DOCSLIB.ORG

Integration of Transcripts and Metabolites Analysis of Resulting

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Integration of Transcripts and Metabolites Analysis of Resulting Biomass and Metabolomics at the MPI for Molecular Plant Physiology Bioen Workshop on Metabolomics of Sugarcane FAPESP, Sao Paulo, 07 December 2009 Lothar Willmitzer Max-Planck-Institut für Molekulare Pflanzenphysiologie 14476 Potsdam-Golm, Germany The Max Planck Society Foundedis a research 1948 organization supposed to work complementary to Universities 276 Departments (led by Max Planck Directors) 12,200 employees (include. 4,200 scientists) + 9,600 junior scientists Budget: 1.3 BEuro = ≤2% of total R&D in Germany government + 16 states (1:1) 78 Institutes our research activities are - focused on basic research - curiosity-based and hypothesis-driven - open to but not focused on applications “Knowledge must precede application” (Max Planck) 17 Nobel prizes since 1948 2007 Chemistry: Gerd Ertl 2005 Physics: Theodor Hänsch 1995 Chemistry: Paul Crutzen 1995 Medicine: Christiane Nüsslein-Volhard 1991 Medicine: Erwin Neher Bert Sakmann 1988 Chemistry: Johann Deisenhofer Robert Huber Hartmut Michel 1986 Physics: Ernst Ruska 1985 Physics: Klaus von Klitzing 1984 Medicine: Georges Köhler 1973 Medicine: Konrad Lorenz 1967 Chemistry: Manfred Eigen 1964 Medicine: Feodor Lynen 1963 Chemistry: Karl Ziegler 1954 Physics: Walter Bothe Commercial success = Technology transfer „Max Planck Innovation GmbH“ since 1979: 2,025 patents filed 1,186 licence contracts 154 M€ patent licences 60 Start Up companies Potsdam-Golm Campus harbors University Potsdam, Fraunhofer Research Institutes and Max-Planck Institutes MPI für Molekulare Pflanzenphysiologie Structure of the MPI-MP • 3 departments hosting 12 research groups mostly led by young scientists on limited contracts • 2 independent Max-Planck research groups • 3 infrastructure groups • 2 university guest groups • 2 Systems Biology guest groups Structure of the MPI-MP • Approx 350 employees • 90+ post-doc´s and 90+ PhD students • More than 50% coming from abroad covering 25+ countries • Working language is english Biological Processes studied at the MPI-MP Plant Energetics (Photosynthesis, Respiration) Biomass Abiotic stress Metabolism and Growth (temperature, nutrients) Cell wall biosynthesis Create genetic diversity, grow it in defined environmental conditions and subject it to broad molecular phenotyping RNA analysis (arrays, RT-PCR) Proteomics facility ( LC-MS, 2D) EnzymeData HTPMining platform (Bioinformatics)Metabolite analysis Single cell analysis Genotyp Environment AnalysisAnaly Genotypeses Environment sis Subcellular analysis Transgenics Natural Variation Arabidopsis, tomato,rice Metabolomics • The metabolome comprises all small molecules present in a given biological system • Metabolomics aims at the quantitative determination of all small molecules • The metabolome contains molecules hugely varying in three parameters : concentration, structure and chemical behaviour • In contrast to RNA and protein metabolites are non-linear to the DNA Metabolomics - Challenges • Increase the fraction of molecules we see.. • Annotate more of them … • Quantitate them ( relative and absolute) .. • Discriminate a true metabolite from a contaminant … • Make sure that what we measure reflects the situation in the cell …. Sampling • subcellular distribution, labelling ( fluxomics) …. Metabolomics - Extraction • Metabolomics aims at a complete coverage of all small molecules • Thus as little prefractionation as possible is applied • We start from a simple methanol/chloroform/water extract which is exposed to three different platforms GC-MS : the workhorse for 100 – 150 metabolites mostly from primary metabolism robotic derivatisation & full extract injection: „What Is This Peak?