DOCSLIB.ORG

UC San Diego UC San Diego Electronic Theses and Dissertations

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
UC San Diego UC San Diego Electronic Theses and Dissertations UC San Diego UC San Diego Electronic Theses and Dissertations Title Colitis, hypothyroidism, and immunological alterations in mice deficient in glycan branching enzymes Permalink https://escholarship.org/uc/item/4hk1z8b3 Author Stone, Erica Lyn Publication Date 2009 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA, SAN DIEGO Colitis, Hypothyroidism, and Immunological Alterations in Mice Deficient in Glycan Branching Enzymes. A Dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Biology by Erica Lyn Stone Committee in charge: Professor Jamey D. Marth, Chair Professor Stephen M. Hedrick, Co-Chair Professor Steven F. Dowdy Professor Ananda W. Goldrath Professor Maho Niwa Copyright Erica Lyn Stone, 2009 All rights reserved. The Dissertation of Erica Lyn Stone is approved, and it is acceptable in quality and form for publication on microfilm and electronically: Co-Chair Chair University of California, San Diego 2009 iii To my brother, David Charles Stone. In recognition of all you taught me about life. iv EPIGRAPH Change will not come if we wait for some other person of some other time. We are the ones we’ve been waiting for. We are the change that we seek. Barack Obama v TABLE OF CONTENTS Signature Page……………………………………………………………………. iii Dedication Page…..………………………………………………………………. iv Epigraph…………………………………………………………………………… v Table of Contents…………………………………………………………………. vi List of Figures and Tables.………………………………………………………. ix List of Abbreviations……………………………………………………………… xii Acknowledgments...……………………………………………………………… xiv Curriculum Vita…….……………………………………………………………... xvii Abstract of the Dissertation……………………………………………………… xix General Introduction….…………………………………………………………… 1 I. Figures and Legends…………………………………………………... 11 II. References……….…………………………………………………….. 13 Chapter 1: Biological Functions of Glycosyltransferase Enzymes Critical in Core O-Glycan Biosynthesis………………………………………... 17 I. Abstract………………………………………………………………..... 17 II. Introduction…………..………………………………………………… 18 III. Materials and Methods……………………………………………….. 20 IV. Results…..…………..………………………………………………… 32 V. Discussion…………....………………………………………………... 42 VI. Tables and legends…………………………………………………. 49 vi VII. Figures and legends………………………………………………… 51 VIII. Acknowledgements…………..…………………………………..... 59 IX. References….……………………………………………………....... 60 Chapter 2: Loss of the glycosyltransferase C2GnT2 impairs the immune response to a mucosal but not a parenteral antigen…………………………. 68 I. Abstract…..……………………………………………………………... 68 II. Introduction…………...……………………………………………….. 68 III. Results……………………………………………………………….... 73 IV. Discussion……………………………………………………………. 77 V. Materials and Methods……………………………………...……….. 83 VI. Table and legends……………………………….………………….. 87 VII. Figures and legends…………..…………….…………………….... 88 VIII. Acknowledgements…………………………………………….…... 90 IX. References……………………………………………………………. 91 Chapter 3: Mammalian N-Glycan Branching Protects against Innate Immune Self-Recognition and Inflammation in Autoimmune Disease Pathogenesis………………………………………………………….. 95 I. Summary………………………………………………………………. 95 II. Introduction……………………………………………………………. 95 III. Results………………………………………………………………... 96 IV. Discussion………………………………………………………….... 101 V. Experimental Procedures…...………………………………………. 104 vii VI. References……………………………………….………………..... 106 VII. Supplemental Data………………………………………………… 108 VIII. Acknowledgements………………………………………………... 114 Future Directions……..…………………………………………………………. 115 I. Abstract………………………………………………………………… 115 II. Specific Aims.………………..……………………………………….. 116 III. Research Design and Methods…...……….………………………. 