DOCSLIB.ORG

Proquest Dissertations

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Proquest Dissertations Genetic and Immunological Characterization of the Major Outer Membrane Protein (OmpS) of Legionella pneumophila. by Risini D. Weeratna Submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Dalhousie University Halifax, Nova Scotia August, 19 95 ©Copyright by Risini D. Weeratna, 1995 I I National Library Bibliotheque nationale 1*1 of Canada du Canada Acquisitions and Direction des acquisitions et Bibliographic Services Branch des services bibliographiques 395 Wellington Street 395, rue Wellington Ottawa, Ontario Ottawa (Ontario) K1A0N4 K1A0N4 Your Me Voire reference Our tile Notre reference The author has granted an L'auteur a accorde une licence irrevocable non-exclusive licence irrevocable et non exclusive allowing the National Library of permettant a la Bibliotheque Canada to reproduce, loan, nationale du Canada de distribute or sell copies of reproduire, prefer, distribuer ou his/her thesis by any means and vendre des copies de sa these in any form or format, making de quelque in an i ere et sous this thesis available to interested quelque forme que ce soit pour persons. mettre des exemplaires de cette these a la disposition des personnes interessees. The author retains ownership of L'auteur conserve la propriete du the copyright in his/her thesis. droit d'auteur qui protege sa Neither the thesis nor substantial these. Ni la these ni des extraits extracts from it may be printed or substantiels de celle-ci ne otherwise reproduced without doivent etre imprimes ou his/her permission. autrement reproduits sans son autorisation. ISBN 0-612-15868-3 Canada I I Name (?tsm i J>hctwtvM^f. Ukgyalfgi Dissertation Abstracts international is arranged by broad, general subject categories Pleats select the on-ject which most nearly describes the con'ent of your dissertation Enter the corresponding four-digit code in the spaces ovided MiC'C'Wlofly ^MB UMI SUBJECT TERM WWCTCOM Subject Categories THE HUMANITIES AND SOCIAl SCIENCES COMMUNICATION: AND THE ARTS PsychcAwy 0525 PHILOSOPHY, RELIGION AND Ancient 0579 Architecture 0729 Reading 0535 THEOLOGY Medieval 0581 Art History 0377 Religious 0527 Modern 0182 Philosophy 0422 Cinema 0900 Sciences 0714 Religion Black 0328 Donee 0378 Secondary 0533 African 0331 General 0318 Social Sciences 0534 Asia, Australia and Oceania 0332 Fine Arts 03 J7 Biblical Studies 0321 Information Science 0723 0334 Sociology of 0340 Clergy 0319 Canadian Journalism 0391 Special 0529 History of 0320 European 0335 Library Science 0399 Teacher Training 0530 0336 Philosophy of 0322 latin American Technology 0710 Mais Comrmmicationi 0708 Theology 0469 Middle Eastern 0333 MUSK 0413 Tests arKiMeosurerrtents 0288 United States 0337 Speech Communication 0459 Vocational 0747 SOCIAL SCIENCES History of Science 0585 Theater 0465 American Studies 0323 Law 0398 LANGUAGE, LITERATURE AND Anmropology Political Sc ence EDUCATION General 0615 LINGUISTICS Archoeofogy 0324 International Law and General 0515 Languag» Cultural 0326 Administration 0514 Relations 0616 General 0679 Physical 0327 Adult and Continuing 0516 Public Administration 0617 Ancient 0289 Business Administration 0814 Agricultural 0517 Linguistics 0290 General 0310 Recreation Art 0273 Modern 0291 Accounting 0272 Sociol Work 0452 Bilingual and Multicultural 0282 Sociology Literature Banking 0770 Business 0688 General 0401 General 0626 Management 0454 0627 Community College 0275 Classical 0294 Marketing 0338 Criminology and Penology Curriculum and Instruction 0727 Comparative 0295 Canadian Studies 0385 Demography 0938 Early Childhood 0518 Medieval 0297 Economics Ethnic and Racial Studies 0631 Elementary 0524 Mcdem 0298 General 0501 Individual and Family Finance 0277 African 0316 Agricultural 0503 Studies 0628 