“ Acquired on 09-Dec-1998 at 12:59:56 8343AO01 Scan EI+ TIC 100 1.20e8 % 0 rt 7.500 10.000 12.500 15.000 17.500 20.000 22.500 25.000 27.500 30.000 32.500 35.000 37.500 40.000 42.500 45.000 LTQ FT Ultra • Resolution – > 1 000 000 • Mass Range – m/z 50-2000 • Dynamic Range – 1 000 Mass Accuracy 102 ppm 0.26 ppm 5.93 ppm + 0.00004 - 0.017 - 0.00103 Phenylalanine [M+H+]+ Formula calculation is depending on mass accuracy and resolution [M+H+]+ Mass 181.07066 allowed chemical elements: C = 30 H = 50 N = 5 O = 10 P = 5 S = 5 500 ppm = 0.09085 Da Error 268 predicted Formulas 100 ppm = 0.01817 Da Error 54 predicted Formulas 10 ppm = 0.00181 Da Error 6 predicted Formulas 1 ppm = 0.00018 Da Error 1 predicted Formula C6H12O6 Metabolite Extraction MeOH:CHCl3:H2O 12 13 Arabidopsis CO2 Arabidopsis CO2 •UPLC FT-ICR MS •Peak Extraction 12C chemical formula 13C chemical formula and retention time and retention time •DB Search Matched 12C/13C formulas with RT tolerance 0.05 min unambiguous ambiguous Annotated formula •Isotope pattern •MS/MS analysis unambiguous 13 Whole metabolome CO2 labelling strategy Parallel analysis of 12/13C labelled compounds allows discrimination of biological from non-biological material and annotation of number of carbon atoms x:\ag willmitzer\...\at_13c_pos1 10/7/2008 10:23:16 PM RT: 0.00 - 13.01 100 NL: 1.62E7 90 8.23min Base Peak MS 80 7.27min At_12C_po s1 70 60 50 40 30 20 10 100 NL: 1.57E7 90 Base Peak MS 80 at_13c_pos 1 70 60 50 40 30 20 10 0 1 2 3 4 5 6 7 8 9 10 11 12 13 X:\AG Willmitzer\...\At_12C_pos1 10/7/2008 8:41:49 PM X:\AG Willmitzer\...\At_12C_pos1 10/7/2008 8:41:49 PM 100 NL: 9.74E6 100 NL: 7.52E6 At_12C_pos1#515 At_12C_pos1#582 90 741.22238 RT: 7.33 AV: 1 T: 90 RT: 8.21 AV: 1 T: 12 FTMS + p NSI Full 382.14236 FTMS + p NSI Full 80 ms 80 12 ms C [100.00-1300.00] [100.00-1300.00] 70 70 C 60 60 50 50 40 40 30 30 20 C 33 20 383.14574 384.13859 10 10 0 0 100 NL: 8.58E6 100 NL: 1.56E6 at_13c_pos1#514 at_13c_pos1#591 90 RT: 7.30 AV: 1 T: 90 RT: 8.27 AV: 1 T: 774.33350 FTMS + p NSI Full 382.14225 FTMS + p NSI Full 80 13 ms 80 13 ms C [100.00-1300.00] [100.00-1300.00] 70 70 C 60 60 50 50 40 40 30 30 20 20 383.14599 10 10 384.13865 0 0 730 735 740 745 750 755 760 765 770 775 780 785 382.0 382.5 383.0 383.5 384.0 m/z m/z Relative quantitation via spiking with a 13C labeled metabolome A 13 Sample 1 Sample 1 Sample 2 Sample 3 CO2 Sample •Metabolite Extraction •UPLC FT-ICR MS •Spike fixed amount (1:1) •Peak Extraction •Spectra Alignment •Differential Peak detection •DB Search 1:1 1:2 1:4 1:20 12C/13C dilution B 35 30 25 20 15 Ratio13C/12C 10 5 0 1:1 1:1 1:1 1:2 1:2 1:2 1:4 1:4 1:4 1:20 1:20 1:20 Mixing Ratio 12C/13C MS/MS for elucidation of structures 13 C H O C15H9O7 13 15 9 7 C27H28O16 301.03397 316.08536 636.23571 100 90 80 70 60 C27H28O16 50 609.14234 m/z 303 Rel. Abundance [%] Abundance Rel. 40 m/z 318 30 20 10 0 100 200 300 400 500 600 700 800 900 1000 m/z IRMPD ESI neg [M-H]- Strategic Overview of the Platform GC-TOF FT-ICR-MS pos. mode aqueous UPLC separation phase Arabidopsis neg. 12 mode CO2 grown Metabolite Extraction MeOHl:CHCl3:H2O pos. mode Arabidopsis chloroform 13 Lipids UPLC fractionation CO2 grown phase neg. mode Compound annotation UPLC peak detection, and result interpretation peak lists extraction and differential database searches Summary Metabolomics • Starting from a MeOH-H2O/CHCl3 extract three platforms allow : • analysis of 150 primary metabolites (GC-TOF) • analysis of 500 – 1000 secondary metabolites (UPLC-FT-ICR-MS) • analysis of about 140 complex lipids Metabolomics : Applications • Metabolomics and Genetics : Annotation of gene function • Metabolomics and Diagnostics : Discrimination/Identification/Prediction of states • Metabolomics and Systems Biology : Integration of different data sets Metabolomics and Genetics : Annotation of gene function using KO populations and overexpressors Metabolic Genomics: From Gene to Function - Directly Metabolic Genomics at metanomics: