DOCSLIB.ORG

Nucleosome Dynamics and Analysis in Breast Cancer Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Nucleosome Dynamics and Analysis in Breast Cancer Cells Nucleosome dynamics and analysis in breast cancer cells Andy Pohl Tesi Doctoral UPF / Any 2014 Director de la tesi Dr. Miguel Beato Department Gene Regulation, Stem Cells, and Cancer Department of the Centre for Genomic Regulation (CRG) Agraïments I am very grateful for all of the help I have received during the PhD. First and foremost, I must acknowledge my supervisor, Miguel Beato. In my time in the lab, he has remained very accessible, even when he had more responsibili- ties as director of the institute. Unlike perhaps many supervisors, he gave me the opportunities to explore almost any idea I had. Not all of my ideas were the best, and he knew that, but he gave me the freedom to try and fail (and fail frequently) on my own. I must acknowledge Roderic Guigó. I perhaps did not take advantage of Roderic’s extensive experience as best as I could have, but being a part of his lab in general helped me stay current with bioin- formatic topics. In addition to that, he funded my final year of study, which has been the most fruitful. In addition to my supervisors, my thesis commit- tee included Eduardo Eyras and Fátima Gebauer (who replaced Raul Méndez in 2011), who gave me very good advice even when discussing a topic outside of their specialty. Beyond my formal supervision, I have to credit all of my labmates who have made possible my transformation from software engineer to capa- ble experimentalist. This starts with Roni Wright. She taught me all the ba- sics of culturing cells, and performing basic assays like Western blots or DNA gels, and also gene cloning techniques and transfection/infection of our cells. Jofre Font, Michael Wierer, Diana Reyes, Marija Kundakovic, Guille Vicent, Flopy Ogara, Priyanka Sharma, Alessandra Ciociola, Alejandro Lagreca, Silvina Nacht, and François Le Dily also helped me a lot in that respect. I learned extensive details about how to perform chromatin immunoprecipita- tions (ChIPs) from Cecilia Ballare. Other people that have benefitted my lab education through informal discussion (in no particular order) include João Tavanez, Bernhard Pätzold, Anna Corrionero, Camilla Ianonne, Gaetano Verde, Christos Gekas, Marina Garcia, Laura Gaveglia, Martin Lange, Payal Jain, Malte Beringer, Paula Pisano, Rory Johnson, Sophie Bonnal, Bill Keyes, Cristina Militti, Ramón Tejedor, Lluis Morey, Alessio Bava, Sergio Barberan, Luisa Vigevani, Luciano Di Croce, Juan Valcarcel, Karthik Arumugam, João Frade, Esteban Rozen, Adam Klosin, Alex Santanach, Elena Martin, Jordi iii Hernández, Bruno Di Stefano, Laure Weill, Timo Zimmermann, Ben Leh- ner, Thomas Graf, Matteo Pecoraro, and Elias Bechara. Also I must thank people that contributed a wealth of information towards furthering my bio- informatic skills. This includes Giancarlo Castellano, Daniel Soronellas, João Curado, Christoforos Nikolaou, Debayan Datta, Hagen Tilgner, Colin Kingswood, Sonja Althammer, Julien Lagarde, Sarah Bonnin, Sarah Djebali, Emilio Palumbo, Brian Raney, Jim Kent, Anna Vlasova, Tobias Warnecke, David Haussler, Guillaume Filion, Alessandra Breschi, Barbara Uszczynska, Marco Mariotti, Dmitri Pervouchine, Raik Grünberg, Almer van der Sloot, Peter Vanhee, Gireesh Bogu, Panagiotis Papasaikas, Micha Sammeth, Cedrik Magis, Paolo Ribeca, Francisco Câmara, Ivan Junier, Davide Baù, Arnau Bria, Rodny Hernandez, Gabriel Gonzalez, Oscar Gonzalez, Judith Flo, Cedric Notredamme, Didac Santesmasses. I will also acknowledge Aitor Busquets, Isma De Mingo, Marc Gonzalez, Núria Janè, Romina Garrido, Imma Fale- ro, Isabel Jurado, Diego Mellibovsky, Zoe Barbarà, Sharon Bel, Rafa Bayona, Carla Senozaín, Lucia Marucci, Lucia Russo, Giacoma Simonte, Francesco Sottile, Francesco Aulicino, Daniela Sanges, Pia Cosma, Livia Caizzi, Fran- cesca Rapino, Mekayla Popoff, Valeria Di Giacomo, Valeria Giangarra, Alba Mas, Kadri Reis, Jia-Ming Chang, Anne Camapgna, Eric Verschueren, Ma- ria Aurelia Ricci, Marc Friedländer, Tony Ferrar, Javier Delgado, Jae-Seong Yang, Solip Park, Mirko Francesconi, Krisztina Arató, Ilda Theka, Esther Lizano, Verónica Llorens, Emilia Szostak, Maria Lluch, Sophia Teichmann, Marcos Perez, Roxana Tovar, Chiara Di Vona, Luca Cozzuto, Jean-François Taly, Magalí Bartomeus, Eli Mateu, Elena Miñones, Carolina Gallo, Carolina Segura, Jo Aigner, Kiana Toufighi, Amy Curwin, James Cotterell, Alexan- dra Grippa, Luigi Aloia, Luigi Ombrato, Karl Wotton, Umberto Di Vicino, Eric Kallin, Julia Röwenstrunk, Marcus Buschbeck, Olivera Vujatovic, Sergi Repullo, Tian Tian, Valentina Schiavone, Silvina Catuara, Carla Bello, Tom Starke, Villy Michaki, Wassim Altarche, and Salvatore Cappadona in general for what I feel is a positive impact they each make on the CRG and why I have enjoyed working here. Many of those that