Guidance and Counseling 0519 American 0591 Commerce Business 0505 Industrial and Labor Health 0630 0629 Asian 0305 Finance 0508 Relations Higher 0745 Canadian [English) 0352 History 0509 Public and Social Welfare 0630 Kstoryof 0520 Canadian (French) 0355 Labor 0510 Social Structure and Home Economics 0278 English 0593 Theory 0511 Development 0700 Industrial 0521 Germanic 03' 1 Folklore 0358 Theory and Methods 0344 language and Literature 0279 Latin American 0312 Geography 0366 Transportation 0709 Mathematics 0280 Urban and Regional Planning Middle Eastern 0315 Gerontology 0351 0999 Music 0522 Romance 0313 History Women s Studies 0453 Philosophy of 0998 Slavic and East European 0314 General 0578 Physical 0523 THE SCIENCES AND ENGINEERING BIOLOGICAL SCIENCES Geodesy 0370 Spe»ch Pathology 0460 Eng neermg Agriculture Geology 0372 Toxicology 0383 General 0537 General 0473 Geophysics 0373 Home Economics 0386 Aerospace 0538 Agronomy 0285 Hydrology 0388 Agricultural 0539 Animal Culture and Mineralogy 0411 PHYSICAL SCIENCES Automotive 0540 Nutrition 0475 Paleobotany 0345 0541 Pure Sciences Biomedical Animal Pathology 0476 Paleoecology 0426 0542 Chemistry Chem cal Food Science and Paleontology 0418 Civil 0543 General 0485 Technology 0359 Paleozoology 0985 Electronics and Electrical 0544 Agnculti -al 0749 Forestry ana Wildlife 0478 Parynoloav 0427 Heat and Thermodynamics 0348 Analytical 0486 Plant Culture 0479 Physical Geography 0368 Hydraulic 0545 Biochemistry 0487 Plant Pathology 0480 Physical Oceanography 0415 Industrial 0546 Inorganic 0488 Plant Physiology 0817 Marine 0547 Nuclear 0738 Range Management 0777 HEALTH AND ENVIRONMENTAL Materials Science 0794 Organic 0490 Wood Technology 0746 SCIENCES Mechanical 0548 Biology Pharmaceutical 0491 0743 Environmental Sciences 0768 Metallurgy General 0306 Physical 0494 0551 Health Sciences Mining Anatomy 0287 Polymer 0495 0552 General 0566 Nuclear B ostatistics 0308 Radiation 0754 0549 Audiology 0300 Packaging Botany 0309 Mathematics 0405 Petroleum 0765 Chemotherapy 0992 Physics 0379 Sanitary and Municipal 0554 Dentistry 0567 •oentral 0605 0790 Ecology 0329 System Science Education 0350 Acoustics 0986 0428 Entomology 0353 Geotechnalogy 0369 Hospital Management 0769 Astronomy and 0776 Genetics Human Development 0758 Operations Research Limnology 0793 Astrophysics 0606 0795 Immunology 0982 Plashes Technology Microbiolcgy 0410 Atmospheric Science 0608 0994 Medicine and Surgery 0564 Textile Technology Molecular 0307 Atomic 0748 Neuroscience 0317 Mental Health 0347 Electronics and Electricity 0607 Nursing 0569 Elementary Particles and PSYCHOLOGY Oceanography 0416 Genera! 062. Nutrition 0570 High Energy 0798 Physiology 0433 Behavioral 0384 Obstetrics and Gynecology 0380 Fluidand Plasma 0759 Radiation 0821 Clinical 0622 0778 Occupational Health ana Molecular 0609 Veterinary Scienre Developmental 0620 Zoology 0472 Therapy 0354 Nuclear 0610 Ophthalmology 038' Experimental 0623 Biophysics Optics 0752 Industr al 0624 Pathology 0571 Radiation 0756 General 0786 Personality 0625 Pharmacology 0419 Solid State 0611 MeHicol 0760 Physiological 0989 Pharmacy 0572 Stah-hcs 0463 Psychobiology 0349 EARTH SCIENCE' Physical therapy 0382 0632 Public Health 0573 Applied Sciences Psychometrics Biogeorhemistry 0425 Applied Mechanics 0346 Social 0451 0996 Rad ology 0574 Geochemistry Recreation 0575 Computer Science 0984 TABLE OF CONTENTS LITERATURE REVIEW , 1 Legionella; morphology and growth 3 The environment 5 Interaction with other microbes 7 Route of infection 9 Clinical manifestations 11 Laboratory diagnosis 13 The disease process , . 