Process Overview Knockout “Gene......................... Donors”: Transfer of additional Genes Transformants A Wild Type Transformants B Arabidopsis thaliana The “domestic pet” Plant about 27.000 Genes Collections Genetic blueprint known Small Grows rapidly Functional Large progeny Performance Analysis Metabolic Analyses Plant Lines Metabolites 0.2 1 2 X-Fold ratio in comparison to Wild Type control Fig.4 Metabolomics and Diagnostics : Discrimination/Identification/Prediction of states Metabolic profiling applied to two ecotypes and one mutant each Col-2 wild type dgd1 mutant C24 wild type sdd1 mutant Arabidopsis Profiling: PCA Cluster Analysis Factor1 Factor4 Factor2 Col2 WT Col2 dgd1 C24 WT C24 sdd Medical applications of Metabolomics • Differentiation of diabetics/nondiabetics • Diagnostics of cancer and non-cancer tissues (kidney cancer) • Prediction of health risk ( myocardial infarct) • Differentiation of responder/non-responder (antidepressiva) Separation of diabetic and nondiabetic male and female patients Metabolic profiling allows assigment of normal and clear cell kidney carcinoma Prediction of myocardial infarction by metabolic signature. 100 80 60 40 SensitivitySensitivity 20 Standard Model and five metabolites Standard Model Age, Sex and five metabolites 0 0 20 40 60 80 100 100-Specificity Prediction was estimated by calculation of receiver-operating-curves (ROC). Prediction of a model including age, sex and the here identified five metabolites (red ROC; AUC 0.844) was not inferior to a standard model including all established risk factors (age, sex, smoking, education, alcohol consumption, physical activity, hormone replacement therapy, BMI, hypertension, diabetes, HDL/total-cholesterol-ratio and C-reactive protein) (blue ROC; AUC 0.86; p=0.385). A model with all established risk factors (standard model) and the five metabolites (AUC 0.89) outperformed the standard model alone (p=0.033). Medical applications of Metabolomics • Differentiation of diabetics/nondiabetics • Diagnostics of cancer and non-cancer tissues (kidney cancer) • Prediction of health risk ( myocardial infarct) • Differentiation of responder/non-responder (antidepressiva) Metabolomics and systems biology: Network analysis and integration with transcript data E.
Load more

Recommended publications
  • Balcomk41251.Pdf (558.9Kb)
    Copyright by Karen Suzanne Balcom 2005 The Dissertation Committee for Karen Suzanne Balcom Certifies that this is the approved version of the following dissertation: Discovery and Information Use Patterns of Nobel Laureates in Physiology or Medicine Committee: E. Glynn Harmon, Supervisor Julie Hallmark Billie Grace Herring James D. Legler Brooke E. Sheldon Discovery and Information Use Patterns of Nobel Laureates in Physiology or Medicine by Karen Suzanne Balcom, B.A., M.L.S. Dissertation Presented to the Faculty of the Graduate School of The University of Texas at Austin in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy The University of Texas at Austin August, 2005 Dedication I dedicate this dissertation to my first teachers: my father, George Sheldon Balcom, who passed away before this task was begun, and to my mother, Marian Dyer Balcom, who passed away before it was completed. I also dedicate it to my dissertation committee members: Drs. Billie Grace Herring, Brooke Sheldon, Julie Hallmark and to my supervisor, Dr. Glynn Harmon. They were all teachers, mentors, and friends who lifted me up when I was down. Acknowledgements I would first like to thank my committee: Julie Hallmark, Billie Grace Herring, Jim Legler, M.D., Brooke E. Sheldon, and Glynn Harmon for their encouragement, patience and support during the nine years that this investigation was a work in progress. I could not have had a better committee. They are my enduring friends and I hope I prove worthy of the faith they have always showed in me. I am grateful to Dr.
