DOCSLIB.ORG

Beta Version

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Beta Version Beta Version Zentrum für Infektionsforschung Research Centre for Infectious Diseases Wissenschaftlicher Bericht Josef-Schneider-Str. 2/D15 Scientific Report 2014–2015 97080 Würzburg Germany T +49-931-3182575 F +49-931-3182578 zentrum für M [email protected] infektionsforschung research centre for infectious diseases research centre for infectious diseases 2014–2015 zentrum für infektionsforschung – scientific report 2014-2015 content 1. general remarks 3.6 Department of Internal Medicine II 98 3.6.1 Hermann Einsele – Interaction of Immune Effector Cells with Aspergillus fumigatus 100 1.1 Speaker‘s Report 2014 – 2015 / Sprecherbericht für den Zeitraum 2014 – 2015 6 3.6.2 Andreas Beilhack – Experimental Stem Cell Transplantation 102 1.2 Directory of People Associated with the ZINF 12 3.6.3 Hartwig Klinker – Division of Infectious Diseases 104 1.3 Structure of the ZINF 18 3.6.4 Jürgen Löffl er – Immunity against Aspergillus spp. 106 1.4 News from the ZINF 20 3.6.5 Andrew Ullmann – Clinical Infectious Diseases 108 2. young investigator groups of the zinf 4. zinf members associated with other institutes 2.1 Cynthia Sharma (ZINF) – Deep Sequencing Approaches to Pathogenesis 28 4.1 Gerhard Bringmann – Natural Products Chemistry 112 2.2 Daniel Lopez (ZINF) – Cell-Cell Communication and Signal Transduction 30 4.2 Thomas Dandekar – Bioinformatics 114 2.3 Nicolai Siegel (ZINF) – Trypanosoma Gene Regulation 32 4.3 Markus Engstler – Molecular and Physical Parasitology 116 2.4 Ana Eulalio (BioSysNet) – Host RNA Metabolism 34 4.4 Ute Hentschel-Humeida – Marine Sponge-Microbe Interactions 118 2.5 Christian Perez (IZKF) – Regulatory Networks in Pathogenesis 36 4.5 Ulrike Holzgrabe – Medicinal Chemistry 120 2.6 Sebastian Geibel (Elite Network Bavaria) – Structural Biology of Mycobacteria 38 4.6 Caroline Kisker – Structure Based Drug Design 122 2.7 Sina Bartfeld (ZINF) – Organoids as Host Model 40 4.7 Gabriela Krasteva-Christ – Pulmonary Neurobiology 124 4.8 August Stich – Tropical Medicine 126 4.9 Heike Walles – Tissue Engineering 128 3. institutions of the research Centre for infectious diseases 3.1 Institute of Molecular Infection Biology 44 5. research programmes and infrastructure 3.1.1 Jörg Vogel – RNA Biology 46 3.1.2 Heidrun Moll – Infection Immunology 48 5.1 SFB 630 – Recognition, Preparation and Functional Analysis of Agents Against Infectious Diseases 132 3.1.3 Joachim Morschhäuser – Mycology 50 5.2 SFB/ Transregio 34 – Pathophysiology of Staphylococci in the Post-Genome Era 132 3.1.4 Knut Ohlsen – Gram-positive Cocci 52 5.3 SFB/ Transregio 124 – Pathogenic Fungi and their Human Host: Networks of Interaction 133 3.1.5 Tobias Ölschläger – Enterobacteria 54 5.4 Research Unit 1680 – Unravelling the Prokaryotic Immune System 134 3.1.6 Wilma Ziebuhr – Nosocomial Infections by Staphylococci 56 5.5 Research Unit 2123 – Sphingolipid Dynamics in Infection Control 134 5.6 DFG SPP 1316 – Host-adapted Metabolism of Bacterial Pathogens 135 3.2 Institute for Hygiene and Microbiology 58 5.7 DFG SPP 1617 – Phenotypic Heterogeneity and Sociobiology of Bacterial Populations 135 3.2.1 Matthias Frosch – Molecular Surveillance of Invasive Bacterial Infections 60 5.8 DFG SPP 1784 – Chemical Biology of Native Nucleic Acid Modifi cations 135 3.2.2 Klaus Brehm – Helminth Infections 62 5.9 German-African Cooperation Projects in Infectiology 136 3.2.3 Christoph Schoen – Evolutionary and Functional Pathogenomics of Neisseria meningitidis 64 5.10 BMBF Medical Infection Genomics 136 3.2.4 Alexandra Schubert-Unkmeir – Host-Pathogen Interactions 66 5.11 BMBF MedVet-Staph 136 3.2.5 Ulrich Vogel – Infection Epidemiology and Pathogenesis of Neisseria meningitidis 68 5.12 The Bavarian Research Network for Molecular Biosystems (BioSysNet) 137 5.13 ERA-NET 137 3.3 Institute for Virology and Immunobiology – Chair of Immunobiology 70 5.14 International Network for Strategic Initiatives in Global HIV Trials (INSIGHT) 139 3.3.1 Thomas Hünig – Immunology 72 5.15 National Reference