have helped me professionally, have also been good friends to me as well. The CRG and Barcelona can take credit for pro- iv viding a wonderful environment, where it is easy to make friends and enjoy life. To that extent I will give special credit to my yoga instructor Alessa Ben- naton and all of my spanish teachers in the past, most recently Alexandra Albuera. The city of Barcelona has given me back my love for running and I imagine I will find myself here again for more marathons. My family is very important to me and they have supported all my life decisions, including moving to Europe and going back to school. This thesis is dedicated to the memory of my great-uncle Garland Petefish (1917-2008). Thank you everyone. Gracias a todos. Gràcies a tothom. v vi Abstract Genome-wide analysis of the nucleosome positioning and histone H1 iso- form content of the T47D breast cancer cell line has found a number of observations, namely that with a gentle digestion of microccocal nuclease (MNase), a nucleosome is visible just upstream of the transcription start site, in the region known as the “nucleosome-free region” (NFR). H1 isoforms bind to chromatin mainly in a redundant manner, but H1.2 and H1.3 show some specificity while H1.5 increases its binding dramatically after a proges- terone stimulus. In the course of these studies, a general-purpose software package was developed for the manipulation and analysis of bigWig files, a data format for storing continuous signal data assigned to genome coordi- nates. Resum En el meu estudi genòmic sobre el posicionament de nucleosomes i sobre el- contingut de les isoformes de la histona H1 en cèl·lules de càncer de mama T47D he dut a terme una sèrie d'observacions. Específicament he trobat que amb una digestió suau amb nucleasa micrococcal, es pot identificar un nucleosoma just abans del lloc d'inici de transcripció, en la regió coneguda com a "regió lliure de nucleosomes". També he vist que les diferents isoformes somàtiques de la histona H1 (H1.0-H1.5, H1x) s'uneixen a la cromatina de manera redundant, però que la H1.2 i la H1.3 presenten certa especifici- tat, mentre que la H1.5 mostra un augment de la unió generalitzat després d'estimular les cèl·lules amb progesterona. En el decurs de la meva recerca, he desenvolupat un programari general per la manipulació i l'anàlisi d'arxius amb format bigWig, un format per a l'emmagetzematge de dades de senyals continus al llarg de les coordenades del genoma. vii viii Prefaci This thesis touches on several different aspects of chromatin biology, in three chapters of results. After an introduction to chromatin biology and gene regulation and the kind of experiments that are done, I describe our work positioning nucleosomes in T47D breast cancer cells. This work is important because it draws attention to nucleosomes found in the badly named “nucle- osome free regions” near gene transcription start sites. The second results chapter describes our work studying the genome-wide binding of linker his- tone H1 variants to chromatin. This study is notable because seven somatic variants of H1 exist in humans, and it is not understood why. Our study is also the first that analyzes the redistribution of H1 after a hormone stimulus to the cells. A side effect of preparing these results was the creation of a utility for genomic continuous-valued signal data, whose function was originally split across a number of smaller more specific-use tools. This software: bwtool, has been released as open source to the bioinformatics community and its article recently published is attached as the third results chapter. Finally, I close with some additional discussion about how emerging trends and technologies may impact future directions of the field. ix x Sumari Acknowledgements .................................................................................................. iii Abstract ...................................................................................................................... vii Preface ..........................................................................................................................ix Introduction ................................................................................................................. 1 Objectives ................................................................................................................... 33 Results I: ..................................................................................................................... 35 Results II:................................................................................................................... 67 Results III: ................................................................................................................103 Conclusions ............................................................................................................