    [Show full text]
  • Guidelines and Information for Feodor Lynen Research Fellows Contents Page
    Guidelines and Information for Feodor Lynen Research Fellows Contents Page PREFACE 4 A. FEODOR LYNEN RESEARCH FELLOWSHIP GUIDELINES 6 A.1. The Feodor Lynen Research Fellowship ....................................... 7 A.1.1. Acceptance ............................................................................. 7 A.1.2. Commencement ...................................................................... 8 A.1.3. Duration .................................................................................. 8 A.1.4. Extension ................................................................................ 8 A.1.5. Calculation of monthly fellowship grant ................................... 9 A.1.5.1. Base fellowship ................................................................. 9 A.1.5.2. Foreign allowance ............................................................. 9 A.1.5.3. Family allowance for marital partners .............................. 11 A.1.5.4. Family allowance for children .......................................... 11 A.1.5.4.1. Child allowance ......................................................... 11 A.1.5.4.2. Substitutional payment for child benefit according to the German Income Tax Act (Einkommensteuergesetz, EStG) . 12 A.1.5.5. Allowance for direct research costs ................................. 13 A.1.6. Host contribution ................................................................... 13 A.1.7. Additional earnings ................................................................ 13 A.1.8. Change of circumstances
    [Show full text]
  • Federation Member Society Nobel Laureates
    FEDERATION MEMBER SOCIETY NOBEL LAUREATES For achievements in Chemistry, Physiology/Medicine, and PHysics. Award Winners announced annually in October. Awards presented on December 10th, the anniversary of Nobel’s death. (-H represents Honorary member, -R represents Retired member) # YEAR AWARD NAME AND SOCIETY DOB DECEASED 1 1904 PM Ivan Petrovich Pavlov (APS-H) 09/14/1849 02/27/1936 for work on the physiology of digestion, through which knowledge on vital aspects of the subject has been transformed and enlarged. 2 1912 PM Alexis Carrel (APS/ASIP) 06/28/1873 01/05/1944 for work on vascular suture and the transplantation of blood vessels and organs 3 1919 PM Jules Bordet (AAI-H) 06/13/1870 04/06/1961 for discoveries relating to immunity 4 1920 PM August Krogh (APS-H) 11/15/1874 09/13/1949 (Schack August Steenberger Krogh) for discovery of the capillary motor regulating mechanism 5 1922 PM A. V. Hill (APS-H) 09/26/1886 06/03/1977 Sir Archibald Vivial Hill for discovery relating to the production of heat in the muscle 6 1922 PM Otto Meyerhof (ASBMB) 04/12/1884 10/07/1951 (Otto Fritz Meyerhof) for discovery of the fixed relationship between the consumption of oxygen and the metabolism of lactic acid in the muscle 7 1923 PM Frederick Grant Banting (ASPET) 11/14/1891 02/21/1941 for the discovery of insulin 8 1923 PM John J.R. Macleod (APS) 09/08/1876 03/16/1935 (John James Richard Macleod) for the discovery of insulin 9 1926 C Theodor Svedberg (ASBMB-H) 08/30/1884 02/26/1971 for work on disperse systems 10 1930 PM Karl Landsteiner (ASIP/AAI) 06/14/1868 06/26/1943 for discovery of human blood groups 11 1931 PM Otto Heinrich Warburg (ASBMB-H) 10/08/1883 08/03/1970 for discovery of the nature and mode of action of the respiratory enzyme 12 1932 PM Lord Edgar D.
