, E., Gorsky, G., Guinther, M., Haentjens, N., Henry, N., Hertau, M., Hochart, C., Hume, B. C. C., Iwankow, G., John, S. G., Karp-boss, L., Kelly, R. L., Kitano, Y., Klinges, G., Koren, I, Labadie, K., Lancelot, J., Lang-yona, N., Le-hoang, J., Lemee, R., Lin, Y., Lombard, F., Marie, D., Mcmind, R., Miguel-gordo, M., Trainic, M., Monmarche, D., Moulin, C., Mucherie, Y., Noel, B., Ottaviani, A., Paoli, L., Pedrotti, M-l, Pesant, S., Pogoreutz, C., Poulain, J., Pujo-pay, M., Reverdin, G., Reynaud, S., Romac, S., Rothig, T., Rottinger, E., Rouan, A., Ruscheweyh, H-j, Salazar, G., Sullivan, M. B., Sunagawa, S., Thomas, O. P., Trouble, R., Vardi, A., Vega-thunder, R., Voolstra, C. R., Wincker, P., Zahed, A., Zamoum, T., Ziegler, M., Zoccola, D., Centre de recherches insulaires et observatoire de l'environnement (CRIOBE), Université de Perpignan Via Domitia (UPVD)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Excellence CORAIL (LabEX CORAIL), Institut de Recherche pour le Développement (IRD)-Université des Antilles et de la Guyane (UAG)-École des hautes études en sciences sociales (EHESS)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de La Réunion (UR)-Université de la Polynésie Française (UPF)-Université de la Nouvelle-Calédonie (UNC)-Institut d'écologie et environnement-Université des Antilles (UA), Centre Scientifique de Monaco (CSM), Tara Expéditions, Shimoda Marine Research Center, Université de Tsukuba = University of Tsukuba, University of Maine, Laboratoire d'océanographie de Villefranche (LOV), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Géochrononologie Traceurs Archéométrie (GEOTRAC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Department of Earth and Planetary Science [Rehovot], Weizmann Institute of Science [Rehovot, Israël], Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire d'Ecogéochimie des environnements benthiques (LECOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Océanographie Microbienne (LOMIC), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Center for Marine Environmental Sciences [Bremen] (MARUM), Universität Bremen, Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ECOlogy of MArine Plankton (ECOMAP), Adaptation et diversité en milieu marin (ADMM), Institut national des sciences de l'Univers (INSU - CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Station biologique de Roscoff (SBR), Ohio State University [Columbus] (OSU), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), National University of Ireland [Galway] (NUI Galway), Oregon State University (OSU), University of Konstanz, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Duke University [Durham], Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Marine Chemistry and Geochemistry (WHOI), Woods Hole Oceanographic Institution (WHOI), Évolution, génomes, comportement et écologie (EGCE), Université Paris-Sud - Paris 11 (UP11)-IRD-Centre National de la Recherche Scientifique (CNRS), Department of Earth Sciences [USC Los Angeles], University of Southern California (USC), Martin Ryan Institute, Laboratoire d'Océanographie et du Climat : Expérimentations et Approches Numériques (LOCEAN), Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Derby [United Kingdom], Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-17-CE02-0020,CORALGENE,Complexité génomique de l'holobionte ' corail ' à l'échelle du Pacifique(2017), Université de Perpignan Via Domitia (UPVD)-École pratique des hautes études (EPHE), Université des Antilles (UA)-Institut d'écologie et environnement-Université de la Nouvelle-Calédonie (UNC)-Université de la Polynésie Française (UPF)-Université de La Réunion (UR)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Université des Antilles et de la Guyane (UAG)-Institut de Recherche pour le Développement (IRD), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire océanologique de Banyuls (OOB), Adaptation et diversité en milieu marin (AD2M), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-IRD-Université Paris-Sud - Paris 11 (UP11), Institut Pierre-Simon-Laplace (IPSL (FR_636)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut de Recherche pour le Développement (IRD)-Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), Justus-Liebig-Universität Gießen (JLU), Institut Universitaire Européen de la Mer (IUEM), and Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO)
Subjects: 0301 basic medicine, Topography, Coral reefs, Effects of global warming on oceans, Coral, Biodiversity, Marine and Aquatic Sciences, Ecosystem services, 0302 clinical medicine, Community Page, Oceans, Biology (General), Islands, [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, geography.geographical_feature_category, Ecology, Microbiota, General Neuroscience, Eukaryota, Coral reef, Anthozoa, Plankton, Holobiont, Corals, Expeditions, General Agricultural and Biological Sciences, Marine ecosystems, QH301-705.5, Climate change, Marine Biology, Biology, Ecosystems, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, ddc:570, Animals, Metabolomics, Marine ecosystem, 14. Life underwater, Symbiosis, [SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography, Landforms, geography, Pacific Ocean, General Immunology and Microbiology, ACL, Ecology and Environmental Sciences, Organisms, Biology and Life Sciences, Geomorphology, Bodies of Water, 15. Life on land, Invertebrates, 030104 developmental biology, 13. Climate action, Earth Sciences, Reefs, Metagenomics, Reef ecosystems, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, 030217 neurology & neurosurgery
Abstract: Coral reefs are the most diverse habitats in the marine realm. Their productivity, structural complexity, and biodiversity critically depend on ecosystem services provided by corals that are threatened because of climate change effects—in particular, ocean warming and acidification. The coral holobiont is composed of the coral animal host, endosymbiotic dinoflagellates, associated viruses, bacteria, and other microeukaryotes. In particular, the mandatory photosymbiosis with microalgae of the family Symbiodiniaceae and its consequences on the evolution, physiology, and stress resilience of the coral holobiont have yet to be fully elucidated. The functioning of the holobiont as a whole is largely unknown, although bacteria and viruses are presumed to play roles in metabolic interactions, immunity, and stress tolerance. In the context of climate change and anthropogenic threats on coral reef ecosystems, the Tara Pacific project aims to provide a baseline of the “-omics” complexity of the coral holobiont and its ecosystem across the Pacific Ocean and for various oceanographically distinct defined areas. Inspired by the previous Tara Oceans expeditions, the Tara Pacific expedition (2016–2018) has applied a pan-ecosystemic approach on coral reefs throughout the Pacific Ocean, drawing an east–west transect from Panama to Papua New Guinea and a south–north transect from Australia to Japan, sampling corals throughout 32 island systems with local replicates. Tara Pacific has developed and applied state-of-the-art technologies in very-high-throughput genetic sequencing and molecular analysis to reveal the entire microbial and chemical diversity as well as functional traits associated with coral holobionts, together with various measures on environmental forcing. This ambitious project aims at revealing a massive amount of novel biodiversity, shedding light on the complex links between genomes, transcriptomes, metabolomes, organisms, and ecosystem functions in coral reefs and providing a reference of the biological state of modern coral reefs in the Anthropocene., This Community Page article presents the Tara Pacific expedition, which aims to shed light on the complex links between genomes, transcriptomes, metabolomes, organisms, and ecosystem functions in coral reefs, and providing a reference of the biological state of modern reef systems.
Published: 2019
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27. Phosphorylation of the VAR2CSA extracellular region is associated with enhanced adhesive properties to the placental receptor CSA

Author: Dominique Dorin-Semblat, Marilou Tétard, Aurélie Claës, Jean-Philippe Semblat, Sébastien Dechavanne, Zaineb Fourati, Romain Hamelin, Florence Armand, Graziella Matesic, Sofia Nunes-Silva, Anand Srivastava, Stéphane Gangnard, Jose-Juan Lopez-Rubio, Marc Moniatte, Christian Doerig, Artur Scherf, Benoît Gamain, Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Institut National de la Transfusion Sanguine [Paris] (INTS), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Proteomics Core Facility [Lausanne, Suisse], Ecole Polytechnique Fédérale de Lausanne (EPFL), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre for Chronic Infectious and Inflammation Disease [Bundoora, VIC, Australie], Biomedical Sciences Cluster [Bundoora, VIC, Australie], School of Health and Biomedical Sciences [Bundoora, VIC, Australie], Royal Melbourne Institute of Technology University (RMIT University)-Royal Melbourne Institute of Technology University (RMIT University)-School of Health and Biomedical Sciences [Bundoora, VIC, Australie], Royal Melbourne Institute of Technology University (RMIT University)-Royal Melbourne Institute of Technology University (RMIT University), This work is supported by the French National Research Agency (ANR-16-CE11-0014-01), grants from Laboratory of Excellence GR-Ex, reference ANR-11-LABX-0051 and the French Parasitology consortium ParaFrap (ANR-11-LABX0024). The labex GR-Ex is funded by the program 'Investissements d’avenir' of the French National Research Agency, reference ANR-11-IDEX-0005-02., ANR-16-CE11-0014,STRUCT-4-PAM,Analyse structurale et fonctionnelle des processus adhésifs associés au paludisme gestationnel(2016), ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), Centre for Molecular Parasitology, University of Glasgow-Wellcome Trust, Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Gènes et pression artérielle (Inserm U772), Collège de France (CdF)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Intégrée du Globule Rouge (BIGR), Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire de Biochimie de l'Ecole polytechnique (BIOC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Proteomics Core Facility, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Controle de la Proliferation Cellulaire Chez Plasmodium Falciparum, Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des Interactions Hôte-Parasite, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bodescot, Myriam, Analyse structurale et fonctionnelle des processus adhésifs associés au paludisme gestationnel - - STRUCT-4-PAM2016 - ANR-16-CE11-0014 - AAPG2016 - VALID, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Laboratoires d'excellence - Alliance française contre les maladies parasitaires - - ParaFrap2011 - ANR-11-LABX-0024 - LABX - VALID, Génétique et évolution des maladies infectieuses (GEMI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Plasmodium, binding, Erythrocytes, Physiology, Placenta, Cell Culture Techniques, Protozoan Proteins, Biochemistry, Database and Informatics Methods, Pregnancy, Animal Cells, Red Blood Cells, Immune Physiology, Medicine and Health Sciences, Biology (General), Malaria, Falciparum, Phosphorylation, Post-Translational Modification, ComputingMilieux_MISCELLANEOUS, chondroitin sulfate, Protozoans, Immune System Proteins, Malarial Parasites, Eukaryota, Antigenic Variation, Recombinant Proteins, Enzymes, Plasmodium Falciparum, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Female, Cellular Types, Sequence Analysis, Protein Binding, Research Article, QH301-705.5, Bioinformatics, Immunology, Antigens, Protozoan, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Research and Analysis Methods, Cell Line, var genes, Sequence Motif Analysis, expression, Parasite Groups, parasitic diseases, Animals, Humans, Parasites, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Antigens, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Blood Cells, Phosphatases, Organisms, Biology and Life Sciences, Proteins, pfemp1, Cell Biology, Parasitic Protozoans, Malaria, cytoadherence, Enzymology, Parasitology, plasmodium-falciparum, Apicomplexa
Abstract: Plasmodium falciparum is the main cause of disease and death from malaria. P. falciparum virulence resides in the ability of infected erythrocytes (IEs) to sequester in various tissues through the interaction between members of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesin family to various host receptors. Here, we investigated the effect of phosphorylation of variant surface antigen 2-CSA (VAR2CSA), a member of the PfEMP1 family associated to placental sequestration, on its capacity to adhere to chondroitin sulfate A (CSA) present on the placental syncytium. We showed that phosphatase treatment of IEs impairs cytoadhesion to CSA. MS analysis of recombinant VAR2CSA phosphosites prior to and after phosphatase treatment, as well as of native VAR2CSA expressed on IEs, identified critical phosphoresidues associated with CSA binding. Site-directed mutagenesis on recombinant VAR2CSA of 3 phosphoresidues localised within the CSA-binding region confirmed in vitro their functional importance. Furthermore, using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease (CRISPR/Cas9), we generated a parasite line in which the phosphoresidue T934 is changed to alanine and showed that this mutation strongly impairs IEs cytoadhesion to CSA. Taken together, these results demonstrate that phosphorylation of the extracellular region of VAR2CSA plays a major role in IEs cytoadhesion to CSA and provide new molecular insights for strategies aiming to reduce the morbidity and mortality of PM., Placental sequestration of malaria-infected erythrocytes is mediated by the interaction between parasite VAR2CSA and the placental receptor chondroitin sulfate A; this study shows that phosphorylation of VAR2CSA plays a major role in this process, with implications for protecting pregnant women and their babies against placental malaria.
Published: 2019
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28. Impact of Hemoglobin S Trait on Cell Surface Antibody Recognition of Plasmodium falciparum-Infected Erythrocytes in Pregnancy-Associated Malaria