119 IV. Other Studies……………………………………………………….. 136 V. Acknowledgements…………………………………………………. 138 VI. References………………………………………………………….. 139 viii LIST OF FIGURES AND TABLES General Introduction: Figure I.1: Biosynthesis of Mucin-type O-glycans..…...………………………. 11 Figure I.2: I-Branching Activity of C2GnT2 and IGnT…..……..……………… 12 Chapter 1: Biological Functions of Glycosyltransferase Enzymes Critical in Core O-Glycan Biosynthesis: Table 1.I: Hematology in the absence of C2GnT2 and C2GnT3……………. 49 Table 1.II: O-Glycan structures in the presence and absence of C2GnTs…. 50 Figure 1.1: Activity and expression of C2GnTs……………………………...... 51 Figure 1.2: Generation of mice singly deficient for C2GnT2 or C2GnT3……………………….……………………………………… 52 Figure 1.3a-c: Selectin ligand expression on neutrophils and T-cells from C2GnT-deficient mice…………........…………………... 53 Figure 1.3d-e: Selectin ligand expression on neutrophils and T-cells from C2GnT-deficient mice…….…………………………….... 54 Figure 1.4: Barrier function and colitis in C2GnT2-deficient mice...…..…….. 55 Figure 1.5: Circulating and mucosal immunoglobulins in wild-type and C2GnT2-deficient mice………………………...…………….. 56 Figure 1.6: Behavior and thyroid function in C2GnT3-deficient mice........... 57 Figure 1.7: Enzyme activity in tissue lysates from mice deficient for C2GnTs......……………………………………………….………… 58 Chapter 2: Loss of the glycosyltransferase C2GnT2 impairs the immune response to a mucosal but not a parenteral antigen: Table 2.1: Glycan structures in C2GnT2-deficient mice that are potential ligands for lectins and glycan binding proteins………... 87 ix Figure 2.1: The humoral response to KLH following i.p. immunization in C2GnT2-deficient mice…..……………..………. 88 Figure 2.2: C2GnT2-deficient mice have a reduced antigen-specific humoral response to KLH as a mucosal antigen………….......... 88 Figure 2.3: Expression of Galectin-1 ligands in the mucosa of C2GnT2- deficient mice……………………………………………………....... 89 Figure 2.4: Preliminary analysis of frequency of various cell types in the GALT from C2GnT2-deficient mice..…………………………….... 89 Chapter 3: Mammalian N-glycan branching protects against innate immune self-recognition and inflammation in autoimmune disease pathogenesis Figure 3.1: Nonhematopoietic origin of autoimmune disease in αM-II deficiency……………………………………………….…... 97 Figure 3.2: Disease in the absence of the adaptive immune system and after intravenous administration of immunoglobulin-G…..…..... 98 Figure 3.3: Pathogenesis in the absence of complement C3.……………... 99 Figure 3.4: Innate immune activation and kidney inflammation..…..……… 100 Figure 3.5: Mesangial cell activation and apoptosis………………………... 101 Figure 3.6: Mannose-binding lectin expression and endogenous ligand formation………………………………….…………….….. 103 Supplemental Figure S3.1: Kidney development among αM-II null mice... 109 Supplemental Figure S3.2: Physical appearance and kidney mass among mice of indicated genotypes…………………………….. 110 Supplemental Figure S3.3: Macrophage activation and innate immune responses………………………………………………………….. 111 Supplemental Figure S3.4: Autoimmune disease pathogenesis in the absence of MBL-A and αM-II……………………...…………….. 112 x Supplemental Figure S3.5: A phylogenic basis of N-glycan branching and innate immune recognition………………………………………. 