14 Host defence against L. pneumophila infection 21 Role of phagocytosis 23 Cell mediated immunity in Legionnaires' disease 25 Immunodominant antigens of L. pneumophila 31 Genetics of Legionella virulence 33 Identifying genes by mutagenesis 35 Identifying genes by complementation of avirulent mutants 41 Salt resistance and Legionella virulence 45 Cloning genes using functional properties of the gene product 46 iv i Zinc metalloprotease 46 Legiolysin 51 Cloning antigens expressed on the cell surface . 52 Macrophage infectivity potentiating protein 53 Peptidoglycan associated protein 55 Heat shock protein 55 Taj or outer membrane protein 5 8 Other proteins implicated in L. pneumophila virulence 5 8 Phospholipase C 59 Phosphatase 60 Protein Kinase 61 Outer membrane porin proteins of gram negative bacteria 62 Major outer membrane protein of L. pneumophila 65 Coordinate regulation of virulence 69 Statement of research objectives 79 MATERIAL AND METHODS 81 Bacterial strains and cloning vectors 81 Extraction of chromosomal DNA 8 5 v Southern blot hybridization assays 87 Colony Southern hybridization 90 RNA extraction 92 Northern blot hybridization asssys 94 Cloning and sequencing of ompS 96 Primer extension reaction 97 Extraction of plasmid DNA 101 Transformation of plasmid DNA into bacterial cells . 103 a: Preparation of competent cells 103 b: Transformation 104 Selective radiolabelling of OmpS expressed in E. coli JF626 104 Sodium chloride challenge and preparation of L. pneumophila cell extracts 107 Gel mobility shift assays 108 Southwestern blot assays 112 ompS promoter:lacZ fusions 115 (3-galactosidase assays 117 DNA sequencing 117 Double stranded DNA sequencing 119 Single stranded DNA sequencing 119 a: Preparing replicative forms (RF) of vi single stranded M13 phage 121 b: Cloning into RF DNA and preparation of ss template DNA for sequencing 123 Sequencing gel electrophoresis 125 DNAsel footprinting assay 129 Attempt to clone the gene coding for the DNA binding protein 129 a: Conventional genetic approach 13 3 b: Purification of DNA binding protein ... 138 Immunological characterization of OmpS 13 8 Guinea pigs 13 9 Skin testing 140 Lymphocyte proliferation assays 141 Human Studies 142
Load more

Recommended publications
  • Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications
    International Journal of Molecular Sciences Review Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications Daniel Fernández-Villa 1, Maria Rosa Aguilar 1,2 and Luis Rojo 1,2,* 1 Instituto de Ciencia y Tecnología de Polímeros, Consejo Superior de Investigaciones Científicas, CSIC, 28006 Madrid, Spain; [email protected] (D.F.-V.); [email protected] (M.R.A.) 2 Consorcio Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina, 28029 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-915-622-900 Received: 18 September 2019; Accepted: 7 October 2019; Published: 9 October 2019 Abstract: Bacterial, protozoan and other microbial infections share an accelerated metabolic rate. In order to ensure a proper functioning of cell replication and proteins and nucleic acids synthesis processes, folate metabolism rate is also increased in these cases. For this reason, folic acid antagonists have been used since their discovery to treat different kinds of microbial infections, taking advantage of this metabolic difference when compared with human cells. However, resistances to these compounds have emerged since then and only combined therapies are currently used in clinic. In addition, some of these compounds have been found to have an immunomodulatory behavior that allows clinicians using them as anti-inflammatory or immunosuppressive drugs. Therefore, the aim of this review is to provide an updated state-of-the-art on the use of antifolates as antibacterial and immunomodulating agents in the clinical setting, as well as to present their action mechanisms and currently investigated biomedical applications. Keywords: folic acid antagonists; antifolates; antibiotics; antibacterials; immunomodulation; sulfonamides; antimalarial 1.
