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Robert Patrick (Bob) Goldstein James L
Robert Patrick (Bob) Goldstein James L. Peacock III Distinguished Professor Biology Department University of North Carolina at Chapel Hill Chapel Hill, NC 27599-3280 USA email bobg @ unc.edu, phone 919 843-8575 http://www.bio.unc.edu/faculty/goldstein/ PROFESSIONAL EXPERIENCE 1999-current Faculty, UNC Chapel Hill Biology Department and Member, Lineberger Comprehensive Cancer Center EDUCATION PhD: University of Texas at Austin, 1992, Zoology BS: Union College, Schenectady, New York, 1988, Biology RESEARCH TRAINING 1996-1999 Miller Institute Postdoctoral Research Fellow, University of California, Berkeley, Department of Molecular and Cell Biology, Laboratory of Dr. David Weisblat. 1992-1996 Postdoctoral Fellow, MRC Laboratory of Molecular Biology, Cambridge, England. Laboratory of Dr. John White 1992-1993. Independent 1993-1996. 1988-1992 PhD student, University of Texas at Austin. Laboratory of Dr. Gary Freeman. AWARDS 2018 Chapman Family Teaching Award, UNC Chapel Hill 2016 James L. Peacock III Distinguished Professor 2008 Elected Life Member of Clare Hall, Cambridge University 2007 Guggenheim Fellow 2007 Visiting Fellow, Clare Hall, Cambridge University 2005 Phillip and Ruth Hettleman Prize for Artistic and Scholarly Achievement by Young Faculty at UNC Chapel Hill 2000-2004 Pew Scholar 2000-2002 March of Dimes Basil O'Connor Scholar 1996-1998 Miller Institute Research Fellow, University of California, Berkeley 1996 Medical Research Council Postdoctoral Fellow, Cambridge, England 1995 Development Traveling Fellow 1994-1996 Human Frontiers -
Single Molecule Enzymology À La Michaelis-Menten
Single molecule enzymology à la Michaelis-Menten Ramon Grima1, Nils G. Walter2 and Santiago Schnell3* 1 School of Biological Sciences and SynthSys, University of Edinburgh, Edinburgh, UK 2 Department of Chemistry, University of Michigan, Ann Arbor, Michigan, USA 3 Department of Molecular & Integrative Physiology, Department of Computational Medicine & Bioinformatics, and Brehm Center for Diabetes Research, University of Michigan Medical School, Ann Arbor, Michigan, USA * To whom the correspondence should be addressed. E-mail: [email protected] Review article accepted for publication to FEBS Journal special issue on Enzyme Kinetics and Allosteric Regulation 1 Abstract In the past one hundred years, deterministic rate equations have been successfully used to infer enzyme-catalysed reaction mechanisms and to estimate rate constants from reaction kinetics experiments conducted in vitro. In recent years, sophisticated experimental techniques have been developed that allow the measurement of enzyme- catalysed and other biopolymer-mediated reactions inside single cells at the single molecule level. Time course data obtained by these methods are considerably noisy because molecule numbers within cells are typically quite small. As a consequence, the interpretation and analysis of single cell data requires stochastic methods, rather than deterministic rate equations. Here we concisely review both experimental and theoretical techniques which enable single molecule analysis with particular emphasis on the major developments in the field of theoretical stochastic enzyme kinetics, from its inception in the mid-twentieth century to its modern day status. We discuss the differences between stochastic and deterministic rate equation models, how these depend on enzyme molecule numbers and substrate inflow into the reaction compartment and how estimation of rate constants from single cell data is possible using recently developed stochastic approaches. -
Philosophy in Biology and Medicine: Biological Individuality and Fetal Parthood, Part I