Author: Murielle Lohezic, Jacqueline Milet, Anaïs Merckx, Marilou Tétard, Emeline Brossier, Luc Denoyel, Margaux Chauvet, Jocelyne Roman, Benoit Gamain, Florentin Aussenac, Nicaise Tuikue Ndam, Adrian J. F. Luty, Marion Hanny, Damien Pineau, Gilles Cottrell, Florence Migot-Nabias, Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Institut de Recherche pour le Développement (IRD), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS)
Subjects: 0301 basic medicine, Thalassemia, [SDV]Life Sciences [q-bio], 030106 microbiology, Population, Cell surface antibody binding, VAR2CSA, Major Articles, 03 medical and health sciences, 0302 clinical medicine, parasitic diseases, pregnancy-associated malaria, Medicine, 030212 general & internal medicine, hemoglobin S, education, ComputingMilieux_MISCELLANEOUS, education.field_of_study, Sickle cell trait, Pregnancy-associated malaria, biology, business.industry, Plasmodium falciparum, medicine.disease, biology.organism_classification, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Oncology, Immunology, biology.protein, Hemoglobin, Antibody, business, Malaria, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background. Sickle cell trait (HbAS) confers partial protection against malaria by reducing the adhesion of Plasmodium falciparum-infected erythrocytes to host receptors, but little is known about its potential protection against placental malaria. Methods. Using flow cytometry, we assessed the recognition of HbAA and HbAS VAR2CSA-expressing infected erythrocytes, by plasma from 159 Beninese pregnant women with either HbAA (normal) or HbAS. Using multivariate linear models adjusted for gravidity, parasite infection at delivery, glucose-6-phosphate dehydrogenase deficiency, and α-thalassemia carriage, we observed significantly reduced cell surface antibody binding of HbAS-infected erythrocytes by plasma from HbAS compared with HbAA women (P < 10-3). Results. The difference in cell surface antibody binding was only observed when infected erythrocytes and plasma were associated according to the same hemoglobin genotype. Similar levels of VAR2CSA-specific antibody were measured by enzyme-linked immunosorbent assay in the 2 groups, suggesting that the altered interaction between VAR2CSA and HbAS women's antibodies could reflect abnormal display of VAR2CSA on HbAS erythrocytes. Conclusions. Our data stress the need for assessments of erythrocyte disorders such as the sickle cell trait in a population group when studying immunological responses to P falciparum.
Published: 2019
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29. Alpha diversity of vascular plants in European forests

Author: Valerijus Rašomavičius, Emiliano Agrillo, Jens-Christian Svenning, Marcela Řezníčková, Thomas Wohlgemuth, Grzegorz Swacha, Jonathan Lenoir, Roberto Venanzoni, Urban Šilc, Ilona Knollová, Joop H.J. Schaminée, Milan Chytrý, Wolfgang Willner, Adrian Indreica, Panayotis Dimopoulos, Federico Fernández-González, Kiril Vassilev, Mirjana Ćuk, Juan Antonio Campos, Andraž Čarni, Jean Claude Gégout, Jan Divíšek, Martin Večeřa, Idoia Biurrun, John S. Rodwell, Borja Jiménez-Alfaro, Ute Jandt, Florian Jansen, Guillermo Crespo Jiménez, Jörg Ewald, Zygmunt Kącki, Masaryk University [Brno] (MUNI), Ecologie et Dynamique des Systèmes Anthropisés - UMR CNRS 7058 (EDYSAN), Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), University of Oviedo, Department of Plant Biology and Ecology, University of the Basque Country UPV/ EHU, Bilbao, Spain, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], National Institute of Biology [Ljubljana] (NIB), University of Castilla-La Mancha (UCLM), University of Novi Sad, University of Patras [Patras], Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), SILVA (SILVA), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL)-AgroParisTech, Transilvania University of Brasov, Philips Research Europe - Hamburg, Sector Medical Imaging Systems, Philips Research, Martin-Luther-University Halle-Wittenberg, University of Rostock, University of Wrocław [Poland] (UWr), Nature Research Centre [Vilnius], Centre for Ecosystem Studies, University of Wageningen, Wageningen University and Research [Wageningen] (WUR), Aarhus University [Aarhus], Bulgarian Academy of Sciences (BAS), Dept Appl Biol, Università degli Studi di Perugia (UNIPG), Vienna Institute for Nature Conservation and Analyses (VINCA), and Swiss Federal Institute for Forest, Snow and Landscape Research WSL
Subjects: 0106 biological sciences, Random Forests, plant community, Bos- en Landschapsecologie, Biodiversity, 01 natural sciences, Vegetation-plot database, Forest and Landscape Ecology, vascular plants, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, 0303 health sciences, Diversity, Ecology, biology, European Vegetation Archive, Vegetation, PE&RC, Europe, Geography, Plantenecologie en Natuurbeheer, Forest vegetation, Vegetatie, Bos- en Landschapsecologie, species-richness patterns, Vascular plant, forest vegetation, Gamma diversity, [SDE.MCG]Environmental Sciences/Global Changes, Plant Ecology and Nature Conservation, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Plant community, 010603 evolutionary biology, diversity, 03 medical and health sciences, Species-richness patterns, Ecology, Evolution, Behavior and Systematics, Vegetatie, 030304 developmental biology, European Vegetation Archive (EVA), predictive modelling, vegetation-plot database, Vascular plants, Predictive modelling, Species diversity, 15. Life on land, biology.organism_classification, Alpha diversity, Vegetation, Forest and Landscape Ecology, Species richness, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: Aim The former continental‐scale studies modelled coarse‐grained plant species‐richness patterns (gamma diversity). Here we aim to refine this information for European forests by (a) modelling the number of vascular plant species that co‐occur in local communities (alpha diversity) within spatial units of 400 m2; and (b) assessing the factors likely determining the observed spatial patterns in alpha diversity. Location Europe roughly within 12°W–30°E and 35–60°N. Taxon Vascular plants. Methods The numbers of co‐occurring vascular plant species were counted in 73,134 georeferenced vegetation plots. Each plot was classified by an expert system into deciduous broadleaf, coniferous or sclerophyllous forest. Random Forest models were used to map and explain spatial patterns in alpha diversity for each forest type separately using 19 environmental, land‐use and historical variables. Results Our models explained from 51.0% to 70.9% of the variation in forest alpha diversity. The modelled alpha‐diversity pattern was dominated by a marked gradient from species‐poor north‐western to species‐rich south‐eastern Europe. The most prominent richness hotspots were identified in the Calcareous Alps and adjacent north‐western Dinarides, the Carpathian foothills in Romania and the Western Carpathians in Slovakia. Energy‐related factors, bedrock types and terrain ruggedness were identified as the main variables underlying the observed richness patterns. Alpha diversity increases especially with temperature seasonality in deciduous broadleaf forests, on limestone bedrock in coniferous forests and in areas with low annual actual evapotranspiration in sclerophyllous forests. Main conclusions We provide the first predictive maps and analyses of environmental factors driving the alpha diversity of vascular plants across European forests. Such information is important for the general understanding of European biodiversity. This study also demonstrates a high potential of vegetation‐plot databases as sources for robust estimation of the number of vascular plant species that co‐occur at fine spatial grains across large areas., M.V., J.D., I.K., M.Ř. and M.C. were supported by the Czech Science Foundation (Centre of Excellence Pladias; project no. 14–36079G). I.B. and J.A.C. were supported by the Basque Government (IT936‐16). B.J.‐A. was supported by the Marie Curie Clarín‐COFUND program of the Principate of Asturias and the European Union (ACB17‐26). J.‐C.S. considers this work a contribution to his VILLUM Investigator project “Biodiversity Dynamics in a Changing World” funded by VILLUM FONDEN (grant 16549) and his Danish Council for Independent Research | Natural Sciences TREECHANGE project (grant 6108‐00078B).
Published: 2019
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30. The RNA export factor Mex67 functions as a mobile nucleoporin