    [Show full text]
  • A National Strategy for the Elimination of Hepatitis B and C: Phase Two Report
    THE NATIONAL ACADEMIES PRESS This PDF is available at http://www.nap.edu/24731 SHARE A National Strategy for the Elimination of Hepatitis B and C: Phase Two Report DETAILS 296 pages | 6 x 9 | PAPERBACK ISBN 978-0-309-45729-3 | DOI: 10.17226/24731 CONTRIBUTORS GET THIS BOOK Gillian J. Buckley and Brian L. Strom, Editors; Committee on a National Strategy for the Elimination of Hepatitis B and C; Board on Population Health and Public Health Practice; Health and Medicine FIND RELATED TITLES Division; National Academies of Sciences, Engineering, and Medicine Visit the National Academies Press at NAP.edu and login or register to get: – Access to free PDF downloads of thousands of scientific reports – 10% off the price of print titles – Email or social media notifications of new titles related to your interests – Special offers and discounts Distribution, posting, or copying of this PDF is strictly prohibited without written permission of the National Academies Press. (Request Permission) Unless otherwise indicated, all materials in this PDF are copyrighted by the National Academy of Sciences. Copyright © National Academy of Sciences. All rights reserved. A National Strategy for the Elimination of Hepatitis B and C: Phase Two Report Gillian J. Buckley and Brian L. Strom, Editors Committee on a National Strategy for the Elimination of Hepatitis B and C Board on Population Health and Public Health Practice Health and Medicine Division A Report of Copyright © National Academy of Sciences. All rights reserved. A National Strategy for the Elimination of Hepatitis B and C: Phase Two Report THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001 This activity was supported by the American Association for the Study of Liver Diseases, the Infectious Diseases Society of America, the National Viral Hepatitis Roundtable, and the U.S.
    [Show full text]
  • Pharmacology
    Step I Pharmacology 'WSMU~ is a ~aint program 0~the lfederatlan° a"• State Meaieal Boaras a~the I!Jntitea States • lne, and the Natianal Baara a1 Medieal Examiners. USMLE·Step 1 Pharmacology Lecture Notes 2006-2007 Edition KAPLA~. I meulca • USMLE is a joint program of the Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners. ©2006 Kaplan, Inc. All rights reserved. No part of this book may be reproduced in any form, by photostat, microfilm, xerography or any other means, or incorporated into any information retrieval system, electronic or mechanical, without the written permission of Kaplan, Inc. Not for resale. Author Lionel P. Rayman, Pharm.D., Ph.D. Department of Pathology Forensic Toxicology Laboratory University of Miami School of Medicine Miami, FL Contributing Authors Director of Medical Curriculum Sonia Reichert, M.D. Craig Davis, Ph.D. Associate Professor Editorial Director University of South Carolina School of Medicine Department of Pharmacology, Physiology, and Neuroscience Kathlyn McGreevy Columbia, SC Production Manager Maris Victor Nora, Pharm.D., Ph.D. Michael Wolff Associate Professor Rush Medical College Production Editor Chicago.Tl. William Ng Anthony Trevor, Ph.D. Cover Design Professor Emeritus Joanna Myllo Department of Cellular and Molecular Pharmacology University of California Cover Art San Francisco, CA Christine Schaar Steven R. Harris, Ph.D. Associate Dean for Basic Sciences Associate Professor of Pharmacology Pikeville College School of Osteopathic Medicine