Oslo, Norway July 7–12, 2019 ISHP SS B BOOK OF ABSTRACTS 2 Index 11 Keynote lectures 17 Diverse format sessions 47 Traditional sessions 367 Individual papers 637 Mixed media and poster presentations A Aaby, Bendik Hellem, 369 Barbosa, Thiago Pinto, 82 Abbott, Jessica, 298 Barker, Matthew, 149 Abir-Am, Pnina Geraldine, 370 Barragán, Carlos Andrés, 391 D’Abramo, Flavio, 371 Battran, Martin, 158 Abrams, Marshall, 372 Bausman, William, 129, 135 Acerbi, Alberto, 156 Baxter, Janella, 56, 57 Ackert, Lloyd, 185 Bayir, Saliha, 536 Agiriano, Arantza Etxeberria, 374 Beasley, Charles, 392 Ahn, Soohyun, 148 Bechtel, William, 259 El Aichouchi, Adil, 375 Bedau, Mark, 393 Airoldi, Giorgio, 376 Ben-Shachar, Erela Teharlev, 395 Allchin, Douglas, 377 Beneduce, Chiara, 396 Allen, Gar, 328 Berry, Dominic, 56, 58 Almeida, Maria Strecht, 377 Bertoldi, Nicola, 397 Amann, Bernd, 40 Betzler, Riana, 398 Andersen, Holly, 19, 20 Bich, Leonardo, 41 Anderson, Gemma, 28 LeBihan, Soazig, 358 Angleraux, Caroline, 378 Birch, Jonathan, 22 Ankeny, Rachel A., 225 Bix, Amy Sue, 399 Anker, Peder, 230 Blais, Cédric, 401 Ardura, Adrian Cerda, 380 Blancke, Stefaan, 609 Armstrong-Ingram, Tiernan, 381 Blell, Mwenza, 488 Arnet, Evan, 383 Blute, Marion, 59, 62 Artiga, Marc, 383 Bognon-Küss, Cécilia, 23 Atanasova, Nina, 20, 21 Bokulich, Alisa, 616 Au, Yin Chung, 384 Bollhagen, Andrew, 402 DesAutels, Lane, 386 Bondarenko, Olesya, 403 Aylward, Alex, 109 Bonilla, Jorge Armando Romo, 404 B Baccelliere, Gabriel Vallejos, 387 Bonnin, Thomas, 405 Baedke, Jan, 49, 50 Boon, Mieke, 235 Baetu, -
Covalent Modification of Reduced Flavin Mononucleotide in Type-2 Isopentenyl Diphosphate Isomerase by Active-Site-Directed Inhibitors
Covalent modification of reduced flavin mononucleotide in type-2 isopentenyl diphosphate isomerase by active-site-directed inhibitors Takuya Nagaia,1, Hideaki Unnob,1, Matthew Walter Janczakc,1, Tohru Yoshimuraa, C. Dale Poulterc,2, and Hisashi Hemmia,2 aDepartment of Applied Molecular Bioscience, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan; bDivision of Chemistry and Materials Science, Graduate School of Engineering, Nagasaki University, Bunkyo-machi, Nagasaki, Nagasaki 852-8521, Japan; and cDepartment of Chemistry, University of Utah, 315 South 1400 East RM2020, Salt Lake City, UT 84112 Contributed by C. Dale Poulter, October 11, 2011 (sent for review July 9, 2011) Evidence for an unusual catalysis of protonation/deprotonation by not detect signals for putative radical intermediates (9). Attempts a reduced flavin mononucleotide cofactor is presented for type-2 to inhibit the enzyme by incubation with a cyclopropyl analogue isopentenyl diphosphate isomerase (IDI-2), which catalyzes isomer- of IPP, designed to rearrange to a homoallylic structure by a ization of the two fundamental building blocks of isoprenoid bio- radical clock mechanism, were unsuccessful (12, 13). Instead, the synthesis, isopentenyl diphosphate and dimethylallyl diphosphate. analogue was an alternate substrate that isomerized to the cor- The covalent adducts formed between irreversible mechanism- responding DMAPP derivative without a cyclopropylcarbinyl- based inhibitors, 3-methylene-4-penten-1-yl diphosphate or 3-oxi- homoallyl radical rearrangement. ranyl-3-buten-1-yl diphosphate, and the flavin cofactor were inves- Mechanism-based inhibitors of IDI-1, which are activated by tigated by X-ray crystallography and UV-visible spectroscopy. Both protonation of epoxide and diene moieties in these compounds, the crystal structures of IDI-2 binding the flavin-inhibitor adduct – and the UV-visible spectra of the adducts indicate that the covalent also inactivate IDI-2 (12 15). -
Maud Menten, a Physician and Biochemist
Maud Menten Canadian medical researcher Maud Menten (1879-1960) has been called the "grandmother of biochemistry," a "radical feminist 1920s flapper," and a "petite dynamo." Not only was she an author of Michaelis-Menten equation for enzyme kinetics (like the plot in indigo in my portrait), she invented the azo-dye coupling for alkaline phosphatase, the first example of enzyme histochemistry, still used in histochemistry imaging of tissues today (which inspired the histology background of the portrait), and she also performed the first electrophoretic separation of blood haemoglobin in 1944! Born in Port Lambton, Ontario, she studied at the University of Toronto, earning her bachelor's in 1904, and then graduated from medical school (M.B., bachelor's of medicine) in 1907. She published her first paper with Archibald Macallum, the Professor of Physiology at U of T (who went on to set up the National Research Council of Canada), on the distribution of chloride ions in nerve cells in 1906. She worked a year at the Rockefeller Institute in New York, where along with Simon Flexner, first director of the Institute, she co-authored a book on radium bromide and cancer, the first publication produced by the Institute - barely 10 years after Marie Curie had discovered radium. She completed the first of two fellowships at Western Reserve University (now Case Western Reserve University), then she earned a doctorate in medical research in 1911 at U of T. She was one of the first Canadian women to earn such an advanced medical degree. She then moved to Berlin (travelling by boat, unfazed by the recent sinking of the Titanic) to work with Leonor Michaelis. -