Author: Pascal Vallotton, Carina Patrizia Derrer, Elisa Dultz, Roberta Mancini, Karsten Weis, Sébastien Huet, Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 31003A_179275, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Cytoplasm, Nucleocytoplasmic Transport Proteins, Saccharomyces cerevisiae Proteins, Active Transport, Cell Nucleus, Saccharomyces cerevisiae, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, RNA Transport, DEAD-box RNA Helicases, 03 medical and health sciences, 0302 clinical medicine, Report, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, otorhinolaryngologic diseases, RNA, Messenger, Nuclear pore, Binding site, Research Articles, 030304 developmental biology, Cell Nucleus, 0303 health sciences, Messenger RNA, Binding Sites, Chemistry, fungi, 030302 biochemistry & molecular biology, food and beverages, Nuclear Proteins, RNA-Binding Proteins, RNA, Cell Biology, Cell biology, Nuclear Pore Complex Proteins, Cell nucleus, stomatognathic diseases, medicine.anatomical_structure, Microscopy, Fluorescence, Nucleoporin, Ribosomes, Nucleus, Gene Deletion, 030217 neurology & neurosurgery, Function (biology), Protein Binding
Abstract: The RNA export factor Mex67 is essential for the transport of mRNA through the nuclear pore complex (NPC) in yeast, but the molecular mechanism of this export process remains poorly understood. Here, we use quantitative fluorescence microscopy techniques in live budding yeast cells to investigate how Mex67 facilitates mRNA export. We show that Mex67 exhibits little interaction with mRNA in the nucleus and localizes to the NPC independently of mRNA, occupying a set of binding sites offered by FG repeats in the NPC. The ATPase Dbp5, which is thought to remove Mex67 from transcripts, does not affect the interaction of Mex67 with the NPC. Strikingly, we find that the essential function of Mex67 is spatially restricted to the NPC since a fusion of Mex67 to the nucleoporin Nup116 rescues a deletion of MEX67. Thus, Mex67 functions as a mobile NPC component, which receives mRNA export substrates in the central channel of the NPC to facilitate their translocation to the cytoplasm., The Journal of Cell Biology, 218 (12), ISSN:0021-9525, ISSN:1540-8140
Published: 2019
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31. Diverse activation pathways in class A GPCRs converge near the G protein-coupling region

Author: Tamara Miljuš, Michel Bouvier, Franziska M. Heydenreich, AJ Venkatakrishnan, M. Madan Babu, Tilman Flock, Christopher G. Tate, Guillaume Lebon, S. Balaji, Dmitry B. Veprintsev, Xavier Deupi, Gebhard F. X. Schertler, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Condensed Matter Theory Group and Laboratory of Biomolecular Research, Paul Scherrer Institute (PSI), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Immunologie et en Cancérologie [UdeM-Montréal] (IRIC), Université de Montréal (UdeM), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Laboratory of Molecular Biology [Cambridge], and Medical Research Council
Subjects: 0301 basic medicine, Models, Molecular, Receptors, Vasopressin, G protein, Biology, Ligands, Rhodopsin-like receptors, Article, Protein Structure, Secondary, Receptors, G-Protein-Coupled, 03 medical and health sciences, Protein structure, Humans, Binding site, Conserved Sequence, G protein-coupled receptor, Multidisciplinary, Binding Sites, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Heterotrimeric GTP-Binding Proteins, Cell biology, Transmembrane domain, 030104 developmental biology, Membrane protein, Structural Homology, Protein, Signal transduction, Signal Transduction
Abstract: International audience; Class A G-protein-coupled receptors (GPCRs) are a large family of membrane proteins that mediate a wide variety of physiological functions, including vision, neurotransmission and immune responses. They are the targets of nearly one-third of all prescribed medicinal drugs such as beta blockers and antipsychotics. GPCR activation is facilitated by extracellular ligands and leads to the recruitment of intracellular G proteins. Structural rearrangements of residue contacts in the transmembrane domain serve as 'activation pathways' that connect the ligand-binding pocket to the G-protein-coupling region within the receptor. In order to investigate the similarities in activation pathways across class A GPCRs, we analysed 27 GPCRs from diverse subgroups for which structures of active, inactive or both states were available. Here we show that, despite the diversity in activation pathways between receptors, the pathways converge near the G-protein-coupling region. This convergence is mediated by a highly conserved structural rearrangement of residue contacts between transmembrane helices 3, 6 and 7 that releases G-protein-contacting residues. The convergence of activation pathways may explain how the activation steps initiated by diverse ligands enable GPCRs to bind a common repertoire of G proteins.
Published: 2016
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32. In situ and high-resolution Cryo-EM structure of the Type VI secretion membrane complex

Author: Riccardo Pellarin, Victoria Schmidt, Yassine Cherrak, Laureen Logger, Rémi Fronzes, Romain Kooger, Chiara Rapisarda, Eric Durand, Eric Cascales, Martin Pilhofer, Institut Européen de Chimie et Biologie (IECB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Bioinformatique structurale - Structural Bioinformatics, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), European Institute of Chemistry and Biology, Université Sciences et Technologies - Bordeaux 1, This work was funded by the Centre National de la Recherche Scientifique, the Aix‐Marseille Université, and grants from the Agence Nationale de la Recherche (ANR‐14‐CE14‐0006‐02, ANR‐17‐CE11‐0039‐01) and the Fondation pour la Recherche Médicale (DEQ20180339165) to EC. ED was supported by the INSERM and an EMBO short‐term fellowship (ASTF 417 – 2015). YC is supported by a Doctoral school PhD fellowship from the FRM (ECO20160736014). VS is supported by a post‐doctoral fellowship from the association Espoir contre la Mucoviscidose. LL was supported by a fourth year PhD fellowship from the FRM (FDT20160435498). MP is funded by the European Research Council, the Swiss National Science Foundation and the Helmut Horten Foundation. RF and CR were supported by IDEX Bordeaux through a 'chaire d'excellence' to RF., ANR-17-CE11-0039,T6-PLATFORM,Une approche multidisciplinaire et intégrative pour comprendre l'assemblage, la structure et la dynamique d'une plateforme de queue contractile(2017), ANR-14-CE14-0006,B-War,Guerre bactérienne: Architecture et Fonction du Système de Sécrétion de Type VI(2014), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1 (UB), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Bioinformatique structurale, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: In situ, MESH: Protein Structure, Quaternary, Cryo-electron microscopy, [SDV]Life Sciences [q-bio], MESH: Type VI Secretion Systems, Single particle analysis, MESH: Escherichia coli Proteins, law.invention, 03 medical and health sciences, law, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Secretion, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH: Bacterial Secretion Systems, 030304 developmental biology, Type VI secretion system, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], MESH: Escherichia coli, 030306 microbiology, Chemistry, Negative stain, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Membrane, Biophysics, MESH: Cryoelectron Microscopy, MESH: Membrane Proteins, Electron microscope, MESH: Models, Molecular, MESH: Cell Membrane
Abstract: Bacteria have evolved macromolecular machineries that secrete effectors and toxins to survive and thrive in diverse environments. The type VI secretion system (T6SS) is a contractile machine that is related to Myoviridae phages. The T6SS is composed of a baseplate that contains a spike onto which an inner tube is built, surrounded by a contractile sheath. Unlike phages that are released to and act in the extracellular medium, the T6SS is an intracellular machine inserted in the bacterial membranes by a trans-envelope complex. This membrane complex (MC) comprises three proteins: TssJ, TssL and TssM. We previously reported the low-resolution negative stain electron microscopy structure of the enteroaggregative Escherichia coli MC and proposed a rotational 5-fold symmetry with a TssJ:TssL:TssM stoichiometry of 2:2:2. Here, cryo-electron tomography analysis of the T6SS MC confirmed the 5-fold symmetry in situ and identified the regions of the structure that insert into the bacterial membranes. A high resolution model obtained by single particle cryo-electron microscopy reveals its global architecture and highlights new features: five additional copies of TssJ, yielding a TssJ:TssL:TssM stoichiometry of 3:2:2, a 11-residue loop in TssM, protruding inside the lumen of the MC and constituting a functionally important periplasmic gate, and hinge regions. Based on these data, we revisit the model on the mechanism of action of the MC during T6SS assembly and function.
Published: 2018
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33. Light induced charge and energy transport in nucleic acids and proteins: general discussion

Author: Chattopadhyay, Amitabha, Cogdell, Richard, Crespo-Hernández, Carlos, Datta, Ankona, De, Arijit, Haacke, Stefan, Hariharan, Mahesh, Helliwell, John, Hughes, Ashley, Improta, Roberto, Jones, Mike, Joseph, Joshy, Karsili, Tolga, Kohler, Bern, Krishnan, Retheesh, Kuriakose, Anvy, L, Mahil, Markovitsi, Dimitra, Medhi, Himani, Periyasamy, Ganga, Pradeepkumar, P., Roy Chowdhury, Priyadarshi, Sarangi, Manas, Schapiro, Igor, Schertler, Gebhard, Schlichting, Ilme, Segarra-Martí, Javier, Swaminathan, Rajaram, V, Vishnu, van Grondelle, Rienk, Venkatraman, Ravi Kumar, Venkatramani, Ravindra, Watts, Anthony, Vayá, Ignacio, Changenet-Barret, Pascale, Gustavsson, Thomas, Zikich, Dragoslav, Kotlyar, Alexander, LaserLaB - Energy, Biophysics Photosynthesis/Energy, Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), CNR – Istituto di Biostrutture e Bioimmagini, Biomolécules Excitées (DICO), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire Interactions, Dynamiques et Lasers (ex SPAM) (LIDyl), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Bowling Green State University (BGSU), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Max Planck Institute for Medical Research [Heidelberg], Max-Planck-Gesellschaft, Institute for Lasers, Life and Biophotonics, Faculty of Sciences, VU University Amsterdam, Processus d'Activation Sélective par Transfert d'Energie Uni-électronique ou Radiatif (UMR 8640) (PASTEUR), Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Dynamique et Interactions en phase Condensée (DICO), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL)
Subjects: Light, Chemistry, Proteins, Charge (physics), DNA, 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Energy Transfer, Biophysics, Nucleic acid, Light induced, Physical and Theoretical Chemistry, 0210 nano-technology, ComputingMilieux_MISCELLANEOUS, Energy transport
Abstract: International audience
Published: 2018
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34. Listeriolysin O-dependent host surfaceome remodeling modulates Listeria monocytogenes invasion