Load more

Recommended publications
  • ANNUAL REVIEW 1 October 2005–30 September
    WELLCOME TRUST ANNUAL REVIEW 1 October 2005–30 September 2006 ANNUAL REVIEW 2006 The Wellcome Trust is the largest charity in the UK and the second largest medical research charity in the world. It funds innovative biomedical research, in the UK and internationally, spending around £500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. www.wellcome.ac.uk THE WELLCOME TRUST The Wellcome Trust is the largest charity in the UK and the second largest medical research charity in the world. 123 CONTENTS BOARD OF GOVERNORS 2 Director’s statement William Castell 4 Advancing knowledge Chairman 16 Using knowledge Martin Bobrow Deputy Chairman 24 Engaging society Adrian Bird 30 Developing people Leszek Borysiewicz 36 Facilitating research Patricia Hodgson 40 Developing our organisation Richard Hynes 41 Wellcome Trust 2005/06 Ronald Plasterk 42 Financial summary 2005/06 Alastair Ross Goobey 44 Funding developments 2005/06 Peter Smith 46 Streams funding 2005/06 Jean Thomas 48 Technology Transfer Edward Walker-Arnott 49 Wellcome Trust Genome Campus As at January 2007 50 Public Engagement 51 Library and information resources 52 Advisory committees Images 1 Surface of the gut. 3 Zebrafish. 5 Cells in a developing This Annual Review covers the 2 Young children in 4 A scene from Y fruit fly. Wellcome Trust’s financial year, from Kenya. Touring’s Every Breath. 6 Data management at the Sanger Institute. 1 October 2005 to 30 September 2006. CONTENTS 1 45 6 EXECUTIVE BOARD MAKING A DIFFERENCE Developing people: To foster a Mark Walport The Wellcome Trust’s mission is research community and individual Director to foster and promote research with researchers who can contribute to the advancement and use of knowledge Ted Bianco the aim of improving human and Director of Technology Transfer animal health.
    [Show full text]
  • Vol 9 No 1 Spring
    A PUBLICATION OF THE AMERICAN SOCIETY FOR MATRIX BIOLOGY SPRING 2010, VOLUME 9, NO. 1 President’s Letter Expanding the Society’s Value to You and Your Role in the Society Since its inception in 2001, the principal function of the ASMB has been to organize the OFFICERS biennial meeting. The value of this meeting to our members cannot be understated. The ASMB meeting has emerged as the matrix-centric President: meeting in North America, and it provides an William Parks (2010) open venue for students, postdocs, fellows, and junior faculty to present their work and to inter- act with established investigators. Speaking for Vice Pres/President Elect myself, I very much look forward to the ASMB Jean Schwarzbauer (2010) meeting, not only because I get to see many Bill Parks friends, but also to hear a lot of incredibly good science. This year’s meeting will be no excep- Past President: tion and promises to be truly outstanding. I applaud Jean Schwarzbauer and the Renato Iozzo (2010) rest of the Program Committee for putting together an exciting meeting loaded with interesting topics and great speakers (please check out the program here). By organizing the meeting, ASMB provides value to you, the membership, but I Secretary/Treasurer think we–the Society–should always be looking to do more; that is, to provide more Joanne Murphy-Ullrich (2011) bang for your dues buck. For this year’s meeting, we have expanded the Travel Awards that will be given to trainees in recognition of outstanding research, and we recently established merit-based Minority Scholarships that will be awarded to eli- Council Members gible students and postdocs.