113 xi LIST OF ABBREVIATIONS αDG: α-dystroglycan; ALT: alanine transaminase; AP: alkaline phosphatase; APRIL: A Proliferation-Inducing ligand; BSA: bovine serum albumin; C2GnT: Core 2 β1,6-N-acetylglucosaminyltransferase; C3GnT: Core 3 β-1,3-N- acetylglucosaminyltransferase; CCR7: C-C Chemokine Receptor 7; CD40L: CD40 ligand; CFA: Complete Freund’s Adjuvant; conA: concanavalin A; Core1-β3GnT: Core 1 Extension-β1,3-N-acetylglucosaminyltransferase; Core 1 GalT: Core 1 β-1,3-galactosyltransferase; CSFE: Carboxyfluorescein succinimidyl ester; CT: cholera toxin; DAI: disease activity index; DC: dendritic cell; DHB: 2,5-dihydroxybenzoic acid; DNP: 2,4-dinitrophenyl hapten; DSS: dextran sodium sulfate; ES: embryonic stem; FucT: α(1,3)fucosyltransferase; GalNAc: N-acetylgalactosamine; GlcNAc: N-acetylglucosamine; GALT: gut- associated lymphoid tissues; HEV: high endothelial venules; HRP: horseradish peroxidase; H&E: hematoxylin and eosin; IBD: Inflammatory Bowel Disease; IFA: Incomplete Freund’s Adjuvant; IFNγ: Interferon-gamma; IGnT: I β-1,6-N- acetylglucosaminyltransferase; IL: Interleukin; i.p.: intraperitoneal; KLH: keyhole limpet hemocyanin; MALDI: Matrix-assisted laser desorption/ionization; MS: mass spectrometry; MS/MS: tandem mass spectrometric; Muc2: Mucin 2; MHC Class II: major histocompatibility complex class II; NHS: N-hydroxysuccinimide; UC: ulcerative colitis; OVA: ovalbumin; PBS: phosphate buffered saline; PBST: PBS plus 0.05% Tween 20; ppGalNAcT: polypeptide N-α-acetylgalactosaminyltransferases; PNA: peanut xii agglutinin; POMGnT1: protein-O-mannose-β1,2-N- acetylglucosaminyltransferase 1; ST3Gal: α-2,3-sialyltransferase; T4: Thyroxine; tk: thymidine kinase; TMB: Tetramethylbenzidine; TNBS: 2,4,6- trinitrobenzene sulfonic acid; TRH: thyrotropin-releasing hormone; TSH: Thyroid Stimulating Hormone xiii ACKNOWLEDGEMENTS I acknowledge Jamey Marth for taking me into his laboratory and funding my research. Very special thanks to Steve Dowdy, Ananda Goldrath, Steve Hedrick, and Maho Niwa for their expertise, advice, and patience that have contributed significantly to my success. Sincere thanks to Kazuaki Ohtsubo for working with me during my rotation in the Marth laboratory and being a constant source of guidance for all matters related to research. A special thanks to Pam Grewal for sharing her expertise, especially in regards to paper writing and figure making, and also for our morning chats. Steve Van Dyken deserves thanks for helping me get settled in the Marth laboratory. A very special thanks to Mallory Beed,
Load more

Recommended publications
  • UCSB Researchers Perform Pioneering Research on Type 2 Diabetes
    Gail Gallessich (805) 893-7220 [email protected] George Foulsham (805) 893-3071 [email protected] January 4, 2013 UCSB Researchers Perform Pioneering Research on Type 2 Diabetes (Santa Barbara, Calif.) –– While legions of medical researchers have been looking to understand the genetic basis of disease and how mutations may affect human health, a group of biomedical researchers at UC Santa Barbara is studying the metabolism of cells and their surrounding tissue, to ferret out ways in which certain diseases begin. This approach, which includes computer modeling, can be applied to Type 2 diabetes, autoimmune diseases, and neurodegenerative diseases, among others. Scientists at UCSB have published groundbreaking results of a study of Type 2 diabetes that point to changes in cellular metabolism as the triggering factor for the disease, rather than genetic predisposition. Type 2 diabetes is a chronic condition in which blood sugar or glucose levels are high. It affects a large and growing segment of the human population, especially among the obese. The team of scientists expects the discovery to become a basis for efforts to prevent and cure this disease. The current work is based on a previous major finding by UCSB’s Jamey Marth, who determined the identity of the molecular building blocks needed in constructing the four types of macromolecules of all cells when he was based at the Howard Hughes Medical Institute in La Jolla in 2008. These include the innate, genetic macromolecules, such as nucleic acids (DNA and RNA) and their encoded proteins, and the acquired metabolic macromolecules known as glycans and lipids.
