Chemical Heritage Foundation Boris Magasanik
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Department of Biology, Report to the President 2016-2017
Department of Biology Academic year 2016–2017 was exciting and productive for the Department of Biology. The department is considered one of the best biological science departments in the world. Our superb faculty members are leaders in biological research and education. Some of the news regarding our faculty, research, and educational programs is highlighted below. Faculty Count and Departures During AY2017, the Department of Biology had 56 faculty members: 44 full professors, eight associate professors, and four assistant professors. Research homes are distributed among Building 68, the Broad Institute, the Koch Institute for Integrative Cancer Research, the Picower Institute for Learning and Memory, and the Whitehead Institute for Biomedical Research. In addition to 56 primary faculty members, there were six faculty members with secondary appointments in Biology. These joint faculty members provide important connections to other departments, including Brain and Cognitive Sciences, Chemistry, Biological Engineering, and Civil and Environmental Engineering. We are saddened by the loss of Professor Susan Lindquist, who passed away in October 2016. Hidde Ploegh (Whitehead Institute) moved to Children’s Hospital in January 2017. Professor William (Chip) Quinn (Biology/Brain and Cognitive Sciences) retired in July 2016. Faculty Awards Department of Biology faculty members are widely recognized for their contributions to the field. Among our core faculty are three Nobel Laureates, 30 members of the National Academy of Sciences, 28 members of the American Academy of Arts and Sciences, 14 fellows of the American Association for the Advancement of Science, four recipients of the National Science Foundation National Medal of Science, and 15 Howard Hughes Medical Institute (HHMI) investigators. -
René Dubos, Tuberculosis, and the “Ecological Facets of Virulence”
HPLS (2017) 39:15 DOI 10.1007/s40656-017-0142-5 ORIGINAL PAPER René Dubos, tuberculosis, and the “ecological facets of virulence” Mark Honigsbaum1 Received: 15 January 2017 / Accepted: 23 June 2017 / Published online: 4 July 2017 © The Author(s) 2017. This article is an open access publication Abstract Reflecting on his scientific career toward the end of his life, the French- educated medical researcher Rene´ Dubos presented his flowering as an ecological thinker as a story of linear progression—the inevitable product of the intellectual seeds planted in his youth. But how much store should we set by Dubos’s account of his ecological journey? Resisting retrospective biographical readings, this paper seeks to relate the development of Dubos’s ecological ideas to his experimental practices and his career as a laboratory researcher. In particular, I focus on Dubos’s studies of tuberculosis at the Rockefeller Institute in the period 1944–1956—studies which began with an inquiry into the tubercle bacillus and the physiochemical determinants of virulence, but which soon encompassed a wider investigation of the influence of environmental forces and host–parasite interactions on susceptibility and resistance to infection in animal models. At the same time, through a close reading of Dubos’s scientific papers and correspondence, I show how he both drew on and distinguished his ecological ideas from those of other medical researchers such as Theobald Smith, Frank Macfarlane Burnet, and Frank Fenner. However, whereas Burnet and Fenner tended to view ecological interactions at the level of populations, Dubos focused on the interface of hosts and parasites in the physio- logical environments of individuals. -
Infectious Disease in Philadelphia, 1690- 1807