Author: Bernd Wollscheid, Juan J. Quereda, Pascale Cossart, Karel Novy, Andreas Kühbacher, Javier Pizarro-Cerdá, Maryse Moya-Nilges, Martin Sachse, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris], 1.Institut Pasteur 2.Institut Pasteur ‘Transversal Research Program’ - PTR5213.Institut National de la Santé et de la Recherche Médicale - Unité 6044.Institut National de la Recherche Agronomique - Unité Sous Contrat 20205.Fondation Louis Jeantet 6.European Research Council Advanced - Grant BacCellEpi 6708237.Pasteur-Paris University International Doctoral Program8.Institut Carnot Maladies Infectieuses.9.National Research Agency (ANR) - grant ANR-15-CE15-0017 StopBugEntry 10.Swiss Science National Foundation11.Swiss Initiative for Systems Biology - Grant 51RT 0_12600812.Howard Hughes Medical Institute, ANR-15-CE15-0017,StopBugEntry,Identification des nouvelles molécules cellulaires cibles pour combattre les infections bactériennes(2015), European Project: 670823,H2020,ERC-2014-ADG,BacCellEpi(2015), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), and Pizarro-Cerda, Javier
Subjects: 0301 basic medicine, Microbiology (medical), Proteome, Endosome, [SDV]Life Sciences [q-bio], Bacterial Toxins, late endosomes, Endosomes, Endocytosis, medicine.disease_cause, Hemolysin Proteins, 03 medical and health sciences, lysosomes, Listeria monocytogenes, medicine, Humans, Immunology and Allergy, pore-forming toxin, Heat-Shock Proteins, Phagosome, Pore-forming toxin, General Immunology and Microbiology, Chemistry, Listeriolysin O, Membrane Proteins, Epithelial Cells, General Medicine, Lysosomal-Associated Membrane Protein 1, 3. Good health, Cell biology, lysosomal-associated membrane protein 1, 030104 developmental biology, Infectious Diseases, Host-Pathogen Interactions, Signal transduction, Research Article, HeLa Cells, Late endosomes, Lysosomes, Lysosomal-associated membrane protein 1
Abstract: Listeria monocytogenes is a pathogenic bacterium that invades epithelial cells by activating host signaling cascades, which promote bacterial engulfment within a phagosome. The pore-forming toxin listeriolysin O (LLO), which is required for bacteria phagosomal escape, has also been associated with the activation of several signaling pathways when secreted by extracellular bacteria, including Ca2+ influx and promotion of L. monocytogenes entry. Quantitative host surfaceome analysis revealed significant quantitative remodeling of a defined set of cell surface glycoproteins upon LLO treatment, including a subset previously identified to play a role in the L. monocytogenes infection process. Our data further shows that the lysosomal-associated membrane proteins LAMP-1 and LAMP-2 are translocated to the cellular surface and those LLO-induced Ca2+ fluxes are required to trigger the surface relocalization of LAMP-1. Finally, we identify late endosomes/lysosomes as the major donor compartments of LAMP-1 upon LLO treatment and by perturbing their function, we suggest that these organelles participate in L. monocytogenes invasion., Host surfaceome remodeling modulates Listeria infection
Published: 2018
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35. The Mechanism of HdeA Unfolding and Chaperone Activation

Author: Şerife Akgül, Frederick Stull, Elan Z. Eisenmesser, James C.A. Bardwell, Linda Foit, Sabrina Sayle, M. Claire Cato, Scott Horowitz, Logan S. Ahlstrom, Loïc Salmon, Hashim M. Al-Hashimi, Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), University of Michigan [Ann Arbor], University of Michigan System, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), University of Colorado [Denver], Duke University [Durham], and Duke University Medical Center
Subjects: 0301 basic medicine, Protein Denaturation, Protein Folding, Protein Conformation, Dimer, [SDV]Life Sciences [q-bio], Glutamic Acid, Protonation, Molecular Dynamics Simulation, Article, 03 medical and health sciences, chemistry.chemical_compound, Molecular dynamics, 0302 clinical medicine, Structural Biology, Escherichia coli, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Protein Unfolding, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Escherichia coli Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Periplasmic space, Hydrogen-Ion Concentration, Dissociation constant, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 030104 developmental biology, Biochemistry, chemistry, Chaperone (protein), Hsp33, Periplasm, biology.protein, Biophysics, Protein folding, 030217 neurology & neurosurgery, Molecular Chaperones
Abstract: HdeA is a periplasmic chaperone that is rapidly activated upon shifting the pH to acidic conditions. This activation is thought to involve monomerization of HdeA. There is evidence that monomerization and partial unfolding allow the chaperone to bind to proteins denatured by low pH, thereby protecting them from aggregation. We analyzed the acid-induced unfolding of HdeA using NMR spectroscopy and fluorescence measurements, and obtained experimental evidence suggesting a complex mechanism in HdeA's acid-induced unfolding pathway, as previously postulated from molecular dynamics simulations. Counterintuitively, dissociation constant measurements show a stabilization of the HdeA dimer upon exposure to mildly acidic conditions. We provide experimental evidence that protonation of Glu37, a glutamate residue embedded in a hydrophobic pocket of HdeA, is important in controlling HdeA stabilization and thus the acid activation of this chaperone. Our data also reveal a sharp transition from folded dimer to unfolded monomer between pH3 and pH 2, and suggest the existence of a low-populated, partially folded intermediate that could assist in chaperone activation or function. Overall, this study provides a detailed experimental investigation into the mechanism by which HdeA unfolds and activates.
Published: 2018
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36. Photocrosslinking between nucleic acids and proteins: general discussion

Author: John R. Helliwell, Pushpangadan Indira Pradeepkumar, Joshy Joseph, Igor Schapiro, Ankona Datta, Frederick D. Lewis, Manas Kumar Sarangi, Stefan Haacke, Arijit K. De, Rienk van Grondelle, Ravindra Venkatramani, Javier Segarra-Martí, Vishnu V, Imon Mandal, Richard J. Cogdell, Gebhard F. X. Schertler, Carlos E. Crespo-Hernández, Ganga Periyasamy, Sneha Paul, Padmaja P. Mishra, Vinayak Bhat, Bern Kohler, Tolga N. V. Karsili, Dimitra Markovitsi, Reji Varghese, Priyadarshi Roy Chowdhury, Rajaram Swaminathan, Mahil L, Devika Sasikumar, Ilme Schlichting, Roberto Improta, Retheesh Krishnan, Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), CNR – Istituto di Biostrutture e Bioimmagini, Dynamique et Interactions en phase Condensée (DICO), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire Interactions, Dynamiques et Lasers (ex SPAM) (LIDyl), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Bowling Green State University (BGSU), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research [Heidelberg], Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Laboratoire de Chimie - UMR5182 (LC), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institute for Lasers, Life and Biophotonics, Faculty of Sciences, VU University Amsterdam, Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Biomolécules Excitées (DICO), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Institut de Chimie du CNRS (INC), LaserLaB - Energy, and Biophysics Photosynthesis/Energy
Subjects: Chemistry, Proteins, DNA, 02 engineering and technology, Photochemical Processes, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, 0104 chemical sciences, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [PHYS.MECA.MEMA]Physics [physics]/Mechanics [physics]/Mechanics of materials [physics.class-ph], Cross-Linking Reagents, Biochemistry, Nucleic acid, [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], Physical and Theoretical Chemistry, 0210 nano-technology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018
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37. The Signature of the Five-Stranded vRRM Fold Defined by Functional, Structural and Computational Analysis of the hnRNP L Protein

Author: Frédéric H.-T. Allain, Stanislaw Dunin-Horkawicz, Inna Grishina, Christophe Maris, Janusz M. Bujnicki, Stéphane Thore, Timm Maier, Albrecht Bindereif, Markus Blatter, Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), International Institute of Molecular and Cell Biology, Warsaw and Faculty of Chemistry, University of Warsaw (UW), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)
Subjects: Genetics, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], RNA recognition motif, 030302 biochemistry & molecular biology, Alternative splicing, RNA, RNA-binding protein, Biology, 03 medical and health sciences, Exon, Structural Biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, ComputingMilieux_MISCELLANEOUS, Function (biology), 030304 developmental biology, Binding domain, Heterogeneous-Nuclear Ribonucleoprotein L
Abstract: The RNA recognition motif (RRM) is the far most abundant RNA binding domain. In addition to the typical β1α1β2β3α2β4 fold, various sub-structural elements have been described and reportedly contribute to the high functional versatility of RRMs. The heterogeneous nuclear ribonucleoprotein L (hnRNP L) is a highly abundant protein of 64 kDa comprising four RRM domains. Involved in many aspects of RNA metabolism, hnRNP L specifically binds to RNAs containing CA repeats or CA-rich clusters. However, a comprehensive structural description of hnRNP L including its sub-structural elements is missing. Here, we present the structural characterization of the RRM domains of hnRNP L and demonstrate their function in repressing exon 4 of SLC2A2. By comparison of the sub-structural elements between the two highly similar paralog families of hnRNP L and PTB, we defined signatures underlying interacting C-terminal coils (ICCs), the RRM34 domain interaction and RRMs with a C-terminal fifth β-strand, a variation we denoted vRRMs. Furthermore, computational analysis revealed new putative ICC-containing RRM families and allowed us to propose an evolutionary scenario explaining the origins of the ICC and fifth β-strand sub-structural extensions. Our studies provide insights of domain requirements in alternative splicing mediated by hnRNP L and molecular descriptions for the sub-structural elements. In addition, the analysis presented may help to classify other abundant RRM extensions and to predict structure–function relationships.
Published: 2015
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38. Lipidic cubic phase serial millisecond crystallography using synchrotron radiation

