Vol. 18 / No. 9 / October 2019

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY

Biochemistry OF A Burger Have you renewed your membership for 2020?

Together, we’ll continue to advocate for science, connect researchers around the world and build a bright future for biochemists and molecular biologists everywhere.

Learn more at www.asbmb.org/membership CONTENTS

NEWS FEATURES PERSPECTIVES 2 32 62 ASBMB ELECTS OFFICERS AND BIOCHEMISTRY OF A BURGER SERVICE BEYOND SCIENCE COUNCIL MEMBERS A professor among prisoners 40 4 UNDER THE SKIN AND OUT 65 MEMBER UPDATE IN THE WORLD ESSAY What I wish people understood 8 46 about being a trans scientist 12 young scientists win PROLAB awards MEET QI-QUN TANG 10 48 32 RETROSPECTIVE Wolfgang Karl Joklik (1926 – 2019) Q&A: SANDHYA VISWESWARIAH 14 NEW MEMBERS 16 First tooth controls where and when 48 the rest come in 18 JOURNAL NEWS 18 Peptides to the rescue 20 Researchers link new protein to Parkinson’s 21 JBC launches program for early-career scientists 40 22 Better samples, better science 24 JLR virtual issue sheds light on a key risk factor for heart disease ANNUAL MEETING 25 LIPID NEWS 54 Bacterial sphingolipids: HOW SCIENCE TOOK OVER THE TOWN AT THE TIP OF CALIFORNIA Perhaps not as rare as we thought? 58 26 SEARCHING FOR DRUGS ON THE OCEAN FLOOR FROM THE JOURNALS 31 A YEAR OF (BIO)CHEMICAL ELEMENTS For October, magnesium helps the leaves stay green

OCTOBER 2019 ASBMB TODAY 1 NEWS

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY ASBMB elects officers OFFICERS COUNCIL MEMBERS Gerald Hart Suzanne Barbour President Joan Broderick and council members Matt Gentry Toni M. Antalis Blake Hill President-elect Audrey Lamb Committees welcome new members, name new chairs Wei Yang James M. Ntambi Secretary Takita Felder Sumter Kelly Ten–Hagen By ASBMB Today Sta Joan Conaway JoAnn Trejo Treasurer ASBMB TODAY EDITORIAL EX-OFFICIO MEMBERS ADVISORY BOARD embers of the American co-chair of the 2016 ASBMB Annu- Robert S. Haltiwanger Rajini Rao Society for Biochemistry al Meeting. Yang is an investigator Carla Koehler Chair Co-chairs, 2020 Annual Ana Maria Barral Mand Molecular Biology have and section chief at the National Meeting Program Committee Natasha Brooks elected new o cers and council Institutes of Health, where her lab Kelly Chaćon Cheryl Bailey members, and the society’s commit- focuses on the structural characteri- Chair, Education and Beronda Montgomery Professional Development Bill Sullivan tees have appointed new members zation of proteins involved in DNA Committee Melissa Vaught Binks Wattenberg and leaders. mismatch repair and translesion Daniel Raben DNA synthesis. Chair, Meetings Committee ASBMB TODAY Sonia Flores Officers Angela Hopp Chair, Minority Aairs Executive Editor Toni Antalis is Council members Committee [email protected] serving for one year, ree members have joined the Nicole Woiowich Comfort Dorn starting in August, society’s governing council. eir Chair, Science Outreach and Managing Editor Communication Committee [email protected] as president-elect, three-year terms began in August. Terri Goss Kinzy Lisa Schnabel followed by two Chair, Public Aairs Graphic Designer Advisory Committee Antalis years as president Suzanne [email protected] Ed Eisenstein John Arnst and then one year Barbour, a past Chair, Membership Committee Science Writer as past-president. She previously member of the Susan Baserga [email protected] served two three-year terms as Education and Chair, Women in Biochemistry Laurel Oldach and Molecular Biology Science Writter ASBMB treasurer and chaired the Professional Committee [email protected] Publications Committee. Antalis Barbour Development Sandra Weller Ed Marklin Chair, Publications Web Editor is a professor of physiology at the Committee, is Committee [email protected] University of Maryland School of dean of the graduate school and Lila M. Gierasch Allison Frick Editor-in-chief, JBC Media Specialist Medicine, where she is also the a professor of biochemistry and A. L. Burlingame [email protected] associate director for training and biophysics and at the University Editor, MCP Barbara Gordon education and the director of the of North Carolina at Chapel Hill. Executive Director Nicholas O. Davidson [email protected] program in molecular medicine and Barbour also has served on the Editor-in-chief, JLR the graduate program in life scienc- Minority Aairs Committee. Kerry-Anne Rye Editor-in-chief, JLR es. Her lab’s research is focused on signaling mechanisms involved in Joan Broderick, For information on advertising, contact Pharmaceutical Media Inc. at 212-904-0374 or [email protected]. vascular disease and cancer. previously a member of the Nominating Wei Yang is serv- Committee, is a ing a three-year term, professor of chemistry also beginning in Broderick and biochemistry www.asbmb.org/asbmbtoday August, as secretary. at Montana State PRINT ISSN 2372-0409 She received the so- University. Her lab uses biochemical,

Articles published in ASBMB Today re ect solely the authors’ views and not Yang ciety’s Mildred Cohn spectroscopic and synthetic approaches the ocial positions of the American Society for Biochemistry and Molecular Award in Biological to elucidate detailed chemical Biology or the institutions with which the authors are aliated. Mentions of products or services are not endorsements. Chemistry in 2017 and served as mechanisms for metal catalysts.

2 ASBMB TODAY OCTOBER 2019 NEWS

Matthew Gentry, formerly chair of Celia Schi er of the University of Massachusetts the Public A airs Advisory Committee, is Medical School and Nicholas Tonks of Cold Spring a professor of molecular and cellular biol- Harbor Laboratory have been named to the Nominations ogy at the University of Kentucky College Committee. of Medicine. His lab studies the role of Terri Goss Kinzy of Western Michigan University

Gentry signal transduction machinery, namely has been named chair of the Public A airs Advisory phosphatases and E3 ubiquitin ligases, in Committee. Ronald Wek of Indiana University School of neurodegenerative disease and biofuels research. Medicine was appointed to the committee. Robert Haltiwanger of the University of Georgia, a Committees co-chair of the 2020 ASBMB Annual Meeting, was elect- Kevin Campbell of the University of Iowa College of ed to the Publications Committee. Medicine was appointed to the Awards Committee. Nicole Woitowich of Northwestern University was Christopher Heinen of the University of named chair of the Science Outreach and Communica- Connecticut School of Medicine, Margaret Kanipes tion Committee. John Tansey of Otterbein University, of North Carolina A&T State University and Saumya Christina Marvin of the University of Wisconsin–Madi- Ramanathan of Fisk University were named to the son and Amy J. Hawkins of University of Utah have been Education and Professional Development Committee. appointed to the committee. Edward Eisenstein of the University of Maryland, a Chad Park of the University of Arizona has been current member of the Membership Committee, has been named to the Student Chapters Committee as the south- named chair of that committee. He previously served on west regional director. the outreach committee. Peter Kennelly of Virginia Poly- Chad Slawson of the University of Kansas Medical technic Institute and State University, a past member of Center and Blanton S. Tolbert of Case Western Re- the Education and Professional Development Committee, serve University have been appointed to the Meetings has become past chair of the Membership Committee. Committee. Joseph Provost of the University of San Diego, also a past Vahe Bandarian of the University of Utah and Ruma member of the EPD, has been appointed to the Member- Banerjee of the University of Michigan Medical School ship Committee. have been named to the Minority A airs Committee.

ASBMB symposia program call for submissions

The ASBMB symposia program aims to provide niche segments of the scienti c community with opportunities to present unique, cutting-edge science and engage in active networking opportunities. Help advance your eld by planning an ASBMB symposium. Proposal deadline: Nov. 1 www.asbmb.org/SpecialSymposia/ Proposals/

OCTOBER 2019 ASBMB TODAY 3 MEMBER UPDATE

Member update

By ASBMB Today Sta

Hartl wins Janssen award Franz-Ulrich Hartl of the Max Planck Institute of and revealed how defects in this Biochemistry won the 2019 Dr. Paul Janssen Award process may contribute to a variety for Biomedical Research along with Arthur Horwich of disorders ranging from metabolic of Yale School of Medicine. to neurodegenerative diseases.” e pair, who were honored with the American e late Paul Janssen had a Hartl Society for Biochemistry and Molecular Biology’s hand in developing more than Tabor Research Award in 2013 and the Albert Lasker 80 medicines, four of which remain on the World Basic Medical Research Award in 2011, are known Health Organization’s list of essential drugs. Johnson around the world for their pioneering studies of the & Johnson established the award in his name in 2004. cell’s protein-folding machinery. ASBMB members who have won the Janssen award “Drs. Hartl and Horwich combined their in the past include Nobel laureate Yoshinori Ohsumi brilliant insights and elegant approaches to overturn (2016) and Emmanuelle Charpentier and Jennifer the dogma of their day about the process of protein Doudna (2014). folding,” David Julius of the University of California, Hartl was elected to the National Academy of San Francisco, chairman of the selection committee, Sciences in 2011 and is a member of the editorial board said in a statement. “eir studies revolutionized our for the Proceedings of the National Academy understanding of how proteins achieve their shape of Sciences.

Pew award for Zhang Sumter named dean at Winthrop Xin Zhang, an assistant professor Takita Felder Sumter, a professor of of chemistry and of biochemistry and chemistry at Winthrop University in molecular biology at Pennsylvania State South Carolina, assumed the role of dean University, has been chosen to join this of the College of Arts and Sciences in July. year’s class of Pew Biomedical Scholars. Sumter has taught at the university since Zhang e program, run by the Pew Sumter 2004; in 2017 she served as interim dean. Charitable Trust, provides four years of Sumter studies the chromatin binding funding for exploratory research by assistant professors. high-mobility group A1, or HmgA1, proteins, which are e aim is to support risky but potentially high-reward overexpressed in cancer. research inquiries. Sumter serves on the ASBMB’s governing council and Zhang’s lab studies protein misfolding and aggre- the National Science Foundation’s advisory committee gation during cellular stress, with special attention to for biology. Deeply committed to education and men- intrinsically disordered proteins that contain prionlike do- torship, she co-founded the ASBMB’s annual Interactive mains. His team visualizes these proteins using tags whose Mentoring Activities for Grantsmanship Enhancement, or uorescence indicates aggregation. e work could help IMAGE, grant writing workshop. She also contributes to in understanding of neurodegenerative disorders driven by biochemistry textbooks and has published on best practic- proteopathy, such as Huntington’s or Alzheimer’s disease. es in teaching chemistry and biochemistry. Zhang, a chemical biologist, earned a Ph.D. in “Takita is well respected by all who know and work chemistry at the California Institute of Technology and with her,” Winthrop University President Dan Mahony pursued postdoctoral research at Scripps Research. He has said. “She clearly made a positive impression on her col- been on the faculty at Penn State since 2015. leagues during her time as interim dean.”

4 ASBMB TODAY OCTOBER 2019 Diamandis wins Canadian service award Blanco concludes media fellowship Eleftherios P. Diamandis, head of Daniel Bastardo Blanco spent the clinical biochemistry at the Mount Sinai summer as an intern at Discover Maga- Hospital and University Health Network, zine through the American Association for has won the 2019 Canadian Academy the Advancement of Sciences’ mass media of Clinical Biochemistry Award for fellowship. Diamandis Outstanding Service to the Profession of Blanco e program allows undergraduate Clinical Biochemistry. and graduate students in science, engineer- e award was established in 1993 to recognize those ing, technology and math elds to spend 10 weeks learn- who have made “unique contributions in laboratory medi- ing the ropes of scientic communication in newsrooms cine and had a worldwide impact in clinical medicine.” Di- around the country. amandis, who also leads the clinical biochemistry division Blanco is a Ph.D. candidate in immunology at St. Ju- at the University of Toronto, conducts translational research de’s Children’s Research Hospital/University of Tennessee on cancer biomarkers using proteomics and genomics. Health Science Center. He was a 2019 ASBMB Hill Day Diamandis will be recognized in a citation read at the advocacy trainee. annual conference of the CACB. He also will receive a While interning at Discover, Blanco wrote about certicate and a $1,500 prize sponsored by Siemens Cana- probiotics, 3D printing spacecraft, climate change, the da, the principal Canadian subsidiary of the multinational microbiome and other topics. company Siemens.

Chewing gum project honored

Dan Dries of Juniata College presented an company, are distributed to the less fortunate. ASBMB Science Fair Award on May 10 to middle e three students of Huntingdon Area Middle school students Gracie Hobbs, McKensie Klauss and School in Huntingdon, Pennsylvania, wanted to Shaelyn McGinnis for their project Rinku Chewy, an appeal to their peers who, they noticed, often chew eco-friendly solution to disposing of used chewing gum. e team also wrote and produced an anime ad gum. to promote the product. When tasked with developing a project for their “It’s so cool to win something this big!” Shaelyn local science, technology, engineering and mathe- said of the award. matics fair, the team wanted to combine an ecologically respon- sible product with outreach to their community. Rinku Chewy is a homemade organic chewing gum that, when returned to the OF DAN DRIES COURTESY company, is repurposed as ller for shoe soles. ese shoes, pro- duced using the revenue of their

Pictured with their winning poster are, left to right, Huntingdon Area Middle School students Shaelyn McGinnis, McKensie Klauss and Gracie Hobbs.

OCTOBER 2019 ASBMB TODAY 5 MEMBER UPDATE

IN MEMORIAM

Henry Koffler John Tymoczko

Henry Kof er, president emeritus of the Univer- John Tymoczko, an emeritus professor at sity of Arizona, died March 10 at age 95. Carleton College in Northeld, Minnesota, died Kof er ed Nazi-occupied Austria in 1940, arriv- May 26 of a heart attack. ing in Arizona at age 17. He attended the University Tymoczko taught at Carleton for 39 years of Arizona, where he met fellow student Phyllis starting in 1976 and is remembered warmly by Piersen; they were married for 71 years. generations of students. Laura Pogemiller Caron, Trained in biochemistry at the University of a former student, wrote, “I think only John could Wisconsin, Kof er joined the faculty at Purdue make that intro material so engaging — and University, eventually becoming the head of the do it over and over. He really got a kick out of university’s division of biological sciences. His watching the lightbulb click every time a new award-winning microbiology research focused on class understood.” agella, structures important for bacterial motility. His teaching extended beyond the Carleton In one line of inquiry, Kof er and colleagues showed campus; along with Jeremy Berg and Gregory that agellar enzymes from thermophilic bacteria are Gatto, Tymoczko co-authored ve editions of the more heat-stable than agella from their less classic textbook “Biochemistry” by Lubert Stryer heat-resistant relatives. used by college students across the country. Beginning in 1975, Kof er took on increas- Berg called Tymoczko “a thoughtful scholar and ingly senior administrative roles at the University a very hard worker, always ready with a bad pun of Minnesota and the University of Massachusetts to lighten a discussion.” Amherst. He then served a nine-year term as pres- Tymoczko is survived by his wife, Alison ident of the University of Arizona, his alma mater. Unger, their son and daughter, and three Colleagues say his leadership was key to expand- grandchildren. ing the faculty, enabling technology transfer and establishing the University of Arizona’s reputation as a research university. Among Kof er’s many honors were recogni- tion as one of Purdue University’s Great Teachers, RETROSPECTIVES founding governorship in the American Academy of We invite you to honor a recently deceased Microbiology, fellowship in the American Association ASBMB member with a personal retrospective for the Advancement of Sciences and knighthood in article in ASBMB Today. For details, email France’s Ordre de Palmes Académiques. [email protected].

6 ASBMB TODAY OCTOBER 2019 Leonard A. Sauer

Leonard A. Sauer, who spent most of his career as a research physician at the Mary Imogene Bassett Hospital in Cooperstown, New York, died April 15. He was 89. Sauer attended high school in Schenectady, New York, but according to a published obituary, he is said to have skipped school often to play pool. He enlisted in the Army in 1948 and for almost four years was a member of the Signal Corps, which to this day manages communica- JLR VIRTUAL ISSUE tions and information systems. When his military service ended, Sauer Solving the enigma attended Cornell University and then earned his medical degree at the University of Rochester of the sphinx, one and his Ph.D. from the Rockefeller Institute in New York. He spent several years doing research sphingolipid at Yale University before joining Bassett in 1975. During his career at Bassett, a teaching at a time hospital now afliated with Columbia University, Sauer published upward of 70 papers on cancer www.jlr.org/site/collections/ metabolism pathways and other topics. He retired in 1996 and spent his later years sphingolipids/ y shing and woodworking at his home on the Bitterroot River in Montana, where he lived with his wife, Mimi, who survives him.