    [Show full text]
  • Principles of Adipobiology: a Gentle Introduction
    Adipobiology ISSN 1313-3705 (online) CONTINUING MEDICAL © Bul garian Society for Cell Biology EDUCATION PRINCIPLES OF ADIPOBIOLOGY: A GENTLE INTRODUCTION George N. Chaldakov* Department of Anatomy and Cell Biology, Medical University, Varna, Bulgaria and Institute for Advanced Study, Varna, Bulgaria Figure 1. Schematic view of cell-to-cell interactions via nexuses (gap junctions, channel junctions, communicating junc- tions, macula communicans) between the neibouring Cell A and Cell B, intercellular space of 2 - 4 nm. One channel of nexus is composed of two connexons (or hemichannels). The hexagonal structure of connexons (cross sectioned) consisting of six proteins termed connexins – Cx) is evident; an arrow runs through one of the chanells. One nexus consists of about 100 connexons. (*Grosely R, Sorgen PL. A history of gap junction structure: Hexagonal arrays to atomic resolution. Cell Commun Adhes 2013; 20. DOI:10.3109/15419061.2013.775256 *Wright JA, Richards T, Becker DL. Connexins and diabetes. Cardiol Res Pract 2012; 2012: 496904. DOI:10.1155/2012/496904) *Received 2 June 2019, revised 10 June 2019, accepted 11 June 2019. Correspondence to: Dr George N. Chaldakov, Department of Anatomy and Cell Biology, Medical University, BG-9002 Varna, Bulgaria Mobile phone: +359 888 679 204 E-mail: [email protected] - to keep students-to-teacher communicating junctions alive and kicking (Fig. 1) 114 Principles of adipobiology: a gentle introduction CONTINUING MEDICAL EDUCATION Prologue Introduction Student – Latin, studеo – devoted to do something; studium – The biological research has already provided a wealth of eager, passion, study. knowledge about individual cellular components and their Teacher ­ To be a teacher is profound responsibility.
    [Show full text]
  • UC Santa Barbara
    DIRECTIONS TO RATHMANN AUDITORIUM L O T 9 12 P 402 451 Phelps Hall 570 489 M Campbell esa 11 R Hall o a 101 P d Engineering 217 Elings Science Henley 10 Hall Buchanan PSB Chemistry 1179 Gate Ellison Hall Hall North P Engineering Ward II Memorial Campus Green Blvd. Kohn PSB Hall South 615 Davidson MRL Library 406 Broida Hall Harold Frank Lagoon Road Hall Webb Hall Bren Hall 1 P N 7 Noble Hall 3 P P Life Pacific Ocean Sciences Bio Psych II UCEN Road 9 P UC Santa Barbara UNIVERSITY OF CALIFORNIA JAMEY MARTH joined the Department of Molecular, Cellular SANTA BARBARA and Developmental Biology and the Biomolecular Science and Engineering Program at UC Santa Barbara in July 2009. He holds a joint appointment with the Sanford-Burnham Medical CHANCELLOR HENRY T. YANG Research Institute and is the Director of The UC Santa Barbara Sanford-Burnham Center for Nanomedicine. Dr. Marth’s cordially invites you to attend the inaugural lecture training and expertise are multi-disciplinary encompassing and reception celebrating the appointment of genetics, pharmacology, biochemistry, immunology, hematology, developmental biology, infectious disease, and glycobiology. His laboratory is known for having DR. JAMEY MARTH developed Cre-loxP conditional mutagenesis, a technique used worldwide to study Professor of Molecular, Cellular, and Developmental Biology biology and disease, and for elucidating mechanisms of autoimmune disease, Type 2 diabetes, and infectious disease. His laboratory is incorporating nanotechnologies TO THE including microfluidic, and microarray platforms to expand basic biological research John Carbon Chair in Biochemistry and Molecular Biology capabilities and further identify the origins of disease.