Laboratory for Meningococci and Haemophilus infl uenzae 139 3.3.2 Niklas Beyersdorf – T Cell Biology 74 5.16 The Consulting Laboratory for Echinococcosis 140 3.3.3 Thomas Herrmann – Immunogenetics 76 5.17 IBD-labnet – Coordination of Activities for Laboratory Surveillance of Invasive Bacteria Diseases 140 3.3.4 Manfred Lutz – Immune Regulation 78 5.18 Wellcome Trust Strategic Award – Flatworm Functional Genomics Initiative 140 5.19 German Centre for Infection Research (DZIF) 141 3.4 Institute for Virology and Immunobiology – Chair of Virology 80 5.20 Interdisciplinary Centre for Clinical Research (IZKF) 141 3.4.1 Lars Dölken – Systems Biology of Herpesvirus Infections 82 5.21 Graduate School of Life Sciences (GSLS) 142 3.4.2 Jürgen Schneider-Schaulies – Morbillivirus Pathogenesis 84 5.22 GRK 2157 3D-Infect – 3D-Tissue Models for Studying Microbial Infections by Human Pathogens 143 3.4.3 Sibylle Schneider Schaulies – Viral Immunomodulation 86 5.23 Core Unit for Systems Medicine 144 3.5 Department of Microbiology, Theodor Boveri Institute, Biocenter 88 3.5.1 Thomas Rudel – Infection Biology of Bacteria 90 6. appendix 3.5.2 Martin Fraunholz – Cellular Microbiology 92 3.5.3 Roy Gross – Endosymbiont Biology 94 6.1 ZINF Young Investigator Group Alumni 148 3.5.4 Vera Kozjak-Pavlovic – Bacterial Invasion and Intracellular Survival 96 6.2 Meetings and workshops organised by ZINF members 150 6.3 Seminars (Microbiology Colloquium, Virology and Immunobiology Seminars) 152 6.4 Funding 156 6.5 Publications 162 2 general remarks 3 01 general remarks speaker’s report In terms of the ZINF members, on the 29th of July 2014 we lost a long-term member, esteemed colleague and 2014 –2015 friend Axel Rethwilm, Chairman of Virology at the Institute of Virology and Immunobiology. Axel will be missed both as a person and for his contribution to infectious diseases research in Würzburg (a retrospective of his ca- reer can be found in the report). In 2015, Lars Dölken replaced Axel as the Chair of Virology. Lars joined us from the University of Cambridge and will continue his systems biology studies of herpesvirus infections. Finally, Gabriela Krasteva-Christ, a new W2 professor at the Department of Anatomy and Cell Biology, also joins the ZINF working on the role specialized mucosal epithelial cells that use the canonical taste transduction cascade Infectious diseases have remained a global challenge to human health and thus a prominent topic of discussion to detect bacterial pathogens. at both the academic and political levels. Human history has been continuously impacted by infectious dis- eases, and despite major progress in understanding their causes and treatment, they remain a significant socio- From 2014 to 2015, several ZINF members were awarded prestigious prizes and appointments. Ute Hentschel- economic burden to mankind. During the years 2014 and 2015, the Ebola virus outbreak in West Africa and the Humeida departs ZINF after accepting a Department Head position at the Helmholtz Centre for Ocean Re- ongoing Zika virus epidemic in South America have reminded us of our vulnerability to emerging pathogens. search in Kiel. Cynthia Sharma received an offer for a Full Professorship (W3) and was awarded the 2015 DFG/ The sweeping spread of antibiotic resistance throughout the world further highlights the risks posed by infec- BMBF Heinz-Maier-Leibnitz-Prize. Vera Kozjak-Pavlovic received an offer for a W2 professorship at Goethe tions. Leading policy-makers placed the issue on the agenda for the G7 summit 2015 in Elmau and discussed University, Frankfurt and was awarded the 2015 Marcella Boveri Research Prize from the University of Würzburg. the actions required to prevent us entering a post-antibiotic era. Andreas Beilhack was awarded the 2015 m4 Award of the Bavarian Ministry of Economic Affairs and Media, Energy and Technology. Ana Eulalio was selected as a 2015 EMBO Young Investigator. Gerhard Bringmann The collaborative Research Centre for Infectious Diseases (ZINF) at the University of Würzburg has been ad- received the 2014 Gusi Peace Prize and