DOCSLIB.ORG

Defining the Host Protective Antigens Secreted by the Murine Whipworm, Trichuris Muris

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Defining the Host Protective Antigens Secreted by the Murine Whipworm, Trichuris Muris Defining the host protective antigens secreted by the murine whipworm, Trichuris muris A thesis submitted to The University of Manchester for the degree of Doctor of Philosophy in the Faculty of Biology, Medicine and Health 2017 Rebecca K Shears School of Biological Sciences Division of Infection, Immunity and Respiratory Medicine Table of contents List of Figures ........................................................................................................ 5 List of Tables .......................................................................................................... 8 Abbreviations ....................................................................................................... 10 Abstract ................................................................................................................ 12 Acknowledgements ............................................................................................. 13 Declaration ........................................................................................................... 14 Copyright statement ............................................................................................ 14 Chapter 1: Introduction ....................................................................................... 15 1.1 Gastrointestinal nematodes: their prevalence, disease burden and the need for prophylactic vaccines ........................................................... 16 1.2 T. muris as a model for T. trichiura ................................................... 18 1.2.1 The life cycle of T. muris .................................................................. 18 1.2.2 Immune response during acute and chronic T. muris infection ....... 20 1.2.3 Mechanisms of T. muris expulsion .................................................. 23 1.2.3.1 Mucus production and other goblet cell secretions .................... 26 1.2.3.2 Increased rate of epithelial cell turnover ..................................... 28 1.2.3.3 Intestinal muscle hyper-contractility ........................................... 29 1.2.3.4 Mast cells and IgE production .................................................... 30 1.2.3.5 IgG antibody production and B cells ........................................... 30 1.2.3.6 Innate lymphoid cells and other early sources of Th2 cytokines 31 1.2.3.7 Regulation of the immune response during T. muris infection .... 32 1.3 Clinical and pre-clinical helminth vaccine candidates .................... 33 1.3.1 Hookworm vaccine candidates ........................................................ 33 1.3.2 Pre-clinical Ascaris vaccine candidates ........................................... 35 1.3.3 Experimental Trichuris vaccines ...................................................... 35 1.3.4 Schistosome vaccines ..................................................................... 39 1.3.5 Cestode vaccine candidates ............................................................ 40 1.3.6 The role of adjuvants in vaccines .................................................... 40 1.4 Extracellular vesicles as a source of antigenic material ................. 43 1.4.1 Exosome biogenesis and isolation from biological samples ............ 43 1.4.2 Exosome release by parasitic helminths ......................................... 45 1.5 Aims and objectives ........................................................................... 48 Chapter 2: Materials and methods ..................................................................... 49 2.1 Maintenance of animals ...................................................................... 50 2.2 Maintenance of parasites, ELV removal and preparation of adult ES 50 2.3 Preparation of larval ES ...................................................................... 51 2.4 Egg infectivity and dosage ................................................................. 52 2.5 Quantification of worm burdens ........................................................ 52 2.6 Collection of sera ................................................................................ 53 2.7 Anti-parasite IgG1 and IgG2a ELISAs ............................................... 53 2.8 Lymphocyte re-stimulation assay ..................................................... 53 2.8.1 Measuring cytokine production in cell supernatants ........................ 54 2.9 Fractionation of adult ES .................................................................... 56 2 2.9.1 Fractionation of adult ES by gel filtration chromatography .............. 56 2.9.2 Fractionation of adult ES and pool 3 by anion exchange and gel filtration chromatography ........................................................................... 57 2.10 SDS-PAGE ........................................................................................... 57 2.10.1 Coomassie blue staining ................................................................ 58 2.10.2 Silver staining of SDS-PAGE gels ................................................. 58 2.11 Assessing protein concentration of samples ................................... 58 2.12 Western blotting .................................................................................. 58 2.12.1 Western blotting using serum from T. muris infected mice ............ 59 2.12.2 Western blotting to detect His-tagged recombinant proteins ......... 59 2.13 Mass spectrometry and proteomic analysis of ES components .... 60 2.13.1 Mass spectrometry analysis of T. muris ELVs ............................... 61 2.14 Vaccination studies ............................................................................ 