    [Show full text]
  • SAC 2014 Celebration of Science Book
    Fostering Innovation at MGH Poster Session Abstracts 67th Annual Meeting of the MGH Scientific Advisory Committee Celebration of Science The MGH Research Institute: Meeting the Challenges that Lie Ahead April 2 & 3, 2014 Simches Auditorium 185 Cambridge Street, 3rd Floor Management Management ECOR Administrative Offices | 50 Staniford Street, 10th Floor | Boston, MA 02114 | [email protected] Fostering Mainstay Mainstay Innovation of MGH of MGH at MGH Management Innovation Management Innovation Welcome elcome to the 67th Annual Meeting of the MGH Scientific Advisory Committee (SAC) on April 2nd and 3rd, 2014. Dr. Richard Lifton has graciously agreed to W chair our SAC meeting again this year. As in past years, we will begin our two-day SAC meeting with a Celebration of Science at MGH. Our poster session begins at 11:00 am on Wednesday, April 2, followed by an afternoon Research Symposium from 2:00 pm to 5:00 pm. The outstanding MGH researchers who will be presenting their work in our Symposium this year are the 2014 Howard Goodman Award recipient Filip Swirski, PhD and the 2014 Martin Basic and Clinical Research Prize recipients, Jayaraj Rajagopal, MD, and Stephanie Seminara, MD. We are honored to have as our keynote speaker, Richard O. Hynes, PhD, from MIT. We will close the first day with a Reception for invited guests at the Russell Museum. On Thursday, April 3, Dr. Kingston will open the SAC meeting with an ECOR Report. After this report, Anne Klibanski, MD, Partners Chief Academic Officer, will give a presentation on the Integration of MGH Research to the Partners Enterprise.
    [Show full text]
  • Hhmi Bulletin 3 4 Hhmi Club
    HHMI BULLETIN 4000 Jones Bridge Road • Chevy Chase, Maryland 20815-6789 Howard Hughes Medical Institute www.hhmi.org One Lump or Two? in this issue Once again, those fast-growing yeast find a way to turn a The Silicon Marvel long-held theory on its head. This time, it’s about prions, • Prions for Good which aren’t as universally nasty as once suspected. Some may actually help organisms evolve. The yeast colony shown here www.hhmi.org A Kaleidoscopic View contains a protein in its prion form. Because the prion, known as PSI+, is self-replicating and forms fibrous amyloids, the yeast look lumpy and bumpy—strikingly different from normally smooth yeast. Susan Lindquist’s group has found 19 yeast proteins that can switch back and forth between a normal and a prion version. The prions are thought to help the yeast adapt to changing conditions (see “A Silver Lining,” page 22). LIGHT MOVES v ol. 23 Heather True / Lindquist lab /no. 02 O b s e r v a t i O n s 16 Secret Agent MAn Skin cells do more than just cover our bodies. As a neurology resident, Stanley Prusiner saw Creutzfeldt–Jakob agent began to emerge. These data established, for the first time, that Keratinocytes, for example, anchor immune cells disease kill a patient in a matter of months. Researchers knew the rare a particular macromolecule was required for infectivity and that this within the epidermis, move and proliferate during neurodegenerative disease and scrapie, a similar disease in sheep, macromolecule was a protein …. wound healing, and even secrete inhibitory molecules were infectious but not as a result of a typical virus.
    [Show full text]
  • Summarised Financial Statements 2012
    Summarised Financial Statements 2012 Contents Chairman’s Statement 02 02 Summary Trustee’s Report 04 04 Vision and Objects, Mission, Focus Areas 04 and Challenges Financial Review 06 Extracts from the Review of Investment Activities 08 Independent Auditors’ Report 10 10 Consolidated Statement of Financial Activities 11 Consolidated Balance Sheet 12 Consolidated Cash Flow Statement 13 Grants Awarded 14 Reference and Administrative Details 16 Chairman’s Statement Sustained investment in research can bring real benefits or Medicine which was shared by a dozens of genomes every day. Their former Governor of the Trust, work is driving the first wave of Professor Sir John Gurdon. His work stratified medicine, improving cancer showed that mature cells had the therapy for patients by examining the potential to be reprogrammed into genetics of individual tumours, and stem cells. Subsequent decades of revealing the genetic basis of the way investment in stem cell research have specific cancers respond to different brought us ever closer to realising the drugs. promise of stem cell therapies. At the same time, ever-improving We saw again this year how sustained technology is giving us an advantage investment in research can bring real against infectious diseases. A study benefits. Genetics has been one of the published this summer demonstrated Trust’s most focused areas of funding how modern genome sequencing Summary of Chairman’s since the mid-1990s. First, we sought could track methicillin-resistant Statement to decode the human genome; then Staphylococcus aureus (MRSA). we had to find ways to apply that Retrospective analysis of samples • We committed £701 million in grant knowledge.