Leonor Michaelis and Maud Leonora Menten Celebrating 100 Years of the Michaelis–Menten Equation
ARTICLE-IN-A-BOX Leonor Michaelis and Maud Leonora Menten Celebrating 100 years of the Michaelis–Menten Equation Leonor Michaelis was an honoured German biochemist and Maud Leonora Menten an honoured Canadian pathologist, during the nineteenth century. Though Michaelis sustained his interest in enzymology and biochemistry, Menten moved to pathology and became a renowned pathologist later in her career. The research collaboration of Michaelis and Menten was phenomenal resulting in the celebrated ‘Michaelis–Menten Equation’. Michaelis and Menten’s classic paper titled ‘Die Kinetik der Invertin wirkung’, published in Biochemische Zeitschrift in 1913 marks its centenary this year. This seminal paper which proved vital for the teaching of enzyme kinetics, was acknowledged with so much appreciation and attention that no textbook in biology for undergraduate and graduate students across the world is complete without a discussion of the Michaelis–Menten Equation. An earlier paper by Victor Henri and Brown lacked one important insight which was reported by Michaelis and Menten: that insight was the analysis of reaction in terms of the initial rate. Michaelis and Menten introduced the concept of measuring the initial activity of the enzyme by mixing it with substrate so that product accumulation would not inhibit the activity. Leonor Michaelis (1875–1949) Leonor Michaelis was born in Berlin, Germany on January 16, 1875. He graduated from the ‘humanistic’ Koellnisches Gymnasium in 1893. This gymnasium was special as unlike the other humanistic gymnasiums, it also included chemistry and physics labs which were not in general use and it was only the keen initiative of two professors that enabled interested students learn the subjects. -
Maud Leonora Menten
Regulars Past Times A woman at the dawn of biochemistry Maud Leonora Menten Athel Cornish-Bowden Ask an average biochemist who was the first to realize that variant proteins could be detected by (Bioénergétique et Ingénierie electrophoresis and sedimentation, and had used this understanding to recognize different forms of des Protéines, CNRS and haemoglobin, the reply would probably refer to Linus Pauling and his work on sickle cell disease. Yet, Aix-Marseille Université, although this work was certainly important, that would be the wrong answer, because Maud Leonora France) and John Lagnado Menten, who sometimes seems to be remembered for one paper only, had this idea several years (Honorary Archivist, the before him, and used it to recognize the differences between foetal and adult haemoglobin1. She was Biochemical Society) unfortunate, however, in that her paper appeared in war time, and was eclipsed a few years later by a far more high-profile study2. In 2013 we celebrate two important centenaries not only of Director, and later the person who appointed Leonor the admission of women to the Biochemical Society (why Michaelis to his position there. With Flexner and James W. did it take so long?), but also of the publication of a paper Jobling, she wrote a book (the first monograph emanating by Maud Menten, who was one of the first women to leave from the Rockefeller Institute) on the effects of radium her mark in biochemistry, with a paper that is cited more bromide on tumours of animals, published in 1910 – often in the 21st Century than it was in the 20th. -
The Biological Laboratory