62 2.14.1 Proteinase K treatment of ES and subsequent vaccination ........... 63 2.14.2 Serum transfer from vaccinated to unvaccinated mice .................. 63 2.14.3 ELV vaccination studies................................................................. 64 2.15 DNA synthesis, transfections and collection of recombinant proteins ........................................................................................................ 65 2.16 Purification of recombinant proteins ................................................ 66 2.17 TEM analysis of ELV samples ............................................................ 67 2.18 DLS of ELVs ......................................................................................... 67 2.19 ELV fusion assay ................................................................................ 68 2.20 Graphing and statistical analysis ...................................................... 68 Chapter 3: Defining the host protective components within the soluble portion of T. muris ES ......................................................................................... 70 3.1 Introduction ......................................................................................... 71 3.2 Preparation of T. muris ES for fractionation using gel filtration chromatography .......................................................................................... 73 3.2.3 Investigating the suitability of gel filtration media to fractionate ES into smaller sub-groups.............................................................................. 74 3.2.2 Division of ES into four sub-groups using Superose 12 gel filtration media ......................................................................................................... 76 3.2.3 Investigating the cellular immune response to pools 2-4 ................. 78 3.2.4 Assessment of anti-parasite IgG serum antibody response during acute T. muris infection .............................................................................. 80 3.3 Vaccination with pools 2 to 4 stimulates protective immunity ....... 82 3.3.1 Assessment of antibody response following vaccination with pools 2 to 4 and subsequent infection .................................................................... 84 3.4 Vaccination with ES induces long-lasting protection against a subsequent low dose infection .................................................................. 89 3.4.1 Assessment of antibody response following long-term vaccination and subsequent infection .................................................................................. 90 3.5 Proteinase K degradation of ES abrogates its protective properties …………………………………………………………………………………94 3.6 Transfer of serum from ES vaccinated mice does not confer resistance to unvaccinated mice ............................................................... 95 3.7 Fractionation of ES by anion exchange chromatography ............... 97 3.8 Fractionation of pool 3 by anion exchange chromatography ......... 99 3.9 Vaccination with L2 ES induces protective immunity ................... 101 3 3.10 Evaluation of the AKR mouse model for vaccination studies ....... 104 3.11 Discussion ......................................................................................... 105 Chapter 4: Identification of immunogenic candidates within T. muris ES ………………………………………………………………………………………..112 4.1 Chapter introduction ......................................................................... 113 4.2 Identification of immunogenic candidates using a size exclusion chromatography and proteomics approach ........................................... 114 4.2.1 Fractionating ES using Superose 12 gel filtration media ............... 114 4.2.2 Fractionation of pool 3 using Superdex 75 gel filtration media ...... 122 4.3 Identification and synthesis of potential
Load more

Recommended publications
  • A Helminth-Derived Suppressor of ST2 Blocks Allergic Responses
    RESEARCH ARTICLE A helminth-derived suppressor of ST2 blocks allergic responses Francesco Vacca1, Caroline Chauche´ 1, Abhishek Jamwal2, Elizabeth C Hinchy3, Graham Heieis4, Holly Webster4, Adefunke Ogunkanbi5, Zala Sekne2, William F Gregory1,6, Martin Wear7, Georgia Perona-Wright4, Matthew K Higgins2, Josquin A Nys3, E Suzanne Cohen3, Henry J McSorley1,5* 1Centre for Inflammation Research, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh, United Kingdom; 2Department of Biochemistry, University of Oxford, Oxford, United Kingdom; 3Bioscience Asthma, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom; 4Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom; 5Division of Cell Signalling and Immunology, School of Life Sciences, Wellcome Trust Building, University of Dundee, Dundee, United Kingdom; 6Division of Microbiology & Parasitology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, United Kingdom; 7The Edinburgh Protein Production Facility (EPPF), Wellcome Trust Centre for Cell Biology (WTCCB), University of Edinburgh, Edinburgh, United Kingdom Abstract The IL-33-ST2 pathway is an important initiator of type 2 immune responses. We previously characterised the HpARI protein secreted by the model intestinal nematode Heligmosomoides polygyrus, which binds and blocks IL-33. Here, we identify H. polygyrus Binds Alarmin Receptor and Inhibits (HpBARI) and HpBARI_Hom2, both of which consist of complement control protein (CCP) domains, similarly to the immunomodulatory HpARI and Hp-TGM proteins. HpBARI binds murine ST2, inhibiting cell surface detection of ST2, preventing IL-33-ST2 interactions, and inhibiting IL-33 responses in vitro and in an in vivo mouse model of asthma. In H. *For correspondence: polygyrus infection, ST2 detection is abrogated in the peritoneal cavity and lung, consistent with [email protected] systemic effects of HpBARI.