ABSTRACT Title of Dissertation: INFECTIOUS DISEASE IN PHILADELPHIA, 1690- 1807: AN ECOLOGICAL PERSPECTIVE Gilda Marie Anroman, Doctor of Philosophy, 2006 Dissertation directed by: Professor Mary Corbin Sies Department of American Studies This dissertation examines the multiple factors that influenced the pattern and distribution of infectious disease in Philadelphia between the years 1690 and 1807, and explores the possible reasons for the astonishingly high level of death from disease throughout the city at this time . What emerges from this study is a complex picture of a city undergoing rapid cultural and epidemiological changes . Large -scale immigration supplied a susceptible population group, as international trade, densely packed street s, unsanitary living conditions, and a stagnant and contaminated water supply combined to create ideal circumstances for the proliferation of both pathogen s and vectors, set ting the stage for the many public health crises that plagued Philadelphia for more than one hundred years. This study uses an ecological perspective to understand how disease worked in Philadelphia . The idea that disease is virtually always a result of the interplay of the environment, the genetic and physical make -up of the individual , and the agent of disease is one of the most importan t cause and effect ideas underpinned by epidemiology. This dissertation integrates me thods from the health sciences, humanities, and social sciences to demonstrate how disease “emergence” in Philadelphia was a dynamic feature of the interrelationships between people and their socio -cultural and physical environments. Classic epidemiological theory , informed by ecological thinking, is used to rev isit the city’s reconstructed demographic data, bills of mortality, selected diaries (notably that of Elizabeth Drinker ), personal letters, contemporary observations and medical literature . -
Erwin Chargaff 1905–2002
NATIONAL ACADEMY OF SCIENCES ERWIN CHARGAFF 1 9 0 5 – 2 0 0 2 A Biographical Memoir by SEYMOUR S. COHEN with selected bibliography by ROBERT LEHMAN Any opinions expressed in this memoir are those of the authors and do not necessarily reflect the views of the National Academy of Sciences. Biographical Memoir 2010 NATIONAL ACADEMY OF SCIENCES WASHINGTON, D.C. ERWIN CHARGAFF August 11, 1905–June 20, 2002 BY SEYMOUR S . COHEN 1 AND ROBERT LEHMAN N 1944, AS VARIOUS ARMIES WERE planning to invade central IEurope, the recently naturalized U.S. citizen and Columbia University biochemist had learned of the report of O. T. Avery and his colleagues that the deoxyribonucleic acid (DNA) of a specific strain of pneumococcus constituted the genetically specific hereditary determinant of that bacterium. Almost alone among the scientists of the time, Chargaff accepted the unusual Avery report and concluded that genetic differ- ences among DNAs must be reflected in chemical differences among these substances. He was actually the first biochemist to reorganize his laboratory to test this hypothesis, which he went on to prove by 1949. His results and the subsequent work on the nature of DNA and heredity transformed biomedical research and training for the next fifty years at least, and established potentialities for the development of biology, which have created economic entities and opportunities, as well as major ethical and political controversies. Trained as an analytical chemist, Chargaff had never imagined that he would help to solve a major cytological problem. Reprinted with the permission from Proceedings of the American Philosophical Society (vol. -
Front Matter (PDF)
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME XXVI COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY Founded in 1933 by REGINALD G. HARRIS Director o/ the Biological Laboratory 1924 to 1936 The Symposia were organized and managed by Dr. Harris until his death. Their continued use- /ulness is a tribute to the soundness o/ his vision. The Symposium volumes are published by the Long Island Biological Association as a part of the work of the Biological Laboratory Cold Spring Harbor, L.I., New York COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY VOLUME XXVI Cellular Regulatory Mechanisms THE BIOLOGICAL LABORATORY COLD SPRING HARBOR, L.I., NEW YORK 1961 COPYRIGHT 1962 BY THE BIOLOGICAL LABORATORY LONG ISLAND BIOLOGICAL ASSOCIATION, INC. Library of Congress Catalog Number: 34-8174 All rights reserved. This book may not be reproduced in whole or in part except by reviewers for the public press without written permission from the publisher PRINTED BY WAVERLY PRESS, INC., BALTIMORE,MARYLAND, U.S.A. FOREWORD During the past twenty years, research in genetics and biochemistry, while superficially directed toward an understanding of different aspects of cell behavior, has been moving to a union which appears to have been completed in the presen- tations at this symposium on Cell Regulatory Mechanisms. Sessions were devoted to the role of the genetic material as an information code in protein synthesis and the mechanism of information transfer from DNA to the site of synthesis. Major attention was devoted to cellular mechanisms governing the rates of enzyme ac- tivity and enzyme synthesis. While most of the research presented dealt with microorganisms, the significance of these efforts for questions of normal and ab- normal growth and development in multicellular forms is quite apparent. -