    [Show full text]
  • Key Enzymes in Cancer: Mechanism of Action and Inhibition with Anticancer Agents
    University of Texas Rio Grande Valley ScholarWorks @ UTRGV Chemistry Faculty Publications and Presentations College of Sciences 2018 Key Enzymes in Cancer: Mechanism of Action and Inhibition With Anticancer Agents Debasish Bandyopadhyay The University of Texas Rio Grande Valley, [email protected] Gabriel Lopez The University of Texas Rio Grande Valley Stephanie Cantu The University of Texas Rio Grande Valley Samantha Balboa The University of Texas Rio Grande Valley Annabel Garcia The University of Texas Rio Grande Valley See next page for additional authors Follow this and additional works at: https://scholarworks.utrgv.edu/chem_fac Part of the Chemistry Commons, and the Life Sciences Commons Recommended Citation Debasish Bandyopadhyay, Gabriel Lopez, Stephanie Cantu, Samantha Balboa, Annabel Garcia, Christina Silva, Diandra Valdes. In Chemistry Research and Applications (Vol. 2): Organic and Medicinal Chemistry, Chapter 9; Key Enzymes in Cancer: Mechanism of Action and Inhibition with Anticancer Agents. 2018, Nova Science Publishers, Inc., Hauppauge, New York, USA (ISBN: 978-1-53614-855-8). This Book is brought to you for free and open access by the College of Sciences at ScholarWorks @ UTRGV. It has been accepted for inclusion in Chemistry Faculty Publications and Presentations by an authorized administrator of ScholarWorks @ UTRGV. For more information, please contact [email protected], [email protected]. Authors Debasish Bandyopadhyay, Gabriel Lopez, Stephanie Cantu, Samantha Balboa, Annabel Garcia, Christina Silva, and Diandra Valdes This book is available at ScholarWorks @ UTRGV: https://scholarworks.utrgv.edu/chem_fac/131 In: Organic and Medicinal Chemistry, Volume 2 ISBN: 978-1-53614-855-8 Editor: Bimal Krishna Banik © 2019 Nova Science Publishers, Inc.
    [Show full text]
  • Activation of Apoptosis Pathways by Different Classes of Anticancer Drugs
    Research Laboratory of Children's Hospital, University of Ulm Chairman: Prof. Dr. Klaus-Michael Debatin Activation of apoptosis pathways by different classes of anticancer drugs Dissertation for the applying for a Doctor Degree of Medicine (Dr. med.) Faculty of Medicine, University of Ulm Presented by Jiahao Liu Born in Hubei, P. R. China 2001 Amtierender Dekan: Prof. Dr. R. Marre 1. Berichterstatter: Prof. Dr. K. M. Debatin 2. Berichterstatter: Prof. Dr. Dr. Dr. A. Grünert Tag der Promotion: 26. 10. 2001 To my family: Chen Longgui & Liu Chang 1 Contents Contents 1 Abbreviations 4 1. Introduction 1.1. Apoptosis: definitions and mechanisms 6 1.1.1. Cell biology of apoptosis 6 1.1.2. Execution of programmed cell death by caspases 7 1.1.3. Two main pathways of apoptosis 8 1.2. Cytotoxic anticancer drugs and apoptosis 9 1.3. Aims and summary of the project 11 2. Materials and Methods 2.1. Materials 14 2.1.1. Reagents and equipment for cell culture 14 2.1.2. Reagents and equipment for flow cytometric analysis 14 2.1.3. Reagents and equipment for western blot 15 2.1.4. Anticancer drugs 16 2.1.5. Antibodies 17 2.2. Methods 19 2.2.1. Cell culture 19 2.2.2. Cell preservation and reconstitution 19 2.2.3. Cell stimulation 19 2.2.4. Inhibitor studies 20 2.2.5. Flow cytometry 20 2.2.5.1. Analysis of annexin V and PI positive cells 20 2.2.5.2. Quantification of DNA fragmentation 21 ∆Ψ 2.2.5.3.