    [Show full text]
  • The Transcriptome of Trichuris Suis – First Molecular Insights Into a Parasite with Curative Properties for Key Immune Diseases of Humans
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by ResearchOnline at James Cook University The Transcriptome of Trichuris suis – First Molecular Insights into a Parasite with Curative Properties for Key Immune Diseases of Humans Cinzia Cantacessi1*, Neil D. Young1, Peter Nejsum2, Aaron R. Jex1, Bronwyn E. Campbell1, Ross S. Hall1, Stig M. Thamsborg2, Jean-Pierre Scheerlinck1,3, Robin B. Gasser1* 1 Department of Veterinary Science, The University of Melbourne, Parkville, Victoria, Australia, 2 Departments of Veterinary Disease Biology and Basic Animal and Veterinary Science, University of Copenhagen, Frederiksberg, Denmark, 3 Centre for Animal Biotechnology, The University of Melbourne, Parkville, Australia Abstract Background: Iatrogenic infection of humans with Trichuris suis (a parasitic nematode of swine) is being evaluated or promoted as a biological, curative treatment of immune diseases, such as inflammatory bowel disease (IBD) and ulcerative colitis, in humans. Although it is understood that short-term T. suis infectioninpeoplewithsuchdiseases usually induces a modified Th2-immune response, nothing is known about the molecules in the parasite that induce this response. Methodology/Principal Findings: As a first step toward filling the gaps in our knowledge of the molecular biology of T. suis, we characterised the transcriptome of the adult stage of this nematode employing next-generation sequencing and bioinformatic techniques. A total of ,65,000,000 reads were generated and assembled into
    [Show full text]
  • Infection Trichuris Muris Failure to Expel in an Altered Th1/Th2
    Absence of CC Chemokine Ligand 2 Results in an Altered Th1/Th2 Cytokine Balance and Failure to Expel Trichuris muris Infection This information is current as Matthew L. deSchoolmeester, Matthew C. Little, Barrett J. of September 29, 2021. Rollins and Kathryn J. Else J Immunol 2003; 170:4693-4700; ; doi: 10.4049/jimmunol.170.9.4693 http://www.jimmunol.org/content/170/9/4693 Downloaded from References This article cites 47 articles, 24 of which you can access for free at: http://www.jimmunol.org/content/170/9/4693.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 29, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2003 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Absence of CC Chemokine Ligand 2 Results in an Altered Th1/Th2 Cytokine Balance and Failure to Expel Trichuris muris Infection1 Matthew L. deSchoolmeester,2* Matthew C. Little,* Barrett J.
    [Show full text]
  • Trichuriasis Importance Trichuriasis Is Caused by Various Species of Trichuris, Nematode Parasites Also Known As Whipworms
    Trichuriasis Importance Trichuriasis is caused by various species of Trichuris, nematode parasites also known as whipworms. Whipworms are common in the intestinal tracts of mammals, Trichocephaliasis, although their prevalence may be low in some host species or regions. Infections are Trichocephalosis, often asymptomatic; however, some individuals develop diarrhea, and more serious Whipworm Infestation effects, including dysentery, intestinal bleeding and anemia, are possible if the worm burden is high or the individual is particularly susceptible. T. trichiura is the species of whipworm normally found in humans. A few clinical cases have been attributed to Last Updated: January 2019 T. vulpis, a whipworm of canids, and T. suis, which normally infects pigs. While such zoonotic infections are generally thought uncommon, recent surveys found T. suis or T. vulpis eggs in a significant number of human fecal samples in some countries. T. suis is also being investigated in human clinical trials as a therapeutic agent for various autoimmune and allergic diseases. The rationale for its use is the correlation between an increased incidence of these conditions and reduced levels of exposure to parasites among people in developed countries. There is relatively little information about cross-species transmission of Trichuris spp. in animals. However, the eggs of T. trichiura have been detected in the feces of some pigs, dogs and cats in tropical areas with poor sanitation, raising the possibility of reverse zoonoses. One double-blind, placebo-controlled study investigated T. vulpis for therapeutic use in dogs with atopic dermatitis, but no significant effects were found. Etiology Trichuriasis is caused by members of the genus Trichuris, nematode parasites in the family Trichuridae.