CHAPTER V Some of the Charter Members
YALE JOURNAL OF BIOLOGY AND MEDICINE 46, 32-51 (1972) CHAPTER V Some of the Charter Members The American Epidemiological Society was, at the start, a small, but fervent organization. The founding fathers who controlled it played an earnest and mean- ingful role in the early life of this organization which could not help but contribute to its success. In order to give some idea of the personalities involved, brief biographical sketches of a few of the charter members are given. Those 26 persons to whom Emerson and Godfrey had sent out letters of invita- tion in October 1927 and from whom they had received favorable replies, I believe, represent the true charter members of our Society. Another and longer list which bears the name of "Charter Members of the AES" has been unearthed among Haven Emerson's notes, made in the early years of his secretaryship. This list of 40, includes the names of 14 who were elected at the first meeting of the Society, but I have chosen the original 26 as the official charter members. In the early years there seemed to be no need to enlarge the Society beyond the group of 40 mentioned on Emerson's second list. At least it was an ideal group for the type of spirited discussions which were held at AES meetings for the next 5 years. It may be of interest to see what the backgrounds of some of this early group of 40 had been. Three of the men (Frost, Leake and Maxcy) had spent longer or shorter periods of apprenticeship on what might be called observational and statistical epidemiological field studies which dealt with subjects such as polio- myelitis, influenza, and murine typhus. -
Active Efflux of Tetracycline Encoded by Four Genetically Different
Proc. Natl. Acad. Sci. USA Vol. 77, No. 7, pp. 3974-3977, July 1980 Biochemistry Active efflux of tetracycline encoded by four genetically different tetracycline resistance determinants in Escherichia coli (everted membrane vesicles/tetracycline transport/transposon TnlO/plasmids) LAURA MCMURRY, RICHARD E. PETRUCCI, JR., AND STUART B. LEVY* Department of Molecular Biology and Microbiology and Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111 Communicated by Boris Magasanik, April 21, 1980 ABSTRACT Tetracycline resistance encoded by four ge- at least partly reversed by energy inhibitors (11), which sug- netically different determinants residing on plasmids in Esch- gested that energy was required for the lowered tetracycline erichia coli was shown to be associated in each case with an accumulation. Using everted membrane vesicles, we now energy-dependent decrease in accumulation of the antibiotic containing any one of four ge- in whole cells in which resistance had been induced. The dif- demonstrate that resistant cells ferent class determinants examined were those on plasmids RP1 netically different plasmid-borne tetracycline resistance de- (class A), R222 (class B), R144 (class C), and RAI (class D). This terminants (5) possess an active efflux system for this antibi- decrease in accumulation was attributable to an active efflux, otic. because everted (inside-out) membrane vesicles made from tetracycline-induced E. coli cells containing any one of the four MATERIALS AND METHODS plasmids were shown to concentrate tetracycline by an active Bacterial Strains and Plasmids. The prototroph E. coli strain influx. This active uptake was not seen in inside-out vesicles from P. D. from sensitive cells or uninduced R222-containing cells. -
Transcriptional Repression at a Distance Through Exclusion of Activator Binding in Vivo