    [Show full text]
  • The American Association of Immunologists Oral History Project
    The American Association of Immunologists Oral History Project Transcript Roger M. Perlmutter, M.D., Ph.D. January 23, 2013 San Francisco, CA Interview conducted by Brien Williams, Ph.D. Transcription: TechniType Transcripts Transcript copy editors: John S. Emrich and Elizabeth R. Walsh Final edit by: John S. Emrich © 2013 The American Association of Immunologists, Inc. Publicly released transcripts of The American Association of Immunologists, Inc. (AAI) Oral History Project are freely available for non-commercial use according to the Fair Use provisions of the United States Copyright Code and International Copyright Law. Advance written permission is required for reproduction, redistribution, and extensive quotation or excerpting. Permission requests should be made to: The American Association of Immunologists, 9650 Rockville Pike, Bethesda, MD 20814-3994. To cite an interview, please use the following general format: [Name of interviewee], interview by [name of interviewer], [date], The American Association of Immunologists Oral History Project. http://www.aai.org/OHP (accessed [date]). Williams: This is an interview with Dr. Roger Perlmutter of The American Association of Immunologists Centennial Oral History Project. Dr. Perlmutter is a consultant to the biopharmaceutical industry at this present time, and he was the president of the American Association of Immunologists from 1999 to 2000 and served as an AAI Council member from ’94 to ’99. We are at Amgen Laboratories in South San Francisco, California. Today is Wednesday, January 23, 2013, and I am Brien Williams. Dr. Perlmutter, thank you very much for being with us today. Perlmutter: It’s my pleasure. Williams: Good. Let’s start with you talking a little bit about your own family background.
    [Show full text]
  • Researchers Discover Mechanistic Link Between High-Fat Diet and Type 2 Diabetes
    DECEMBER 29, 2005 Researchers Discover Mechanistic Link Between High-Fat Diet and Type 2 Diabetes Howard Hughes Medical Institute researchers have discovered a molecular link between a high-fat, Western-style diet, and the onset of type 2 diabetes. In studies in mice, the scientists showed that a high-fat diet interferes with a genetic mechanism they discovered that promotes insulin production, resulting in the classic signs of type 2 diabetes. In an article published in the December 29, 2005, issue of the journal Cell, the researchers report that knocking out a single gene encoding the enzyme GnT-4a glycosyltransferase (GnT-4a ) disrupts insulin production. Importantly, the scientists showed that a high-fat diet suppresses the activity of GnT-4a and leads to type 2 diabetes due to failure of the pancreatic beta cells. "We have discovered a mechanistic explanation for beta cell failure in response to a high-fat diet and obesity, a molecular trigger which begins the chain of events leading from hyperglycemia to insulin resistance and type 2 diabetes." -- Jamey D. Marth We have discovered a mechanistic explanation for beta cell failure in response to a high-fat diet and obesity, a molecular trigger which begins the chain of events leading from hyperglycemia to insulin resistance and type 2 diabetes, said Jamey Marth, a Howard Hughes Medical Institute investigator at the University of California, San Diego (UCSD). Marth and first author Kazuaki Ohtsubo at UCSD collaborated on the studies with researchers from the Kirin Brewery Co. Ltd., and the University of Fukui, both in Japan. The discovery of the link between diet and insulin production offers new information that may aid in the development of treatments that target the early stages of type 2 diabetes.