    [Show full text]
  • February 7, 2007 (Download PDF)
    Volume 51 – Number 16 Wednesday – February 7, 2007 TechTalk S ERVING T HE M I T C OMMUNITY Reactivated gene shrinks tumors, MIT study finds Anne Trafton cancer treatments,” said David Kirsch of known whether such activity would actu- properly, it activates DNA repair mecha- News Office MIT’s Center for Cancer Research and ally reverse tumor growth in primary nisms and prevents cells with damaged Harvard Medical School, one of the lead tumors. DNA from dividing. If DNA damage is co-authors of the paper. The new MIT study shows that re-acti- irreparable, p53 induces the cell to destroy Many cancers arise due to defects in The study appeared in the Jan. 25 vating p53 in mouse tumors dramatically itself by undergoing apoptosis, or pro- genes that normally suppress tumor issue of Nature. It was conducted in the reduces the size of the tumors, in some grammed cell death. growth. Now, for the first time, MIT laboratory of Tyler Jacks, director of the cases by 100 percent. When p53 is turned off by mutation researchers have shown that re-activat- Center for Cancer Research, the David H. “This study provides critical genetic or deletion, cells are much more likely ing one of those genes in mice can cause Koch Professor of Biology and a Howard evidence that continuous repression of a to become cancerous, because they will tumors to shrink or disappear. Hughes Medical Institute investigator. tumor suppressor gene is required for a divide uncontrollably even when DNA is The study offers evidence that the P53 has long been known to play a tumor to survive,” said Andrea Ventura, an damaged.
    [Show full text]
  • 2019: the Year in Experimental Medicine Why Submit to Jem?
    2019: THE YEAR IN EXPERIMENTAL MEDICINE WHY SUBMIT TO JEM? FORMAT NEUTRAL You may submit your papers in ANY format. 92% OF INVITED REVISIONS ARE ACCEPTED TRANSFER POLICY We welcome submissions that include reviewer comments from another journal. You may also request manuscript transfer between Rockefeller University Press journals, and we can confidentially send reviewer reports and identities to another journal beyond RUP. INITIAL DECISION IN 6 DAYS FAIR AND FAST We limit rounds of revision, and we strive to provide clear, detailed decisions that illustrate what is expected in the revisions. Articles appear online one to two days after author proofs are returned. TIME IN PEER REVIEW 38 DAYS OPEN ACCESS OPTIONS Our options include Immediate Open Access (CC-BY) and open access six months after publication (CC-BY-NC-SA). *Median 2019 An Editorial Process Guided by Your Community At JEM, all editorial decisions on research manuscripts are made through collaborative consultation between professional scientific editors and the academic editorial board. Submission or transfer Academic and scientific If appropriate, sent Academic and scientific Informed decisions editors review to Peer Review editors review comments sent to authors Revised manuscript Academic and scientific 92% of invited Published online Circulated via alerts and submission and rereview editors review revisions accepted* 1-2 days after author social media to readers proofs returned around the world 2019: THE YEAR IN EXPERIMENTAL MEDICINE t the beginning of 2020, the start of a new decade, the Journal of Experimental Medicine (JEM) is proud to present our annual Year in Experimental Medicine collection to highlight some of the articles that were of greatest interest to our readers last year.