    [Show full text]
  • Gerald Edelman - Wikipedia, the Free Encyclopedia
    Gerald Edelman - Wikipedia, the free encyclopedia Create account Log in Article Talk Read Edit View history Gerald Edelman From Wikipedia, the free encyclopedia Main page Gerald Maurice Edelman (born July 1, 1929) is an Contents American biologist who shared the 1972 Nobel Prize in Gerald Maurice Edelman Featured content Physiology or Medicine for work with Rodney Robert Born July 1, 1929 (age 83) Current events Porter on the immune system.[1] Edelman's Nobel Prize- Ozone Park, Queens, New York Nationality Random article winning research concerned discovery of the structure of American [2] Fields Donate to Wikipedia antibody molecules. In interviews, he has said that the immunology; neuroscience way the components of the immune system evolve over Alma Ursinus College, University of Interaction the life of the individual is analogous to the way the mater Pennsylvania School of Medicine Help components of the brain evolve in a lifetime. There is a Known for immune system About Wikipedia continuity in this way between his work on the immune system, for which he won the Nobel Prize, and his later Notable Nobel Prize in Physiology or Community portal work in neuroscience and in philosophy of mind. awards Medicine in 1972 Recent changes Contact Wikipedia Contents [hide] Toolbox 1 Education and career 2 Nobel Prize Print/export 2.1 Disulphide bonds 2.2 Molecular models of antibody structure Languages 2.3 Antibody sequencing 2.4 Topobiology 3 Theory of consciousness Беларуская 3.1 Neural Darwinism Български 4 Evolution Theory Català 5 Personal Deutsch 6 See also Español 7 References Euskara 8 Bibliography Français 9 Further reading 10 External links Hrvatski Ido Education and career [edit] Bahasa Indonesia Italiano Gerald Edelman was born in 1929 in Ozone Park, Queens, New York to Jewish parents, physician Edward Edelman, and Anna Freedman Edelman, who worked in the insurance industry.[3] After עברית Kiswahili being raised in New York, he attended college in Pennsylvania where he graduated magna cum Nederlands laude with a B.S.
    [Show full text]
  • Nobel Laureates in Physiology Or Medicine
    All Nobel Laureates in Physiology or Medicine 1901 Emil A. von Behring Germany ”for his work on serum therapy, especially its application against diphtheria, by which he has opened a new road in the domain of medical science and thereby placed in the hands of the physician a victorious weapon against illness and deaths” 1902 Sir Ronald Ross Great Britain ”for his work on malaria, by which he has shown how it enters the organism and thereby has laid the foundation for successful research on this disease and methods of combating it” 1903 Niels R. Finsen Denmark ”in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science” 1904 Ivan P. Pavlov Russia ”in recognition of his work on the physiology of digestion, through which knowledge on vital aspects of the subject has been transformed and enlarged” 1905 Robert Koch Germany ”for his investigations and discoveries in relation to tuberculosis” 1906 Camillo Golgi Italy "in recognition of their work on the structure of the nervous system" Santiago Ramon y Cajal Spain 1907 Charles L. A. Laveran France "in recognition of his work on the role played by protozoa in causing diseases" 1908 Paul Ehrlich Germany "in recognition of their work on immunity" Elie Metchniko France 1909 Emil Theodor Kocher Switzerland "for his work on the physiology, pathology and surgery of the thyroid gland" 1910 Albrecht Kossel Germany "in recognition of the contributions to our knowledge of cell chemistry made through his work on proteins, including the nucleic substances" 1911 Allvar Gullstrand Sweden "for his work on the dioptrics of the eye" 1912 Alexis Carrel France "in recognition of his work on vascular suture and the transplantation of blood vessels and organs" 1913 Charles R.
    [Show full text]
  • Recombinant DNA Controversies
    a passion for DNA Genes, Genomes, and Society With three new essays by the author added for this paperback edition James D. Watson SOFTbank E-Book Center Tehran, Phone: 66403879,66493070 For Educational Use. A PASSION FOR DNA Genes, Genomes, and Society SOFTbank E-Book Center Tehran, Phone: 66403879,66493070 For Educational Use. This Page Intentionally Left Blank SOFTbank E-Book Center Tehran, Phone: 66403879,66493070 For Educational Use. A PASSION FOR DNA Genes, Genomes, and Society With three new essays by the author James D. Watson Introduction, Afterword, and Annotations by Walter Gratzer Cold Spring Harbor Laboratory Press SOFTbank E-Book Center Tehran, Phone: 66403879,66493070 For Educational Use. Cold Spring Harbor, New York A Passion for DNA Genes, Genomes, and Society All rights reserved Copyright 2001 by James D. Watson Published by Cold Spring Harbor Laboratory Press Printed in the United States of America Developmental Editor John Inglis Project Coordinator Elizabeth Powers Production Editor Pat Barker Desktop Editor Susan Schaefer Cover Designer Andrew Meaden Interior Designer Denise Weiss Library of Congress Cataloging-in-Publication Data Watson, James D., 1928– A passion for DNA : genes, genomes, and society / James D. Watson ; with an introduction, afterword, and annotations by Walter Gratzer. p. cm. Includes index. ISBN 0-87969-609-5 (pbk. : alk. paper) 1. Genetics--Social aspects. 2. Medical genetics. 3. Science and civilization. I. Title QH438.7 .W38 2001 572.8--dc21 2001028438 10 9 8 7 6 5 4 3 2 1 Authorization to photocopy items for internal or personal use, or the internal or personal use of spe- cific clients, is granted by Cold Spring Harbor Laboratory Press, provided that the appropriate fee is paid directly to the Copyright Clearance Center (CCC).