    [Show full text]
  • Microsoft Outlook
    Salk Bulletin Monday, July 18, 2016 Monday, July 18, 2016 4:00 pm “Brain-Immune Crosstalk in Neuropsychiatric Conditions: Current Evidence and Future Directions” Suzi Hong, Ph.D., Associate Professor, Department of Psychiatry UNIVERSITY OF CALIFORNIA, SAN DIEGO Biomedical Sciences Building (BSB), 2071 Contact: Carla Ingle, [email protected] Tuesday, July 19, 2016 Tuesday, July 19, 2016 12:00 pm “Memory T Cell Subsets in Protective and Pathogenic Immune Responses” 1 Federica Sallusto and Antonio Lanzavecchia, Institute for Research in Biomedicine, Bellinzona, Switzerland LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY Ishizaka Seminar Room Hosts: Alessandro Sette and Bjoern Peters Wednesday, July 20, 2016 Wednesday, July 20, 2016 12:00 pm “The Aging and Turnover of Secreted Proteins in Sepsis and Intestinal Inflammation” Jamey Marth, Ph.D., Carbon Professor of Biochemistry and Molecular Biology, Mellichamp Professor of Systems Biology, University of California, Santa Barbara LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY Ishizaka Seminar Room Host: Mitchell Kronenberg, Ph.D. Thursday, July 21, 2016 No Seminar Listings At This Time Friday, July 22, 2016 No Seminar Listings At This Time Monday, July 25, 2016 2 No Seminar Listings At This Time Salk Bulletin Extra Saturday, July 30, 2016 8:30 am - 2:00 pm Technology Licensing Workshop UC San Diego Extension Host: UC San Diego Extension Contact: Julia Dunlap, [email protected] Register: http://extension.ucsd.edu/studyarea/index.cfm?vAction=saDetail&vStudyAr eaID=111 August 22-23, 2016 PATRIC Bioinformatics Resource Center Eorkshop Featuring Data and Analysis Tools for Bacterial Genomes and ‘Omics DATA SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE Building 10, Room 1308 Host: Bioinformatics Program at SBP Contact: Andrei Osterman, [email protected] or Cindy Cook, [email protected] Register: Send email to [email protected] Friday, September 9, 2016 9:00 am – 4:30 pm 28th Annual Usha Mahajani Symposium on Molecular Medicine “RNA and Cancer” SALK INSTITUTE FOR BIOLOGICAL STUDIES Conrad T.
    [Show full text]
  • View a PDF Copy of the Embodi Brochure
    MACULAR DEGENERATION HEART DISEASE CANCER We are in a new era of human health research where progress depends on disciplines University of California Santa Barbara working together to understand the complex mechanisms of disease and illness that impact millions of lives worldwide. UC Santa Barbara sets the global precedent for collaboration. Our biological sciences, engineering, and physical sciences join forces Engineering Medicine Biology Discovery Innovation to develop innovative basic research and technological solutions. Our researchers work in partnership with academic, industry, and medical communities around the world to confront society’s most pressing medical problems. THIS IS THE neW medicine ALZHEIMERSDIABETES DRUG DELIVERY BRAIN QUANTITATIVE BIOLOGY COLLABORATING FOR A CURE FOR BLINDNESS Among the most influential leaders in stem A stem cell is essentially a “blank” cell, capable cell research worldwide, UC Santa Barbara’s of becoming another more differentiated cell researchers are spearheading the charge in type in the body, such as a skin cell, a muscle regenerative medicine. Dennis Clegg (left), cell, or a nerve cell. They can serve as a built-in Tom Soh (middle), James Thomson (upper repair system for the human body, replenishing right), and Peter Coffey (lower right), are as other cells as long as a person is alive. Stem versatile as the pluripotent stem cells they cell research and treatments represent perhaps are studying. These award-winning faculty mankind’s greatest opportunity to fulfill the are passionate about understanding the ancient call to “heal the sick,” relieve suffering, complexities of human vision and finding and improve the quality of life for an untold cures for neurodegenerative diseases.