OCTOBER 2019 ASBMB TODAY 7 NEWS

12 young scientists win PROLAB awards

welve emerging scientists will receive grants this year for Biochemistry and Molecular Biology, and the from the Promoting Research Opportunities for International Union for Biochemistry and Molecular T Latin American Biochemists program to advance Biology have given 71 biochemists these travel awards. their research by working directly with collaborators in is year’s PROLAB travel grants are going to Ph.D. laboratories in the United States, Canada and Spain. students and postdoctoral fellows from Argentina, Brazil, Since 2012, the American Society for Biochemistry Chile, Mexico, Spain and Uruguay. All but one will work and Molecular Biology, the Pan-American Society in the United States.

e 2019 recipients are: Ferran Barrachina, a Ph.D. student that can only be answered with advanced experimental at the University of Barcelona in Spain, equipment,” Figueroa said. will go to the lab of Sylvie Breton, who is a liated with the Massachusetts General Ricardo Lima–Filho, a Ph.D. student Hospital and Harvard Medical School. at the Federal University of Rio de Janeiro Barrachina is studying the role of the in Brazil, will be hosted by the lab of Barrachina extracellular vesicles in epididymal sperm Bruce McEwen at the Rockefeller Univer- maturation and function. “is great opportunity will sity in New York. Lima–Filho studies the allow me to expand my knowledge in reproductive biology, Lima-Filho molecular mechanisms by which exercise learn a sophisticated variety of techniques, such as high-reso- regulates mood. “(R)esults from these lution microscopy, and interact with outstanding researchers experiments will extend the robustness and signicance and physicians,” Barrachina said. of our project and nourish an important collaboration to help unveil the eects of exercise-related molecules in the Laura Bonnet, a Ph.D. student at depressed brain,” Lima–Filho said. the National University of Córdoba in Spain, will spend time in the lab of Anna Carolina Oliveira, a Ph.D. student at Kashina at the University of Pennsyl- the University of the Republic in Uruguay, vania. Bonnet, who studies the role of will go to the lab of omas Kislinger Bonnet post-translational arginylation of proteins, at Princess Margaret Cancer Centre in said of her plans: “I hope this project sheds Toronto. Oliveira studies the role of the light on the neuronal role of Ate1 during the autophag- Oliveira noncoding RNA nc886 in prostate cancer ic degradation process. e identication of Ate1 as a progression. “I strongly believe that this regulator of this process in the central nervous system will is an excellent opportunity for me to learn about and open new avenues of investigation into the arginylated (apply) advanced proteomic techniques to a very active proteins involved in neuronal proteostasis regulation.” eld of noncoding RNA research,” Oliveira said. “Also, I will have the opportunity to share and discuss our results Alfredo Figueroa is a graduate and perspectives with scientists of one of the top cancer student at the Center for Scientic research centers in the world.” Research and Higher Education at Ensenada in Mexico. He will be spending María José Pascual is a graduate stu- time in the lab of Mary Munson at the dent at the National University of General Figueroa University of Massachusetts at Amherst San Martín in Buenos Aires, Argentina. to advance his studies of the C-terminus She will travel to the Stowers Institute of the protein Sec10 in exocyst assembly in the bread for Medical Research in Kansas City, mold Neurospora crassa. “is is a great chance to put Pascual Missouri, to advance her studies of how my graduate research to the test and answer questions dengue infection aects tRNA repertoire

8 ASBMB TODAY OCTOBER 2019 and mRNA stability of the host cell. Working in the lab new molecular biology techniques and to deeply under- of Ariel Bazzini “will be a completely dierent experience stand the nanosystem I am studying. Moreover, working compared to my present work in Argentina,” she said. “I with prestigious scientists will undoubtedly enrich my will be learning lots of new techniques and (have access career and knowledge on the subject.” to) facilities that will expand my horizons.” Juliana Vago, a postdoctoral research- Margarita Jacaranda Rosendo er at the Federal University of Minas Pineda, a Ph.D. student at the National Gerais in Brazil, will travel to La Jolla, Autonomous University of Mexico, will California, to work in Lindsey Miles’ lab work in the lab of Claudia Moreno at at Scripps Research. Vago studies the plas-

the University of Washington. In Mexico Vago minogen system and its role in the control City, Pineda studies the modulation and of inammatory/infectious diseases. “I Pineda localization of NMDA receptors during believe this is a great opportunity to improve my profes- mitosis. Spending time at the Seattle campus “is a great sional and personal skills,” she said. “I hope that the inter- opportunity for increasing my skills in electrophysiology action with prestigious scientists will enhance my network and super-resolution techniques,” she said. and allow me to further collaborate with them in the near future. Also, I hope to apply in my home institution what Felipe Campos Ribeiro, a Ph.D. I will learn and improve the quality of my work.” student at the Federal University of Rio de Janeiro, Brazil, will work in the lab Maira Rivera Valdés, a postdoctor- of Ottavio Arancio, a cellular neurobi- al researcher at the Pontical Catholic ologist at Columbia University. Ribeiro University of Chile, will spend time in the Ribeiro said he plans “to test if enhancement of lab of Elizabeth Komives at the University proteasome activity could hold therapeutic of California, San Diego. Rivera studies potential on Alzheimer’s disease models” during his stint Valdés KaiB, a cyanobacterial metamorphic pro- in New York. tein. “Dr. Komives’ lab has vast experience in the study of protein biophysics using mass spectrom- Paula Belen Salazar is a Ph.D. etry. Using this technique to analyze the refolding of the student at the Instituto Superior de circadian clock protein KaiB, I will obtain promising Investigaciones Biológicas in San Miguel results and also enrich my knowledge about this tech- de Tucumán, Argentina. She will work nique to implement it in our own instrument in Chile,” in Guillermo Altenberg’s lab at the Texas Rivera said. Salazar Tech University Health Sciences Center in Lubbock. Salazar studies inhibitors of the human enzyme acetylcholinesterase. Altenberg’s lab “has profound knowledge on membrane proteins,” Salazar said. “I’ll certainly learn state of the art biophysical techniques, which is quite exciting. Hopefully, the project will provide LEARN MORE important insights into the mechanism of inhibition of The ASBMB welcomes applications for PROLAB acetylcholinesterase by polyphenols.” scholarships from trainees and new investigators (not more than five years past postdoctoral work) from all Natalia Scilletta, a Ph.D. student at countries in the Pan-American Society for Biochemistry the Institute of Nanoscience and Nano- and Molecular Biology, including Spain and Portugal. technology in Argentina, will work in the The awards o set the costs of travel and living expenses lab of Ali Khademhosseini at the Uni- for one to six months up to a maximum of $5,000. versity of California, Los Angeles. “I will The deadline for 2020 applications is May 1. Scilletta study the biological processes that occur in eukaryotic cells while growing on the For more information, go to ASBMB.org/pabmb. biomaterial coating I am developing,” she said of her plans in L.A. “In this way, this experience will allow me to learn

OCTOBER 2019 ASBMB TODAY 9 RETROSPECTIVE

Wolfgang Karl Joklik (1926 – 2019) By Jack D. Keene, Charles E. Samuel & John J. Skehel DUKE UNIVERSITY

Bill Joklik was recruited in 1968 to the Duke University School of Medicine as professor and chairman of the department of microbiology and immunology.

Wolfgang Karl “Bill” Joklik, a molecular virolo- Sydney. His initial research training was in enzymology, gist who pioneered numerous contributions to science studying the hydrogenase from Escherichia coli. He then and our understanding of Poxviridae and Reoviri- attended the Sir William Dunn School of Pathology at dae, died July 7. Oxford, U.K., as an Australian National University schol- Bill Joklik’s research addressed fundamental ar to study virology using the T1 and T2 bacteriophages problems of virus replication by investigating mech- under the mentoring of Sir Paul Fildes. While working anisms of expression of viral genetic information, the toward his Doctor of Philosophy from Oxford, he pub- function of virus-encoded proteins, host responses to lished several seminal papers, among them “ e In uence infection and the actions of anti-virals. Bill was a of Cortisone on Cell Division,” co-authored with Howard superb mentor, a generous contributor and an out- W. Florey, who won a Nobel Prize for the development of standing leader both within his profession and in the penicillin. wider community. Bill did postdoctoral work in Herman Kalckar’s laboratory at the University of Copenhagen. He and Paul Early years and education Berg, later a Nobel laureate, discovered and characterized Wolfgang Joklik was born Nov. 16, 1926, in Vi- nucleoside diphosphokinase. Bill returned to Australia in enna, Austria, where he received his initial schooling. 1953 as a member of the department of microbiology at When he was 11, his family moved to Sydney, Australia. the John Curtin School for Medical Research in Can-  ere, he and his younger brother Günther assumed the berra, where he remained until 1962.  ere he initiated English nicknames Bill and Frank, and the two attended studies of animal viruses with Frank Fenner and others, Cranbrook School. Bill earned his Bachelor of Science focusing on laboratory models of smallpox virus, myxoma with  rst class honors in 1947 and his Master of Science virus and vaccinia virus, and making novel discoveries on in biochemistry in 1948, both from the University of the reactivation of heat-inactivated poxviruses.

10 ASBMB TODAY OCTOBER 2019 Research in the U.S. recognized department at Duke with strength across mi- During a sabbatical with Harry Eagle, a leader in the crobiology and immunology, increasing the faculty from development of dened cell culture media at the National 6 to 33. He also was a co-founder of the Duke Compre- Institutes of Health, Bill developed the Joklik modica- hensive Cancer Center in 1971 and founder and rst tion of Eagle’s minimum essential medium, which permit- president of the American Society for Virology in 1982. ted the growth of cells in suspension culture and purica- He served on numerous administrative and advisory tion of viruses. Upon returning to Australia in 1962, he committees in academic institutions and governmental devised methodologies for the purication of poxviruses agencies both nationally and internationally. that set the stage for his subsequent molecular studies. Bill was a leader at the journal Virology for 30 years Within a year, Eagle recruited Bill back to the U.S. to as an associate editor, editor and nally as editor-in-chief work at the Albert Einstein College of Medicine, so Bill from 1976 to 1994. He was an associate editor of the and his family moved to New York, where he joined the Journal of Biological Chemistry from 1978 to 1988 and department of cell biology at Einstein as an associate pro- editor-in-chief of Microbiological Reviews from 1991 fessor. In 1965, he became the Siegfried Ullman professor to 1995. of cell biology. Highly regarded as a dedicated teacher and mentor, Bill’s laboratory carried out innovative studies on Bill was a popular lecturer in both graduate and medical poxvirus multiplication that led to landmark discoveries, student courses at Duke. He trained nearly 100 graduate largely using vaccinia and rabbitpox virus. ese studies students and postdoctoral fellows in his research labora- included work on the temporal regulation of poxvirus tory, many of whom went on to successful independent mRNA expression, early and late; the formation of careers. He was the editor of multiple editions of polyribosomes containing viral RNA; the characterization of the replication and coating of poxvirus DNA; and the characterization of poxvirus enzymes and proteins synthesized during infection. Using vaccinia virus, Bill also studied the biochemical mechanism of the anti-viral action of interferon. Bill was recruited in 1968 to the Duke University School of Medicine as professor and chairman of the department of microbiology and immunology. He became DUKE UNIVERSITY James B. Duke professor of microbiology in 1972, a posi- tion he held until becoming professor emeritus in 1996. While Bill’s interest in poxviruses continued at Duke, he increasingly focused on reovirus research initiated at Einstein. Among his lab’s innovative ndings in both loca- tions were characterization of the reovirus segmented dou- ble-stranded RNA genome and its transcripts, identica- tion and characterization of reovirion proteins and viral nonstructural proteins produced in infected cells, and elu- cidation of the functions of reovirus proteins during virus replication. Bill applied new technologies to his studies of reoviruses, including the molecular cloning of viral RNAs, the sequencing of viral RNAs and cDNA clones, and the isolation and characterization of hybridomas producing monoclonal antibodies against viral proteins.

Service and leadership While at Duke, Bill Joklik’s research increasingly Bill was an extraordinary leader. He built a nationally focused on reovirus.

OCTOBER 2019 ASBMB TODAY 11 RETROSPECTIVE

“Zinsser’s Microbiology,” for several years a leading text- book for medical students. Bill was elected to the National Academy of Sciences in 1981 and the Institute of Medicine of the NAS in DUKE UNIVERSITY 1982. He received the Senior U.S. Investigator Humboldt Prize in 1986, the International Chemical and Nuclear Pharmaceutical Corporation International Prize in Vi- rology in 1991 and a Lifetime Achievement Award from Duke University in 2013.

Sports and lebensfreude Bill was equally adept with a tennis racket in either his left or right hand. He enjoyed a round of golf and was a dedicated fan of Duke basketball but also followed cricket on the radio and television. He greatly enjoyed travel throughout his life both for science and for pleasure. He said he was “equally at home in two cultures,” Austrian/ German and British/American, and he maintained an interest in global politics. e impact of Bill Joklik as a scholar and as a leader is immense. He had a wonderful career and life that the three of us and many others are honored to have observed and shared.

On the web e Duke University Medical Alumni Association produced a video about Bill Joklik in 2013 when Bill Joklik was a longtime member of the American Society for they honored him with the William G. Anlyan Lifetime Biochemistry and Molecular Biology and an associate editor of the Journal Achievement Award. To see the video, go to of Biological Chemistry from 1978 to 1988. asbmb.org/asbmbtoday.

CRANBROOK ACADEMY Jack D. Keene ([email protected]) is the James B. Duke professor of molecular genetics and microbiology at the Duke University School of Medicine.

Charles E. Samuel ([email protected]) is a research professor, C. A. Storke professor, and distinguished professor emeritus at the University of California, Santa Barbara. The Joklik brothers, Bill and Frank, are pictured with their mother,Tom AugustHelene, talks with Johns Hopkins colleague Yadong Wei at his apartment in in 1943, when both boys were students at Cranbrook Academy.Baltimore, Bill, born about a monthJohn before J. Skehel his death.([email protected]) August kept working ison an his emeritus latest scientist at the Francis Crick Institute, London, and former director of the in 1926, was elected to the National Academy of Sciences andvaccine Frank, development projectNational until Institute the very for end.Medical When Research, he could Mill no longerHill, London. go to born in 1928, was elected to the National Academy of Engineeringhis lab, at Wei would stop by the apartment a few times each week. approximately the same time. Frank presented a eulogy at Bill’s funeral.

A12 ASBMB ASBMB TODAY TODAY OCTOBER 2019 CALL FOR SUBMISSIONS The wellness issue — January 2020 DEADLINE EXTENDED: OCT. 28 What keeps you well? Exercise? Sleep? Faith? Family? Pets? Something else? Tell us about what works for you and/or your wellness challenges. For information, email [email protected] or go to asbmb.org/asbmbtoday and click SUBMIT.