Proc. Natl. Acad. Sci. USA Vol. 94, pp. 790–795, February 1997 Biochemistry Transcriptional repression at a distance through exclusion of activator binding in vivo MITSUHIRO SHIMIZU*†,WEISHI LI‡,HEISABURO SHINDO*, AND AARON P. MITCHELL†‡ *School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-03, Japan; and ‡Department of Microbiology and Institute of Cancer Research, Columbia University, New York, NY 10032 Communicated by Boris Magasanik, Massachusetts Institute of Technology, Cambridge, MA, December 3, 1996 (received for review October 8, 1996) ABSTRACT The yeast repressor Rme1p acts from distant Repression by Rme1p is unusual in that it is exerted over a binding sites to block transcription of the chromosomal IME1 considerable distance. The Rme1p binding sites lie over 1600 gene. Rme1p can also repress the heterologous CYC1 promoter bp upstream of IME1 RNA start sites and over 600 bp when Rme1p binding sites are placed 250–300 bp upstream of upstream of the IME1 upstream activation sequence (UAS) CYC1 transcriptional activator binding sites (UAS1 and region (refs. 16 and 17; see Fig. 1A). Other yeast repressors UAS2). Here, in vivo footprinting studies indicate that Rme1p generally act over smaller distances in chromosomal promoter acts over this distance by preventing the binding of the CYC1 regions (18–20). Repression depends upon both Rme1p bind- transcriptional activators to UAS1 and UAS2. Inhibition of ing sites and upon flanking chromosomal sequences. A min- activator binding by Rme1p has the same genetic require- imal region for repression has been defined through insertions ments as repression: both depend upon sequences flanking the of IME1 sequences upstream of a CYC1-lacZ reporter gene Rme1p binding sites and upon Rgr1p and Sin4p, two subunits (13). -
How Microbial Proteomics Got Startedã
Proteomics 2011, 11, 2943–2946 DOI 10.1002/pmic.201000780 2943 REVIEW How microbial proteomics got startedà Frederick C. Neidhardt Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, USA Publication in 1975 by Patrick O’Farrell of a procedure to separate the proteins of Escherichia Received: December 13, 2010 coli in a two-dimensional array on polyacrylamide gels marked the birth of the field now Accepted: January 18, 2011 called proteomics. Although O’Farrell’s contribution was soon to have wide ranging effects on research in many fields, the initial impact was greatest in the arena of whole cell physiology. Refinements and amplification of the original procedure, including improved standardization and reproducibility of gel patterns, introduction of techniques to measure the quantity of protein in individual spots, and biochemical identification of the protein spots, afforded investigators the ability to explore for the first time the integrated working of control circuits in the living cell. From O’Farrell’s contribution has grown the rich array of techniques currently employed and still being developed in the diverse field of microbial proteomics. Keywords: Integrative biology / Microbial physiology / Microbiology / Proteomics origin It is an honor to be asked to write an introductory review on microbial proteomics in 1975 would forever change the the origin of microbial proteomics for this special issue of direction of bacterial physiology. Some colleagues are Proteomics. Professor Michael Hecker, himself a pioneer in mentionedy those whose proximity to the author allowed the field, has graciously invited me to say whatever I wish in us to share the excitement of the times. -
The Jordan Report 20Th Anniversary: Accelerated Development Of
USA ES IC V R E S N A M U H & D H H E T P L A A R E T H M F F E N O T Accelerated Development of Vaccines Preface In 1982, the National Institute of Allergy and Infectious Dis Along with these technological advances, there has been a eases (NIAID) established the Program for the Accelerated heightened awareness of the importance of vaccines for global Development of Vaccines. For 20 years, this program has helped health and security. Acquired immunodeficiency syndrome stimulate the energy, intellect, and ability of scientists in micro (AIDS), malaria, and tuberculosis have demonstrated to the biology, immunology, and infectious diseases. Vaccine research world the importance of public health in economic development. has certainly benefited. The status report reflecting this Most recently, the threat of bioterrorism has reminded many progress in vaccine research has come to be known as the Jor Americans of the value of vaccines as public health tools. dan Report in recognition