    [Show full text]
  • James D. Watson Bibliography Articles
    James D. Watson Bibliography Articles Watson, James D. 1950. The properties of X-ray-inactivated bacteriophage. I. Inactivation by direct effect. Journal of Bacteriology 60(6): 97-718. Maaløe, O.and Watson, James D. 1951. The transfer of radioactive phosphorous from parental to progeny phage. Proceedings of the National Academy of Sciences 37: 507-513. Watson, James D. 1952. The properties of X-ray-inactivated bacteriophage. II. Inactivation of indirect effects. Journal of Bacteriology 63(4): 473-485. Watson, James D. and Maaløe, O. 1953. Nucleic acid transfer from parental to progeny bacteriophage. Biochimica et Biophysica Acta 10: 432-442. Watson, James D. and Hayes, W. 1953. Genetic exchange in Escherichia coli K12: Evidence for three linkage groups. Proceedings of the National Academy of Sciences 39: 416-426. Ephrussi, B., Leopold, U., Watson, James D., and Weigle, J. 1953. Terminology in bacterial genetics. Nature 171: 701. Watson, James D. and Crick, Francis H.C. 1953. Molecular structure of nucleic acids - A structure for deoxyribose nucleic acid. Nature 171: 737-738. Watson, James D. and Crick, Francis H.C. 1953. Genetic implications of the structure of deoxyribonucleic acid. Nature 171: 964-967. Watson, James D. and Crick, Francis H.C. 1953. The structure of DNA. Cold Spring Harbor Symposia on Quantitative Biology 18: 123-131. Watson, James D. and Crick, Francis H.C. 1954. The complementary structure of deoxyribonucleic acid. Proceedings of the Royal Society A 223: 80-96. Watson, James D. 1954. The structure of tobacco mosaic virus. I. X-ray evidence of a helical arrangement of sub-units around the longitudinal axis.
    [Show full text]
  • Stadtman Biographies Biographies
    Stadtman Biographies Biographies Anfinsen, Christian Boehmer (1916-1995) American biochemist Ames, Bruce N. (1928-) American biochemist and geneticist Barker, Horace Albert (1907-2000) American biochemist Beijerinck, Martinus W. (1851-1931) Dutch microbiologist Berzelius, Jöns Jacob (1779-1848) Swedish chemist Brown, Michael Stuart (1941-) American biochemist and molecular geneticist Hodgkin, Dorothy Crowfoot (1910-1994) British crystallographer Kluyver, Albert Jan (1888-1956) Dutch microbiologist Lipmann, Fritz Albert (1899-1986) German-American biochemist Lynen, Feodor (1911-1979) German biochemist Nirenberg, Marshall (1927-) American biochemist and molecular biologist Prusiner, Stanley B. (1942-) American neurologist Stetten, DeWitt, Jr. (1909-1990) American biochemist and medical educator Vagelos, P. Roy (1929-) American biochemist and businessman Van Niel, Cornelis Bernardus Kees (1897-1985) Dutch microbiologist. Warburg, Otto Heinrich (1883-1970) German biochemist. Winogradsky, Sergey Nikolaevich (1856-1953) (also spelled Vinogradsky) Russian microbiologist Anfinsen, Christian Boehmer (1916-1995) American biochemist Anfinsen was educated at Swarthmore College, the University of Pennsylvania, and Harvard, where he obtained his Ph.D. in 1943. Subsequently he taught at Harvard Medical School until 1950. He then moved to the National Heart Institute at Bethesda, Maryland, where he served as chief of the laboratory of cellular physiology. In 1963 Anfinsen joined the National Institute of Arthritis and Metabolic Diseases, another institute within the National Institutes of Health, as chief of the laboratory of chemical biology. In 1982 he moved to the Johns Hopkins University as professor of biology. By 1960 Stanford Moore and William Stein had determined fully the sequence of the 124 amino acids in ribonuclease, the first enzyme to be so analyzed. Anfinsen, however, was more concerned with the shape and structure of the enzyme and the forces that permitted it always to adopt the same unique configuration.