    [Show full text]
  • Evaluation of Acid Ceramidase As Response Predictor and Therapeutic Target in Neoadjuvant Chemoradiotherapy for Rectal Cancer
    Evaluation of Acid Ceramidase as Response Predictor and Therapeutic Target in Neoadjuvant Chemoradiotherapy for Rectal Cancer Thesis submitted in accordance with the requirements of the University of Liverpool for the degree of Doctor of Medicine by David Lewis Bowden November 2018 Dedication To my family – you are my inspiration and motivation, thank you for all your love and support. x R A E J x i Declaration The work presented in this thesis was carried out in the Institute of Translational Medicine at the University of Liverpool and facilitated by the Madel research fellowship, supported by Health Education North West. The material contained within this thesis has not been, nor is currently being presented wholly, or in part, for any other degree or qualification. I declare that all the work presented in this thesis has been carried out by me except where indicated below: • Histopathological assessment of tumour regression grading and immunohistochemical expression of acid ceramidase was performed by Dr Michael Wall (FRCPath, Countess of Chester Hospital) • Tissue microarray construction and sectioning was performed by Mr Michael Neill (Liverpool Bio-Innovation Hub Biobank) David Bowden ii Acknowledgements I am indebted to everyone who has helped me with this research. Thank you. I would firstly like to thank my supervisors: Mr Dale Vimalachandran, Dr Neil Kitteringham, Dr Jason Parsons and Mr Paul Sutton. Your doors have always been open and your guidance and advice invaluable. Thank you particularly for your patience. One of the more laborious aspects of the work undertaken was in the assessment of histopathological tumour response and immunohistochemical expression of acid ceramidase on the tissue microarrays.
    [Show full text]
  • Discovery of a Paenibacillus Isolate for Biocontrol of Black Rot in Brassicas
    Lincoln University Digital Thesis Copyright Statement The digital copy of this thesis is protected by the Copyright Act 1994 (New Zealand). This thesis may be consulted by you, provided you comply with the provisions of the Act and the following conditions of use: you will use the copy only for the purposes of research or private study you will recognise the author's right to be identified as the author of the thesis and due acknowledgement will be made to the author where appropriate you will obtain the author's permission before publishing any material from the thesis. Discovery of a Paenibacillus isolate for biocontrol of black rot in brassicas A thesis submitted in partial fulfilment of the requirements for the Degree of Doctor of Philosophy at Lincoln University by Hoda Ghazalibiglar Lincoln University 2014 DECLARATION This dissertation/thesis (please circle one) is submitted in partial fulfilment of the requirements for the Lincoln University Degree of ________________________________________ The regulations for the degree are set out in the Lincoln University Calendar and are elaborated in a practice manual known as House Rules for the Study of Doctor of Philosophy or Masters Degrees at Lincoln University. Supervisor’s Declaration I confirm that, to the best of my knowledge: • the research was carried out and the dissertation was prepared under my direct supervision; • except where otherwise approved by the Academic Administration Committee of Lincoln University, the research was conducted in accordance with the degree regulations and house rules; • the dissertation/thesis (please circle one)represents the original research work of the candidate; • the contribution made to the research by me, by other members of the supervisory team, by other members of staff of the University and by others was consistent with normal supervisory practice.