Author: Markus Metz, Vadim Cherezov, Peter Berntsen, Dingjie Wang, Richard Neutze, Wenting Wu, Gebhard F. X. Schertler, Linda C. Johansson, Isabel Moraes, Dominik Oberthuer, Thomas A. White, Henry N. Chapman, Valerie Panneels, Kathrin Jaeger, Petra Båth, Daniel James, Anastasya Shilova, Michael Heymann, Manfred Burghammer, Cecilia Wickstrand, Garrett Nelson, Uwe Weierstall, Joerg Standfuss, Nadia A. Zatsepin, Przemyslaw Nogly, Haiguang Liu, John David Spence, Paul Scherrer Inst, Lab Biomol Res, CH-5232 Villigen, Switzerland, Arizona State University [Tempe] (ASU), DESY, Ctr Free Electron Laser Sci, D-22607 Hamburg, Germany, European Synchrotron Radiation Facility (ESRF), Scripps Research Institute, Ctr Ultrafast Imaging, D-22607 Hamburg, Germany, University of Gothenburg (GU), Univ Hamburg, Dept Phys, D-22607 Hamburg, Germany, Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Department of Physics [Tempe], Diamond Light Source, Membrane Prot Lab, Chilton OX11 0DE, Oxon, England, Rutherford Appleton Lab, Didcot OX11 0FA, Oxon, England, Univ London Imperial Coll Sci Technol & Med, Dept Life Sci, London, England, and Universiteit Gent = Ghent University [Belgium] (UGENT)
Subjects: Materials science, Physics::Optics, Synchrotron radiation, 02 engineering and technology, Biochemistry, law.invention, Quantitative Biology::Subcellular Processes, 03 medical and health sciences, law, protein crystallography, Proton transport, [CHIM]Chemical Sciences, ddc:530, General Materials Science, lcsh:Science, 030304 developmental biology, Physics::Biological Physics, Quantitative Biology::Biomolecules, 0303 health sciences, Millisecond, biology, bacteriorhodopsin, lipidic cubic phases, XFEL, Resolution (electron density), Bacteriorhodopsin, General Chemistry, equipment and supplies, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Research Papers, Synchrotron, Crystallography, Lipidic cubic phases, Protein crystallography, biological sciences, X-ray crystallography, Femtosecond, biology.protein, Physics::Accelerator Physics, lcsh:Q, lipids (amino acids, peptides, and proteins), 0210 nano-technology
Abstract: Lipidic cubic phases (LCPs) have emerged as successful matrixes for the crystallization of membrane proteins. Moreover, the viscous LCP also provides a highly effective delivery medium for serial femtosecond crystallography (SFX) at X-ray free-electron lasers (XFELs). Here, the adaptation of this technology to perform serial millisecond crystallography (SMX) at more widely available synchrotron microfocus beamlines is described. Compared with conventional microcrystallography, LCP-SMX eliminates the need for difficult handling of individual crystals and allows for data collection at room temperature. The technology is demonstrated by solving a structure of the light-driven proton-pump bacteriorhodopsin (bR) at a resolution of 2.4 Å. The room-temperature structure of bR is very similar to previous cryogenic structures but shows small yet distinct differences in the retinal ligand and proton-transfer pathway., IUCrJ, 2 (2), ISSN:2052-2525
Published: 2015
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39. Transposon Sequencing Uncovers an Essential Regulatory Function of Phosphoribulokinase for Methylotrophy

Author: Matthias Christen, Beat Christen, Julia A. Vorholt, Rémi Peyraud, Lucas Hemmerle, Andrea M. Ochsner, Institute of Microbiology, Department of Biology, ETH Zurich, Institute of Microbiology, Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Laboratoire des interactions plantes micro-organismes (LIPM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Swiss SystemsX.ch initiative, Swiss National Science Foundation : 31003A_166476, ETH Zurich : ETH-08 16-1, ETH-41 14-2, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), and Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Proteomics, 0301 basic medicine, 030106 microbiology, Genome, Mass Spectrometry, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Metabolomics, Bacterial Proteins, Methylobacterium extorquens, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Gene, Genetics, biology, Phosphoribulokinase, Sequence Analysis, DNA, biology.organism_classification, one-carbon metabolism, methylotrophy, autotrophy, carbon assimilation, TnSeq, essentiality, mutagenesis, methanol, serine cycle, proteomics, Phosphotransferases (Alcohol Group Acceptor), 030104 developmental biology, DNA Transposable Elements, Methylotroph, Transposon mutagenesis, General Agricultural and Biological Sciences, Genome, Bacterial
Abstract: Summary Methylotrophy is the ability of organisms to grow at the expense of reduced one-carbon compounds, such as methanol or methane. Here, we used transposon sequencing combining hyper-saturated transposon mutagenesis with high-throughput sequencing to define the essential methylotrophy genome of Methylobacterium extorquens PA1, a model methylotroph. To distinguish genomic regions required for growth only on methanol from general required genes, we contrasted growth on methanol with growth on succinate, a non-methylotrophic reference substrate. About 500,000 insertions were mapped for each condition, resulting in a median insertion distance of five base pairs. We identified 147 genes and 76 genes as specific for growth on methanol and succinate, respectively, and a set of 590 genes as required under both growth conditions. For the integration of metabolic functions, we reconstructed a genome-scale metabolic model and performed in silico essentiality analysis. In total, the approach uncovered 95 genes not previously described as crucial for methylotrophy, including genes involved in respiration, carbon metabolism, transport, and regulation. Strikingly, regardless of the absence of the Calvin cycle in the methylotroph, the screen led to the identification of the gene for phosphoribulokinase as essential during growth on methanol, but not during growth on succinate. Genetic experiments in addition to metabolomics and proteomics revealed that phosphoribulokinase serves a key regulatory function. Our data support a model according to which ribulose-1,5-bisphosphate is an essential metabolite that induces a transcriptional regulator driving one-carbon assimilation.
Published: 2017
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40. Peroxisome Proliferator Activated Receptor Gamma Controls Mature Brown Adipocyte Inducibility through Glycerol Kinase

Author: Lukas Varga, Pirjo Nuutila, Wenfei Sun, Sven Enerbäck, Patrik Stefanicka, Christian Wolfrum, Walter Wahli, Bettina Tall, Nicola Zamboni, Kirsi A. Virtanen, Elke Kiehlmann, Petra Krznar, Ez-Zoubir Amri, Lennart Opitz, Jozef Ukropec, Miroslav Balaz, Matthias Rosenwald, Martin E. Lidell, David Lasar, DNA Microarray Facility, Georg-August-University [Göttingen], Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Turku PET Centre, University of Turku, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), University of Zurich, Wolfrum, Christian, and Lee Kong Chian School of Medicine (LKCMedicine)
Subjects: 0301 basic medicine, Adult, Male, Glycerol kinase, [SDV]Life Sciences [q-bio], Peroxisome proliferator-activated receptor, Adipose tissue, 610 Medicine & health, 10071 Functional Genomics Center Zurich, ta3111, General Biochemistry, Genetics and Molecular Biology, PPAR Gamma, 03 medical and health sciences, chemistry.chemical_compound, Mice, Adipose Tissue, Brown, 1300 General Biochemistry, Genetics and Molecular Biology, Glycerol Kinase, Brown adipose tissue, medicine, Adipocytes, Animals, Humans, PPAR alpha, Receptor, lcsh:QH301-705.5, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, Fatty acid metabolism, Chemistry, non-shivering thermogenesis, brown adipose tissue, Thermogenesis, Peroxisome, Cell biology, Mice, Inbred C57BL, PPAR gamma, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), Brown Adipose Tissue, 570 Life sciences, biology, Female, Adipocytes/cytology, Adipocytes/enzymology, Adipocytes/metabolism, Adipose Tissue, Brown/cytology, Adipose Tissue, Brown/enzymology, Adipose Tissue, Brown/metabolism, Glycerol Kinase/metabolism, PPAR gamma/metabolism, glycerol kinase
Abstract: Peroxisome proliferator-activated receptors (PPARs) have been suggested as the master regulators of adipose tissue formation. However, their role in regulating brown fat functionality has not been resolved. To address this question, we generated mice with inducible brown fat-specific deletions of PPARα, β/δ, and γ, respectively. We found that both PPARα and β/δδ are dispensable for brown fat function. In contrast, we could show that ablation of PPARγ in vitro and in vivo led to a reduced thermogenic capacity accompanied by a loss of inducibility by β-adrenergic signaling, as well as a shift from oxidative fatty acid metabolism to glucose utilization. We identified glycerol kinase (Gyk) as a partial mediator of PPARγ function and could show that Gyk expression correlates with brown fat thermogenic capacity in human brown fat biopsies. Thus, Gyk might constitute the link between PPARγ-mediated regulation of brown fat function and activation by β-adrenergic signaling. Published version
Published: 2017
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41. PknG senses amino acid availability to control metabolism and virulence of Mycobacterium tuberculosis

Author: Alessandro Cascioferro, Michael B. Zimmermann, Uwe Sauer, Wafa Frigui, Giulia Degiacomi, Francesca Boldrin, Marco Bellinzoni, Riccardo Manganelli, Natalie R. Lazar-Adler, Helen M. O'Hare, Andrew R. Bottrill, María-Natalia Lisa, Barbara Rieck, Pedro M. Alzari, Fabien Le Chevalier, Liem Nguyen, Roland Brosch, University of Leicester, Universita degli Studi di Padova, Yale University School of Medicine, Pathogénomique mycobactérienne intégrée, Institut Pasteur [Paris], Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), Case Western Reserve University [Cleveland], Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), We acknowledge financial support from the BBSRC (BB/H007865/10) (HMO), the Agence Nationale pour la Recherche (France) grant 09 BLAN 0400 01 (RB) and the European Commission 260872 (MM4TB) (MB and PMA). This research was, in part, funded by EU FP7 project SysteMTb (MZ and US). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., ANR-09-BLAN-0400,MuKit(2009), European Project: 260872,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,MM4TB(2011), European Project: 241587,EC:FP7:HEALTH,FP7-HEALTH-2009-two-stage,SYSTEMTB(2010), Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), ANR-09-BLAN-0400,MuKit,Development of multiple kinase target (MuKiT) inhibitors for treating tuberculosis(2009), Università degli Studi di Padova = University of Padua (Unipd), Yale School of Medicine [New Haven, Connecticut] (YSM), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, QH301-705.5, Amino Acids, Animals, Aspartic Acid, Bacterial Proteins, Glutamic Acid, Homeostasis, Macrophages, Mice, Phosphorylation, Protein-Serine-Threonine Kinases, Tuberculosis, Virulence, Metabolomics, Mycobacterium tuberculosis, Parasitology, Microbiology, Immunology, Molecular Biology, Genetics, Virology, [SDV]Life Sciences [q-bio], 030106 microbiology, Serine, 03 medical and health sciences, Amino acid homeostasis, Protein phosphorylation, Biology (General), biology, RC581-607, biology.organism_classification, 3. Good health, Citric acid cycle, 030104 developmental biology, Immunologic diseases. Allergy, cGMP-dependent protein kinase
Abstract: Sensing and response to changes in nutrient availability are essential for the lifestyle of environmental and pathogenic bacteria. Serine/threonine protein kinase G (PknG) is required for virulence of the human pathogen Mycobacterium tuberculosis, and its putative substrate GarA regulates the tricarboxylic acid cycle in M. tuberculosis and other Actinobacteria by protein-protein binding. We sought to understand the stimuli that lead to phosphorylation of GarA, and the roles of this regulatory system in pathogenic and non-pathogenic bacteria. We discovered that M. tuberculosis lacking garA was severely attenuated in mice and macrophages and furthermore that GarA lacking phosphorylation sites failed to restore the growth of garA deficient M. tuberculosis in macrophages. Additionally we examined the impact of genetic disruption of pknG or garA upon protein phosphorylation, nutrient utilization and the intracellular metabolome. We found that phosphorylation of GarA requires PknG and depends on nutrient availability, with glutamate and aspartate being the main stimuli. Disruption of pknG or garA caused opposing effects on metabolism: a defect in glutamate catabolism or depletion of intracellular glutamate, respectively. Strikingly, disruption of the phosphorylation sites of GarA was sufficient to recapitulate defects caused by pknG deletion. The results suggest that GarA is a cellular target of PknG and the metabolomics data demonstrate that the function of this signaling system is in metabolic regulation. This function in amino acid homeostasis is conserved amongst the Actinobacteria and provides an example of the close relationship between metabolism and virulence. ISSN:1553-7374 ISSN:1553-7366
Published: 2017
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42. Genome-wide small interfering RNA screens reveal VAMP3 as a novel host factor required for Uukuniemi virus late penetration