Upcoming ASBMB events and deadlines

1 ASBMB degree-program accreditation deadline 6–11 Mental Illness Awareness Week 7 Art of Science Communication fall course begins 11 National Depression Screening Day 15 Deadline for priority-consideration abstracts for 2020 annual meeting 20–24 ASBMB–BSC Symposium on the Interplay Between Epigenetic Regulation and Genome Integrity OCTOBER 24–27 Emerging Roles in Nucleolus symposium 25–26 Student Chapters northwest regional meeting

1 Proposals for 2021 symposia due 3 Student Chapters northeast regional meeting 14 Deadline for abstracts for 2020 annual meeting 16 Student Chapters Outreach Grant deadline 18–24 U.S. Antibiotic Awareness Week 20 Student Chapters renewal deadline NOVEMBER 27 Deadline for 2020 annual meeting travel award applications

2–8 National Influenza Vaccination Week 5 ASBMB–Deuel Conference on Lipids early registration deadline DECEMBER

OCTOBER 2019 ASBMB TODAY 13 NEW MEMBERS

Olubu Adiji, Vardhan Dikshit, Spartan Jeff Jaureguy, California State Frank Menke, University of North Texas Health Sciences University University San Marcos The Sainsbury Laboratory

Yiwei Ai, Salyl Dobhal, Spartan Health Fei Jiang, Benjamin Minor, Johns Hopkins University Sciences University College of William and Mary Mercer University School of Medicine Andrew Alpert, PolyLC Inc. Gregory Doloresco Arlen Johnson, University of Texas at Austin Jeanine Nasser, Mia Antinone, Destiny Dozier, College Northeastern University West Virginia University of William and Mary Margaret Kanipes, North Carolina A&T Bao Nguyen V., Takeshi Bamba, Riley Drexler, State University Plymouth State University Kyushu University Calyxo Biosystems Kylan Kelley, Linh Nguyen, Brian Barth, University Ian Dubery, University College of William and Mary Colorado State University of New Hampshire of Johannesburg Allison Kellner, Thu Nguyen, University John Beale, St. Louis Margaret Dunlap, Colorado State University of Illinois at Chicago College of Pharmacy Boston University School of Medicine Julia Kim, Jerry O’Dweyer, Babatunde Bello, Whitehead Institute College of William and Mary Georgia State University Mason Duran, University of Delaware Eric Klein, Rutgers Stephanie Olivier Van Agnes Berki, University–Camden Stichelen, Medical College Caldwell University Nadire Duru, of Wisconsin University of Maryland Josh Knight, Berry College Grant Blouse, Ryan Otto, University Catalyst Biosciences Katie Fike, Virginia Tech Darcey Kobs, of Texas Southwestern Houston Baptist University Medical Center Lauren Boutz, Amanda Garner, Arizona State University University of Michigan Josh Kraus, Virginia Tech Vipin Paliwal, Milwaukee School of Engineering Amber Bowman, College Anjelika Gasilina, Georgetown Florika Krushnan, Spartan of William and Mary University/National Institutes Health Sciences University Arvind PG, Spartan Health of Health/National Cancer Sciences University Shelby Bradford, Institute Ashok Kumar, New York West Virginia University Medical College Quinn Poyneer, Emma Gergel, College Towson University Carson Bryant, of William and Mary Spencer Leibow, Yale University College of William and Mary Tatiana Prioleau, Evan Goodell, College College of William and Mary Anne Carlson, of William and Mary Xinhao Li, University of Pittsburgh College of William and Mary Yi Qi, Shenheng Guan, College of William and Mary Brittany Carpenter, Van University of Waterloo Kostana Ligori, Andel Research Institute Wayne State University Rajeshree Raut, Spartan Anyonya Guntur, Health Sciences University Joshua Chandler, Maine Medical Center Manish Lokande, Spartan Plymouth State University Research Institute Health Sciences University Eric Reits, University of Amsterdam Godfrey Chukwuemeka, Mayssa Hachem, David Lukac, Rutgers Michael Okpara University Amity University Dubai University; New Jersey Garrett Riggleman, of Agriculture Umudike Medical School West Virginia University Olivia Hage, Pennsylvania School of Medicine Aedin Culhane, Dana–Farber State University Miguel Macias, University Cancer Institute, Harvard of California, Davis Rozi Rubina Parveen, Spartan School of Public Health Arne Holmgren, Health Sciences University Karolinska Institute Roshan Madhavan, Spartan Christian Cunningham, Health Sciences University Johannes Schlondorff, Genentech Inc. Jonathan Hosler, Beth Israel Deaconess University of Mississippi Carly Martin, Medical Center/Harvard Chiemeka David Arize, Medical Center Wayne State University Medical School Spartan Health Sciences University Yuji Imaizumi, Nagoya City Francesca Massi, James Scoles, University, Graduate School University of Massachusetts Viterbo University Dominic Del Re, of Pharmaceutical Sciences Medical School Rutgers University Sanjana Sen, University Matthew Jackson, Mason McCool, of California, Irvine Ingrid Dijkgraaf, Hill’s Pet Nutrition Yale University Maastricht University Science and Technology

14 ASBMB TODAY OCTOBER 2019 NEWS

Preksha Shah, Spartan Kacie Waiters, Health Sciences University University of Houston

Ashirwad Shriwastava, Pei Wang, Icahn School Lipoprotein (a): Many Spartan Health Sciences of Medicine at Mount Sinai University strides made, yet there is Timothy Wiles, University Carolina Silva, of Colorado Skaggs a long road ahead College of William and Mary School of Pharmacy and Pharmaceutical Sciences Kushagra Singh, Spartan Health Sciences University Minhang Xu, JLR VIRTUAL ISSUE College of William and Mary Amit Thakaran, Spartan jlr.org/site/collections/lpa/ Health Sciences University Snehal Yadav, Spartan Health Sciences University Ankit Thapa, Spartan Health Sciences University Weimin Yu, School of Pharmaceutical Sciences, Douglas Trach, Chonqqing University Towson University Qunying Yuan, Lindsay Turner, Alabama A&M University University of Mississippi Medical Center

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OCTOBER 2019 ASBMB TODAY 15 NEWS

First tooth controls where and when the rest come in By Karen Bascom

hether it’s a baby human, baby Bowdoin College in Maine studying dow passed, they were able to induce zebrash or anything else with tooth formation in these tiny sh. the growth of a 4V1 –like tooth, Wteeth, those rst pearly whites “It’s more di cult to study which was followed by 3V1 and form in an orderly fashion. ey development in mammals because 5V1, all in their regular locations. start with a single tooth, followed by they take so much longer to devel- In another experiment, they used its immediate neighbors, then their op,” Gibert said. “However, zebrash retinoic acid, a chemical signal used neighbors, creating neat streets grow from an embryo to free-feeding in growth and development, to make of teeth. larva in ve days.” a 4V1 tooth form in an area of the is timing of teeth wasn’t lost Zebrash embryos start to grow throat where it doesn’t usually grow. on A. Gordon Edmund, a paleontol- their rst tooth, called 4V1 for its e neighbors soon followed. ogist at the Royal Ontario Museum, place along a row that sits in the “Our results show that by mod- who in 1960 proposed an idea as to eventual sh’s throat, about 48 hours ifying the formation of the initiator why: that the rst tooth controls the post-fertilization. Its neighbors, 3V1 tooth it is possible to control the process by sending a message along and 5V1, begin to form in the fol- formation of a dental row,” the jaw that stimulates the formation lowing hours. To determine if 4V1 is Gibert said. of the other teeth. responsible for the creation of the In terms of the actual signal that Fifty-nine years later, a team of other teeth, Gibert and his collabora- the initiator tooth used, Gibert and scientists demonstrated how this ear- tors designed a series of experiments team showed that 4V1 produces a ly tooth guides the rest of the dental that altered that rst tooth’s timing, broblast growth factor, or FGF, formation process. Published in location and biochemistry. another chemical signal used for the Proceedings of the Royal Society First, they used a chemical growth and wound repair, during B on June 12, the paper’s lead author to block 4V1 from forming and the time that 3V1 and 5V1 form. is Yann Gibert, associate professor observed that 3V1 and 5V1 didn’t By blocking the embryo’s ability to of cell and molecular biology at the form either. However, even after the make FGF after 4V1 had formed, University of Mississippi tooth’s normal developmental win- they were able to stop the subsequent Medical Center. teeth from developing. “In just about every species, Lacking the molecular tools development of the dental row starts available today, “Edmund based his with a single tooth or pair of teeth, idea of a signal coming from the and that tooth initiates a wave of tooth on anatomy and histology new teeth proximally and distally,” alone,” Gibert said. “We expected to said Gibert, who joined UMMC and show that this rst tooth was both the Cancer Institute and Research necessary and su cient for the other

Center in 2018. WILLIAM JACKMAN, BOWDOIN COLLEGE teeth to form but didn’t think we In his research, Gibert uses would fully show that FGF is the zebrash primarily to study new likely transmitter.” therapeutics for cancer and meta- “e fundamental question bolic diseases such as diabetes and behind this research is ‘How do teeth obesity. He also has a longstanding Zebrafish teeth (labeled with a green get organized into rows’”? said study collaboration with colleagues at the fluorescent protein) along the pharyngeal jaw co-author William Jackman, an asso- University of Lyon in France and about five days post-fertilization. ciate professor of biology at Bowdoin

16 ASBMB TODAY OCTOBER 2019 College who studies organ formation UMMC in animals. “ere’s this develop- mental clockwork that is instructing the cells to make teeth in a particular place, and we’re trying to understand the mechanism behind that.” Jackman said that even though animal teeth display a great diversity in their number, size and ability to regenerate, teeth and their row pat- terning have been present in animals for hundreds of millions of years. “If a system works, evolution will keep it around,” Gibert said. e same is true for other aspects of anat- omy, physiology and biochemistry. “If you look at a zebrash pancreas, you will see the same molecular and cellular mechanisms as a mammal pancreas.” is tendency of distantly related species to share traits makes mod- el organisms useful in biomedical Yann Gibert, associate professor of cell and molecular biology at the University of Mississippi Medical research, whether it be studies aimed Center, uses zebrafish to study disease and development. at treating cancer or tooth loss. “Tooth development in shes and reptiles is very e cient. ink for ways to regrow teeth, using they would be a billionaire,” Gibert of sharks, who can replace teeth techniques including gum line-de- said. “is is just step one.” continually throughout their lives,” rived cells and lasers. After all, he said, “It took 59 Gibert said. But over the course of “What do we need to have in years to conrm Edmund’s idea. evolutionary time, “humans and terms of genetic instruction in order at’s how science works.” most other mammals lost the ability to create new human teeth?” Gibert DOI: 10.1098/rspb.2019.0401 to regenerate teeth.” said. He laid out a scenario where is article was originally According to the Centers for scientists could run experiments us- published on umc.edu. Disease Control and Prevention, ing dental pulp-derived stem cells to only half of adults aged 20 to 64 test in vitro models of tooth regener- Karen Bascom have a full set of non-wisdom, ation, testing molecular switches that ([email protected]) is a health science permanent teeth. Dental implants are analogous to the genes that allow research editor–writer in are made of ceramics and metal, teeth to form in our nned friends. the Ofce of Institutional Advancement, University and they break. Scientists at oth- “If someone could gure out a of Mississippi Medical er universities are already looking way to regenerate teeth in humans, Center.

OCTOBER 2019 ASBMB TODAY 17 JOURNAL NEWS

Peptides to the rescue

By Martin J. Spiering

nsulin and glucagon are well- venting or managing type 2 diabetes, known peptide hormones that in which beta-cell apoptosis may Ikeep our glucose levels within a contribute to insu cient pancreatic healthy range. But they are only part insulin production. of a complex network that controls Yazhou Li and Daniel Drucker concentrations of this ubiquitous at Toronto General Hospital in On- sugar in blood and tissues. Oth- tario, Canada, along with colleagues, er molecules regulate glucose by exposed wild-type and GLP-1R– controlling insulin secretion from knockout mice to the compound the pancreas or protecting pancreatic streptozotocin, which induces be- RESEARCH INSTITUTE LUNENFELD–TANENBAUM beta cells against stresses that lead to ta-cell death, in the presence and ab- dysfunction or cell death. sence of the specic GLP-1R agonist One of these protective regu- exendin-4. e authors then assessed lators is glucagonlike peptide 1, or the eect of the GLP-1R stimulation GLP-1. It’s 30 amino acids long and on glucose tolerance, blood and pan- Daniel Drucker is the senior author on a seminal is produced in specialized epithelial creatic insulin levels, and pancreatic 2003 Journal of Biological Chemistry paper that cells of the intestine called L cells cell viability and proliferation. showed that GLP-1R signaling protects beta and also in the brain and other To nd out what spurred this cells from cell death. organs and tissues. seminal paper and learn more about GLP-1 belongs to a group of its ndings, JBC reached out to peptides that mediate the incretin Drucker, now at the Lunenfeld– discoveries. First, pharmacological eect, an endocrine response to Tanenbaum Research Institute, Mt. activation of the GLP-1R with glucose arising from food digestion Sinai Hospital, in Toronto. exendin-4 reduced beta-cell death in the intestines. is response helps that had been produced by experi- regulate food intake and the fate of What prompted your investigation? mental pancreatic injury in mice. We dietary glucose. Specically, GLP- In particular, what was unknown noted that this reduction in beta-cell 1, which is released when food is about GLP-1 and GLP-1R and their apoptosis is associated with preserva- ingested, binds to and activates the effects on beta-cell viability, and tion of beta-cell function and glucose GLP-1 receptor, or GLP-1R, what motivated you to study these homeostasis in the mice. a G protein–coupled receptor on questions? Second, we found that basal many cell types, including beta cells GLP-1 had previously been GLP-1R signaling is physiologically in which GLP-1R signaling stimu- shown to expand beta-cell mass by essential for beta-cell survival, as the lates insulin synthesis and secretion. stimulating beta-cell proliferation. We GLP-1R knockout mice exhibited e incretin eect stimulates insulin wondered whether GLP-1 might also enhanced beta-cell injury when chal- secretion from pancreatic beta cells contribute to the control of beta-cell lenged with streptozotocin. more strongly than exposure to mass by reducing cell death. We were ird, we saw that GLP-1’s an- glucose alone. also aware that cell survival pathways ti-apoptotic activities are direct, and A 2003 article published in the were activated by cAMP, an import- we, that is, our collaborator Philippe Journal of Biological Chemistry ant downstream messenger that is Halban, could also demonstrate added to our understanding of the increased by GLP-1R activation. them ex vivo in puried rat beta incretin eect by showing that GLP- cells exposed to cytotoxic cytokines, 1R signaling protects beta cells from What were your main findings? a model of tissue inammation. cell death. is is signicant for pre- We made several interesting We also discovered that GLP-1’s

18 ASBMB TODAY OCTOBER 2019 anti-apoptotic properties are not increase heighten the risk for relevance of GLP-1 has expanded unique to beta cells and can be con- uncontrolled cell growth/cancer? tremendously since 2003. GLP-1R ferred to heterologous cells transfect-  is has always been a theoretical agonists are approved for treating ed with the gene encoding GLP-1R. concern, but there’s no evidence that patients with diabetes or obesity and would support it.  e  rst GLP-1R under investigation for nonalcohol- Why did you use exendin-4 rather agonist (exenatide, the common ic steatohepatitis and neurological than GLP-1 to stimulate GLP-1R? drug name for exendin-4, used in disorders. We continue to explore We used exendin-4 because it’s diabetes management) was approved the mechanisms underlying GLP-1 a highly stable, degradation-resis- for clinical use as an anti-diabetic action in numerous cells and tissues. tant GLP-1R agonist that is more medication in April 2005. After 14 In 2002, only 196 published studies biologically potent in animals and years of clinical use, with multiple of GLP-1 were listed in PubMed. In humans than GLP-1. It was also the drugs and millions of patients taking 2018 alone, there were 1,461, and lead GLP-1R agonist in clinical trials the medication, we have not seen an the  eld continues to grow. and became the  rst GLP-1 drug ap- increase in cancer rates due to exen- proved for management of diabetes. atide or GLP-1R agonist use. What was the impact of your paper on the fi eld of diabetes and clinical Does repeated exendin-4 Is GLP-1 the major incretin research in general? stimulation downregulate the hormone, or does it have some  is is a little di cult to appre- receptor as is sometimes the case overlapping functions with other ciate.  e paper has been widely with repeated receptor stimulation? incretins, and do other incretin cited (author’s note: at this writing, it In most tissues, there is little hormones also promote beta-cell has been cited 712 times in Google evidence that continuous GLP-1R mass? Scholar), and it was one of the  rst activation by agonists downregulates Both GLP-1 and another pep- studies to highlight a cytoprotective this receptor.  is fortuitous  nding tide, gastric inhibitory polypeptide, role and not just an insulin-secretory enables the development of long-act- or GIP, are important naturally role for GLP-1. ing GLP-1R agonists for managing occurring incretin hormones. GIP is It’s also noteworthy that GLP-1 diabetes and obesity. likely the more important incretin has recently shown some promise in under physiological conditions. And clinical trials investigating its ther- As your JBC paper has shown, yes, most peptide ligands that, like apeutic role in human neurodegen- the GLP-1R stimulation prevents GLP-1, increase cAMP levels in B erative disorders such as Parkinson’s beta-cell apoptosis and increases cells — such as pituitary adenylate disease and continues to be explored pancreatic islet mass. Could this cyclase–activating polypeptide, for therapeutic intervention in GIP, and fatty acids — also reduce Alzheimer’s disease. So the concept beta-cell apoptosis. that GLP-1 might generally protect vulnerable cells continues to have Were your fi ndings expected, and high clinical relevance. how has your own work and the Drucker and Li’s paper was nomi- fi eld progressed since your paper’s nated as a JBC Classic by JBC Associ- publication? ate Editor Eric Fearon at the Univer- Before our study, I don’t think sity of Michigan Medical School.  is anyone had clearly addressed the article originally appeared in JBC. It question of whether GLP-1R sig- has been edited for ASBMB Today.