    [Show full text]
  • History of the Department of Microbiology 1868 – 2009
    June 2015 HISTORY OF THE DEPARTMENT OF MICROBIOLOGY 1868 – 2009 University of Illinois at Urbana-Champaign 1 A HISTORY OF THE DEPARTMENT OF MICROBIOLOGY 1868 – 2009 This 141 year history of the Department of Microbiology includes an article (Chapter 1), written and published in 1959 by the Department, which covers the period 1868 to 1959. I joined the Department in 1953, and my recounting of the Department’s history includes personal observations as well as anecdotes told to me by H. O. Halvorson and others. Later I realized what a unique experience it had been to join a first-class department, and I resolved to play a role in maintaining its research stature. Ralph Wolfe 2 Department of Microbiology History of the Headship: 1950 – 1959 Halvor Halvorson 1960 – 1963 Kim Atwood 1963 – 1972 Leon Campbell 1972 – 1982 Ralph DeMoss 1982 – 1987 Samuel Kaplan 1987 – 1990 Jordan Konisky 1990 – 1991 Ralph Wolfe (Acting Head) 1991 – 1997 Charles Miller 1997 – 2002 John Cronan 2003 – 2004 Jeffrey Gardner (Acting Head) 2005 – Present John Cronan 3 Organization of the History of the Department In Chapters 2 to 6 the data are divided into Academic Decades, each containing the following sections: Section I, an overview of the decade; Section II, some events for each year of the decade; Section III, a summary of the research interests, honors received, publications, and invited off-campus lectures or seminars for each faculty member. These data have been obtained from the annual reports of the faculty submitted to the departmental secretary. 4 CHAPTER 1 1868 – 1959 During this time period the name of the Department was Department of Bacteriology (Anecdotes by Ralph Wolfe) A SHORT HISTORY OF THE DEPARTMENT OF BACTERIOLOGY H.
    [Show full text]
  • University of Cincinnati
    UNIVERSITY OF CINCINNATI Date:__09/27/2004_________________ I, _Katherine L. Lillard___________________________, hereby submit this work as part of the requirements for the degree of: Doctor of Philosophy in: Molecular Genetics, Biochemistry, and Microbiology It is entitled: The BLM helicase functions in alternative lengthening of telomeres. This work and its defense approved by: Chair: Joanna Groden____________ Iain Cartwright__________ Carolyn Price____________ James Stringer___________ Kathleen Dixon___________ THE BLM HELICASE FUNCTIONS IN ALTERNATIVE LENGTHENING OF TELOMERES A dissertation submitted to the Division of Research and Advanced Studies Of the University of Cincinnati in partial fulfillment of the requirements for the degree of DOCTORATE OF PHILOSOPHY (Ph.D.) In the Department of Molecular Genetics, Biochemistry & Microbiology Of the College of Medicine 2004 by Kate Lillard-Wetherell B.S., University of Texas at Austin, 1998 Committee Chair: Joanna Groden, Ph.D. ABSTRACT Somatic cells from persons with the inherited chromosome breakage syndrome Bloom syndrome (BS) feature excessive chromosome breakage, intra-and inter- chromosomal homologous exchanges and telomeric associations. The gene mutated in BS, BLM, encodes a RecQ-like ATP-dependent 3’-to-5’ helicase that presumably functions in some types of DNA transactions. As the absence of BLM is associated with excessive recombination, in vitro experiments have tested the ability of BLM to suppress recombination and/or resolve recombination intermediates. In vitro, BLM promotes branch migration of Holliday junctions, resolves D-loops and unwinds G-quadruplex DNA. A function for BLM in maintaining telomeres is suggested by the latter, since D- loops and perhaps G-quadruplex structures are thought to be present at telomeres. In the present study, the association of BLM with telomeres was investigated.