    [Show full text]
  • MSU Commencement Ceremonies Fall 2020
    COMMENCEMENT CEREMONIES FALL 2020 “Go forth with Spartan pride and confdence, and never lose the love for learning and the drive to make a diference that brought you to MSU.” Samuel L. Stanley Jr., M.D. President Michigan State University Photo above: an MSU entrance marker of brick and limestone, displaying our proud history as the nation’s pioneer land-grant university. On this—and other markers—is a band of alternating samara and acorns derived from maple and oak trees commonly found on campus. This pattern is repeated on the University Mace (see page 10). Inside Cover: Pattern of alternating samara and acorns. Michigan State University photos provided by University Communications. ENVIRONMENTAL TABLE OF CONTENTS STEWARDSHIP Mock Diplomas and the COMMENCEMENT Commencement Program Booklet 3 Virtual Commencement Ceremonies Commencement mock diplomas, 4 The Michigan State University Board of Trustees which are presented to degree 5 Michigan State University Mission Statement candidates at their commencement 6–8 Congratulatory Letters from the President, Provost, and Executive Vice President ceremonies, are 30% post-consumer 9 Michigan State University recycled content. The Commencement 10 Ceremony Lyrics program booklet is 100% post- 11 University Mace consumer recycled content. 12 Academic Attire 13 Keynote Speakers Caps and Gowns 14–16 Keynote Speaker Profles Graduating seniors’ caps and gowns and master’s degrees’ caps and BACCALAUREATE DEGREES gowns are made of post-consumer 18 Honors recycled content; each cap and 19 Order of Ceremonies gown is made of a minimum of 20–21 College of Agriculture and Natural Resources 23 plastic bottles. 22 Residential College in the Arts and Humanities 23–24 College of Arts and Letters Recycle Your Cap and Gown 25–26 The Eli Broad College of Business Once all of your favorite photos are 27–29 College of Communication Arts and Sciences taken on campus, please recycle 30 College of Education your gown at the MSU Union 31–32 College of Engineering Spartan Spirit Shop.
    [Show full text]
  • H. Robert Horvitz
    WORMS, LIFE AND DEATH Nobel Lecture, December 8, 2002 by H. ROBERT HORVITZ Howard Hughes Medical Institute, McGovern Institute for Brain Research, Department of Biology, Massachusetts Institute of Technology, 77 Massachus- etts Ave., Cambridge, MA 02139, U.S.A. I never expected to spend most of my life studying worms. However, when it came time for me to choose an area for my postdoctoral research, I was in- trigued both with the problems of neurobiology and with the approaches of genetics. Having heard that a new “genetic organism” with a remarkably sim- ple nervous system was being explored by Sydney Brenner – the microscopic soil nematode Caenorhabditis elegans – I decided to join Sydney in his efforts. THE CELL LINEAGE After arriving at the Medical Research Council Laboratory of Molecular Biology (the “LMB”) in Cambridge, England, in November, 1974, I began my studies of C. elegans (Figure 1) as a collaboration with John Sulston. John, Figure 1. Caenorhabditis elegans adults. Hermaphrodite above, male below. John Sulston took these photographs, and I drew the diagrams. Bar, 20 microns. From (2). 320 Figur 2. John White. trained as an organic chemist, had become a Staff Scientist in Sydney’s group five years earlier. John’s aim was to use his chemistry background to analyze the neurochemistry of the nematode. By the time I arrived, John had turned his attention to the problem of cell lineage, the pattern of cell divisions and cell fates that occurs as a fertilized egg generates a complex multicellular or- ganism. John could place a newly hatched C. elegans larva on a glass micro- scope slide dabbed with a sample of the bacterium Escherichia coli (nematode food) and, using Nomarski differential interference contrast optics, observe individual cells within the living animal.
    [Show full text]
  • Table of Contents
    Umeå University Medical Dissertations New Series No 1080 • ISSN 0346-6612 • ISBN 978-91-7264-246-1 ___________________________________________________________________________ Protein Tyrosine Kinases and The Regulation of Signalling and Adhesion in Drosophila melanogaster Caroline Grabbe Umeå Centre for Molecular Pathogenesis Umeå University Umeå, Sweden, 2007 Copyright © 2007 by Caroline Grabbe ISBN 978-91-7264-246-1 _______________________________________________________ Printed in Sweden by Solfjädern Offset AB Umeå, 2007 2 To Chance, and Life Itself… (I det långa loppet träffar man bara det man siktat på. Så även om man missar sitt mål i första försöket så är det lika bra att sikta högt.) Henry David Thoreau 3 TABLE OF CONTENTS ABBREVIATIONS ................................................................................................................ 6 SUMMARY............................................................................................................................. 8 PAPERS INCLUDED IN THIS THESIS............................................................................. 9 PAPERS NOT INCLUDED IN THIS THESIS ................................................................... 9 INTRODUCTION................................................................................................................ 10 Drosophila melanogaster as a model system....................................................................... 10 Historical perspective............................................................................................................