SWEDBERG ET AL./JBC naling can inhibit beta-cell death. Read more JBC Classics at jbc.org. Since our JBC publication, GLP-1R

signaling has been shown to reduce Martin J. Spiering cell death in many cell types, from ([email protected]) The small peptide GLP-1 (green ribbon) binds is the technical editor at beta cells to neurons to endothelial the Journal of Biological to and activates the GLP-1R (gray, red and blue cells and cardiomyocytes. Chemistry. Follow him structure) on beta cells and thereby protects As for the  eld, research into on Twitter @spieringmj. them against injury and death. both the basic science and clinical

OCTOBER 2019 ASBMB TODAY 19 JOURNAL NEWS

Researchers link new protein to Parkinson’s

By Laurel Oldach

esearchers in Japan are report- This image of cells with ing new insight into how the damaged mitochondria shows overlap, in yellow, between RParkinson’s disease-associated ET AL./JBC 2019 KOYANO protein parkin selects its targets. e parkin protein in green and the nding might improve experimental mitochondria, shown in red. therapies for Parkinson’s that aim to boost parkin activity. Cells depend on parkin to help get rid of damaged mitochondria. e research, published in the Journal of Biological Chemistry, suggests that parkin depends on other proteins, including one called MITOL that has not been linked previously to Par- kinson’s disease, to direct it to those damaged mitochondria. Parkin adds a degradation tag ing protein with ubiquitin — even addition of more ubiquitins. In most called ubiquitin to proteins on the a bacterial protein not ordinarily cases, the researchers found, this seed mitochondrial surface. In some found in the cell — as long ubiquitin is added by a protein called patients with familial Parkinson’s as it’s present at the surface of MITOL, which had not been linked disease, parkin activity is disrupted the mitochondria. previously to Parkinson’s. and bad mitochondria cannot be “Parkin is not regulated by its e research could contribute to destroyed. Harmful byproducts substrate specicity,” Koyano said the design of new drugs, some from those bad mitochondria can of the nding. Instead, control of of which aim to boost parkin damage neurons. By understanding parkin activity comes from how it activity to slow the advance of how parkin works and what goes is recruited and activated by other Parkinson’s disease. wrong when it’s mutated, researchers proteins. “If we achieve upregulation of hope also to help patients with other e discovery that activated seed ubiquitylation on mitochon- forms of Parkinson’s disease. parkin is not terribly selective led dria,” Koyano said, “it might accel- While other ubiquitin-tagging Koyano and her colleagues to take erate parkin recruitment and parkin proteins, known as E3 ligases, rec- a closer look at parkin’s recruitment activation to eliminate damaged ognize specic amino acid sequences and activation. Some details of that mitochondria more e ciently.” on their substrates, parkin has many process are well known; for example, DOI: 10.1074/jbc.RA118.006302 known substrates that don’t seem to a protein called PINK1 is known to share a sequence in common. While boost parkin activity. But Koyano

studying how parkin chooses its and colleagues discovered a new step Laurel Oldach substrates, researchers led by Fumika that must happen before PINK1 can ([email protected]) is a science writer for the Koyano in Noriyuki Matsuda’s lab contribute to parkin activation. ey ASBMB. Follow her on at the Tokyo Metropolitan Institute found that parkin acts more rapidly Twitter @LaurelOld. of Medical Science discovered that when a rst ubiquitin molecule is al- parkin can tag any lysine-contain- ready present, acting as a seed for the

20 ASBMB TODAY OCTOBER 2019 JOURNAL NEWS

JBC launches program for early-career scientists Postdocs and new investigators invited to participate in peer review By Angela Hopp

he Journal of Biological Chemistry has launched it should be published or needs more work. Supple- a program designed to involve scientists at early mentary evaluations by early-career reviewers will be Tstages of their careers in peer review. assessed by associate editors, who will work with the  e JBC Early-Career Reviewer Board o ers post- early-career reviewers to hone their recommendations doctoral researchers and newly independent investiga- for authors. tors a structured path for developing peer-review skills “By getting feedback on the clarity of their written and learning about the scholarly publishing process. reports and advice on the level of detail and emphasis In addition, editors said, the program promises to in critiques, the ECRs will gain valuable information diversify the community of peer reviewers and make about how to constructively participate in the publish- use of untapped scienti c expertise. ing process,” Gierasch wrote. “Peer review is the cornerstone of the trust [scien- She emphasized that the initiative will provide tists] place in each other,” JBC Editor-in-Chief Lila emerging scientists with valuable training and provide Gierasch of the University of Massachusetts Amherst the journal with fresh and diverse perspectives: “We wrote in a recent editorial. When a research group anticipate that some of our ECRs will go on to serve submits a paper to the JBC, an associate editor shep- as full editorial board members, further establishing herds it through the review process. Historically, the their credentials as experts in the  eld.” associate editor has recruited professors from the jour- Learn more at jbc.org/site/ecr. nal’s editorial board and, if needed, external specialists to provide expert evaluations of the  ndings. Angela Hopp ([email protected]) is the Now associate editors have the option of adding ASBMB’s communications director and executive editor of ASBMB Today. Follow her an early-career reviewer to that roster of reviewers. on Twitter @angelahopp. All of them will work together to assess the scienti c approaches, results and conclusions of each manu- script submitted to the JBC to determine whether

VIRTUAL ISSUE Antibiotic activities and mechanisms of resistance

jpc.org/site/vi/antibiotic_resistance

OCTOBER 2019 ASBMB TODAY 21

C

B A JOURNAL NEWS

Better samples, better science Study explores integrity of research specimens By Richard Harth

ective diagnosis and treatment properly handled is the rst step in zero in the quest for dependable of disease draw on painstaking careful research that meets the neces- science, yet researchers hoping to Eresearch, which often relies on sary high standards of reliability and publish their work may have a dis- biological samples. e avalanche of reproducibility. e new test, which incentive to spend the time to probe studies used to better understand ill- relies on accurate measurement of the integrity of their specimens. nesses and design eective therapies the relative proportions of two forms Should they uncover a problem, it cost billions of dollars and potential- of the protein albumin present in may throw their data into question ly aects millions of lives. blood, recently was described in and preclude publication—a serious So it would seem reasonable to the journal Molecular & Cellular setback, with little for the researcher assume that the reliability of bio- Proteomics. to show for it. ere is a danger of logical samples, on which accurate an ignorance-is-bliss mentality. results depend, would be of par- Houston, we have a problem Addressing the problem requires amount concern for the scientic e immediacy of the issue of two things, Borges noted. First, a community. sample quality became apparent regulatory body such as the NIH According to Chad Borges, a to Borges during his own research, needs to issue strict guidelines that researcher in the Biodesign Insti- which involved experiments on bio- include detailed documentation tute’s Virginia G. Piper Center for logical samples slated for distribution of sample history and handling. Personalized Diagnostics at Arizona by the National Institutes of Health. Some scientic journals do require State University, that assumption is “We got a little suspicious that documentation of specimen storage often wrong. something wasn’t quite right about conditions prior to publication, but “One of the major reasons that the sample set,” he said. Borges ap- such records are often inadequate there are so many discoveries of plied the newly designed test to the for ensuring a high level of sample biomarkers in the literature but so samples, with surprising results. “Lo integrity. Secondly, researchers need few positive validations that con- and behold, there was a major dier- reliable methods for testing their rm those ndings is the fact that ence between the cases and controls samples to ensure they meet exacting in many cases, during the discov- for this specimen integrity marker.” standards. e technique described ery, samples were used that have a Borges found that the freezer in the current study is an important history or an integrity that’s simply in which the control samples were advance in this direction. unknown.” stored had lost power for several Biological samples can be sus- days during a natural disaster. “at QC for blood ceptible to changes over time, which information is really important with e new biomarker sets cuto often occur when they are removed regard to the quality of the samples values for blood plasma and serum, from deep refrigeration. Degrad- and the stability of the markers that allowing researchers easily to assess ed samples can produce spurious were in them.” the quality of samples and their results in research. To address these e implications of this discrep- suitability for given experiments, concerns, Borges and his colleagues ancy plainly went beyond his own even if a detailed record of sample have designed a sensitive test that research. “Who knows how many handling and storage is unavailable. can be used to establish the integrity other markers are dierentiated For the rst time, plasma and serum of blood plasma and serum, the most simply because of the way in which —the most commonly used biospec- common biosamples used in medical the cases and controls were handled,” imens for medical research — can be research. Borges said. tracked with a reliable biomarker. Ensuring such samples have been Biological samples are ground e biomarker, which relies on

22 ASBMB TODAY OCTOBER 2019 JOURNAL NEWS

relative proportions of two isoforms the biomarker acts as a kind of a project sponsored by the Defense of albumin, requires only a low molecular stopwatch that can gauge Advanced Research Projects Agen- volume of plasma or serum and min- precisely the elapsed time a particular cy, which uses epigenetic markers imal sample preparation. (Dierent sample has remained in a thawed in blood to identify exposure to isoforms of this protein are func- state. weapons of mass destruction or tionally similar, but an oxygen-in- e biomarker described is inex- their precursor chemicals. e new duced modication that occurs to pensive, easy and rapid to use, and biomarker will be used to ensure the an abnormal extent outside of the can be fully automated, making it a quality of blood samples, further body is used to identify mishandled strong candidate to serve as the new establishing the power and versatility samples.) gold standard for plasma and serum of this approach. Albumin is the most abundant analysis. It is capable of detecting DOI:10.1047/mcp.TIR119.001659 protein in blood plasma and serum, biospecimen exposure to room constituting roughly half of all protein temperature conditions for as little is article originally was content in these biouids. Outside as two hours, quickly and accurately published on biodesign.asu.edu. It has the body, the natural unmodied identifying mishandled or poorly been edited for ASBMB Today. form of albumin becomes oxidized stored samples and preventing their with time. is can be detected by inclusion in clinical research. Richard Harth observing a change in protein mass In addition to more conventional ([email protected]) is a senior science writer using mass spectrometry. clinical research, the new biomarker for the Biodesign Institute By describing a chemical rate law is poised to make inroads in a variety at Arizona State University. for this protein oxidation reaction of health-related investigations. It that takes place in plasma and serum, recently has been incorporated into

OCTOBER 2019 ASBMB TODAY 23 JOURNAL NEWS

JLR virtual issue sheds light on a key risk factor for heart disease

By Jonathan Grin

ecause lipids such as cholesterol

and triglycerides are hydropho- LUCIANA GIONO Bbic and tend to clump up, rather than dissolve, in water, they need help getting around inside the body. Lipoproteins are complex assemblies with hydrophilic outer shells that package hydrophobic lipids in their core, allowing them to hitch a ride through the bloodstream. ese delivery particles play an important role in the absorption of dietary lip- ids from the small intestine and also transport lipids to and from the liver. High levels of one particular class of lipoprotein, known as lipoprotein (a), are associated with atherosclero- sis, inammation and thrombosis, but no treatments are available in the clinic that specically lower Lp(a), and much of what governs Lp(a) The cover of the JLR virtual issue depicts the Lp(a) particle assembly is still unknown. following the steps of a walking path, getting bigger as the road A new virtual issue from the stretches into infinity. Journal of Lipid Research titled “Lipoprotein (a): Many strides made, yet there is a long road ahead” alirocumab — an inhibitor of the cardiovascular disease. explores the past, present and future lipid-binding enzyme PCSK9 — Another review, penned by status of Lp(a) research and show- could lower Lp(a) levels regardless of George anassoulis at McGill cases researchers pushing this eld the isoform of proteins in Lp(a). University, describes the association forward. is issue was assembled by A study by Frederick Raal and of Lp(a) with aortic valve disease JLR Junior Associate Editor Gissette an international team of researchers and outlines steps toward developing Reyes-Soer from Columbia Univer- suggests that another PCSK9 inhibi- much-needed preventive and thera- sity Irving Medical Center in New tor, evolocumab, reduces Lp(a) levels peutic strategies. York City. partly by increasing the expression of Several papers collected in this LDL receptors.

issue oer insights into how various Elisa Waldmann and Klaus Jonathan Grif n Lp(a)-reducing drugs work. In one Parhofer at Ludwig Maximilian (jonmgrifn93@gmail. of these studies, Enkhmaa Byambaa University of Munich wrote a review com) is a freelance science writer. and colleagues at the University of that discusses apheresis as an eective Follow him on Twitter California, Davis, and the University method of selectively clearing Lp(a) @spelledjon. of Hong Kong demonstrated that from the blood and reducing risk of

24 ASBMB TODAY OCTOBER 2019 LIPID NEWS

Bacterial sphingolipids: Perhaps not as rare as we thought?

By Eric A. Klein

mong the ways cells adapt to uronosyl-ceramide glycosphingo- changes in their environment, lipid, or GSL. Ceramide-based Aregulation of the lipidome is GSLs are ubiquitous in eukaryotic critical for maintaining cellular in- organisms, but in bacteria they had tegrity. Species that lack temperature been observed previously only in the OF ENERGY/WIKIMEDIA COMMONS U.S. DEPARTMENT homeostasis adapt by modulating Sphingomonadaceae family, where acyl chain saturation to resist changes they function as a substitute for out- in membrane uidity. Bacteria such er-membrane lipopolysaccharides, or Eric Klein’s lab showed that the Gram-negative as Escherichia coli desaturate their LPS. Unlike Sphingomonas species, aquatic bacterium Caulobacter crescentus fatty acids as temperatures decrease; C. crescentus produces LPS even synthesizes a novel glycosphingolipid when the double bonds formed by acyl during phosphate starvation; phosphates in its environment are limited. chain desaturation introduce kinks in this organism, the GSLs appear in the fatty acids that inhibit lipid to play a role in resistance to equivalent proteins cannot be iden- packing and increase membrane phage-mediated killing. tied by sequence homology or (2) uidity to counteract the eects of Now that we know that bac- bacterial ceramide synthesis evolved lower temperature. terial GSLs are not limited to just independently using novel enzymes Temperature is not the only en- the Sphingomonadaceae, just how and/or synthetic pathways. If the vironmental variable that necessitates widespread are these lipid species? genes required for ceramide synthesis membrane remodeling. In many e honest answer is that we simply are identied, researchers will be able settings, nutrient availability can vary don’t know. While the lipidomes of to take a bioinformatic approach to widely. For example, nutrient levels many bacteria have been character- nding additional species that might in fresh-water lakes uctuate with ized, our ndings in C. crescentus produce these lipids. the seasons, and plant decomposition demonstrate that lipid abundance A growing body of work demon- aects soil. In particular, oscillations can vary with growth conditions. strates that bacterially produced in phosphate concentration can limit Indeed, previous characterizations in sphingolipids may play an important bacterial growth. rich growth media did not identify role in aspects of human health such When phosphates are limited, GSLs in C. crescentus. as gut homeostasis and oral pathol- the synthesis of membrane phospho- Another major challenge is that, ogy. Uncovering the mechanism of lipids becomes an obvious challenge. unlike for eukaryotes, we do not prokaryotic ceramide synthesis will Studies have shown that alphapro- know which enzymes are responsible help determine how widespread teobacteria, such as Agrobacterium for ceramide synthesis in prokary- these lipids are in bacteria and also tumefaciens and Mesorhizobium otes. Only the enzyme that catalyzes may provide a novel route for phar- loti, adapt to phosphate starvation the rst step of ceramide synthesis, macological intervention. by increasing production of diacyl- serine palmitoyltransferase, has clear glycerol-based glyceroglycolipids and homologues in bacteria as described Eric A. Klein (ek525@ ornithine lipids. in a recent review by Dominic Cam- camden.rutgers.edu) is In our lab, we recently showed popiano and colleagues. is implies an assistant professor in the biology department that the Gram-negative aquatic that either (1) bacteria carry out the and the Center for bacterium Caulobacter crescentus same synthetic chemistry as eukary- Computational and Integrative Biology at responds to phosphate limitation otes, but these enzymes diverged Rutgers University– by synthesizing a novel hexosyl-hex- so long ago that the functionally Camden.