    [Show full text]
  • Fifty Years of Neuropsychopharmacology
    Z. Lacković Fifty years of neuropsychopharmacology FIFTY YEARS OF NEUROPSYCHOPHARMACOLOGY Zdravko Lacković Laboratory of Molecular Neuropsihopharmacology, Department of Pharmacology & Croatian Brain Research Institute, University of Zagreb School of Medicine In the fi fty years since the fi rst Pula congress a lot of methodology of reverse pharmacology – instead has changed in neuropsychopharmacology. Granted, of a classic approach, nowadays receptors are more the major groups of psychoactive drugs had already and more often synthesized from the human genome been discovered: neuroleptics, antidepressants, ben- followed by search for their endogenous ligands and zodiazepine anxiolitics, psychostimulants... Neu- possibilities of their pharmacological manipulation. rology was using the basic antiepileptics while, for Th rough this, we now have orexines (hypocretins) example, the treatments for vascular and immuno- as key neurotransmitters of wakefulness. By reverse logical diseases were more expectative. At the time pharmacology we have discovered such receptors as of the fi rst Pula congress in 1960 we had only just the new opioid receptor ORL1 and its endogenous discovered that myasthenia gravis is an autoimmune ligand, nociceptin and fi nally, after several decades disease. It is also the year when dopamine defi ciency of diff erent assumptions, the prolactin-stimulating in the brain of Parkinsonian patients was discovered, a factor. What is especially intriguing and motivating fi nding which was to revolutionize understanding and is the fact that there are still hundreds of G-protein treatment of this disease. Th e last fi fty years have also receptors, nuclear receptors and synaptic receptors seen a proliferation of approaches to therapy and the waiting for researchers to discover their function and success of these medical fi elds has grown considerably.
    [Show full text]
  • Verzeichnis Der Nobelpreisträger List of Nobel Prize Winners
    Verzeichnis der Nobelpreisträger List of Nobel Prize Winners Nobel Prize Winners 281 Nobelpreis für Physik/Nobel 1936 Peter Debye (Deutschland/Ger.)2 1969 Max Ludwig Delbrück (USA)2 Prize for physics 1943 Georg Karl von Hevesy mit/with Alfred Day Hershey (USA) (Schweden/Sweden)2 und/and Salvador Edward Luria 1921 Albert Einstein (Deutschland/Ger.)2 1962 Max Ferdinand Perutz (USA) 1925 James Franck (Deutschland/Ger.)-' ! 1970 Sir Bernard Kau mit/with Gustav Hertz (Großbritannien/U. K.) (Großbritannien/U. K.)2 (Deutschland/Ger.) mit/with John Cowdery Kendrew mit/with Julius Axelrod (USA) 1933 Erwin Schrödinger (Großbritannien/U. K.) 2 2 und/and Ulf Svante Euler-Chelpin (Österreich/Aus.) 1971 Gerhard Hemberg (Kanada/Can.) (Schweden/Swedcn) mit/with Paul Dirac (Großbritannien/U.K.) 1936 Victor Hess (Österreich/Aus.)2 mit/with Carl David Anderson (USA) Nobelpreis für Physiologie uod Nobelpreis für Literatur/Nobel 1943 Otto Stern (USA)2 2 Medizin/Nobel Prize for 1952 Felix Bloch (USA) Prize for literature physiology and medicine 1929 Thomas Mann (Deutschland/Ger.)2 mit/with Edward Mills Purcell 1922 Otto Fritz Meyerhof 1966 Nelly Sachs (Schweden/Sweden)2 (USA) (Deutschland/Ger.)2 mit/with Shmuel Josef Agnon 1954 Max Born (Bundesrepublik mit/with Archibald Vivian Hill (Israel) Deutschland/Fed. Rep. Ger.)2 (Großbritannien/U. K.) 1981 Elias Canetti mit/with Walter Bothe 1936 Otto Loewi (Österreich/Aus.)2 (Großbritannien/U. K.)2 (Bundesrepublik Deutschland/Fed. mit/with Sir Henry Halle» Dale Rep. Ger.) (Großbritannien/U. K.) 1967 Hans Albrecht Bethe (USA)2 1945 Sir Ernst Boris Chain 1971 Dennis Gabor (Großbritannien/U. K.)2 2 (GroBbritannien/U.