a doctorate honoris causa of the Université des Pays des Grands Lacs dressing the molecular principles of host-pathogen interactions since 1993, by bringing together experts in (ULPGL) in Goma (Democratic Republic of the Congo). Finally, Jörg Vogel was elected to the European Acad- microbiology, parasitology, virology and immunology as well as chemists and clinicians. Founded by Volker ter emy of Microbiology in 2015. Meulen, Werner Goebel and colleagues with initial financial contributions from the Federal Ministry of Educa- tion and Research (BMBF), ZINF developed into a major scientific research programme at the University of ZINF members serve the scientific community by holding important positions in several societies and cor- Würzburg under the long-term leadership of Jörg Hacker. In recognition of its extraordinary success, the Bavar- porations. Hartwig Klinker has been appointed a board member of Deutsche Gesellschaft für Infektiologie ian Government and the University of Würzburg have continued to fund this programme. I have had the honour (2015-2017). Thomas Dandekar was nominated to the selection Committee of the Alexander von Humboldt to serve as the Spokesperson of ZINF since 2011. Foundation. Jörg Vogel was nominated to the DFG Scientific Equipment Committee and the EMBO Long-term Fellowship Committee. Cynthia Sharma was elected to the DGHM Study Group Board member for “Gastroin- The present report covering the 2014–2015 period highlights the scientific projects and achievements of the testinal Infections” and the GBM Study Group Board member for “RNA Biochemistry”. Young Investigator groups that lie at the heart of ZINF, and aims to provide an overview of the research activities of ZINF members with relevance to infectious diseases. These were exceptionally busy and exciting years, with Infectious diseases research at the University of Würzburg is supported through both national and international respect to changes in personnel, as well as networking and scientific achievements. funding initiatives. Milestones in 2014–2015 included the funding of a number of newly established Infect- ERA research networks.
Load more

Recommended publications
  • Molecular Analysis of Small Rna and Small Protein Regulation of Escherichia Coli Stress Responses
    MOLECULAR ANALYSIS OF SMALL RNA AND SMALL PROTEIN REGULATION OF ESCHERICHIA COLI STRESS RESPONSES BY CHELSEA R. LLOYD DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Microbiology in the Graduate College of the University of Illinois at Urbana-Champaign, 2018 Urbana, Illinois Doctoral Committee: Associate Professor Carin K. Vanderpool, Chair Professor John E. Cronan Professor William W. Metcalf Professor Peter A. B. Orlean Abstract Small RNA (sRNA) regulators control gene expression throughout all domains of life. In bacteria, they typically affect virulence, metabolism, and stress response genes posttranscriptionally through imperfect antisense pairing with their mRNAs. While most sRNAs are non-coding, a small number act as mRNAs themselves by encoding functional proteins. This study examines the regulatory and physiological effects of both a non-coding sRNA, DicF, and the protein product of a dual-function sRNA, SgrS in Eschericha coli. The sRNA SgrS encodes the small 43-amino acid protein SgrT. Both molecules are expressed during glucose-phosphate stress - a bacteriostatic condition in which phosphosugars accumulate in the cell either because of mutations in glycolysis or because of the transport of non-metabolizable glucose analogs such as αMG or 2DG. While both SgrT and SgrS base pairing can independently mitigate glucose-phosphate stress, they do so through distinct mechanisms. SgrS base pairing destabilizes the mRNA of the respective major and minor glucose transporters PtsG and ManXYZ, thereby inhibiting synthesis of additional glucose permeases and restricting further influx of non- metabolizable sugars. In this study we demonstrate that SgrT acts to specifically inhibit the transport activity of preexisting PtsG transporters, but does not affect ManXYZ.