OCTOBER 2019 ASBMB TODAY 25 JOURNAL NEWS

From the journals

By Gelareh Abulwerdi, Jonathan Grin & Elizabeth Stivison

Cholesterol transport conformation to neurodegeneration Specically, proteins derived from disruption in Alzheimer’s has not been characterized. Jessica species of Clostridales and Bacteroi- Scientists know that cholesterol Froula of the University of Alabama dales decreased, while proteins from plays a role in Alzheimer’s disease, at Birmingham and an international Lactobacillales increased. However, but that role is not fully understood. team produced monomers, beta- they did not see this metaproteomic In a recent study in the Journal sheet oligomers and bril fragments change when they looked at species of Lipid Research, Cinzia Marchi of alpha-syn and injected them number by fecal microbial analysis. of the University of Parma and into mouse striatum. ey found is shows that fecal metaproteomics colleagues in Italy describe another that while beta-sheet oligomers is a promising tool for identifying piece of the cholesterol–Alzheimer’s exhibited some toxicity, bril biomarkers to predict the risk of puzzle. fragments produced Parkinson’s- DIO after exposure to high-fat diet. With a growing body of work like phenotypes, driving inclusion DOI: 10.1074/mcp.RA119.001623 linking disruption of cholesterol formation, loss of dopamine neurons homeostasis to Alzheimer’s disease, and motor-behavior defects. ese New models for the study Marchi’s team asked specically results, published in the Journal of of sarcoma treatments whether eux of high-density Biological Chemistry, point toward e genes encoding the lipoproteinlike particles is disrupt- alpha-syn brils as a potential target RNA-binding proteins FUS and ed in Alzheimer’s. ey examined for Parkinson’s disease treatment. EWSR1 are prone to chromosomal the cerebrospinal uid, or CSF, of DOI: 10.1074/jbc.RA119.007743 translocation events that produce Alzheimer’s patients, non-Alzheimer’s proteins that underpin liposarco- dementia patients and healthy con- Microbiota and obesity ma and Ewing’s sarcoma. Jeremy trol subjects, measuring the ability Obesity and related conditions Ryan and a team of researchers at of the CSF to promote cholesterol such as heart disease and type 2 Washington University and the eux through membrane trans- diabetes are major public health University of Pennsylvania report porters. In the Alzheimer’s patients’ problems, generating an estimated new yeast models that overexpress CSF, cholesterol eux capacity $147 billion in medical costs annual- the aberrantly fused proteins and was reduced dramatically; this was ly in the United States. Diet-induced replicate the toxicity and aggregation not true in the healthy controls or obesity, or DIO, is a form of obesity patterns seen in sarcoma patients. In non-Alzheimer’s dementia patients. with a nongenetic cause. Hao Tran their study published in the Jour- Future research may shed light on at Georgia State University and col- nal of Biological Chemistry, the the intricacies of the causal role of leagues in Georgia and California set researchers used the models to show cholesterol homeostasis in Alzhei- out to identify biomarkers indicating that engineered potentiated Hsp104 mer’s disease progression. proneness to DIO in gut microbiota, proteins suppress the toxicity of the DOI: 10.1194/jlr.P091033 the diverse community of microor- chromosomal translocations. e ganisms that inhabit the gastrointes- authors suggest that the yeast models Refining the culprits tinal tract. could be useful platforms for study- behind Parkinson’s In their recent paper in the jour- ing both the underlying mechanisms Amyloid inclusions primarily nal Molecular & Cellular Proteom- of and treatments for sarcoma. composed of alpha-synuclein ics, the researchers looked at correla- DOI: 10.1074/jbc.RA119.009494 protein, or alpha-syn, are a hallmark tion between microbial species and of Parkinson’s disease. Dierent protein abundance. After feeding a New role for the farnesoid species of alpha-syn exist, but high-fat diet to mice, they saw a shift X receptor in adipocytes the relative contribution of each in the mice’s feces metaproteome. e farnesoid X receptor, or

26 ASBMB TODAY OCTOBER 2019 The role of ECM proteins in heart regeneration

The extracellular matrix provides a cell with mechani- the number of ECM proteins. In comparison with older cal and structural support and plays a role in biochemical methods, this ECM protein isolation retains the integrity of signaling to neighboring cells. The ECM is composed of ECM to provide a more robust panel of change. To identify proteins including collagens, proteoglycans and glyco- changes in ECM proteins, the researchers decellular- proteins (brillin and bronectin). These ECM proteins ized zebrash ventricles at seven, 14 and 30 days after play a role in tissue regeneration, the process by which amputation and analyzed the proteins with liquid chroma- injured tissue is restored to nearly normal function. In tography-mass spectrometry, or LC-MS. The largest ECM adult mammals, there is limited recovery of heart tissue protein prole changes between intact and amputated after injury that results in a brotic scar, which may lead to hearts occurred after seven days. Several ECM proteins — reduced heart performance. Therefore, studying regenera- such as brinogen a, b and g; bronectin 1b; and periostin tive processes to design medicinal strategies is important. b — increased after seven days, while levels of collagens Nonmammalian vertebrates such as zebrash can recover and brillin 2b decreased. large portions of their hearts after amputation, so studying A biomechanical property of ECM is its stiffness, cardiomyocyte regeneration in zebra sh can help re- which plays a role in cell proliferation, differentiation and searchers design regenerative strategies for cardiovascular regulation. Using atomic force microscopy, the research- disease, a leading cause of death in humans. ers evaluated changes in zebrash heart stiffness during Anna Garcia–Puig at the Center of Regenerative regeneration. They saw a signicant decrease in ventricular Medicine in Barcelona and colleagues in Spain studied ECM stiffness after seven days, which returned to normal the genomic and proteomic changes in ECM during heart by 14 days. These data support the LC-MS ndings that regeneration in zebrash. In a recent paper in the journal showed collagen was reduced after seven days; collagen Molecular & Cellular Proteomics, they describe a novel concentration contributes to stiff myocardium. method of decellularization of amputated adult zebraf- DOI: 10.1074/mcp.RA118.001193 ish ventricles, using a detergent treatment to increase — Gelareh Abulwerdi

This image shows the plasma membrane with extracellular matrix components. The ECM helps maintain the integrity of COURTESY OF LAUREN WINES COURTESY the cell and plays a role in cellular communication and regeneration of organs.

OCTOBER 2019 ASBMB TODAY 27 JOURNAL NEWS

FXR, is a nuclear receptor activated and metastatic tumor growth in a in Alzheimer’s disease, undergoes by bile acids. However, research has TRAP1-dependent fashion. liquid-liquid phase separation, shown that its eects go beyond DOI: 10.1074/jbc.AC119.008656 or LLPS, but the mechanism by the intestine. FXR is moderate- which this happens remains mostly ly expressed in adipocytes, and a A model system to study unknown. In a study in the Journal new study in the Journal of Lipid heart development of Biological Chemistry, Solo- Research digs into what it might be In cell signaling, information miia Boyko and colleagues at Case doing there. from the exterior of the cell is trans- Western Reserve University used Tim van Zutphen of the Uni- mitted to the interior. e Notch polyethylene glycol to induce tau versity of Groningen and colleagues signaling pathway, one of the many LLPS and characterized the resulting in Europe and the U.S. showed that signaling pathways in a cell, is con- droplets with uorescence recovery when human FXR is expressed in served in many cell types and has an after photobleaching. e authors mouse adipocytes, a number of met- important role in the development of report that tau LLPS is driven largely abolic disease–relevant phenotypes organs such as the heart. by electrostatic interactions and does appear, from whole-body insulin Notch signaling plays a role in not require phosphorylation. is in- resistance to increased adipocyte size the development of heart chambers sight provides a foundation to better to ectopic fat deposition. Metabolic and valves, and alterations in Notch understand how post-translational disease is increasingly common in signaling can lead to cardiac disease. modications could inuence tau modern society, and understanding Early in the development of heart LLPS in both normal and patholog- its biology is essential to nding tissue, the heart tube is formed ical states. treatments. is study gives new through outer epithelial myocardi- DOI: 10.1074/jbc.AC119.009198 insight into the complex web of in- um and the inner endocardial layer. teractions in metabolic diseases such Proper signaling between endocar- Defining the birth as diabetes. dium and myocardium is crucial for of ribosomes DOI: 10.1194/jlr.M094508 the development of heart structures. Ribosome assembly is a complex Studying the signaling mecha- process that determines the rate of An unexpected metabolic nism involved can help researchers protein synthesis. Although pre- target in cancer understand cardiac diseases and nd cursor ribosomal particles, known A dependence on glycolysis over therapeutic interventions. as preribosomal complexes, have oxidative phosphorylation is thought In a recent paper in the journal been detected in eukaryotes, their to be a hallmark of cancer cells, but Molecular & Cellular Proteomics, assembly remains poorly understood. recent work has demonstrated mito- Rebeca Torregrosa–Carrion of the Danysh Abetov and an international chondria still are functioning in most Centro Nacional de Investigaciones team of researchers present a new cancers. In a report in the Journal of Cardiovasculares Carlos III and method to isolate and characterize Biological Chemistry, Ekta Agarwal colleagues in the U.S. and Spain preribosomes in mammalian cells. and colleagues provide new evidence manipulated Notch activity in mouse By optimizing nuclear lysis con- for the reliance of cancer cells on mi- embryonic endocardial cells fol- ditions, the authors preserved the tochondrial oxidative phosphoryla- lowed by mass spectrometry–based complexes and characterized them tion. Using multiple techniques and proteomics to study Notch-depen- with mass spectrometry and North- cancer cell lines, the team showed dent embryonic factors secreted by ern blotting-based rRNA detection. that two oncogenic proteins, c-Myc heart endocardium involved in heart ey identied two new types of and N-Myc, control the expression development and disease. preribosomes and found that their of the mitochondrial chaperone DOI: 10.1074/mcp.RA119.001492 formation was nutrient-dependent, TRAP1. Moreover, they found that elucidating a critical step in the Myc-mediated regulation enabled Bringing Alzheimer’s- process of ribosome assembly. e oxidative bioenergetics through path- associated proteins together results were published in the Journal ways that, when shut down within Recent reports indicate that tau of Biological Chemistry. an organism, suppressed primary protein, which forms aggregates DOI: 10.1074/jbc.AC119.008378

28 ASBMB TODAY OCTOBER 2019 Whipping an acid into shape improves biofuel production

With fossil fuel shortages and carbon dioxide emis- pH, creating an acidic environment that slows ADO activity. sions, alternative energy sources are increasingly import- Juthamas Jaroensuk and Pattarawan Intasian of the Vidy- ant. Biofuels converted from waste products like fat-rich asirimedhi Institute of Science and Technology and col- feedstock are one alternative source, but their production leagues aimed to increase alkane production by converting is not yet ef cient enough to meet the demands of many formic acid into something more useful for ADO activity. countries. Researchers in Thailand report in the Journal of Through bioinformatics analysis, the researchers found Biological Chemistry that the enzyme formate dehydroge- that the enzyme FDH from the bacteria Xanthobacter sp. nase, or FDH, can signi cantly boost bacterial production 91 potentially could bene t ADO activity in two ways. Their of alkanes, which can be used as fuel for transportation, analysis showed that FDH can remove excess formate by cooking and material synthesis. oxidizing it into carbon dioxide. This conversion also results Using synthetic biology approaches, researchers had in the generation of NADPH, which ADO uses to convert previously designed a metabolic pathway that converts aldehydes into alkanes. The authors found that insert- fatty acids into alkanes in bacteria. The yield of alkane ing the gene for FDH into an alkane-producing pathway from this pathway is about 35%, however, which is quite expressed in Escherichia coli brought cellular pH closer to low. One reason is the limited activity of the enzyme neutral and increased concentrations of NADPH. Cells ex- aldehyde-deformylating oxygenase, or ADO, which carries pressing FDH reached conversion yields of 50%, the best out the  nal step of the process — the conversion of fatty yield yet for alkane production by whole-cell bioconversion. aldehydes into alkanes with formic acid as a byproduct. DOI: 10.1074/jbc.RA119.008246 If produced in excess, formic acid can decrease cellular — Jonathan Grif n JAROENSUK ET AL.

A metabolic pathway refi ned for enhanced alkane production: Enzymes and proteins associated with alkane production, formic acid elimination and detoxifi cation of reactive oxygen species are shown in green, blue and red, respectively.

OCTOBER 2019 ASBMB TODAY 29 JOURNAL NEWS

New tools to study sphingolipid metabolism

Sphingolipid metabolism is essential to many cellular targeted these enzymes to the inner plasma membrane, processes, and this becomes obvious when defects con- nucleus, mitochondria, endoplasmic reticulum, Golgi and tribute to diseases that range from developmental disor- cytoplasm of HeLa cells and analyzed the lipids produced ders to cancer. In a recent paper in the Journal of Lipid in each case. Research, Wataru Sakamoto of Stony Brook University and The researchers found that SMase expression consis- colleagues in New York and Japan describe new tools for tently increases ceramides in the cell, but the type of cera- the study of sphingolipid metabolism. mide produced varies based on the organelle. For example, Ceramides are a family of related lipids, and the SMase in the plasma membrane acted on long-chain sphin- researchers’ work is framed by what they call the “many gomyelin but not on very long-chain, while SMase in the ceramides” hypothesis that the biological activity of each endoplasmic reticulum acted on both. They also showed ceramide is determined by its localization, which is in turn that CDase expression alone does not change ceramide determined by the localization of enzymes that metabolize levels but does so in conjunction with SMase expression, ceramides. Sakamoto’s team investigated this hypothesis which warrants further investigation. by developing a system to target sphingomyelinase, or This work sheds light on the compartment-speci c SMase, which converts sphingomyelin into ceramides, and effects of sphingolipid metabolism and provides new tools ceramidase, or CDase, which degrades ceramides into that can be used for future studies. free fatty acids, to different compartments in the cell. They DOI: 10.1194/jlr.M094722 — Elizabeth Stivison

New tools created by Wataru Sakamoto and colleagues

SAKAMOTO ET AL./JLR target sphingomyelinase and ceramidase to specifi c cellular compartments.

Gelareh Abulwerdi Jonathan Grif n Elizabeth Stivison ([email protected]) (jonmgrif n93@gmail. ([email protected]) is a Ph.D. candidate at the com) is a freelance science is a Ph.D. student at University of Maryland, writer. Follow him on Twitter Columbia University studying Baltimore. Follow her on @spelledjon. mechanisms of DNA repair. Twitter @gelareh_science.

30 ASBMB TODAY OCTOBER 2019 A YEAR OF (BIO)CHEMICAL ELEMENTS For October, magnesium helps the leaves stay green

By Quira Zeidan

e mark the 150th anniversary carbon nucleus. Supernova explo- of Dimitri Mendeleev’s periodic sions disperse magnesium into space, Wtable of chemical elements this where it falls onto the surface of JYNTO/WIKIMEDIA COMMONS year by highlighting elements with planets, and into the interstellar me- fundamental roles in biochemistry and dium, where it’s recycled into other molecular biology. So far, we’ve covered star systems. hydrogen, iron, sodium, potassium, On Earth, magnesium is the chlorine, copper, calcium, phospho- fourth most common element after rus, carbon, nitrogen, oxygen and iron, oxygen and silicon. It is the manganese. eighth most abundant element in October is the month for peak the Earth’s crust, where it forms large fall foliage in states across the north- mineral deposits of magnesite, do- MAGNESIUM ern and central U.S. Leaves turn lomite and other rocks. Magnesium yellow, orange and red as chlorophyll salts easily dissolve in water, making — the photosynthetic pigment that oceans and rivers the most abun- The chemical structure of chlorophyll shows gives plants their green color — dant source of biologically available a magnesium ion in green sequestered at the breaks down due to limited sunlight magnesium. center of a porphyrin ring, which is attached to and cooler temperatures. Chloro- In vertebrates, magnesium is the a long hydrocarbon tail. phyll consists of a porphyrin ring — fourth most common metal ion and a molecule made of carbon, nitrogen the second most abundant intracel- regulates processes like neurotrans- and hydrogen — attached to a long lular cation after potassium. Protein mitter release and muscle contraction hydrocarbon tail. At the center of transporters that carry magnesium and relaxation. Magnesium bound the porphyrin ring, a magnesium ion across biological membranes must to protein plays a structural role as stabilizes the chlorophyll molecule recognize the cation’s large hydra- part of the protein’s conformation and transfers electrons down an tion shell and deliver the naked ion. or a regulatory role by activating or electron transport chain to drive the Examples of magnesium trans- inhibiting enzyme activity. Magne- photosynthetic process. porters are the XntAp protein in sium within mitochondria a ects Magnesium — with symbol the freshwater ciliate Paramecium, the enzymes of energy metabolism Mg and atomic number 12 — is the MgtA and MgtB system in the and the process of programmed a reactive alkaline earth metal that pathogenic bacteria Salmonella, and cell death, or apoptosis. And in the readily can lose two electrons to form the SLC41A1 carrier in the plasma nucleus, most of the magnesium is a cation with charge +2. In nature, membrane of mammals. associated with nucleic acids and free it occurs mostly in compounds with Inside the cell, magnesium can nucleotides, neutralizing the negative other elements such as carbon, sul- be found in the cytosol or stored charge of phosphate groups. fate, oxygen and chlorine. in intracellular compartments. +2 Magnesium is the ninth most Free cytosolic Mg alters the cell’s Quira Zeidan abundant element in the known electrical properties by regulating the ([email protected]) is universe. It is produced in large function of voltage-dependent Ca+2 the ASBMB’s education and public outreach coordinator. + stars when helium fuses with neon and K channels.  is has import- Follow her on Twitter or in supernovas when three atoms ant consequences in excitable cells @quirazeidan. of helium fuse sequentially with a such as neurons and muscles, and it

OCTOBER 2019 ASBMB TODAY 31 FEATURE Biochemistry OF ABurger Impossible Foods does science, makes food and tries to change the world By Laurel Oldach

n what has become a journalistic cliché, “ ey’re not targeting the vegan or I took my boyfriend, a vegetarian for the vegetarian consumer,” Welch said. “ ey’re past 10 years, to our local greasy spoon to targeting the meat eater who is being more try out an Impossible Burger. conscious about their decision.” I He didn’t care for it. Impossible Foods’ second claim to fame He had lost his taste for ground beef is its scienti c approach to imitating meat, and found the experience of a plant-based, which relies on reductionist biochemistry and completely vegan yet beefy-tasting burger less an unusually sourced key ingredient.  is it than appealing. I, on the other hand, was a owes to its founder, Pat Brown, a biochemist fan; his burger tasted better to me than my and former Stanford University professor own, which was made the old-fashioned way, with a long history of shaking things up. with beef. “We were approaching (meat) the same People like me are exactly the people Im- way you might approach  guring out the possible Burger is targeting: millennials who entire system for replicating genes,” Brown eat meat sometimes but fret about its impacts said during an interview in June. “Basically, on a crowded, warming world. start looking at what are all the possible com- David Welch is the director of science ponents that could be players … and then and technology at the Good Food Institute, deconstruct and reconstitute the biochemical a think tank promoting the burgeoning system.” plant-based meat industry. He said one of the reasons Impossible Foods and its strongest Market and mission competitor, Beyond Meat, have garnered so  e world eats a lot of beef: 57 pounds much interest from investors is their average per person per year in the U.S., with con- customer. sumption increasing worldwide. Because

32 ASBMB TODAY OCTOBER 2019 cattle are the least e cient livestock animal make a killing if they are the rst mover to Impossible at converting feed into edible meat, environ- replace animals in food production technolo- Foods mentalists have argued for years that reducing gy,” he said in 2017. “at was stupid.” beef consumption is an important conserva- When the food industry didn’t bite and approached tion act. a workshop he organized at the National meat “the Brown, who has been vegetarian for Academies resulted in no discernible policy same way you decades, says that those arguments have not change, Brown decided to do it himself. been eective, even when made by parties as “I was not a savvy business person, but might approach inuential as the Chinese government. “at I had the very good fortune of living in the figuring out the experiment has been done,” he told an audi- epicenter of venture capital,” he said. e ence of microbiologists during the American funding may have had less to do with Brown’s entire system Society for Microbiology’s keynote lecture in physical proximity to the venture capital for replicating June, which he delivered wearing a “no cows” rms of San Francisco than his track record genes.” T-shirt. “You don’t solve the problem by of disrupting scientic elds (see box on page asking people to change their diets.” 34: A research career). —Pat Brown Brown frames the problem instead as Early on, Brown hired mostly biochem- relying on an outdated technology — namely ists, many from his professional circles at the cow — for beef production. He wants to solve the problem by making meat imitations so appealing that they’ll outcompete what he calls the legacy industry. Impossible Foods explicitly states that its mission is to eliminate all animals from the food production system by 2035.