    [Show full text]
  • Mitogenomics and Evolutionary History of Rodent Whipworms (Trichuris Spp.) Originating from Three Biogeographic Regions
    life Article Mitogenomics and Evolutionary History of Rodent Whipworms (Trichuris spp.) Originating from Three Biogeographic Regions Jan Petružela 1,2,*, Alexis Ribas 3 and Joëlle Goüy de Bellocq 1,4 1 Institute of Vertebrate Biology, Czech Academy of Sciences, Kvˇetná 8, 603 65 Brno, Czech Republic; [email protected] 2 Department of Botany and Zoology, Faculty of Science, Masaryk University, Kotláˇrská 2, 602 00 Brno, Czech Republic 3 Section of Parasitology, Department of Biology, Healthcare and the Environment, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08007 Barcelona, Spain; [email protected] 4 Department of Zoology and Fisheries, Faculty of Agrobiology, Food and Natural Resources, Czech University of Life Sciences Prague, Kamýcká 129, 165 21 Prague, Czech Republic * Correspondence: [email protected] Abstract: Trichuris spp. is a widespread nematode which parasitizes a wide range of mammalian hosts including rodents, the most diverse mammalian order. However, genetic data on rodent whipworms are still scarce, with only one published whole genome (Trichuris muris) despite an increasing demand for whole genome data. We sequenced the whipworm mitogenomes from seven rodent hosts belonging to three biogeographic regions (Palearctic, Afrotropical, and Indomalayan), including three previously described species: Trichuris cossoni, Trichuris arvicolae, and Trichuris mastomysi. We assembled and annotated two complete and five almost complete mitogenomes (lacking only the long non-coding region) and performed comparative genomic and phylogenetic analyses. All the Citation: Petružela, J.; Ribas, A.; mitogenomes are circular, have the same organisation, and consist of 13 protein-coding, 2 rRNA, and de Bellocq, J.G. Mitogenomics and 22 tRNA genes. The phylogenetic analysis supports geographical clustering of whipworm species Evolutionary History of Rodent and indicates that T.
    [Show full text]
  • Proteomic Insights Into the Biology of the Most Important Foodborne Parasites in Europe
    foods Review Proteomic Insights into the Biology of the Most Important Foodborne Parasites in Europe Robert Stryi ´nski 1,* , El˙zbietaŁopie ´nska-Biernat 1 and Mónica Carrera 2,* 1 Department of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland; [email protected] 2 Department of Food Technology, Marine Research Institute (IIM), Spanish National Research Council (CSIC), 36-208 Vigo, Spain * Correspondence: [email protected] (R.S.); [email protected] (M.C.) Received: 18 August 2020; Accepted: 27 September 2020; Published: 3 October 2020 Abstract: Foodborne parasitoses compared with bacterial and viral-caused diseases seem to be neglected, and their unrecognition is a serious issue. Parasitic diseases transmitted by food are currently becoming more common. Constantly changing eating habits, new culinary trends, and easier access to food make foodborne parasites’ transmission effortless, and the increase in the diagnosis of foodborne parasitic diseases in noted worldwide. This work presents the applications of numerous proteomic methods into the studies on foodborne parasites and their possible use in targeted diagnostics. Potential directions for the future are also provided. Keywords: foodborne parasite; food; proteomics; biomarker; liquid chromatography-tandem mass spectrometry (LC-MS/MS) 1. Introduction Foodborne parasites (FBPs) are becoming recognized as serious pathogens that are considered neglect in relation to bacteria and viruses that can be transmitted by food [1]. The mode of infection is usually by eating the host of the parasite as human food. Many of these organisms are spread through food products like uncooked fish and mollusks; raw meat; raw vegetables or fresh water plants contaminated with human or animal excrement.
    [Show full text]
  • Comparative Analysis of Trichuris Muris Surface Using Conventional, Low Vacuum, Environmental and field Emission Scanning Electron Microscopy
    Veterinary Parasitology 196 (2013) 409–416 Contents lists available at SciVerse ScienceDirect Veterinary Parasitology journal homepage: www.elsevier.com/locate/vetpar Comparative analysis of Trichuris muris surface using conventional, low vacuum, environmental and field emission scanning electron microscopy Eduardo José Lopes Torres a,b,c, Wanderley de Souza b,c,d, Kildare Miranda b,d,∗ a Laboratório de Helmintologia Roberto Lascasas Porto, Departamento de Microbiologia, Imunologia e Parasitologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Av. Professor Manoel de Abreu 444/5◦ andar, Vila Isabel, Rio de Janeiro CEP 20511-070, RJ, Brazil b Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho and Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagens, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco G subsolo, Cidade Universitária, Ilha do Fundão, Rio de Janeiro 21941-902, RJ, Brazil c Laboratório de Biologia de Helmintos Otto Wucherer, Programa de Biologia Celular e Parasitologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, Bloco I, 2◦ andar, sala 35, Cidade Universitária, Ilha do Fundão, Rio de Janeiro CEP 21949-902, RJ, Brazil d Diretoria de Programas, Instituto Nacional de Metrologia, Qualidade e Tecnologia (Inmetro), Xerém, Duque de Caxias, RJ, Brazil article info abstract Article history: The whipworm of the genus Trichuris Roederer, 1791, is a nematode of worldwide distribu- Received 17 December 2012 tion and comprises species that parasitize humans and other mammals. Infections caused Received in revised form 4 February 2013 by Trichuris spp.