    [Show full text]
  • Report 1978 Cold Spring Harbor Laboratory
    COLDLABORATORY SPRING HARBOR ANNUAL REPORT 1978 COLD SPRING HARBOR LABORATORY COLD SPRING HARBOR, NEW YORK Cover: Participants at 1978 Symposium (top to bottom) G. Selzer, F. Stahl, and J. Strathern; A. Kornberg, A. Falaschi, and R. Holliday; W. Arber and D. Nathans; W. Udry, A. Bukhari, and D. Baltimore Picture credits: Cover, 82, 90, 140, Ross Meurer; 14, Cindy Carpenter; 19, W. Udry; 11, 12,13, 17, 20, 67, 136, 142, 143, 153, Robert Yaffe COLD SPRING HARBOR LABORATORY COLD SPRING HARBOR, LONG ISLAND, NEW YORK OFFICERS OF THE CORPORATION Dr. Harry Eagle, Chairman Edward Pulling, Vice-Chairman Dr. Bayard Clarkson, Secretary Clarence E. Galston, Treasurer Robert L. Cummings, Assistant Treasurer William R. Udry, Administrative Director BOARD OF TRUSTEES Institutional Trustees Albert Einstein College of Medicine University of Wisconsin Dr. Harry Julian Davies Columbia University Wawepex Society Dr. Charles R. Cantor Bache Bleecker Duke University Dr. Walter Guild Individual Trustees Long Island Biological Association Emilio G. Collado Edward Pulling Robert L. Cummings Massachusetts Institute of Technology Roderick H. Cushman Dr. Herman Eisen Norris Darrell Memorial Sloan-Kettering Cancer Center Walter N. Frank, Jr. Dr. Bayard Clarkson Clarence E. Galston Mary Lindsay New York University Medical Center William S. Robertson Dr. Vittorio Defendi Mrs. Franz Schneider Princeton University Alexander C. Tomlinson Dr. Arnold J. Levine Dr. James D. Watson The Rockefeller University Dr. Rollin Hotchkiss Honorary trustees State University of New York Dr. H. Bentley Glass at Stony Brook Dr. Alexander Hollaender Dr. Joseph R. Kates Officers and trustees listed are as of December 31, 1978 DIRECTOR'S REPORT The collective decisions of knowledgeable men go sourone likes to advertise that we may have no meaningful more often than we want.
    [Show full text]
  • General Kofi A. Annan the United Nations United Nations Plaza
    MASSACHUSETTS INSTITUTE OF TECHNOLOGY DEPARTMENT OF PHYSICS CAMBRIDGE, MASSACHUSETTS O2 1 39 October 10, 1997 HENRY W. KENDALL ROOM 2.4-51 4 (617) 253-7584 JULIUS A. STRATTON PROFESSOR OF PHYSICS Secretary- General Kofi A. Annan The United Nations United Nations Plaza . ..\ U New York City NY Dear Mr. Secretary-General: I have received your letter of October 1 , which you sent to me and my fellow Nobel laureates, inquiring whetHeTrwould, from time to time, provide advice and ideas so as to aid your organization in becoming more effective and responsive in its global tasks. I am grateful to be asked to support you and the United Nations for the contributions you can make to resolving the problems that now face the world are great ones. I would be pleased to help in whatever ways that I can. ~~ I have been involved in many of the issues that you deal with for many years, both as Chairman of the Union of Concerne., Scientists and, more recently, as an advisor to the World Bank. On several occasions I have participated in or initiated activities that brought together numbers of Nobel laureates to lend their voices in support of important international changes. -* . I include several examples of such activities: copies of documents, stemming from the . r work, that set out our views. I initiated the World Bank and the Union of Concerned Scientists' examples but responded to President Clinton's Round Table initiative. Again, my appreciation for your request;' I look forward to opportunities to contribute usefully. Sincerely yours ; Henry; W.
    [Show full text]