Staffing with scientists Becoming a CEO wasn’t in Brown’s orig- inal plan. Compared with being a professor, he thought a job in business would be dull. He rst set out to eradicate animal agricul- ture while on sabbatical from Stanford in 2009 and thought he could do it by persuad- ing someone else to take on disrupting the industry. He anticipated that an established food producer would adopt the meat-alternative idea as enthusiastically as he had. “I went KATZ MARTY around to food industry conferences and gave Pat Brown, CEO of Impossible Foods, pictured in 2009. a spiel to the eect that someone’s going to

OCTOBER 2019 ASBMB TODAY 33 FEATURE

A research career

Before launching Impossible Foods, Pat professor at Stanford, where he would remain Brown was already well known for a 30-year on the faculty for 25 years. The scienti c work career in research and scienti c activism. he’s most famous for in that time is devel- Now, he’s so famous as an entrepreneur that oping the DNA microarray, a technique that news articles sometimes mention that  rst originally was envisioned for genetic mapping life — during which he established the  eld but became popular as the  rst method to of functional genomics and started rolling measure changes to a whole transcriptome. a rock that’s now an avalanche of open-ac- To interpret the data on regulation of cess publication in the life sciences — as an thousands of genes produced by a microar- afterthought. ray, Brown and his team hoped to mine the According to his colleagues, Brown always scienti c literature, which was beginning to be has excelled at coming up with creative solu- available online. But they found that journals, tions to dif cult problems. Throughout his ca- which depended on subscriptions, weren’t reer, these problems have grown in scale and open to the idea. With Varmus and Michael expanded in impact beyond the lab bench. Eisen, a postdoc in his lab, Brown embarked Brown learned the process of detailed on an advocacy project for open access to the biochemical investigation, which his team scienti c literature that started with a pro- would later apply to the humble hamburger, posal to expand PubMed and culminated in from some of the most noted biochemists founding a new publisher, the Public Library of the 20th century. As a graduate student of Science. at the University of Chicago, he trained with When Brown decided to run Impossible the late Nicholas Cozzarelli. After  nishing a Foods full time, he left Stanford, giving up his Ph.D. and a medical residency, Brown joined status as a Howard Hughes Medical Insti- the lab of biochemist J. Michael Bishop at the tute investigator. J. Michael Bishop, a Nobel University of California, San Francisco, as a laureate who advised Brown as a postdoc, postdoc, where he collaborated closely with attended the HHMI meeting where Brown members of Harold Varmus’ lab to study HIV gave notice of his decision. molecular biology. “Instead of giving a valedictory with his Bruce Bowerman, who worked closely science, he gave a 20-minute talk on the eco- with Brown at UCSF, recollected a sign over logical problem that he wanted to address,” Brown’s lab bench “that said, in bold black Bishop said. It wasn’t a swan song; it was a letters, ‘If I have seen farther, it is by standing presentation on his next big project. on the shoulders of —’ and instead of ‘giants,’ “I think we were all surprised that some- which is the Newton quote, he had written, one as well situated as he was academically ‘idiots.’ … and who still had a passion for the science “Pat was not a modest person,” he said. would make that change,” Varmus said. “But he wasn’t unpleasant at all.” “But I’d say it worked out pretty damn well In 1988, Brown was hired as an assistant for him.”

34 ASBMB TODAY OCTOBER 2019 All in the family There’s plenty of science in Stanford — along with some of his closest food science at the University of Massachu- Impossible Foods founder Pat relatives (see box: All in the family). “I knew setts at Amherst, said that Impossible Foods Brown’s family; his wife, Sue a lot of talented students and postdocs, and is not unique in hiring scientists with no food Klapholz, whom he met at the a lot of my friends were scientists and they science training. University of Chicago, holds an knew a lot of people,” he said. “Of course, “ere have been biochemists — and M.D. and a Ph.D. and works as there was no eld of creating meat directly organic chemists, and analytical chemists the company’s vice president from plants, so they came from all kinds of — in the food sector for decades,” Decker of nutrition and health. One of backgrounds. All I really wanted was raw said. “And avor houses have been trying to Brown’s brothers, a neurosci- scientic talent.” replicate meat for a long time.” entist, has worked at the com- According to the Good Food Institute’s Rather, he said, what sets Impossible pany for about three years as a David Welch, sta ng at Impossible Foods is Foods apart are its startup-style business sensory perception expert. But unlike that at more established meat-alterna- model, which has allowed the company the most startling team mem- tive companies. to invest tremendous resources in a single ber is Brown’s daughter, Ariel “At tech-focused companies like Impos- product, and its patented plant-based heme Klapholz–Brown, who studied sible Foods and Beyond Meat, the R&D protein ingredients. lm in college before starting teams are full of biochemists,” he said. “A as an early employee in the more traditional plant-based meat company Flavor chemistry labs of the company that would may have had a dierent balance in terms e team at Impossible Foods set out become Impossible Foods. of the scientic talent within that company, to dene a burger biochemically by heating Today she’s a senior research with much more focus on food science and grocery store ground beef and, with a gas associate on Impossible Foods’ culinary aspects of assembling ingredients.” chromatography system and a mass spec- materials and texture team. Brown said that he looked for scientists trometer, characterizing the products of the “I love working with who were up for a challenge. “I had the most complex reactions that resulted as it cooked. my daughter,” Brown said, awesome recruiting tool, which is that I en, instead of trying to incorporate all the adding that she’d always could tell them with a straight face that we aromatic chemicals they identied into a veg- been a talented math and are working on unequivocally the most im- gie patty, Brown’s team used precursors to the science student. “She notices portant scientic problem in the world, and nal avor compounds, letting the chemistry everything, which is just a great it’s really challenging. If you want to get great happen during cooking. quality for the role that she’s in. scientists to work for you, that’s pretty much “One of the things that I think sets us There’s an art to creating new what you need.” apart,” Kliman said, “is that we really took prototypes, and also there’s an For people like Laura Kliman, a senior the time to research meat on the molecular incredibly important demand avor scientist at Impossible Foods, the level and understand all the actual reactions on observation. You have to company’s environmental mission was a that are happening and what the products are pick up subtle things that selling point. In 2016, Kliman, an organic that are being created.” you’re not looking for.” chemist by training, was working as a pastry According to most coverage of Impossible On working with family and chef. She had just left a job as a chemist at a Foods, its scientists were the very rst to take friends, he added, “If you have company that once developed biofuels but a reductionist approach to replicating the people that you know are all-in was transitioning to natural gas. She heard avor of meat. e scientic literature tells a on what you’re doing and tal- about Impossible Foods from a news story on more complex story. ented, and you know for sure the radio. An industry report for the National Cat- that you can tolerate them, “I couldn’t believe how exciting and per- tlemen’s Beef Association in 2006 summariz- that they’re going to be good fect it was,” she said. “Obviously extremely es a literature spanning decades of analytical colleagues, then that’s great.” focused on sustainability, while incorporating chemistry work in numerous food science culinary (aspects) as well as chemistry.” journals, most of which aimed to identify the Eric Decker, head of the department of most important avor compounds in beef

OCTOBER 2019 ASBMB TODAY 35 FEATURE

and determine what aected them; Brown Inorganic iron was known to speed up and colleagues had a lot of background to Maillard reactions. But a key part of Impos- work with. sible Foods’ story is its discovery of a new at report focused on optimizing eect of heme iron, which the company calls husbandry, meat handling and process- its “magic ingredient,” on the avor of meat. ing practices to improve the nal avor. But in other contexts, scientists have worked The magic molecule for years to develop additives based on a “How does it taste?” Brown said. “Basi- David Welch thorough understanding of meat chemistry. cally, that’s just an assay — like radioactive As early as the 1960s, food companies like thymidine incorporation in the early days Procter and Gamble patented precursors of DNA replication. It’s just an assay that that could give bland protein isolates a beefy tells you whether what you’re trying to get to avor upon heating. happen is actually happening. And then, you Chemists working to recreate beef avors deconstruct and reconstitute the biochemical have long focused on two major types of system.” reactions that occur when a piece of meat If a researcher heats a simple solution of hits a hot grill: lipid oxidation and Maillard cysteine and glucose, an Impossible Foods reactions. patent asserts, the product will have a faint Eric Decker Lipid oxidation occurs when reactive rotten-egg smell. Should that researcher add oxygen species oxidize lipids, especially ferrous gluconate, which contains an iron polyunsaturated fatty acids, at their double cation similar to the one in heme, again the bonds. e reaction can generate low–molec- product smells sulfurous. But replace the ular-weight ssion products and, sometimes, gluconate with a heme protein, and that short-lived epoxide compounds; some of unappetizing odor is replaced with smells these taste appealing, but most do not. that evoke chicken broth, burnt mushrooms “Iron is the major problem in any (food) and bread. that undergoes oxidation,” Decker said. Biochemically, what’s so special about Mark O’Brian Either free or balanced in the aromatic, heme? Unsurprisingly, Impossible Foods has heterocyclic ring complex of heme, iron can not volunteered chemical specics. Given the catalyze oxidation of polyunsaturated fatty odors mentioned in the patent, it’s tempting acids, resulting in a warmed-over avor. to speculate that the answer may have some- Maillard reactions, the second major thing to do with interaction between heme reaction family driving beef avor, happen and hydrogen sulde derived from cysteine. when an amino acid and a sugar are mixed According to Ruma Banerjee, whose lab and heated. e reaction, an umbrella term at the University of Michigan Medical School for condensation between a nucleophilic studies hydrogen sulde signaling, such amine and an electrophilic carbonyl, is im- speculation is not unreasonable. Banerjee’s Ruma Banerjee portant in cooking chemistry from brown- lab discovered that hemoglobin in red blood ing pretzels to avoring roasts. One of the cells, which lack normal hydrogen sulde best-studied Maillard reactions involved in turnover pathways, can oxidize hydrogen avoring meat takes place when ribose and sulde to generate more complex sulfur-con- cysteine are heated, creating a range of cyclic taining molecules. volatile compounds that contribute charac- “e biochemical evidence for this chem- teristic avor notes to meat. Hydrogen sulde istry is very strong,” Banerjee said. “It’s not derived from cysteine plays an important just reversible binding; the sulde is actually role in making some of those compounds, transformed by the heme in air to oxidized catalyzing addition of sulfhydryl groups to products.” Sharon Long reaction products. Perhaps such catalysis is part of how

36 ASBMB TODAY OCTOBER 2019 ROWAN ADAMS/WIKIMEDIA COMMONS heme diminishes the o-putting odors and kind of Rube Goldberg contraptions,” Brown promotes more palatable avors in the simple said in a podcast with the American Society two-ingredient mixture. By adding additional for Microbiology’s Julie Wolf. molecules — ribose, thiamine, various amino It turned out that harvesting and cleaning acids and lipids — the researcher can make root nodules and extracting their leghemo- the product both more complex and more globin, while possible, was impractical at an reminiscent of meat. industrial scale. Instead, the team pivoted to is, in essence, is the approach the producing heme-binding proteins in yeast. Impossible Foods team took. A patent de- scribes a mixture of amino acids, sugars and Constant optimization Nodules on the roots of legumes, like metabolites titrated to match meat tissue; ough heme as a magic molecule is key these Wisteria roots, are home to when heated with leghemoglobin, it enables to the company’s brand narrative, Brown of- symbiotic bacteria that fix nitrogen. the key reactions that build a meat avor ten stresses that there’s more to an Impossible Impossible Burgers contain a nodule prole. Meanwhile, according to Decker, Burger than that. protein called leghemoglobin, cloned levels of polyunsaturated fats are lower in “If you’ve nailed the avor chemistry and from soy and produced in yeast. the Impossible Burger than in meat, which nothing else, well, you have beef broth,” he may prevent the added heme from boosting unpleasant avors. But applying insights from a simple mixture of two or three ingredients to the complex chemical and material mixture in a Buering oxygen vegetable patty is a di cult task. Legumes — plants like soy, pea and clover — are well known “As an organic chemist, you have so for converting atmospheric nitrogen into ammonia, which is a much control over what’s in your reaction. source of nutritional nitrogen. The reducing reaction called nitro- And that’s just not the case with food,” Kli- gen xation, for which the plants often get credit, is in fact carried man said. “ere are so many reactions that out by symbiotic bacteria that live in specialized organs in the it’s hard to track them all and to know what plants’ roots. Mark O’Brian, chair of the biochemistry department products are being produced from what sort at the University at Buffalo, studies nitrogen xation by Bradyrhi- of precursors.” zobium japonicum, which colonizes soy roots. A Bradyrhizobium enzyme called nitrogenase breaks the Globins without animals bonds in atmospheric nitrogen, O’Brian explained. The process When characterizing meat, Brown said, demands a tremendous amount of energy, which Bradyrhizobium “e thesis was that there’s absolutely noth- supplies through aerobic respiration. But an appetite for oxygen, ing that was required that was specic to ani- the ultimate oxidizer, is perilous for the nitrogenase. Plant tissue mals. at could have been wrong. It turned in root nodules express a high level of leghemoglobin, a protein out to be right, which was good.” that, like other heme proteins, coordinates oxygen cooperatively. Brown thought he knew a good place “You need oxygen for the bacteria to respire, but you can’t to harvest heme without killing an animal: have a lot of free oxygen because it’s going to kill the nitroge- the root nodules of legumes. Sharon Long, a nase. Leghemoglobin really resolves that paradox,” O’Brian said, colleague on the biochemistry faculty at Stan- by binding with high afnity to free oxygen and releasing it only ford, studied these tiny hotbeds of nitrogen when the concentration of oxygen is low. “Essentially, it’s facilitat- xation, and Brown was familiar with their ing oxygen diffusion, which is similar to what myoglobin does in iron-rich microecosystem (see box: Buering the muscle of animals.” oxygen). Since Impossible Foods has become prominent, O’Brian said, “We spent quite a lot of money and quite he has found it easier to describe his research to nonscientists. a large fraction of our time in the rst year “If you say, ‘We work on ABCD,’ it’ll put people to sleep. But and a half on this quest to gure out a way to if you say, ‘This is being used for the Impossible Burger,’ people harvest root nodules … and creating all these are interested.”