    [Show full text]
  • Nematoda: Trichuridae) Parasitizing Heteromys Salvini (Rodentia: Heteromyidae) from Costa Rica, with a Key to Trichuris Species Described from Heteromyidae
    Original Article ISSN 1984-2961 (Electronic) www.cbpv.org.br/rbpv New species of Trichuris (Nematoda: Trichuridae) parasitizing Heteromys salvini (Rodentia: Heteromyidae) from Costa Rica, with a key to Trichuris species described from Heteromyidae Nova espécie de Trichuris (Nematoda: Trichuridae) de Heteromys salvini (Rodentia: Heteromyidae) na Costa Rica, com uma chave para as espécies de Trichuris descritas em Heteromyidae Jorge Falcón-Ordaz1; René Josué Monzalvo-López1; Luis García-Prieto2* 1 Laboratorio de Morfología Animal, Universidad Autónoma del Estado de Hidalgo, Mineral de la Reforma, Hidalgo, México 2 Instituto de Biología, Universidad Nacional Autónoma de México, México D.F., Mexico How to cite: Falcón-Ordaz J, Monzalvo-López RJ, García-Prieto L. New species of Trichuris (Nematoda: Trichuridae) parasitizing Heteromys salvini (Rodentia: Heteromyidae) from Costa Rica, with a key to Trichuris species described from Heteromyidae. Braz J Vet Parasitol 2020; 29(2): e022019. https://doi.org/10.1590/S1984-29612020028 Abstract Trichuris guanacastei n sp., a parasite isolated from the Salvin’ spiny mouse Heteromys salvini, collected from the Guanacaste Conservation Area, Costa Rica, during February 1996 is described. The new species was compared morphologically with the 29 known species that parasitize rodents distributed in 12 families in North and South America; T. guanacastei n. sp. it is characterized by the following set of traits: presence of a spicular tube (measuring 0.72-0.99); thick proximal cloacal tube and a short distal cloacal tube with a total length of 0.72-1.36; eggs 0.03-0.05 long and a semi-protrusible vulva. The new species represents the first one described in the genus in Costa Rica and the fifth one described in the Americas that parasite Heteromyidae.
    [Show full text]
  • Trichuris Muris As a Tool for Holistic Discovery Research: from Translational Research to Cambridge.Org/Par Environmental Bio-Tagging
    Parasitology Trichuris muris as a tool for holistic discovery research: from translational research to cambridge.org/par environmental bio-tagging Review Iris Mair , Kathryn J. Else and Ruth Forman Cite this article: Mair I, Else KJ, Forman R Faculty of Biology, Medicine and Health, Lydia Becker Institute of Immunology and Inflammation, Manchester (2021). Trichuris muris as a tool for holistic Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester M13 9PT, UK discovery research: from translational research to environmental bio-tagging. Parasitology Abstract 1–13. https://doi.org/10.1017/ S003118202100069X Trichuris spp. (whipworms) are intestinal nematode parasites which cause chronic infections associated with significant morbidities. Trichuris muris in a mouse is the most well studied of Received: 24 February 2021 the whipworms and research on this species has been approached from a number of different Revised: 16 April 2021 Accepted: 19 April 2021 disciplines. Research on T. muris in a laboratory mouse has provided vital insights into the host–parasite interaction through analyses of the immune responses to infection, identifying Key words: factors underpinning host susceptibility and resistance. Laboratory studies have also informed Ecoimmunology; host–parasite interaction; strategies for disease control through anthelmintics and vaccine research. On the contrary, immunology; population ecology; translational research; Trichuris research on naturally occurring infections with Trichuris spp. allows the analysis of the host–parasite co-evolutionary relationships and parasite genetic diversity. Furthermore, eco- Authors for correspondence: Iris Mair, logical studies utilizing Trichuris have aided our knowledge of the intricate relationships E-mail: [email protected]; amongst parasite, host and environment.