    [Show full text]
  • DAVID Green’S Death in 1983, Frank a Huennekens, One of Green’S Postdoctoral Fellows, Wrote in His Personal Recollections
    NATIONAL ACADEMY OF SCIENCES DAVID EZRA GREEN 1910–1983 A Biographical Memoir by HELMUT BEINERT, PAUL K. STUMPF, AND SALIH J. WAKIL 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 Memoirs, VOLUME 84 PUBLISHED 2003 BY THE NATIONAL ACADEMIES PRESS WASHINGTON, D.C. Courtesy of the University of Wisconsin Department of Photography, Madison DAVID EZRA GREEN August 5, 1910–July 8, 1983 BY HELMUT BEINERT, PAUL K STUMPF, AND SALIH J. WAKIL T THE TIME OF DAVID Green’s death in 1983, Frank A Huennekens, one of Green’s postdoctoral fellows, wrote in his personal recollections: David Green was a remarkable person. Endowed with a keen intellect, an insatiable curiosity about Nature, a vivid imagination and boundless en- ergy, he pursued a career devoted entirely to research. Over a period of four decades he and his colleagues published nearly 700 journal articles and reviews covering a broad spectrum of enzymology and bioenergetics. And, he was the author, co-author or editor of eight books. A legion of postdoctorals and visiting investigators received training in his laboratory. History will surely record that he was one of the giants of 20th-century biochemistry. Green’s professional career had four distinct periods, during which he explored, developed, and refined the ex- panding concepts of enzymology. They were his educational experiences at New York University and at Cambridge; his return to the United States to begin his American career for one year at Harvard; his first academic appointment at Columbia College of Physicians and Surgeons in New York City; and finally his selection as codirector of the Institute for Enzyme Research at the University of Wisconsin at Madi- son, where he remained until his untimely death in 1983.
    [Show full text]
  • Thomas Cech CV
    CURRICULUM VITAE Thomas R. Cech Education and Training B.A. in Chemistry, Grinnell College, Grinnell, Iowa 1970 Ph.D. in Chemistry, University of California, Berkeley with Prof. John E. Hearst 1975 Postdoctoral Fellow, Dept. of Biology, Massachusetts Institute of Technology with Prof. Mary Lou Pardue 1975-77 Positions University of Colorado Boulder Assistant Professor of Chemistry 1978-82 Associate Professor of Chemistry 1982-83 Professor of Chemistry and Biochemistry 1983- Professor of Molecular, Cellular and Developmental Biology (joint appointment) 1983- American Cancer Society Professor 1987- University of Colorado Anschutz Medical Campus Professor of Biochemistry and Molecular Genetics Member, CU Cancer Center 1988- Investigator, Howard Hughes Medical Institute 1988-99; 2009- University of Colorado Distinguished Professor 1990- President, Howard Hughes Medical Institute 2000-09 Director, University of Colorado BioFrontiers Institute (formerly the 2009- Colorado Initiative in Molecular Biotechnology) Honors and Awards National Science Foundation Graduate Fellow 1970-75 Public Health Service Research Fellow, National Cancer Institute 1975-77 Research Career Development Award, National Cancer Institute 1980-85 Passano Foundation Young Scientist Award 1984 Harrison Howe Award 1984 Guggenheim Fellow 1985-86 Pfizer Award in Enzyme Chemistry 1985 Esquire Magazine Register 1985 Denver Post Westerner of the Year 1986 U. S. Steel Award in Molecular Biology 1987 Member, National Academy of Sciences 1987 Honorary Degree, Doctor of Science, Grinnell College 1987 V. D. Mattia Award 1987 Member, American Academy of Arts and Sciences 1988 Newcombe-Cleveland Award, AAAS (with Arthur J. Zaug) 1988 Heineken Prize, Royal Netherlands Academy of Sciences 1988 Gairdner Foundation International Award 1988 Louisa Gross Horwitz Prize (with Phillip A.
    [Show full text]