    [Show full text]
  • Effect of Carbon Source on the Glycosylation Pathway Of
    Department of Chemistry and Biomolecular Sciences Effect of carbon source on the glycosylation pathway of Trichoderma reesei RUT-C30 Chris Ashwood Bachelor of Forensic Science 10th of October, 2014 A dissertation submitted in partial fulfilment of the Master of Research degree Table of Contents Declaration ....................................................................................................................................... iii Acknowledgements .......................................................................................................................... iv Abstract ............................................................................................................................................. v Abbreviations and symbol nomenclature ........................................................................................ vi Chapter 1 – Introduction ................................................................................................................... 1 1.1 The fungus Trichoderma reesei RUT-C30: a protein production machine. ............................. 1 1.1.1 History of the strain .......................................................................................................... 1 1.1.2 Protein glycosylation in Trichoderma reesei ..................................................................... 2 1.2 Metabolomics .......................................................................................................................... 6 1.2.1 Metabolomics in cellular physiology
    [Show full text]
  • 2017-SFG-Abstracts-FINAL.Pdf
    PROGRAM AND ABSTRACTS FOR 2017 ANNUAL MEETING OF THE SOCIETY FOR GLYCOBIOLOGY November 5–8, 2017 Portland, Oregon, USA SFG Meeting 2017 Poster Program SFG MEETING 2017 Sunday November 5, 2017 9 am-1 pm Glycoprotein Technologies Satellite Chair: Parastoo Azadi (CCRC/University of Georgia) 9 am-3 pm Trainee Mentoring Program Chairs: Lance Wells (CCRC/University of Georgia) Karen Colley (University of Illinois at Chicago) 10 am-5 pm Bioinformatics Satellite Chair: Rene Ranzinger (CCRC/University of Georgia) 3:30-5:00 pm Board of Directors Meeting Session 1. Meyer and Kornfeld Awards Lectures Chair: Karen Colley (University of Illinois at Chicago) 5:30-5:45 Opening Remarks 5:45-6:30 Karl Meyer Award Lecture Jamey Marth (University of California, Santa Barbara) 6:30-7:15 Rosalind Kornfeld Award Lecture Gillian Air (University of Oklahoma) 7:30-9:30 Reception Monday November 6, 2017 Session 2. Glycans in metabolic regulation and development (8:30-10:00 am) Chair: Kelley Moremen (CCRC/University of Georgia) 8:30-9:00 Heparan sulfate in lipid and iron homeostasis. Jeff Esko (University of California, San Diego) and Maura Poli (University of Brescia, Brescia, Italy) 9:00-9:20 Studying atypical dystroglycanopathies using zebrafish models. Chiara Manzini (George Washington University) 9:20-9:50 Cell-specific regulation and roles of O-GlcNAc: key to understanding brain function. Jerry Hart (Johns Hopkins) and Olof Lagerlöf (Karolinska Institute). 9:50-9:55 Poster talk: Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode. Jiaoyang Jiang (University of Wisconsin-Madison) 9:55-10:00 Poster talk: Dynamic splicing of a glycosyltransferase modulates enzyme activity and secretory granule morphology.