Author: Christian von Mering, Peter Horvath, Roger Meier, Ari Helenius, Marilou Tétard, Pierre-Yves Lozach, Andrea Franceschini, Roberta Mancini, Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), This work was supported by grants from InfectX to C.V.M., from theEuropean Research Council, the Swiss National Foundation for Research,ETH Zurich, and LipidX to A.H., and from the Natural Sciences andEngineering Research Council of Canada and the Banting Research Foundationto P.Y.L., and University of Zurich
Subjects: Small interfering RNA, 1109 Insect Science, Time Factors, Vesicle-Associated Membrane Protein 3, [SDV]Life Sciences [q-bio], Immunology, Endosomes, Biology, Microbiology, Virus, UFSP13-7 Evolution in Action: From Genomes to Ecosystems, Virology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, Gene silencing, Humans, Gene Silencing, Genetic Testing, RNA, Small Interfering, Host factor, 2403 Immunology, Uukuniemi virus, 2404 Microbiology, Lysosome-Associated Membrane Glycoproteins, Epithelial Cells, Virus Internalization, biology.organism_classification, 10124 Institute of Molecular Life Sciences, 3. Good health, Cell biology, Virus-Cell Interactions, Viral replication, Insect Science, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 2406 Virology, 570 Life sciences, biology, Bunyaviridae, U7 Systems Biology / Functional Genomics, HeLa Cells
Abstract: The Bunyaviridae constitute a large family of enveloped animal viruses, many of which are important emerging pathogens. How bunyaviruses enter and infect mammalian cells remains largely uncharacterized. We used two genome-wide silencing screens with distinct small interfering RNA (siRNA) libraries to investigate host proteins required during infection of human cells by the bunyavirus Uukuniemi virus (UUKV), a late-penetrating virus. Sequence analysis of the libraries revealed that many siRNAs in the screens inhibited infection by silencing not only the intended targets but additional genes in a microRNA (miRNA)-like manner. That the 7-nucleotide seed regions in the siRNAs can cause a perturbation in infection was confirmed by using synthetic miRNAs (miRs). One of the miRs tested, miR-142-3p, was shown to interfere with the intracellular trafficking of incoming viruses by regulating the v-SNARE VAMP3, a strong hit shared by both siRNA screens. Inactivation of VAMP3 by the tetanus toxin led to a block in infection. Using fluorescence-based techniques in fixed and live cells, we found that the viruses enter VAMP3 + endosomal vesicles 5 min after internalization and that colocalization was maximal 15 min thereafter. At this time, LAMP1 was associated with the VAMP3 + virus-containing endosomes. In cells depleted of VAMP3, viruses were mainly trapped in LAMP1-negative compartments. Together, our results indicated that UUKV relies on VAMP3 for penetration, providing an indication of added complexity in the trafficking of viruses through the endocytic network. IMPORTANCE Bunyaviruses represent a growing threat to humans and livestock globally. Unfortunately, relatively little is known about these emerging pathogens. We report here the first human genome-wide siRNA screens for a bunyavirus. The screens resulted in the identification of 562 host cell factors with a potential role in cell entry and virus replication. To demonstrate the robustness of our approach, we confirmed and analyzed the role of the v-SNARE VAMP3 in Uukuniemi virus entry and infection. The information gained lays the basis for future research into the cell biology of bunyavirus infection and new antiviral strategies. In addition, by shedding light on serious caveats in large-scale siRNA screening, our experimental and bioinformatics procedures will be valuable in the comprehensive analysis of past and future high-content screening data.
Published: 2014
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43. Uukuniemi Virus as a Tick-Borne Virus Model

Author: Roberta Mancini, Michael T. Zumstein, Magalie Mazelier, Pierre-Yves Lozach, Lesley Bell-Sakyi, Ronan N. Rouxel, Heidelberg University Hospital [Heidelberg], Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), The Pirbright Institute, and This work was supported by grants from CellNetworks Research Group funds, the Natural Sciences and Engineering Research Council of Canada (grant 419538-2012), and the Banting Research Foundation to P.-Y.L. This work was also supported by the Swiss National Foundation and ETH Zurich. L.B.-S. is supported by United Kingdom Biotechnology and Biological Sciences Research Council funding (grant BBS/E/1/00001741) provided to The Pirbright Institute.We thank Ari Helenius for helpful discussions and support.
Subjects: 0301 basic medicine, reverse genetics system, Ixodes ricinus, Glycosylation, dc-sign, Viral protein, viruses, [SDV]Life Sciences [q-bio], Immunology, valley fever virus, Tick, medicine.disease_cause, Bunyaviridae Infections, Microbiology, Arbovirus, Virus, nucleotide-sequence, ixodes-ricinus ticks, 03 medical and health sciences, Virology, parasitic diseases, medicine, Animals, Humans, Spotlight, thrombocytopenia syndrome virus, rna segment, nonstructural protein nss, cell-lines, family bunyaviridae, Infectivity, biology, Ixodes, Uukuniemi virus, Virion, biology.organism_classification, medicine.disease, 3. Good health, Nucleoprotein, Virus-Cell Interactions, Tick Infestations, Disease Models, Animal, 030104 developmental biology, Insect Science, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HeLa Cells
Abstract: In the last decade, novel tick-borne pathogenic phleboviruses in the family Bunyaviridae , all closely related to Uukuniemi virus (UUKV), have emerged on different continents. To reproduce the tick-mammal switch in vitro , we first established a reverse genetics system to rescue UUKV with a genome close to that of the authentic virus isolated from the Ixodes ricinus tick reservoir. The IRE/CTVM19 and IRE/CTVM20 cell lines, both derived from I. ricinus , were susceptible to the virus rescued from plasmid DNAs and supported production of the virus over many weeks, indicating that infection was persistent. The glycoprotein G C was mainly highly mannosylated on tick cell-derived viral progeny. The second envelope viral protein, G N , carried mostly N -glycans not recognized by the classical glycosidases peptide- N -glycosidase F (PNGase F) and endoglycosidase H (Endo H). Treatment with β-mercaptoethanol did not impact the apparent molecular weight of G N . On viruses originating from mammalian BHK-21 cells, G N glycosylations were exclusively sensitive to PNGase F, and the electrophoretic mobility of the protein was substantially slower after the reduction of disulfide bonds. Furthermore, the amount of viral nucleoprotein per focus forming unit differed markedly whether viruses were produced in tick or BHK-21 cells, suggesting a higher infectivity for tick cell-derived viruses. Together, our results indicate that UUKV particles derived from vector tick cells have glycosylation and structural specificities that may influence the initial infection in mammalian hosts. This study also highlights the importance of working with viruses originating from arthropod vector cells in investigations of the cell biology of arbovirus transmission and entry into mammalian hosts. IMPORTANCE Tick-borne phleboviruses represent a growing threat to humans globally. Although ticks are important vectors of infectious emerging diseases, previous studies have mainly involved virus stocks produced in mammalian cells. This limitation tends to minimize the importance of host alternation in virus transmission to humans and initial infection at the molecular level. With this study, we have developed an in vitro tick cell-based model that allows production of the tick-borne Uukuniemi virus to high titers. Using this system, we found that virions derived from tick cells have specific structural properties and N -glycans that may enhance virus infectivity for mammalian cells. By shedding light on molecular aspects of tick-derived viral particles, our data illustrate the importance of considering the host switch in studying early virus-mammalian receptor/cell interactions. The information gained here lays the basis for future research on not only tick-borne phleboviruses but also all viruses and other pathogens transmitted by ticks.
Published: 2016
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44. A high-throughput metabolomics method to predict high concentration cytotoxicity of drugs from low concentration profiles