    [Show full text]
  • Determinants of Target Prioritization and Regulatory Hierarchy for the Bacterial Small RNA Sgrs
    Molecular Microbiology (2019) 112(4), 1199–1218 doi:10.1111/mmi.14355 First published online 6 August 2019 Determinants of target prioritization and regulatory hierarchy for the bacterial small RNA SgrS Maksym Bobrovskyy,1,† Muhammad S. Azam,1 of regulation of SgrS targets. The RNA chaperone Jane K. Frandsen,2,3,‡ Jichuan Zhang,4 Hfq uses distinct modes of binding to different SgrS Anustup Poddar,4 Xiangqian Ma,1 Tina M. Henkin,2 mRNA targets, which differentially influences posi- Taekjip Ha4,5 and Carin K. Vanderpool 1* tive and negative regulation. The RNA degradosome 1 Department of Microbiology, University of Illinois at plays a larger role in regulation of some SgrS targets Urbana-Champaign, 601 S. Goodwin Ave., Urbana, compared to others. Collectively, our results sug- IL 61801, USA. gest that sRNA selection of target mRNAs and regu- 2 Department of Microbiology and Center for RNA latory hierarchy are influenced by several molecular Biology, The Ohio State University, Columbus, features and that the combination of these features OH 43210, USA. precisely tunes the efficiency of regulation of multi- 3 Biochemistry Program, The Ohio State University, target sRNA regulons. Columbus, OH 43210, USA. 4 Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, Baltimore, MD 21205, USA. Introduction 5 Howard Hughes Medical Institute, Baltimore, Bacteria live in diverse niches, often encountering rapidly MD 21205, USA. changing and stressful environments. Bacterial stress responses can mitigate the negative effects of stress on cell structure and function. Stress responses are usually coordinated by regulators, either RNAs or proteins, that Summary alter expression of a regulon comprised of multiple genes.
    [Show full text]
  • Identification of Regulation in Central Carbon Metabolism Among Related
    Identification of differential regulation in central carbon metabolism between related cell lines DISSERTATION zur Erlangung des akademischen Grades Doctor rerum naturalium (Dr. rer. nat.) im Fach Biophysik eingereicht an der Lebenswissenschaftlichen Fakultät der Humboldt-Universität zu Berlin von M.Sc. Roman Josef Rainer Präsidentin/Präsident der Humboldt-Universität zu Berlin: Prof. Dr.-Ing. Dr. Sabine Kunst Dekanin/Dekan der Lebenswissenschaftlichen Fakultät der Humboldt-Universität zu Berlin: Prof. Dr. Bernhard Grimm Gutachter/innen: 1. Prof. Dr. Dr. h.c. Edda Klipp 2. Prof. Dr. Birgit Sawitzki 3. Prof. Julio R. Banga Tag der mündlichen Prüfung: 29.10.2020 Abstract Colon cancer cells and T cells regulate central carbon metabolism to meet their anabolic needs. In KRAS and BRAF tumors, metabolic reprogramming is a premise to support rapid prolif- eration. In T cells, the mitochondrial T cell activation inhibitor (TCAIM) is known to affect mitochondrial morphology but its effect on cellular metabolism is not well understood. Via math- ematical modelling, I