    [Show full text]
  • Trichuris Muris Whey Acidic Protein Induces Type 2 Protective Immunity Against Whipworm
    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 8-2018 TRICHURIS MURIS WHEY ACIDIC PROTEIN INDUCES TYPE 2 PROTECTIVE IMMUNITY AGAINST WHIPWORM Neima Briggs Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Parasitic Diseases Commons, and the Translational Medical Research Commons Recommended Citation Briggs, Neima, "TRICHURIS MURIS WHEY ACIDIC PROTEIN INDUCES TYPE 2 PROTECTIVE IMMUNITY AGAINST WHIPWORM" (2018). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 883. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/883 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]. TRICHURIS MURIS WHEY ACIDIC PROTEIN INDUCES TYPE 2 PROTECTIVE IMMUNITY AGAINST WHIPWORM by Neima Briggs, B.S., D.T.M. APPROVED: _______________________________
    [Show full text]
  • Whipworm Genome and Dual-Species Transcriptome Analyses Provide Molecular Insights Into an Intimate Host-Parasite Interaction
    Europe PMC Funders Group Author Manuscript Nat Genet. Author manuscript; available in PMC 2016 September 06. Published in final edited form as: Nat Genet. 2014 July ; 46(7): 693–700. doi:10.1038/ng.3010. Europe PMC Funders Author Manuscripts Whipworm genome and dual-species transcriptome analyses provide molecular insights into an intimate host-parasite interaction Bernardo J. Foth#1, Isheng J. Tsai#1,2, Adam J. Reid#1, Allison J. Bancroft#3, Sarah Nichol1, Alan Tracey1, Nancy Holroyd1, James A. Cotton1, Eleanor J. Stanley1, Magdalena Zarowiecki1, Jimmy Z. Liu4, Thomas Huckvale1, Philip J. Cooper5,6, Richard K. Grencis3, and Matthew Berriman1 1Parasite Genomics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK 2Division of Parasitology, Department of Infectious Disease, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan 3Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK 4Statistical Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK 5Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK 6Centro de Investigación en Enfermedades Infecciosas, Escuela de Biología, Pontificia Europe PMC Funders Author Manuscripts Universidad Católica del Ecuador, Quito, Ecuador # These authors contributed equally to this work. Abstract Whipworms are common soil-transmitted helminths that cause debilitating chronic infections in man. These nematodes are only distantly related to Caenorhabditis elegans and have evolved to Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Correspondence and requests for materials should be addressed to M.B.
    [Show full text]
  • Operons Are a Conserved Feature of Nematode Genomes
    Genetics: Early Online, published on June 14, 2014 as 10.1534/genetics.114.162875 Operons are a conserved feature of nematode genomes Jonathan Pettitt, Lucas Philippe, Debjani Sarkar, Christopher Johnston, Henrike Johanna Gothe, Diane Massie, Bernadette Connolly and Berndt Müller School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK T. spiralis and T. muris mRNA 5’ ends are deposited under GenBank accession numbers KF442418-KF442435; KF511776; KF511777; KF768019. 1 Copyright 2014. Running Title: Conservation of nematode operons Keywords: operons; SL trans-splicing; nematode genome Corresponding Author: Jonathan Pettitt School of Medical Sciences Institute of Medical Sciences Aberdeen AB25 2ZD UK Tel.: +44 (0)1224 437516 FAX: +44 (0)1224 437465 Email: [email protected] 2 ABSTRACT The organisation of genes into operons, clusters of genes that are co-transcribed to produce polycistronic pre-mRNAs, is a trait found in a wide-range of eukaryotic groups, including multiple animal phyla. Operons are present in the class Chromadorea, one of the two main nematode classes, but their distribution in the other class, the Enoplea, is not known. We have surveyed the genomes of Trichinella spiralis, Trichuris muris and Romanomermis culicivorax and identified the first putative operons in members of the Enoplea. Consistent with the mechanism of polycistronic RNA resolution in other nematodes, the mRNAs produced by genes downstream of the first gene in the T. spiralis and T. muris operons are trans-spliced to spliced leader RNAs, and we are able to detect polycistronic RNAs derived from these operons. Importantly, a putative intercistronic region from one of these potential enoplean operons confers polycistronic processing activity when expressed as part of a chimeric operon in C.
    [Show full text]