Author: Stéphanie Heux, Uwe Sauer, Thomas J. Fuchs, Nicola Zamboni, Joachim M. Buhmann, Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), and Marie Curie Intra-European Fellowships F6P-2005
Subjects: Drug, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Clinical Biochemistry, Off-target drug effects, Method, Biology, Pharmacology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Metabolomics, Yeast metabolism, Metabolome, Drug enzyme interaction, Cytotoxicity, Machine-learning, 030304 developmental biology, media_common, 0303 health sciences, Robustness (evolution), Orders of magnitude (mass), 3. Good health, Toxicity, 030217 neurology & neurosurgery, Intracellular
Abstract: Metabolomics 943SV Times Cited:5 Cited References Count:37; International audience; A major source of drug attrition in pharmacological development is drug toxicity, which eventually manifests itself in detrimental physiological effects. These effects can be assessed in large sample cohorts, but generating rich sets of output variables that are necessary to predict toxicity from lower drug dosages is problematic. Currently the throughput of methods that enable multi-parametric cellular readouts over many drugs and large ranges of concentrations is limited. Since metabolism is at the core of drug toxicity, we develop here a high-throughput intracellular metabolomics platform for relative measurement of 50–100 targeted metabolites by flow injection-tandem mass spectrometry. Specifically we focused on central metabolism of the yeast Saccharomyces cerevisiae because potential cytotoxic effects of drugs can be expected to affect this ubiquitous core network. By machine learning based on intracellular metabolite responses to 41 drugs that were administered at seven concentrations over three orders of magnitude, we demonstrate prediction of cytotoxicity in yeast from intracellular metabolome patterns obtained at much lower drug concentrations that exert no physiological toxicity. Furthermore, the 13C-determined intracellular response of metabolic fluxes to drug treatment demonstrates the functional performance of the network to be rather robust, until growth was compromised. Thus we provide evidence that phenotypic robustness to drug challenges is achieved by a flexible make-up of the metabolome.
Published: 2011
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45. CcpN Controls Central Carbon Fluxes in Bacillus subtilis

Author: Eliane Fischer, Dominique Le Coq, Emmanuel Jamet, Thierry Doan, Stéphane Aymerich, Simon Tännler, Uwe Sauer, Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Microbiologie et Génétique Moléculaire (MGM), Institut National de la Recherche Agronomique (INRA)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), and Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)
Subjects: Mutant, flux métaboliques, Genetics and Molecular Biology, Pentose phosphate pathway, Biology, métabolisme carboné, Microbiology, Pentose Phosphate Pathway, 03 medical and health sciences, Bacterial Proteins, Glyceraldehyde-3-Phosphate Dehydrogenase (NADP+)(Phosphorylating), régulation, CcpN, Glycolysis, Molecular Biology, Derepression, 030304 developmental biology, Carbon Isotopes, 0303 health sciences, 030306 microbiology, Gene Expression Profiling, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Gene Expression Regulation, Bacterial, Pyruvate carboxylase, DNA-Binding Proteins, Repressor Proteins, Citric acid cycle, Glucose, Phenotype, Biochemistry, Phosphoenolpyruvate carboxykinase, transcriptome, Phosphoenolpyruvate Carboxykinase (ATP), Pyruvate kinase, Bacillus subtilis
Abstract: The transcriptional regulator CcpN of Bacillus subtilis has been recently characterized as a repressor of two gluconeogenic genes, gapB and pckA , and of a small noncoding regulatory RNA, sr1 , involved in arginine catabolism. Deletion of ccpN impairs growth on glucose and strongly alters the distribution of intracellular fluxes, rerouting the main glucose catabolism from glycolysis to the pentose phosphate (PP) pathway. Using transcriptome analysis, we show that during growth on glucose, gapB and pckA are the only protein-coding genes directly repressed by CcpN. By quantifying intracellular fluxes in deletion mutants, we demonstrate that derepression of pckA under glycolytic condition causes the growth defect observed in the ccpN mutant due to extensive futile cycling through the pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and pyruvate kinase. Beyond ATP dissipation via this cycle, PckA activity causes a drain on tricarboxylic acid cycle intermediates, which we show to be the main reason for the reduced growth of a ccpN mutant. The high flux through the PP pathway in the ccpN mutant is modulated by the flux through the alternative glyceraldehyde-3-phosphate dehydrogenases, GapA and GapB. Strongly increased concentrations of intermediates in upper glycolysis indicate that GapB overexpression causes a metabolic jamming of this pathway and, consequently, increases the relative flux through the PP pathway. In contrast, derepression of sr1 , the third known target of CcpN, plays only a marginal role in ccpN mutant phenotypes.
Published: 2008
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46. Kinesin Kip2 enhances microtubule growth in vitro through length-dependent feedback on polymerization and catastrophe

Author: Anneke Hibbel, Jonathon Howard, Erik Schäffer, Aliona Bogdanova, Mohammed Mahamdeh, Marko Storch, Anita Jannasch, Dimitris Liakopoulos, Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Yale University [New Haven], Zentrum für Molekularbiologie der Pflanzen (ZMBP), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Department of Life Sciences, Imperial College London, London, United Kingdom, Centre de recherche en Biologie Cellulaire (CRBM), and Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)
Subjects: Saccharomyces cerevisiae Proteins, QH301-705.5, Science, Dynein, Short Report, S. cerevisiae, Saccharomyces cerevisiae, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Microtubules, General Biochemistry, Genetics and Molecular Biology, Motor protein, 03 medical and health sciences, 0302 clinical medicine, length regulation, Microtubule, motor protein, Negative feedback, biophysics, cell biology, Basal body, structural biology, Biology (General), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Microtubule nucleation, Feedback, Physiological, 0303 health sciences, General Immunology and Microbiology, General Neuroscience, Molecular Motor Proteins, positive feedback, General Medicine, Biophysics and Structural Biology, microtubule dynamics, 3. Good health, Cell biology, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Medicine, Kinesin, Protein Multimerization, Astral microtubules, Microtubule-Associated Proteins, 030217 neurology & neurosurgery
Abstract: The size and position of mitotic spindles is determined by the lengths of their constituent microtubules. Regulation of microtubule length requires feedback to set the balance between growth and shrinkage. Whereas negative feedback mechanisms for microtubule length control, based on depolymerizing kinesins and severing proteins, have been studied extensively, positive feedback mechanisms are not known. Here, we report that the budding yeast kinesin Kip2 is a microtubule polymerase and catastrophe inhibitor in vitro that uses its processive motor activity as part of a feedback loop to further promote microtubule growth. Positive feedback arises because longer microtubules bind more motors, which walk to the ends where they reinforce growth and inhibit catastrophe. We propose that positive feedback, common in biochemical pathways to switch between signaling states, can also be used in a mechanical signaling pathway to switch between structural states, in this case between short and long polymers. DOI: http://dx.doi.org/10.7554/eLife.10542.001, eLife digest Cells contain an extensive network of long filaments called microtubules, which are made of a protein called tubulin and are essential for a wide variety of processes such as enabling cells to divide and move. Microtubules also serve as tracks along which motor proteins transport molecules from one part of the cell to another. In yeast cells, a motor protein called Kip2 transports its cargo to one end (known as the “plus end”) of the microtubules. This is the fastest-growing end of the microtubule, although it frequently switches between phases of growth and shrinkage. Previous research has shown that cells containing reduced amounts of Kip2 have much shorter filaments than normal cells. One suggested explanation of these results is that Kip2 controls microtubule growth by transporting a protein that regulates filament length to the plus end of the microtubule. However, by adding purified Kip2 to microtubules Hibbel et al. have now shown that Kip2 on its own can increase the length of filaments. The microtubules also switch much less frequently between growth and shrinkage in the presence of Kip2. This is because Kip2 moves along filaments at a speed that is greater than the rate at which microtubules grow. This sets up a positive feedback loop that causes microtubule growth to accelerate, as more copies of Kip2 can bind to longer microtubules. Each of these motor proteins can then move to the plus end of the microtubule and help the filament to grow even longer. Several challenges remain. What is the molecular mechanism by which Kip2 increases the rate at which tubulin subunits are added to the microtubule end: does Kip2 carry tubulin dimers to the end in a shuttle-type mechanism? How does Kip2 prevent other proteins from promoting shrinkage? What stops microtubules from growing when they reach the end of the cell? DOI: http://dx.doi.org/10.7554/eLife.10542.002
Published: 2015
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47. Molecular Basis of the Rapamycin Insensitivity of Target Of Rapamycin Complex 2

Author: Alexander Leitner, Ruedi Aebersold, Delphine Rispal, Manikandan Karuppasamy, Taiana Maia de Oliveira, Robbie Loewith, Manoel Prouteau, Georgia Konstantinidou, Sandra Eltschinger, Christl Gaubitz, Christiane Schaffitzel, Graham C Robinson, Stéphane Thore, Department of Molecular Biology [Geneva, Switzerland], University of Geneva [Switzerland], Laboratoire européen de biologie moléculaire - European Molecular Biology Laboratory (EMBL Grenoble), European Molecular Biology Laboratory [Grenoble] (EMBL), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)
Subjects: Antifungal Agents, Cell Cycle Proteins/chemistry/genetics/metabolism, Drug Resistance/genetics, Multiprotein Complexes/chemistry/genetics/metabolism, Regulator, Drug Resistance, Cell Cycle Proteins, medicine.disease_cause, Binding Sites/genetics, Mass Spectrometry, Phosphatidylinositol 3-Kinases, ddc:590, Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism/ultrastructure, 610 Medicine & health, ComputingMilieux_MISCELLANEOUS, Mutation, Microscopy, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Sirolimus/metabolism/pharmacology, Blotting, Rhomboid, TOR Serine-Threonine Kinases, Cell Cycle, TOR Serine-Threonine Kinases/chemistry/genetics/metabolism, Cell biology, Biochemistry, Eukaryote, Western, Protein Structure, Saccharomyces cerevisiae Proteins, Protein subunit, Blotting, Western, Saccharomyces cerevisiae, Mechanistic Target of Rapamycin Complex 2, Electron, Lipid biosynthesis, ddc:570, Phosphatidylinositol 3-Kinases/chemistry/genetics/metabolism, medicine, Molecular Biology, Mass Spectrometry/methods, Sirolimus, Binding Sites, Carrier Proteins/chemistry/genetics/metabolism, Cell Biology, Biocatalysis/drug effects, biology.organism_classification, Protein Structure, Tertiary, Microscopy, Electron, Multiprotein Complexes, Biocatalysis, Saccharomyces cerevisiae/drug effects/genetics/metabolism, Carrier Proteins, Antifungal Agents/metabolism/pharmacology, Function (biology), Tertiary, Cell Cycle/drug effects/genetics
Abstract: Target of Rapamycin (TOR) plays central roles in the regulation of eukaryote growth as the hub of two essential multiprotein complexes: TORC1, which is rapamycin-sensitive, and the lesser characterized TORC2, which is not. TORC2 is a key regulator of lipid biosynthesis and Akt-mediated survival signaling. In spite of its importance, its structure and the molecular basis of its rapamycin insensitivity are unknown. Using crosslinking-mass spectrometry and electron microscopy, we determined the architecture of TORC2. TORC2 displays a rhomboid shape with pseudo-2-fold symmetry and a prominent central cavity. Our data indicate that the C-terminal part of Avo3, a subunit unique to TORC2, is close to the FKBP12-rapamycin-binding domain of Tor2. Removal of this sequence generated a FKBP12-rapamycin-sensitive TORC2 variant, which provides a powerful tool for deciphering TORC2 function in vivo. Using this variant, we demonstrate a role for TORC2 in G2/M cell-cycle progression.
Published: 2015
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48. YtsJ Has the Major Physiological Role of the Four Paralogous Malic Enzyme Isoforms in Bacillus subtilis