investigate the differential regulation of closely related cell lines. I present the first mathematical model for colon cancer and T cell metabolism, unraveling differential regulation between related cell lines. The model shows that CaCO2-BRAFV600Ecells are mostly downregulated compared to CaCO2-KRASG12Vand CaCO2-control. Additionally, it demon- strates the critical role of monocarboxylate transporter (MCT), especially for CaCO2-KRASG12V. Concerning T cells, I compare wild-type T cells to homozygous TCAIM T cells. This unveils that TCAIM homozygous cells have a mostly downregulated TCA cycle, validated by RNASeq data, and are less metabolically active than wild-type T cells. Furthermore, if the glycolytic flux is not sufficient to support lactate export and biomass production, the model reveals that the TCA cy- cle is reversed as it requires less regulation.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Computational Methods for the Identification and Characterization
    Computational Methods for the Identification and Characterization of Non-Coding RNAs in Bacteria Dissertation der Mathematisch-Naturwissenschaftlichen Fakult¨at der Eberhard Karls Universit¨atT¨ubingen zur Erlangung des Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) vorgelegt von Alexander Herbig aus Altenkirchen T¨ubingen 2014 Tag der m¨undlichenQualifikation: 30.01.2015 Dekan: Prof. Dr. Wolfgang Rosenstiel 1. Berichterstatterin: PD Dr. Kay Nieselt 2. Berichterstatter: Prof. Dr. Daniel Huson 3. Berichterstatter: Prof. Dr. Rolf Backofen Zusammenfassung Forschungsergebnisse vergangener Jahre konnten zeigen wie komplex die Struktur und Regulation selbst bakterieller Transkriptome sein kann. Auch die wichtige Rolle nicht-kodierender RNAs (ncRNA), die nicht in Proteine translatiert werden, wird dabei immer deutlicher. Diese Molek¨uleerf¨ullen in der Zelle verschiedenste Aufgaben wie zum Beispiel die Regulation von Stoffwechselprozessen. Daher ist die Charakter- isierung der ncRNA-Gene eines Organismus immer mehr zu einem unverzichtbaren Teil von Systembiologie-Projekten geworden. Hierbei erlauben moderne Hochdurch- satzverfahren im Bereich der DNA- und RNA-Sequenzierung das im hohen Maße detaillierte Studium von Genomen und Transkriptomen. Die daraus resultierenden Daten m¨usseneiner vergleichenden Analyse unterzogen werden, um Variationen des Transkriptoms zwischen verschiedenen Organismen und Umweltbedingungen untersuchen zu k¨onnen.Hierf¨urwerden effiziente Computerprogramme ben¨otigt, die in der Lage sind genomische und transkriptomische Daten zu kombinieren und entsprechende Analysen automatisiert und reproduzierbar durchzuf¨uhren.Zu- dem m¨ussendiese Ans¨atzenicht-kodierende Elemente im genomischen Kontext lokalisieren und annotieren k¨onnen. In dieser Dissertation pr¨asentiere ich Computerprogramme zur L¨osungdieser Aufgaben. So wurde das Programm nocoRNAc entwickelt, welches ncRNAs in bakteriellen Genomen detektiert und diese bez¨uglich verschiedener Eigenschaften charakterisiert.