    [Show full text]
  • Do 68 Molecules Hold the Key to Understanding Disease? 4 September 2008
    Do 68 molecules hold the key to understanding disease? 4 September 2008 and eight kinds of lipids (which compose cell membranes) along with the more well-known 20 amino acids that are used to make proteins and the eight nucleosides that compose the nucleic acids, DNA and RNA. "These 68 building blocks provide the structural basis for the molecular choreography that constitutes the entire life of a cell," said Marth. "And two of the four cellular components are produced by these molecular building blocks in processes that cannot be encoded by the genes. These cellular components – the glycans and lipids – may Illustration of basic molecular building blocks. Credit: now hold the keys to uncovering the origins of UCSD School of Medicine many grievous diseases that continue to evade understanding." Currently, the vast majority of medical research Why is it that the origins of many serious diseases looks to the human genome and proteome for remain a mystery? In considering that question, a answers, but those answers remain elusive, and scientist at the University of California, San Diego perhaps for good reason. School of Medicine has come up with a unified molecular view of the indivisible unit of life, the cell, "We have now found instances where the which may provide an answer. pathogenesis of widespread and chronic diseases can be attributed to a change in the glycome, for Reviewing findings from multiple disciplines, example, in the absence of definable changes in Jamey Marth, Ph.D., UC San Diego Professor of the genome or proteome," Marth said, adding that, Cellular and Molecular Medicine and Investigator as biomedical researchers, "we need to begin to with the Howard Hughes Medical Institute, realized cultivate the integration of disciplines in a holistic that only 68 molecular building blocks are used to and rigorous way in order to perceive and most construct these four fundamental components of effectively manipulate the biological mechanisms of cells: the nucleic acids (DNA and RNA), proteins, health and disease." glycans and lipids.
    [Show full text]
  • Glycomic Analysis of Biomedically Important O-Glycoconjugates Mohd Nazri Ismail
    Glycomic Analysis of Biomedically Important O-glycoconjugates A thesis submitted for the Degree of Doctor of Philosophy of Imperial College London Submitted by Mohd Nazri Ismail Imperial College London Division of Molecular Biosciences Department of Life Sciences Faculty of Natural Sciences South Kensington London SW7 2AZ United Kingdom 2 Declaration I hereby declare that the work presented in this thesis has not been previously or concurrently submitted for any other degree, diploma or other qualification at any other university, and it is the result of my own independent research unless otherwise indicated. Mohd Nazri Ismail 3 Acknowledgements This PhD work would not have been possible without the support of many people. I would like to express my deepest gratitude to my supervisor, Prof. Anne Dell who was abundantly helpful and offered invaluable assistance, support and guidance. Deepest appreciation is also due to my second supervisor, Dr. Stuart Haslam, without whose knowledge and assistance this thesis would not have been successful. Special thanks also to all former and current group members, Prof. Howard Morris, Dr. Maria Panico, Dr. Berangere Tissot, Dr. Mark Sutton-Smith, Dr. Aristotelis Antonopoulos, Alana Trollope, Rebecca Harrison, Kevin Canis, Dr. Poh-Choo Pang, Dr. Paul Hitchen, Dr. Rositsa Karamanska, David Damerell, Dr. Simon Parry, Dr. Alessio Ceroni and Dr. Simon North, for sharing knowledge and invaluable assistance. Not forgetting to my friends who always been there and making my life journey in this wonderful but challenging city of London much smoother. It was an honour for me to collaborate with some of the best scientists in this field, including Prof Jamey Marth, Dr.
    [Show full text]
  • UC San Diego UC San Diego Electronic Theses and Dissertations
    UC San Diego UC San Diego Electronic Theses and Dissertations Title CD8⁺ T lymphocyte apoptosis is regulated by protein O- glycosylation Permalink https://escholarship.org/uc/item/2793t53h Author Van Dyken, Steven John Publication Date 2006 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA, SAN DIEGO CD8+ T Lymphocyte Apoptosis is Regulated by Protein O-Glycosylation A dissertation submitted in partial satisfaction of the requirement for the degree Doctor of Philosophy in Biomedical Sciences by Steven John Van Dyken Committee in charge: Professor Jamey D. Marth, Chair Professor Steven F. Dowdy Professor Ananda W. Goldrath Professor Mitchell Kronenberg Professor Ajit P. Varki 2006 Copyright Steven John Van Dyken, 2006 All rights reserved DEDICATION To my parents, My role models, John and Sandy Van Dyken, For their unconditional love and support And To my wife, Jennifer My heart and soul, For her infinite love, endurance, and devotion, I love you iv TABLE OF CONTENTS Signature Page .......................................................................................................... iii Dedication.................................................................................................................. iv Table of Contents........................................................................................................v List of Figures .........................................................................................................
    [Show full text]