Author: Nicola Zamboni, Guillaume Lerondel, Thierry Doan, Stéphane Aymerich, Uwe Sauer, Microbiologie et Génétique Moléculaire (MGM), Institut National de la Recherche Agronomique (INRA)-Institut National Agronomique Paris-Grignon (INA P-G)-Centre National de la Recherche Scientifique (CNRS), Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), EU Quality of Life and Management of Living Resources program grant QL GZ-CT-1999-O1455, and Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)
Subjects: MESH: Malate Dehydrogenase, Physiology and Metabolism, Mutant, Malates, Malic enzyme, Bacillus subtilis, Biology, medicine.disease_cause, Microbiology, Malate dehydrogenase, 03 medical and health sciences, Bacterial Proteins, Malate Dehydrogenase, medicine, Malic enzyme activity, MESH: Bacterial Proteins, Molecular Biology, Escherichia coli, MESH: Malates, 030304 developmental biology, chemistry.chemical_classification, MESH: Gene Expression Regulation, Bacterial, 0303 health sciences, 030306 microbiology, Bacterial, MESH: NAD, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Gene Expression Regulation, Bacterial, MESH: Bacillus subtilis, NAD, biology.organism_classification, Molecular biology, Culture Media, MESH: Glucose, Glucose, Enzyme, Genes, Gene Expression Regulation, chemistry, Biochemistry, Genes, Bacterial, Multigene Family, MESH: Culture Media, MESH: Multigene Family, NAD+ kinase, MESH: Genes, Bacterial, MESH: NADP, NADP
Abstract: The Bacillus subtilis genome contains several sets of paralogs. An extreme case is the four putative malic enzyme genes maeA , malS , ytsJ , and mleA. maeA was demonstrated to encode malic enzyme activity, to be inducible by malate, but also to be dispensable for growth on malate. We report systematic experiments to test whether these four genes ensure backup or cover different functions. Analysis of single- and multiple-mutant strains demonstrated that ytsJ has a major physiological role in malate utilization for which none of the other three genes could compensate. In contrast, maeA , malS , and mleA had distinct roles in malate utilization for which they could compensate one another. The four proteins exhibited malic enzyme activity; MalS, MleA, and MaeA exhibited 4- to 90-fold higher activities with NAD + than with NADP + . YtsJ activity, in contrast, was 70-fold higher with NADP + than with NAD + , with K m values of 0.055 and 2.8 mM, respectively. lacZ fusions revealed strong transcription of ytsJ , twofold higher in malate than in glucose medium, but weak transcription of malS and mleA . In contrast, mleA was strongly transcribed in complex medium. Metabolic flux analysis confirmed the major role of YtsJ in malate-to-pyruvate interconversion. While overexpression of the NADP-dependent Escherichia coli malic enzyme MaeB did not suppress the growth defect of a ytsJ mutant on malate, overexpression of the transhydrogenase UdhA from E. coli partially suppressed it. These results suggest an additional physiological role of YtsJ beyond that of malate-to-pyruvate conversion.
Published: 2006
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49. Different phosphatase-dependent mechanisms mediate long-term depression and depotentiation of long-term potentiation in mouse hippocampal CA1 area

Author: Ursula Haditsch, A. Jouvenceau, Patrick Dutar, Jean-Marie Billard, Isabelle M. Mansuy, Neurobiologie de la Croissance et de la Senescence, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Mobilités : Vieillissement, Pathologie, Santé (COMETE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Brain Research Institute and Swiss Federal Institute of Technology, University of Zürich [Zürich] (UZH), Institut de psychiatrie et neurosciences (U894 / UMS 1266), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: N-Methylaspartate, Time Factors, Long-Term Potentiation, Presynaptic Terminals, Hippocampus, Mice, Transgenic, In Vitro Techniques, Biology, Tacrolimus, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Okadaic Acid, Excitatory Amino Acid Agonists, Animals, Enzyme Inhibitors, Long-term depression, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Long-Term Synaptic Depression, General Neuroscience, Excitatory Postsynaptic Potentials, Neural Inhibition, Long-term potentiation, Protein phosphatase 2, Okadaic acid, Electric Stimulation, Phosphoric Monoester Hydrolases, Electrophysiology, Calcineurin, Synaptic fatigue, chemistry, Mutation, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Depotentiation, Neuroscience, 030217 neurology & neurosurgery
Abstract: Two types of synaptic depression have been described in the hippocampus, long-term depression and depotentiation of long-term potentiation known to recruit the serine/threonine protein phosphatases PP1, PP2A and PP2B (calcineurin). The contribution of each of these protein phosphatases is controversial. To examine the role of the Ca2+/calmodulin-dependent protein phosphatase calcineurin in long-term depression and depotentiation, we analysed the effect of genetically inhibiting calcineurin reversibly in the hippocampus, using the doxycycline-dependent rtTA system in transgenic mice. We show that reducing calcineurin activity has no effect on long-term depression but reversibly affects depotentiation. Consistently, the calcineurin inhibitor FK-506 reproduces the depotentiation impairment observed in the mutant mice but does not affect long-term depression in control animals. In contrast, the PP1/PP2A inhibitor okadaic acid fully blocks both long-term depression and depotentiation. These data demonstrate that the nature of signalling cascades induced by synaptic activity depends on the initial synaptic state. While depression of potentiated synaptic responses requires activation of PP1/PP2A and/or calcineurin, depression of basal synaptic responses depends only on PP1/PP2A activation.
Published: 2003
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50. Structural and biochemical characterization of the Cop9 signalosome CSN5/CSN6 heterodimer

Author: Yinshan Yang, Aude Echalier, Melissa Birol, Stéphane Betzi, Radoslav I. Enchev, André Padilla, Christian Dumas, Ruedi Aebersold, Florian Stengel, François Hoh, Matthias Peter, Centre de Biochimie Structurale [Montpellier] (CBS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institute of Biochemistry [ETH Zürich], Department of Biology [ETH Zürich] (D-BIOL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Institute for Molecular Systems Biology [ETH Zurich] (IMSB), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ningxia Medical College, Reproduction et développement des plantes (RDP), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Swiss National Science Foundation, European Project: 246543,EC:FP7:PEOPLE,FP7-PEOPLE-COFUND-2008,ETHFELLOWS(2011), European Project: 095951,WT::(2011), European Project: 233226,EC:FP7:ERC,ERC-2008-AdG,PROTEOMICS V3.0(2009), PADILLA, André, ETH Zurich Postdoctoral Fellowship Program - ETHFELLOWS - - EC:FP7:PEOPLE2011-03-01 - 2016-02-29 - 246543 - VALID, The assembly mechanism of higher order protein assemblies. - - WT::2011-01-06 - 2015-05-31 - 095951 - VALID, Proteomics v3.0: Development, Implementation and Dissemination of a Third Generation Proteomics Technology - PROTEOMICS V3.0 - - EC:FP7:ERC2009-04-01 - 2014-03-31 - 233226 - VALID, École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)
Subjects: Models, Molecular, Ubiquitin-Proteasome System, Protein Conformation, lcsh:Medicine, NEDD8, Biochemistry, Protein structure, Signalosomes, Biochemical Simulations, Post-Translational Modification, lcsh:Science, 0303 health sciences, Multidisciplinary, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Hydrolysis, 030302 biochemistry & molecular biology, Intracellular Signaling Peptides and Proteins, Proteases, Recombinant Proteins, 3. Good health, Ubiquitin ligase, Cell biology, Enzymes, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Molecular docking, Protein Structure Determination, Function and Dysfunction of the Nervous System, Cullin, Protein Binding, Research Article, Protein Structure, NEDD8 Protein, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Protein subunit, Biology, 03 medical and health sciences, ddc:570, Humans, Protein Interaction Domains and Motifs, COP9 signalosome, Protein Interactions, Ubiquitins, 030304 developmental biology, Adaptor Proteins, Signal Transducing, COP9 Signalosome Complex, Crystal structure, lcsh:R, Ubiquitination, Biology and Life Sciences, Proteins, Protein Complexes, Computational Biology, Proteasomes, Dimers (Chemical physics), Protein structure databases, Biochemical Activity, Isopeptidase activity, Protein Subunits, Protein-Protein Interactions, Multiprotein Complexes, Enzyme Structure, biology.protein, Enzymology, Metalloproteases, Anisotropy, lcsh:Q, Protein Multimerization, Peptide Hydrolases
Abstract: International audience; The Cop9 signalosome complex (CSN) regulates the functional cycle of the major E3 ubiquitin ligase family, the cullin RING E3 ubiquitin ligases (CRLs). Activated CRLs are covalently modified by the ubiquitin-like protein Nedd8 (neural precursor cell expressed developmentally down-regulated protein 8). CSN serves an essential role in myriad cellular processes by reversing this modification through the isopeptidase activity of its CSN5 subunit. CSN5 alone is inactive due to an auto-inhibited conformation of its catalytic domain. Here we report the molecular basis of CSN5 catalytic domain activation and unravel a molecular hierarchy in CSN deneddylation activity. The association of CSN5 and CSN6 MPN (for Mpr1/Pad1 N-terminal) domains activates its isopeptidase activity. The CSN5/CSN6 module, however, is inefficient in CRL deneddylation, indicating a requirement of further elements in this reaction such as other CSN subunits. A hybrid molecular model of CSN5/CSN6 provides a structural framework to explain these functional observations. Docking this model into a published CSN electron density map and using distance constraints obtained from cross-linking coupled to mass-spectrometry, we find that the C-termini of the CSN subunits could form a helical bundle in the centre of the structure. They likely play a key scaffolding role in the spatial organization of CSN and precise positioning of the dimeric MPN catalytic core.
Published: 2014
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