of Dr. William Jordan, past director of NIAID’s Division of Microbiology and Infectious Diseases Articles by outside experts in this edition highlight many of the (DMID) and the program’s earliest advocate. scientific advances, challenges, and issues of vaccine research during these two decades. As we look to the decade ahead, the This anniversary edition of the Jordan Report summarizes 20 payoffs from basic research will continue to invigorate vaccine years of achievements in vaccine research driven by the explo development, but economic, risk communication, and safety sive technological advances in genomics, immunology, and challenges are likely to influence the licensing of new vaccines. -
Pdf/ Psittacosisqa Brachman PS, Editors
A Peer-Reviewed Journal Tracking and Analyzing Disease Trends pages 361–518 EDITOR-IN-CHIEF D. Peter Drotman EDITORIAL STAFF EDITORIAL BOARD Dennis Alexander, Addlestone Surrey, United Kingdom Founding Editor Ban Allos, Nashville, Tennessee, USA Joseph E. McDade, Rome, Georgia, USA Michael Apicella, Iowa City, Iowa, USA Managing Senior Editor Barry J. Beaty, Ft. Collins, Colorado, USA Martin J. Blaser, New York, New York, USA Polyxeni Potter, Atlanta, Georgia, USA David Brandling-Bennet, Washington, D.C., USA Associate Editors Donald S. Burke, Baltimore, Maryland, USA Charles Ben Beard, Ft. Collins, Colorado, USA Jay C. Butler, Anchorage, Alaska David Bell, Atlanta, Georgia, USA Charles H. Calisher, Ft. Collins, Colorado, USA Arturo Casadevall, New York, New York, USA Patrice Courvalin, Paris, France Kenneth C. Castro, Atlanta, Georgia, USA Stephanie James, Bethesda, Maryland, USA Thomas Cleary, Houston, Texas, USA Brian W.J. Mahy, Atlanta, Georgia, USA Anne DeGroot, Providence, Rhode Island, USA Takeshi Kurata, Tokyo, Japan Vincent Deubel, Shanghai, China Martin I. Meltzer, Atlanta, Georgia, USA Ed Eitzen, Washington, D.C., USA Duane J. Gubler, Honolulu, Hawaii, USA David Morens, Bethesda, Maryland, USA Scott Halstead, Arlington, Virginia, USA J. Glenn Morris, Baltimore, Maryland, USA David L. Heymann, Geneva, Switzerland Tanja Popovic, Atlanta, Georgia, USA Sakae Inouye, Tokyo, Japan Patricia M. Quinlisk, Des Moines, Iowa, USA Charles King, Cleveland, Ohio, USA Keith Klugman, Atlanta, Georgia, USA Gabriel Rabinovich, Buenos Aires, Argentina S.K. Lam, Kuala Lumpur, Malaysia Didier Raoult, Marseilles, France Bruce R. Levin, Atlanta, Georgia, USA Pierre Rollin, Atlanta, Georgia, USA Myron Levine, Baltimore, Maryland, USA David Walker, Galveston, Texas, USA Stuart Levy, Boston, Massachusetts, USA John S. -
Profile of Graham C. Walker
PROFILE PROFILE Profile of Graham C. Walker Jennifer Viegas Science Writer When biologist Graham Walker was intro- DNA, however, changed those plans. “Iknew duced to DNA during a biology course at just enough about the state of quantum Carleton University in Canada, it was fasci- mechanics in 1966 to realize that it wasn’t nation at first sight. “IthoughtDNAwasthe quite ready to deal with a molecule as big as coolest molecule in the world and decided I DNA, so I decided to become an organic wanted to work on it,” says the recently elec- chemist instead so that I could synthesize ted National Academy of Sciences member. it,” he says. Since then, Walker’s research has helped ex- plicate the structure and function of proteins Focus on Nucleic Acids involved in DNA repair and mutagenesis, Carleton chemistry professor Robert Wight- with potential applications for cancer treat- man was an early, influential mentor. As “ ments and antibiotics. His work has also Walker says, He not only ignited the fire in contributed to our understanding of how my belly for experimentation by letting me bacteria infect plants and mammals. synthesize a methylated nucleoside in his lab Fornearlyfourdecades Walker has taught for my honors thesis, but tolerated with good at the Massachusetts Institute of Technology humor the large explosion that occurred (MIT), where he is in charge of the biology when my reaction generating diazomethane undergraduate program. “I am proud of hav- got out of control.” ing been able to make my research contri- Wightman arranged for Walker to work in butions at the same time that I was devoting the laboratory of molecular biologist Saran considerable time and effort towards im- Narang at the National Research Council in Graham C.