    [Show full text]
  • The Ancestral Sgrs RNA Discriminates Horizontally Acquired Salmonella Mrnas Through a Single G-U Wobble Pair
    The ancestral SgrS RNA discriminates horizontally acquired Salmonella mRNAs through a single G-U wobble pair Kai Papenforta, Dimitri Podkaminskia, Jay C. D. Hintonb, and Jörg Vogela,1 aRNA Biology Group, Institute for Molecular Infection Biology, University of Würzburg, D-97080 Würzburg, Germany; and bDepartment of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland AUTHOR SUMMARY Small noncoding RNAs A characteristic of HGT (sRNAs) constitute a vital group genes is that they are more likely of so-called posttranscriptional to undergo duplication than so- SgrS RNA regulators that shape the gene Core genome Horizontally acquired called core genes. Gene dupli- expression of eukaryotic and elements pathogenicity genes cation is a well-studied phe- prokaryotic organisms. In bac- nomenon accelerating evolu- teria, sRNAs generally act duplication tionary change in bacterial through base pairing to reduce pathogens (4). For example, the Hfq or increase the translation of ptsG/manXYZ mRNAs sopD mRNA sopD2 mRNA sopD gene has been duplicated target mRNAs into protein. target (G-C base-pair) pseudotarget (G-U base-pair) to generate sopD2 throughout Most of our current knowledge the S. enterica species, except in of sRNA numbers and functions the ancestral S. bongori (1). A Fig. P1. Posttranscriptional interaction between the core and stems from two species, Escher- horizontally acquired genome through Hfq and sRNAs. The SgrS sRNA bioinformatic comparison of the ichia coli and Salmonella enterica is encoded by the Salmonella core genome and conserved in many sopD and sopD2 sequences serovar Typhimurium. Both bacterial species, including E. coli and Salmonella. Aided by the RNA showed that the SgrS targeting organisms display a high degree chaperone Hfq, SgrS reduces the expression of mRNAs encoding for region is well-conserved be- of sequence conservation across sugar transport proteins (ptsG and manXYZ), both of which are core tween both genes; in other about three-quarters of the genomic elements.
    [Show full text]
  • Small RNA-Mediated Activation of Sugar Phosphatase Mrna Regulates Glucose Homeostasis
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Small RNA-Mediated Activation of Sugar Phosphatase mRNA Regulates Glucose Homeostasis Kai Papenfort,1,2 Yan Sun,3 Masatoshi Miyakoshi,1 Carin K. Vanderpool,3,* and Jo¨ rg Vogel1,* 1Institute for Molecular Infection Biology, University of Wu¨ rzburg, Wu¨ rzburg 97070, Germany 2Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA 3Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA *Correspondence: [email protected] (C.K.V.), [email protected] (J.V.) http://dx.doi.org/10.1016/j.cell.2013.03.003 SUMMARY glycolytic flux, their intracellular levels must be tightly regulated since high levels are toxic and strongly impair cell growth (Irani Glucose homeostasis is strictly controlled in all and Maitra, 1977; Kadner et al., 1992) and cause DNA damage domains of life. Bacteria that are unable to balance (Bucala et al., 1985; Lee and Cerami, 1987). Similarly, many non- intracellular sugar levels and deal with potentially metabolizable sugars can cause phosphosugar stress. For toxic phosphosugars cease growth and risk being example, the glucose analog a-methyl-glucoside (a-MG) is outcompeted. Here, we identify the conserved haloa- efficiently imported by PtsG, the major glucose transporter of a cid dehalogenase (HAD)-like enzyme YigL as the pre- Escherichia coli and Salmonella (Jahreis et al., 2008). -MG-6- phosphate accumulates in the cytoplasm and can terminate viously hypothesized phosphatase for detoxification bacterial growth (Pikis et al., 2006; Rogers and Yu, 1962).
    [Show full text]
  • An E. Coli Small Rna Inhibits Translation Initiation from a Distance
    AN E. COLI SMALL RNA INHIBITS TRANSLATION INITIATION FROM A DISTANCE BY MUHAMMAD SHAFIUL AZAM DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Microbiology in the Graduate College of the University of Illinois at Urbana-Champaign, 2019 Urbana, Illinois Doctoral Committee: Professor Carin K. Vanderpool, Chair Professor Rachel J. Whitaker Professor James M. Slauch Professor Gary J. Olsen ABSTRACT In bacterial systems, small RNA (sRNA)-dependent translational repression is commonly carried out via sRNA-mRNA base pairing interactions near the Shine- Dalgarno (SD) region. In this so-called “canonical” mechanism, the sRNA is the direct regulator; it competes with the initiating ribosomes while the chaperone protein Hfq plays a supporting role. Contrary to this widely accepted model, there are a few examples in the literature where the sRNA base pairs far from the SD region, yet translation of the target mRNA is still inhibited. Mechanistically, non-canonical translation regulation is one of the least understood aspects of sRNA biology. In the targetome of an E. coli sRNA SgrS, manXYZ is a non-canonical target where SgrS base pairs at two distinct sites that are far from the SD regions of manX and manY , yet translation of these two cistrons are repressed by SgrS. We found that manX translation is controlled by a molecular role- reversal mechanism where an Hfq binding site is directly adjacent to the manX ribosome binding site. In this regulatory mechanism, SgrS plays the role of a guide to recruit Hfq to the appropriate binding site to form the silencing complex.