OCTOBER 2019 ASBMB TODAY 37 FEATURE

IMPOSSIBLE FOODS said. “And if you’ve nailed the texture, and heit. And it’s across the (San Francisco) Bay.’ you don’t have the avor, you have crab And within 24 hours, a hundred people had cakes. … Basically, the more progress we volunteered.” make on one dimension, the more we He tells the story with evident pride in think, ‘Oh, we’ve gotta make more his team’s dedication to the mission. On the progress on the next.’” website Glassdoor, where workers can post e rst prototype ranked somewhere reviews of their employers, anonymous posts below crab cakes or beef broth. Supertasters reveal mixed feelings about the company’s on sta compared it to “rancid polenta.” monthslong production sprint, and several But, according to Brown, improvement was note a lack of food industry know-how. swift after that. is is part of the company’s Others, however, like the challenge. mindset; a perfect reproduction of ground Kliman, the avor scientist, said, “In an beef is not its end goal. If chemists can academic lab — this is sort of a sweeping improve on the eating experience, producing generalization — you have a lot of time, This year, Impossible Foods introduced something with fewer o avors or a more and you have almost no money. So you get a new recipe and overcame a production palatable texture, then they will. creative about ways to solve problems. In an shortage. Its scientists plan to continue “In a certain sense, we’ll declare victory industry (lab), let’s say pharma, it’s very much testing new ingredients to optimize plant- when the incumbent industry is in the rear- about the bottom line, and time is money. based meat. view mirror,” Brown said. “But, on the other Here at Impossible, it’s like the best of both hand, to the extent that we can make people worlds,” with a dual focus on optimizing the happier and our product more aordable company’s products and contributing ideas and versatile and food secure, we’re going to for new ones. She cited periodic innovation just keep working and working. I’m not sure weeks when the research and development whether it will ever end.” team spends all its time trying new ideas or experiments. Production problems In April, Impossible Foods hired Dennis is year, Impossible Foods introduced Woodside, a lawyer by training with some 16 a new formulation that chefs say is a better years of corporate leadership experience, into “Flavor houses match for beef, but the company was also the newly created role of president. Having have been trying hindered by its own runaway success. After a president, Brown said in June, would free launching the new recipe, this spring the him up to focus on future innovations — to replicate company became unable to keep up with as soon as the company caught up to its meat for a long accelerating demand for its products. e manufacturing shortfall. “I want to spend a time.” timing was unfortunate; the company was in lot more time on R&D, but even our R&D the midst of a regional pilot partnership with team are all hands on deck trying to get this —Eric Decker Burger King. manufacturing caught up,” he said. Brown told e New York Times that the In July, the company declared an end to company’s eorts to scale up production had the shortage and announced its plans to open been “like changing the tires while driving a second production plant in Chicago. down the freeway.” Talking to ASBMB Today, he elaborated Changing the meat industry on their reaction to the shortage. “When we For the Impossible Foods plan to succeed, realized that manufacturing was limiting, ranching needs to go from marginally protable I sent out a call to everybody in our R&D to losing money. is is not at all popular in facility operation, basically saying, ‘OK, the beef industry, which has lobbied for restric- I need volunteers to work 12-hour shifts tions on marketing plant-based foods as meat. that either start or end at 3 a.m., just doing e product, on the other hand, is growing in whatever it takes in a room that’s 37 Fahren- popularity — and improving as a substitute.

38 ASBMB TODAY OCTOBER 2019 According to market analyses, in 2019 “If the technology we develop is used to As a scientist, plant-based meat is a $12 billion industry, produce a signicant fraction of the world’s “if you say, ‘This and it’s expected to grow. Impossible Foods, food supply and protein and so forth, it’s a which is privately owned, does not report huge responsibility,” he said in June. “Im- is being used for its sales gures. But its closest competitor, Be- possible Foods the company is not going to the Impossible yond Meat, reported that its revenues more be responsible for all of that — but we’re Burger,’ people than doubled from 2017 to 2018. developing the technology to enable (it).” In light of that reality, more of the food e company has announced that proto- are interested.” industry is beginning to adopt plant-based types of chicken, sh and even eggs, all made —Mark O’Brian protein production. is year, Tyson Foods, without animal products, are in hand. Mean- the largest meat company in the United while, a crop of smaller competitors also are States, appointed a vice president for alterna- developing and introducing their replicas of tive proteins and sustainability and an- those foods. nounced a new brand that’s set to launch this Now, Brown is thinking about what fall. Even legacy companies like Morningstar plant ingredients to use as source material. Farms, which has been making plant-based One possibility that seems to have caught his protein foods for 40 years, have introduced imagination — lately he has volunteered it new faux meats that seek to compete more a lot in interviews — is to replace plant-de- successfully against Impossible Foods and rived protein from grains and legumes with Beyond Meat. protein from leaves. Impossible Foods has Somewhat upstream from burger pro- patented an approach to purify the protein duction, ingredient companies are aiming to rubisco in bulk from the leaves of alfalfa, a catch the plant-based meat wave by providing crop presently used for animal fodder, or oth- pure protein and other ingredients. For ex- er plants. But according to David Welch, the ample, Motif is a Boston startup that focuses protein feedstocks of the future are as likely on using biotechnology methods to produce to be generated from bacteria, algae or fungi components other food companies can use. as from traditional crops. “Motif is somewhat unique in that they’re “We’re constantly screening things,” taking a synthetic biology or recombinant Kliman said. “Anything you can think of to biology approach to creating new ingredi- generate a plant-based protein, or other sorts ents,” Welch said. e approach is similar to of nutrients and ingredients, we’re interested the way Impossible Foods generated a yeast in looking at that and seeing if we can turn it strain to produce soy leghemoglobin at scale. into something amazing.” Welch said that Motif is trying to do similar “People are always telling me, ‘You’ve got things with other possible ingredients, such to focus more,’” Brown said. “And I feel like as milk proteins. being unfocused is incredibly valuable … ere’s also some evidence that the surge when you know where you want to go, but in popularity of plant-based meat is changing there’s no road map, and you have to gure American crop elds. “We’re starting to see out how to get there. some examples of it now,” Welch said. “I “e last thing you want to do is say, think, in the future, we’ll see more examples ‘I’m just going to go down this trail and I’m of crops being grown that are specically bred gonna keep going until I fall o a cli.’ No. for plant-based meat applications.” I’m going to explore and wander.” And as a postscript: is fall, my Protein foods for the future vegetarian boyfriend gave the Impossible Laurel Oldach ([email protected]) is With characteristic condence, Brown Whopper a try. He enjoyed it enough to a science writer for the has moved on to making plans to further order a second — Impossible Foods converts ASBMB. Follow her on Twitter @LaurelOld. redene the food industry of the future. another customer.

OCTOBER 2019 ASBMB TODAY 39 FEATURE Under the skin out in the world& Elaine Fuchs’ legacy of stem cells and love

of exploration By John Arnst

f Elaine Fuchs had been born a century earlier, she her eye on the Peace Corps. She hoped to teach chemistry may have been a naturalist rather than one of the most in Chile, where Salvador Allende recently had become decorated cell biologists of her generation. the rst Marxist elected president in a Western liberal “I grew up in a family of scientists. But … I think democracy. Iwhat really inspired me was getting a buttery net “Growing up during the Cold War, I thought, ‘How from my mother, who put it together and sent me out to can that happen, where people elected to have a Marxist the elds,” said Fuchs, who was raised outside of Chicago government even though they had 100 years of democra- near Argonne National Laboratories, where her father cy?’” Fuchs said. worked as a geochemist. “at, and taking buckets and She spent a year learning Spanish, studying Latin SEPTIMUS PHOTOGRAPHY MATTHEW going out to the swamp and seeing what I could nd.” American history and writing papers on Chilean agrarian For more than four decades, Fuchs, now 69, has in- reform. But the Peace Corps had other plans. vestigated the properties of adult stem cells that reside in “I got accepted to Uganda, and Idi Amin was in skin. Much of what we know about human skin’s capacity charge. He was a tyrant — he was killing his own people to heal and regenerate — and, in cases of mutation, to and just ruthless,” Fuchs said. “I thought about it, and I succumb to diseases like epidermolysis bullosa — has decided in the end to go to graduate school.” been made possible by Fuchs’ work, from her rst lab ough the Peace Corps dream didn’t pan out, Fuchs at the University of Chicago to her current position as has been an ardent traveler since her days as a graduate the Rebecca C. Lanceeld investigator at the Rockefeller student at Princeton University. Her work also has taken University. her across oceans. In 2018, she was appointed to the Pontical Academy of Sciences, a papal think tank estab- Landing in the lab lished in 1936 as a successor to the Accademia dei Lincei As an undergraduate, Fuchs had no plans to become a founded in 1603 under the stewardship of Galileo. In that researcher — at least not immediately. During her senior role, and on occasion before she was appointed, Fuchs has year of college, she protested the Vietnam War and had attended scientic workshops at the Vatican to help keep

40 ASBMB TODAY OCTOBER 2019 &

Elaine Fuchs established her lab at Rockefeller University in 2002. She has been a Howard Hughes Medical Institute investigator since 1988.

the Roman Catholic Church’s highest leader apprised of a dierent name. the regenerative potential of stem cells derived from all “Human epidermal keratinocytes. A very boring areas of the body. name,” she said. “We now, of course, know that virtually “ey’re excited by the prospect that dierent tissues every tissue of our body has long-lived stem cells that are harbor stem cells that have in some cases, like skin, able to regenerate tissue, both to repair dying cells and considerable regenerative capabilities,” she said. “ey also to repair wounds, so it’s virtually a universal property have a very broad base of scientists with dierent areas of of the tissues of our body. But back then, there was very expertise.” little known about it.” For Fuchs, that area of expertise is stem cells. At that time, Fuchs was a postdoctoral fellow at the Massachusetts Institute of Technology in the lab of How- Building a field ard Green, a cell biologist who pioneered skin grafting When Fuchs started working on skin-derived stem by growing human cells in culture. When Fuchs was a cells during the eld’s nascency in 1978, the cells went by graduate student at Princeton working on bacterial spor-

OCTOBER 2019 ASBMB TODAY 41 FEATURE

ulation, she had attended a guest seminar by Green about sister–little sister dynamic,” Watts said. “But now we’ve culturing cells from human skin. founded these massive dynasties. And they all have these “I just immediately thought, ‘at’s what I want to wonderful networks of relationships amongst each other.” work on for my postdoctoral work,’” Fuchs said. “It was at the time where a few people were starting to do mam- Female bonding malian cell culture, but they were all on transformed cells, Fuchs’ knack for building supportive networks was es- cancer cells, or cells where people weren’t really studying pecially useful at the University of Chicago, where she was their ability to regenerate tissue.” the rst woman hired at the department of biochemistry. In Green’s lab at MIT, she met Fiona Watt, anoth- When she was setting up her laboratory, a technician er postdoc who had just nished her Ph.D. at Oxford from another lab asked her if she was Dr. Fuchs’ new University. technician. She replied, “I am Dr. Fuchs.” “I always describe her as the big sister that I never Such interactions weren’t new to Fuchs; in her under- had,” said Watt, now the director of the Centre for Stem graduate physics class at the University of Illinois, she was Cells & Regenerative Medicine at King’s College London. one of three women in a lecture hall of 200. “If I needed to know how to do something, she would “I would see, in retrospect, a tremendous amount help me. But I think pretty soon after I got to the lab, she of discrimination, but I didn’t recognize it as that,” she was learning to think about her independent career and said. “I just took it as the need to do better. My adviser at where she would go next. You could really, I suppose, in Princeton didn’t think women belonged in science, and I hindsight, see the scientist she was going to become.” just thought, ‘Well, that means I need to work that much In Green’s lab, Watt worked to culture cells from harder.’ human skin, while Fuchs attempted to clone the keratin “It was a little annoying (receiving) really derogatory gene. “is was really cutting-edge molecular biology, comments made by some of my colleagues if they would nobody else in the lab knew how to do that,” Watt said. get irritated over a remark I would make. On the other “So there was a sense that she was really pushing the hand, you kind of take that as water o a duck’s back.” boundaries.” By Fuchs’ account, a turning point at the University After nishing her postdoc in Green’s lab, Watt of Chicago came when she and her colleagues Janet Row- returned to the U.K. to start her own lab at the Kennedy ley and Susan Lindquist took advantage of a departmental Institute of Rheumatology in London; she has continued reorganization to join the department of molecular genet- to investigate the role of stem cells in adult tissue main- ics and cell biology. tenance. is overlaps with Fuchs’ research, so they have “Each department had their token woman or two, remained close colleagues over the years. ey also have and, when we organized and were allowed to join one built a highly collegial eld of study. department, we all decided to join the same department,” “More than 10 years ago … we were at a conference Fuchs said. “And it was really only then that I think it in Toronto, and people from her lab invited people from really did start to feel dierent, because I did have col- my lab out for a meal,” Watt said. “And I remember leagues who thought the same way and weren’t derogato- saying to my lab, ‘Look, they’re just going to want to ry.” suck your brains out, know everything you’re doing, but Within that new environment, she was able to stake remember you can probably drink more than they can.’ out her support for equality at the university. And that evening, I wasn’t there. I don’t think Elaine was “It’s important to pick the battles that you have, and either. But it was transformative for the eld. Because the so I picked them with issues that were grossly unfair in scientists in each of our labs at the time were some of the terms of say, salary, or now, in terms of the importance of best we’ve ever trained. ey got on really well with one just having representation at scientic meetings.” another, and instead of feeling that you’re either in the Fuchs’ camaraderie with women scientists cuts across Fuchs lab or the Watt lab, it was, ‘is is the eld that we elds. For Mina Bissell, former head of life sciences at care about. And we have to help one another.’” Lawrence Berkeley National Laboratory, a galvanizing By their lab’s records, Fuchs and Watt collectively have moment in their friendship came in the early 1990s at a trained more than 200 Ph.D. students and postdocs in large scientic meeting in Chicago. the decades since they left Green’s lab at MIT. At that meeting, Fuchs took the podium to present “We may have started out with that with that big research ndings that expressing a mutant keratin in mice

42 ASBMB TODAY OCTOBER 2019 could make them display a skin-blistering phenotype identical to epidermolysis bullosa simplex, or EBS, in humans. According to Bissell, who had met Fuchs a few years earlier when she had visited LBNL, Fuchs soon was as- sailed by a senior keratin researcher from Australia. “I have never seen anything so arrogant,” Bissell said. “is man was so biting: ‘And you mean that this mouse

is replicating human disease? at’s nonsense.’ I mean, he DAMON RUNYON CANCER RESEARCH FOUNDATION just went on and on. “I got so mad that I stood up. I said, ‘Excuse me, what’s your problem? She very nicely has described her data; she’s made the mice imitate human disease. And you Following in the footsteps of their postdoctoral mentor Elaine Fuchs, don’t believe it? Go to your own lab and do it. For crying Shruti Naik (left) and Julie Segre (right) both received the Damon Runyon out loud, do it yourself. What are you doing being so Postdoctoral Fellowship Award. mean?’” By Fuchs’ account, Bissell’s defense was the catalyst for the chair of dermatology at the University of Pennsylvania to corroborate Fuchs’ diagnosis of EBS. Eight months later, her work displaying mutant keratin overexpression as a cause of EBS in mice appeared in the journal Cell. COURTESY OF ELAINE FUCHS COURTESY Leadership ough Fuchs has been an active leader in the scien- tic community (see box: Awards and accomplishments), research and mentorship have remained priorities for most of her career. “I’ve never chaired a department. I’ve never been a dean, I’ve never been the president of the university. I’ve never wanted to be any of those,” she said. “I really take Fuchs with her friend Mina Bissell and her husband, David Hansen. the professor’s side very seriously. It’s not just the research that we do, it’s also important for me to mentor students as part of my professorship. So that’s where I funneled the bulk of my energy over my career.” project, but then at a certain point, the project would Julie Segre, now a senior investigator at the National capture Elaine’s imagination. She would decide that you Human Genome Research Institute who examines the were close to nishing, and then you would kind of go composition of the human skin microbiome and tracks into overdrive … she was pretty amazing at never having hospital-associated bacterial pathogens, joined Fuchs’ lab anything sit.” at the University of Chicago as a postdoctoral fellow in After four years in Fuchs’ lab, Segre took a position at 1996. the NHGRI of the National Institutes of Health, where Segre had been involved with the Human Genome she was promoted to senior investigator in 2007. Project at MIT while working on her Ph.D. and was “Elaine has continued to be engaged in my scientic interested in combining her genomic and technological development and scientic life, and I still consider her skill set with biological questions regarding proliferation the mentor that I would go to for both scientic advice and dierentiation in organ systems. In the Fuchs lab, she and (scientic) conversation,” Segre said. “It’s always nice was able to explore those questions in a subgroup devoted when people say, ‘Oh, now we’re just colleagues.’ And I’m to cell dierentiation. like, I would never give up being one of Elaine’s mentees, “Elaine is ercely involved in every scientic proj- because she has so much to give that I still do want. I have ect in her lab,” Segre said. “You had time to develop a a lot of colleagues, but I only have one postdoc adviser.”

OCTOBER 2019 ASBMB TODAY 43 FEATURE ELAINE FUCHS

Outside of the lab, Elaine Fuchs loves documenting her travels through photography. See more of her work at asbmb.org/asbmbtoday.