    [Show full text]
  • National Institute of Genetics Japan
    ISSN 0077-4995 NATIONAL INSTITUTE OF GENETICS JAPAN ANNUAL REPORT No. 39 1988 Published by THE NATIONAL INSTITUTE OF GENETICS Misima, Sizuoka-ken, Japan 1989 Annual Report of the National Institute of Genetics No. 39, 1988 Published by The National Institute of Genetics, Japan 1989 CONTENTS General statement .............................................. 1 Staff 7 Council and Advisory Committee '" .. .. 10 Association for propagation of the knowledge of genetics 12 Projects of research for 1988 13 Research activities in 1988 18 1. Molecular Genetics Promoter selectivity of E. coli RNA polymerase: Cloning and characterization ofE. coli promoters. KUBOTA, M., YAMAZAKI, Y., FUJITA, N. and ISHIHAMA, A. 18 Promoter selectivity of E. coli RNA polymerase: Subunit (j) plays an essential role in stringent control. IGARASHI, K., FUJITA, N., OKAMOTO, H. and ISHIHAMA, A. 19 RNA polymerase sigma-related protein in Escherichia coli: Puri­ fication and characterization of proteins which crossreact with anti-sigma peptide antibodies. UESHIMA, R., FUJITA, N. and ISHIHAMA, A. 20 RNA polymerase and transcription signals of Micrococcus luteus. NAKAYAMA, M., FUJITA, N., OSAWA, S. and ISHIHAMA, A. '" 20 Molecular mechanism of influenza virus RNA transcription. I. Analysis of promoters for viral RNA polymerase. ISHIHAMA, A., PARVIN, J. D., PALESE, P., KRYSTAL, M., HONDA, A., KATO, A., UEDA, S., YOKOIYAMA, A., YAMAZAKI, Y., YAMA- NAKA, K. and NAGATA, K. 21 Molecular mechanism of influenza virus RNA transcription. II. Matrix protein epitopes involved in transcription inhibition. HANKINS, R. W., NAGATA, K., BUCHER, D. J., and ISHIHAMA, A 22 Molecular mechanism of influenza virus RNA transcription. III. Binding mode of influenza virus nucleoprotein to RNA. YAMANAKA, K., OGASAWARA, N., YOSHIKAWA, H., NAGATA, K.
    [Show full text]
  • The Role of Nucleolin in B-Cell Lymphomas and Fas-Mediated Apoptotic Signaling
    The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 5-2013 The Role of Nucleolin in B-cell Lymphomas and Fas-Mediated Apoptotic Signaling Jillian F. Wise Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Cancer Biology Commons, and the Medicine and Health Sciences Commons Recommended Citation Wise, Jillian F., "The Role of Nucleolin in B-cell Lymphomas and Fas-Mediated Apoptotic Signaling" (2013). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 339. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/339 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. The Role of Nucleolin in B-cell Lymphomas and Fas-Mediated Apoptotic Signaling by Jillian F Wise, BS Approved: ___________________________________________________ Felipe
    [Show full text]
  • University of Cincinnati
    UNIVERSITY OF CINCINNATI _____________ , 20 _____ I,______________________________________________, hereby submit this as part of the requirements for the degree of: ________________________________________________ in: ________________________________________________ It is entitled: ________________________________________________ ________________________________________________ ________________________________________________ ________________________________________________ Approved by: ________________________ ________________________ ________________________ ________________________ ________________________ BLM is a Suppressor of DNA Recombination A dissertation submitted to the Division of Research and Advanced Studies Of the University of Cincinnati In partial fulfillment of the Requirements for the degree of Doctorate of Philosophy (Ph.D.) In the Department of Molecular Genetics, Microbiology, and Biochemistry Of the College of Arts and Sciences 2002 by Joel E. Straughen B.S., The Ohio State University, 1985 M.D., University of Cincinnati, 2002 Committee Chair: Joanna Groden, Ph.D. i ABSTRACT Bloom’s syndrome (BS) is a rare, recessive chromosome breakage disorder characterized by small stature, sun sensitivity, facial erythema, immunodeficiency, female subfertility, male infertility, and a predisposition to a variety of cancers. When this body of work was started, the gene for Bloom’s syndrome (BLM)hadyettobe identified. This work presents characterization of the genomic region at BLM and the identification of BLM. With the cloning
    [Show full text]