LONG ISLAND BIOLOGICAL ASSOCIATION ANNUAL REPORT OF THE BIOLOGICAL LABORATORY COLD SPRING HARBOR LONG ISLAND, NEW YORK 1939 LONG ISLAND BIOLOGICAL ASSOCIATION INCORPORATED 1924 ANNUAL REPORT OF THE BIOLOGICAL LABORATORY FOUNDED 1890 FIFTIETH YEAR 1939 SCIENTIFIC ADVISORY COMMITTEE J. H. Bodine, Chairman,State University of Iowa Harold A. Abramson,College of Physicians and Surgeons, Columbia University Edgar Allen, Yale University,School of Medicine Stanley A. Cain, Universityof Tennessee Robert Chambers, WashingtonSquare College, New York University Harry A. Charipper,Washington Square College, New York University Kenneth S. Cole, College of Physiciansand Surgeons, Columbia University William H. Cole, Rutgers University Henry S. Conard, GrinnellCollege George W. Corner, Universityof Rochester, School of Medicine and Dentistry W. J. Crozier, Harvard University Charles B. Davenport, Carnegie Institution of Washington Alden B. Dawson, Harvard University S. R. Detwiler, College of Physicians and Surgeons,Columbia University Hugo Fricke, The Biological Laboratory Robert Gaunt, Washington Square College, New York University A. J. Grout, Newfane, Vt. Ross G. Harrison, Yale University Hans 0. Haterius, Wayne University, College of Medicine S.I. Kornhauser, University of Louisville Medical School Duncan A. Maclnnes, The Rockefeller Institute for Medical Research fHarold Mestre, Bard College Stuart Mudd, University of Pennsylvania, School of Medicine Hans Mueller, Massachusetts Institute of Technology J.S. Nicholas, Yale University W. J. V. Osterhout, The Rockefeller Institute for Medical Research Eric Ponder, The Biological Laboratory Asa A. Schaeffer, Temple University Herman T. Spieth, College of the City of New York 'Charles R. Stockard, Cornell University Medical College W. W. Swingle, Princeton University Ivon R. Taylor, Brown University Harold C. Urey, Columbia University H. -
Keith Roberts Porter: 1912–1997
Keith Roberts Porter: 1912–1997 eith Roberts Porter died on May 2, 1997, just over a month short of his 85th birthday. He had the K perspicacity, good fortune, and patience to take advantage of the fast moving frontier of analytical biology after the Second World War to provide many of the tech- niques and experimental approaches that established the new field of biomedical research now known as cell biol- ogy. He was renowned for taking the first electron micro- graph of an intact cell, but his contributions went far be- yond that seminal instance. They ranged from technical developments, such as the roller flask for cell culture and the Porter-Blum ultramicrotome, to experimental and ob- servational achievements, such as studies on the synthesis and assembly of collagen, on the role of coated vesicles in endocytosis, on lipid digestion in the intestine, and on the universality of the 9 1 2 axoneme in cilia. The initial ultra- structure descriptions of the endoplasmic reticulum and the sarcoplasmic reticulum, identification of the role of T-tubules in excitation–contraction coupling in muscle and the role of the cytoskeleton in cell transformation and shape change, were his, as were many other contributions, described in some detail elsewhere (Peachey and Brinkley, 1983; Moberg, 1996). Absent from this list are his early pi- oneering work establishing the androgenetic haploid in frogs, an exercise in nuclear transplantation with conse- quences for the recent cloning of mammals, and his later ad- ventures with pigment migration in fish chromatophores. In addition to his specific scientific contributions, Keith Porter also made more important philosophical contribu- tions to the field that he helped to shape. -
Biological Bulletin
Vol. 131, No. 1 August, 1966 THE BIOLOGICAL BULLETIN PUBLISHED BY THE MARINE BIOLOGICAL LABORATORY THE MARINE BIOLOGICAL LABORATORY SIXTY-EIGHTH REPORT, FOR THE YEAR 1965—SEVENTY-EIGHTH YEAR I. TRUSTEESAND EXECUTIVECOMMITTEE(AS OFAUGUST 14, 1965) 1 II. ACT OF INCORPORATION 4 III. BYLAWS OF THE CORPORATION 5 IV. REPORT OF THE Dnu@cToR 7 Addenda: 1. Memorials 9 2.The5taff 12 3. Investigators, Lalor and Grass Fellows, and Students 22 4. Fellowships and Scholarships 36 5. Training Programs 36 6. Tabular View of Attendance, 1961—1965 39 7. Institutions Represented 39 8. Evening Lectures 42 9. Evening Seminars 42 10. Members of the Corporation 44 V. REPORT OF THE LIBRARIAN 68 VI. REPORT OF THE TREASURER 69 I. TRUSTEES GERARD SWOPE, JR., Chairman of the Board of Trustees, 570 Lexington Avenue, New York 22, New York *ARTHUR K. PARPART, President of the Corporation, Princeton University *JAMES H. WICKERSHAM, Treasurer, 791 Park Avenue, New York 21, New York PHILIP B. ARMSTRONG, Director, State University of New York, College of Medicine at Syracuse