    [Show full text]
  • Human Induced Pluripotent Stem Cell–Derived Podocytes Mature Into Vascularized Glomeruli Upon Experimental Transplantation
    BASIC RESEARCH www.jasn.org Human Induced Pluripotent Stem Cell–Derived Podocytes Mature into Vascularized Glomeruli upon Experimental Transplantation † Sazia Sharmin,* Atsuhiro Taguchi,* Yusuke Kaku,* Yasuhiro Yoshimura,* Tomoko Ohmori,* ‡ † ‡ Tetsushi Sakuma, Masashi Mukoyama, Takashi Yamamoto, Hidetake Kurihara,§ and | Ryuichi Nishinakamura* *Department of Kidney Development, Institute of Molecular Embryology and Genetics, and †Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; ‡Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Hiroshima, Japan; §Division of Anatomy, Juntendo University School of Medicine, Tokyo, Japan; and |Japan Science and Technology Agency, CREST, Kumamoto, Japan ABSTRACT Glomerular podocytes express proteins, such as nephrin, that constitute the slit diaphragm, thereby contributing to the filtration process in the kidney. Glomerular development has been analyzed mainly in mice, whereas analysis of human kidney development has been minimal because of limited access to embryonic kidneys. We previously reported the induction of three-dimensional primordial glomeruli from human induced pluripotent stem (iPS) cells. Here, using transcription activator–like effector nuclease-mediated homologous recombination, we generated human iPS cell lines that express green fluorescent protein (GFP) in the NPHS1 locus, which encodes nephrin, and we show that GFP expression facilitated accurate visualization of nephrin-positive podocyte formation in
    [Show full text]
  • Mechanistic and Physiological Insights Into Post- Transcriptional Regulation by Small Rnas Sgrs and Dicf
    MECHANISTIC AND PHYSIOLOGICAL INSIGHTS INTO POST- TRANSCRIPTIONAL REGULATION BY SMALL RNAS SGRS AND DICF BY DIVYA BALASUBRAMANIAN DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Microbiology in the Graduate College of the University of Illinois at Urbana-Champaign, 2014 Urbana, Illinois Doctoral Commitee: Associate Professor Carin K. Vanderpool, Chair Professor Jeffrey F. Gardner Professor William W. Metcalf Professor James M. Slauch Abstract Base pairing small regulatory RNAs (sRNAs) are important post-transcriptional regulators of gene expression in bacteria. These sRNAs deploy novel mechanisms to regulate mRNA targets leading to various physiological outcomes during stress conditions including, but not limited to, iron starvation, carbon flux and metabolism, virulence, and quorum sensing. In this study, we investigate the multitude of clever mechanisms that two sRNAs, SgrS and DicF, utilize to regulate gene expression, and the physiological consequences of such regulation. The SgrS sRNA participates in a response to a growth inhibitory stress condition called sugar-phosphate stress caused by the toxic accumulation of phosphorylated sugars. SgrS combats this stress with its RNA base pairing function by silencing translation of sugar transporters that import the stress molecules. SgrS was previously shown to negatively regulate the manXYZ broad sugar-substrate transporter. In this study we demonstrate that SgrS binds at manX and in the intergenic region of manXY to translationally silence this operon. We show that pairing at both these sites is critical for degradation of the manXYZ polycistron, and is also crucial for providing maximal relief from stress. SgrS is a dual-function sRNA in that in addition to its RNA function, it also produces a peptide called SgrT.
    [Show full text]
  • Discovery of Small Rnas and Characterization of Their Regulatory Roles in Mycobacterium Tuberculosis
    Discovery of Small RNAs and Characterization of Their Regulatory Roles in Mycobacterium Tuberculosis The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Gerrick, Elias Roth. 2018. Discovery of Small RNAs and Characterization of Their Regulatory Roles in Mycobacterium Tuberculosis. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:41129159 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use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
    [Show full text]