ALEXANDER T. DAIGNAULT, Assistant Treasurer, 7 Hanover Street, New York 5, New York GEORGE W. DE VILLAFRANCA, Clerk of the Corporation, Smith College * Deceased. Copyright © 1966, by the Marine Biological Laboratory Library of Congress Card No. A38-518 2 MARINE BIOLOGICAL LABORATORY EMERITI WILLIAM R. AMBERSON, Marine Biological Laboratory C. LALORBURDICK,The Lalor Foundation C. LLOYD CLAFF, Randolph, Massachusetts *W. C. CURTIS,504 West Mount Avenue, Columbia, Missouri PAUL S. GALTSOFF, Woods Hole, Massachusetts *E. B. HARVEY, Woods Hole, Massachusetts M. H. JACOBS,University of Pennsylvania CHARLESW METZ,Woods Hole, Massachusetts CHARLES PACKARD, Woods Hole, Massachusetts A. -
Chemical Reactor Design
Chemical Reactor Design Youn-Woo Lee School of Chemical and Biological Engineering Seoul National University 155-741, 599 Gwanangro, Gwanak-gu, Seoul, Korea ywlee@snu. ac.kr http://sfpl. snu. ac. kr 第7章 化學反應裝置設計 Chemical Reactor Design Reaction Mechanisms , Pathways, Bioreactions and Bioreactors Seoul National University Objective Discuss the pseudo-steady-state-hypothesis and explain how it can be used to solve reaction engineering problems Write reaction pathways for complex reactions. Explain what an enzyme is and how it acts as a catalyst. Describe Michealis-Menten enzyme kinetics and rate law along with its temperature dependence. Discss h ow t o di stin gui sh th e diff er ent t ypes of enz yme inhibition. Discuss stages of cell growth and rate laws used to describe growth. Write material balances on cells, substrates, and products in bioreactors to size chemostats and plot concentration-time trajectoriesin batch reactors. Describe how physiologically-based pharmocokinetic models can be used to model alcohol metabolism. Seoul National University 7.1 Active Intermediates and Nonelementary Rate law • Elementary rate law - the reaction order of each species is identical with the stoichiometric coefficient of that species for the reaction as written n rA kC A • Non-elementary rate law - no direct correspondence between reaction order and stoichiometry 3 / 2 CH CHO CH + CO r kC 3 4 CH 3CHO CH 3CHO k C C 3/ 2 1 H 2 Br2 H2+Br+ Br2 2HBr rHBr CHBr k2CBr Seoul National University Non-elementary Reaction Non-elementary rate laws involve a number of elementary reactions and at least one active intermediate. -
Enzyme Kinetics at the Molecular Level∗
GENERAL ARTICLE Enzyme Kinetics at the Molecular Level∗ Arti Dua The celebrated Michaelis–Menten (MM) expression provides a fundamental relation between the rate of enzyme cataly- sis and substrate concentration. The validity of this classical expression is, however, restricted to macroscopic amounts of enzymes and substrates and, thus, to processes with negligi- ble fluctuations. Recent experiments have measured fluctu- ations in the catalytic rate to reveal that the MM equation, though valid for bulk amounts, is not obeyed at the molecu- Arti Dua is an Associate lar level. In this review, we show how new statistical measures Professor in the Indian of fluctuations in the catalytic rate identify a regime in which Institute of Technology Madras. She is a theoretical the MM equation is always violated. This regime, character- chemist, working in the area ized by temporal correlations between enzymatic turnovers, of stochastic reaction is absent for a single enzyme and is unobservably short in the dynamics and statistical classical limit. mechanics of complex fluids. 1. Classical Enzyme Kinetics Enzymes are biological catalysts that accelerate chemical reac- tions manyfold, without getting consumed in the catalytic pro- cess. Several biological processes involving the conversion of substrates to products, thus, rely crucially on the catalytic activity of enzymes. Specific enzymes control and regulate a wide range of life-sustaining processes that vary from digestion, metabolism, absorption, and blood clotting to reproduction. While specificity Keywords depends on the detailed chemical structure of enzyme proteins, Biological catalysts, enzymes, rate kinetics, stochastic enzyme the rate at which the enzymes carry out the catalytic conversion kinetics, Michaelis–Menten depends less on their chemical structure but more on the physical mechanism, enzymatic velocity, parameters, including the amounts of enzymes, substrates, tem- molecular noise.