Traveling partners the surgery. “(But), if you use it, it is going to wear down, During her semester breaks as a graduate student and I tend to be active.” at Princeton, Fuchs made the most of the Spanish she’d Fuchs’ love of travel led to one of her favorite hobbies, honed for the Peace Corps, traveling to Guatemala, Mexi- photography. co, Ecuador, Bolivia and Peru. Subsequent trips found her “My favorite are pictures of people,” she said. “But visiting Greece, Turkey, Egypt and Nepal. (recently) I’ve gotten really fascinated with leopards, and A few years later at the University of Chicago, her also with birds.” colleague and close friend Susan Lindquist introduced her She and Hansen are planning a trip to the Galápagos to David Hansen, a history bu and fellow academic who Islands this winter, where she is excited to photograph the had done a stint with the Peace Corps in Sierra Leone. panoply of birds that call the archipelago home.  e two hit it o over their mutual interest in traveling “In another life, I think I would want to be out with and soon visited South Africa together. National Geographic,” she said. “We just started traveling places that we hadn’t been In this life, her professional evolution has stuck to between the two of us,” Fuchs said. “Our honeymoon science. was Zimbabwe and Botswana — Victoria Falls instead of “I was a chemistry major at the University of Illinois, Niagara Falls.” in Champaign–Urbana, and I was good at it. But I knew In recent years, Fuchs and Hansen have been to Indo- it wasn’t my calling. And then at Princeton, I was doing nesia, Laos, Tanzania and, on several occasions, Myanmar. biochemistry, seeing if I could  nd something more bio- All that travel takes a toll; earlier this summer, Fuchs medically oriented. And that really wasn’t it either. And had hip replacement surgery, a procedure she took in then it was that spark of hearing Howard Green speak. stride. And I knew then that that’s really what I wanted to do. So “ ese days, it’s basically like going down and getting I think it’s a progressive maturation, honing our scienti c an oil change for your car. It’s fairly routine,” she said of star that’s inside of us.”

44 ASBMB TODAY OCTOBER 2019 Awards Accomplishments& SANDY SCHAEFFER/NSF

Elaine Fuchs received the National Medal of Science from President Barack Obama on Oct. 8, 2009.

Throughout her career, Elaine Fuchs has been an advocate for women in science; for this, in addition to her groundbreaking research, she received a L’Oréal–UNESCO Award for Women in Science in 2010. Her accolades also include a National Medal of Science in 2008 and, this year, the American Association for Cancer Research’s Clowes Memorial Award. Fuchs was elected to the American Academy of Arts and Sciences in 1994, the National Academy of Sciences in 1996, and the American Association for the Advancement of Science in 2008. She has served as president of the American Society for Cell Biology, the International Society for Stem Cell Research and the Harvey Society; has contributed to numerous scientifi c advisory boards and review panels; and has served on the board of governors for the New York Academy of Sciences and the board of directors for the Damon John Arnst ([email protected]) is Runyon Cancer Foundation. ASBMB Today’s science writer. Follow him on Twitter @arnstjohn.

OCTOBER 2019 ASBMB TODAY 45 FEATURE

MEET

Qi-Qun Tang By John Arnst

The adipocyte expert and JBC associate editor wants to see better research papers from China

rown fat generates heat and sistant professor at Hopkins in 2002. of adipocytes; it’s also stem cells, white fat increases our risk of He returned to Fudan University in immune cells and preadipocytes. Bmetabolic disease, but what of 2005, and he now divides his time We’re also looking at angiogenesis of the beige that lies between? At Fudan between his lab in Shanghai and his blood vessels. We’re really interested University Shanghai Medical College, family in Baltimore. He became the in plasticity and how adipose tissue is Qi-Qun Tang and his colleagues are Journal of Biological Chemistry’s rst remodeled. investigating the metabolic processes associate editor in China in late 2017 We always think of adipose tissue by which stem cells become white, and now evaluates research papers on as fairly important for storing energy brown or beige fat; the third of these adipocyte development and function, that can be released when required. exhibits some of the heat-generating, carbohydrate metabolism, and cellular Normally, the adipose tissue itself circulation-inducing characteristics of signaling related to liver metabolism. is really healthy. But later, when it its brown counterpart. As vice president of the Chinese becomes chronically inamed, this After receiving a medical degree Society for Biochemistry and Molec- tissue becomes unhealthy, or there is in 1990 and a Ph.D. in 1995 from ular Biology, Tang helped coordinate a risk for metabolic diseases. So we’re Fudan University Shanghai Medical the society’s annual meeting this currently focused on subcutaneous, College, Tang did his postdoctoral month in Taiuyan; its close to 2,500 or white, fat because it accounts research at Johns Hopkins Univer- attendees will include a dozen JBC for most of the fat in bodies it can sity in the lab of M. Daniel Lane, a editorial board members. He also actually be induced to be beige, or pioneer in understanding adipocyte helped organize a joint symposium by brownlike, adipose tissue. dierentiation. Tang became an as- the CSBMB and the ASBMB, “Epi- genetic Control of the Epigenome,” That beige fat has characteristics this month in Suzhou, near Shanghai. somewhere between white and Since Qi-Qun Tang started Tang spoke with John Arnst, an brown fat, right? as an assistant editor ASBMB Today science writer, about Correct. During exposure to cold at the Journal of Biological his work. e interview has been temperatures or exercise, those white Chemistry, more than edited for clarity and length. adipocytes can actually be induced to a third of the papers become beige cells. And then later, he’s edited have come What is your research group at after that stimulation is removed, from primary and Fudan University working on? they tend to turn back. at model- senior authors based at We originally worked on adi- ing and remodeling also stimulates institutions in China. pogenesis, which is how stem cells angiogenesis, the generation of blood can become fat cells. ese days, we vessels, and induces change to the mainly focus on adipose tissue as a immune system’s macrophages.

COURTESY OF QI-QUN TANG COURTESY whole, because it doesn’t just consist It’s a whole host of changes, and

46 ASBMB TODAY OCTOBER 2019 we’re trying to really unravel those time, we were trying to understand how you divide your time between physiological processes. It’s an ex- how a preadipocyte turns into an China and the United States. citing area, because these beige cells adipocyte. I mainly focused on C/ I spend most of my time in were only identied around 10 years EBP beta (author’s note: CCAAT/ China right now. We have a sum- ago, but the eld is now moving very enhancer-binding protein beta), which mer break and a winter break, and fast. is an upstream transcription factor for I sometimes come back here for One of the cytokines we’ve been the C/EBP alpha and PPAR gamma. meetings during the middle, like working on is BMP4, which can ey are really a master transportation ASBMB’s annual meeting. I prob- induce the adipocytes to transform regulator for adipocyte genes, and they ably spend eight or nine months of to beige cells. It also upregulates are transcription factors that can turn the year in China. the production of M2 macrophages on almost all the genes involved in the and activates them, and it induces adipocyte dierentiation. A few years That’s an impressive balancing act. angiogenesis. It’s one of many factors back, I wrote a JBC review about how Do you have advice for early-career we’re looking at, and we’re also trying C/EBP beta regulates all of these genes. scientists about balancing life in to use some of the latest omics to the lab and life outside of the lab? identify new factors. Keeping some outside activity “Right now, I’m is really important. ese days, I It seems like a burgeoning field. really interested in go to the gym a lot, and I’ve hired e eld is very hot right now. a personal trainer. I was diagnosed We’re also using screens to test the helping to promote the as being prediabetic in 2004, and ability of chemical compounds to journal in China.” because I work in understanding induce white adipocytes to become metabolism, I wanted to be on top of beige. One is called artemisinin, dealing with it. which was originally used to treat And you’ve been involved with I think another good outlet for malaria. It’s a famous compound subsequent JBC reviews. What has when you get really stressed out, es- extracted from sweet wormwood your work looked like with JBC in pecially early on, is going swimming (author’s note: Chinese chemist recent years? for a while. en, you can totally Youyou Tu won a 2015 Nobel Prize I published my rst of several forget about stress, you can refresh in medicine for isolating and chem- papers in JBC in 2009 and was your mind to start working again. I ically identifying the compound, invited to become an editorial board used to go in the afternoon, and after which had long been used in folk member a few years later. I’d come back, I’d feel refreshed. medicine). at’s just one of the Right now, I’m really interested compounds that we are working on. in helping to promote the journal in There is definitely something unique China. to swimming in that regard. The How did you find yourself involved e journal has always been only thing you have to focus on is in adipogenesis? helpful to young scientists who are the bottom of the pool, and maybe I was training for my M.D. in trying to understand how to improve the upcoming wall. forensic medicine, but I didn’t like it the quality of their papers. In China, You can just let your brain very much. the stakes for submission are very completely relax and go wherever it During my second year of high, but JBC’s acceptance rate is needs to. And then when you come medical training, in 1988, one of my low. I think at least part of the reason back, your mind is crystal clear to do supervisors saw this and let me know is the quality. So I think that we can your work. that molecular biology was booming work with the journal to have a lot and that it could be a really exciting of impact on the societies within the John Arnst career. So, once I wrapped up my CSBMB society. ([email protected]) is ASBMB Today’s science M.D., I got started on my Ph.D. writer. Follow him on Twitter I started with the adipocyte I’m glad you mentioned the Chinese @ arnstjohn. research after I got to Hopkins for Society for Biochemistry and my postdoctoral training. At the Molecular Biology. I was wondering

OCTOBER 2019 ASBMB TODAY 47 FEATURE Q&A PADMA TEJESWANI Sandhya Visweswariah does a balancing act

between science and her society By Isha Dey

hile the global scientic community still leans toward patriarchy, Sandhya Visweswariah has made a mark for herself as one of the most prominent wom- en in science in India. Visweswariah chairs the department of molecular reproduction, develop- ment and genetics at the Indian Institute of Science in Bangalore, India, and Wco-chairs the institute’s Center for BioSystems Science and Engineering, which she helped establish in 2015. She has won international recognition for her work on watery diarrhea COURTESY OF SANDHYA VISWESWARIAH OF SANDHYA COURTESY and cyclic nucleotides in the form of grants and awards from the likes of the Royal Society and the Bill and Melinda Gates Foundation. Born in India, Visweswariah did her early schooling in England and then Zambia. At the age of 17, she returned to India and earned a bachelor’s degree in botany, chemistry and zoology from Osmania University followed by a master’s in chemistry from the Indian Institute of Technology, Kanpur. She went on to earn a Ph.D. in biochemistry from the IISc. Over the years, Visweswariah has explored scientic interests in industry as well as in academia; she worked at AstraZeneca before joining the faculty at the IISc. Her initiatives In addition to her study of the to improve translational research in India earned her the Margadarshi fellowship from the implications of cyclic nucleotides Wellcome Trust/DBT India Alliance in 2017, which provides biomedical scientists with in diarrhea, Sandhya Visweswariah an opportunity to lead cutting-edge interdisciplinary research programs. She was elected works to remove roadblocks for a fellow of the World Academy of Sciences in 2018. In addition to her research work, she women in science in India. constantly strives to remove roadblocks for women in science in India; in one notable step, she worked to modify the rules at the IISc to extend the tenure assessment period for women on the faculty by one year per child.

48 ASBMB TODAY OCTOBER 2019 TEJESWANI PADMA TEJESWANI

This cartoon by Tejeswani Padma, a former project assistant in Visweswariah’s laboratory, depicts the lab’s research interests.

OCTOBER 2019 ASBMB TODAY 49 FEATURE

Visweswariah spoke with ASBMB Today When I came back to India for college, contributor Isha Dey about her research and I continued with my scienti c pursuits. Look- addressed questions about scienti c advance- ing back, I feel things worked out the way Q&Ament in India and women’s representation they should, because I realize that I am more in science.  e interview has been edited for of a scientist than an artist. length and style. Who would you consider to be your mentor/ Tell us about the research in your lab. infl uencer? “Looking back, My lab is interested in looking at old-fash- Growing up, I won’t say I had a vision I feel things ioned cyclic nucleotides like cAMP and of one day becoming a scientist. However, if cGMP and their implications in diarrhea. there is any one person who inspired me to worked out the Being a biochemist by training, what interests do science, it was Srinivasan Chandrasekaran, way they should, me is how protein structure and function are an organic chemistry professor at the Indian because I realize coupled to cellular physiology like cell-to-cell Institute of Technology, Kanpur, where I did and cell-to-environment communication. So my master’s. that I am more of I look at receptor proteins, which transmit During this time, I realized what it was to a scientist than signals from other cells or the environment to do real research. Before that, I never felt that elicit a response within a cell. there was any magic in scienti c discovery; it an artist.” We study guanylyl cyclase C, a receptor was more like memorizing what is written in expressed in the gut, which has an extremely the textbook. But his approach to science and complex structure with multiple domains, and the way he ran his laboratory inspired me and try to understand how these domains commu- continue to in uence me even now. nicate with each other. We, along with clini- cians in Europe, were the  rst to report that Being a graduate student and now a mutations in this receptor cause congenital professor at the IISc, how do you think secretory diarrhea. We have received funding funding and opportunities for translational from the Bill and Melinda Gates Foundation research in India have changed over the to make relevant mouse models to better study years? this disease. A lot. Resources and funding at my time One of my former students some years ago as a Ph.D. student were in no way comparable wanted to look at cAMP in microbes, so we to international standards. We had to think of picked up Mycobacterium tuberculosis as a research ideas that were smart but not resource model system. We soon realized that there was intensive. Funding and interdisciplinary little information on the enzymes that regulate research have dramatically increased in the last cAMP levels in Mycobacteria. So that project decade because of initiatives from the govern- has also been a major focus in my lab for the ment of India as well as international research past decade. collaborations between governments like India and France or India and the U.K. How did you become interested in science?  e biggest game changer has been the My  rst interest during my schooling Wellcome Trust/DBT funding supporting in England was the arts. I was interested in basic and translational research.  rough this Western music, literature and languages. I was initiative, we have set up a collaboration with learning German, French, Russian and Latin. Christian Medical College in Vellore for an However, when I moved to Zambia with M.D.–Ph.D. program and closer interactions my parents at the age of 16, the only subject with faculty in IISc.  is is to encourage M.D. options given to me in school were physics, students in India to become clinician-research- chemistry, biology and mathematics. ers, which are rare in this country.

50 ASBMB TODAY OCTOBER 2019 What are your thoughts on gender bias against women in science? What we call bias against women need not be correlated to any kind of harassment; nei- ther is there any conscious prejudice against women by men in science. It is just that men are not sensitized to understand the needs VISWESWARIAH OF SANDHYA COURTESY of women during decision making, because they may not be aware that women may have a dierent view on things. Given my current position in the institute, I have become acute- ly conscious of this in the last ve or six years. For example, ensuring that the tenure process is sensitive to motherhood and that instances of sexual harassment are dealt with sensitive- ly and promptly. at’s when I realized that unless you have women in decision-making positions in leading institutions, you cannot bring in change for the next generation of women. Because India is a patriarchal society, men are brought up without sensitization toward women’s needs. It is not that they want to exclude women, but there is no positive desire to include them. In the West, over the past de- cade or so, men have become aware that there are things that women can bring to the table Students at the Indian Institute of Science explain basic science to younger school children and have made very conscious eorts to in- during an IISc Open Day. clude women at all levels in decision making. Unfortunately, in India, we have a long way to go before we reach that level of inclusion. to become movie stars just because they see “Unless you successful female movie stars. Women should have women Fewer than 14% of researchers in India and be allowed to choose their career paths and see fewer than 30% of researchers worldwide more varied role models so that we have more in decision- are women. What can be done to increase women represented in every sphere of activity, making positions women’s representation in science? not just science. in leading All of this comes from a perceived bias as to what a woman can and can’t do. Women Talk about your work as a fellow of the World institutions, you are told from an early age that they are not Academy of Sciences in advancing science cannot bring in good in science and engineering. So this is an in developing countries. upbringing problem coupled with the fact that We go to local schools and colleges all change for the there aren’t enough women in every sphere over the country and communicate our next generation of activity. Consider teaching, for example; research and scientic thoughts and ideas of women.” men in general do not consider teaching to the students in a language that they can in elementary school as a good profession, comprehend. Last year, I attended the rst because they are hardly ever taught by men at induction meeting of the World Academy that stage. Girls in this country might aspire of Sciences, and I was absolutely inspired by

OCTOBER 2019 ASBMB TODAY 51 FEATURE

Sandhya Visweswariah earned her Ph.D. at the QIndian& Institute of ScienceA T-SHIRT in Bangalore, India, (right) where she now chairs the department of molecular reproduction, development and genetics. CONTEST IISC ALUMNI All ASBMB members are young scientists from countries where there is have a child and still succeed? Can I disagree so much turmoil, like Sudan, Iraq, Iran, Syria, with my mother-in-law and come in to work? eligible to submit Zimbabwe and Palestine, coming and talking I was fortunate in being brought up by about science. I realized how lucky we are to parents who never made a distinction between a T-shirt design related be in India. my brother and me and never told me there to biochemistry and molecular were things I could not do.  erefore, any How can we tackle prejudices against questions I had along these lines were those biology. scientifi c development, such as religious that I myself raised after having a child, but I superstitions and avoiding vaccination? had the con dence given to me by my parents, We need to educate people about basic especially my mother, that I could do it all. The winning T-shirt will science and scienti c advancement. In parts  e minute we doubt ourselves, we are ready of India, people marry members of their own to give up. So women just have to believe that be sold at the 2020 ASBMB families, which sometimes results in transmis- they can do as well if not better than their sion of genetic diseases. But they consider the male colleagues. Annual Meeting in illness a curse of God or fate without being San Diego. aware of the dominant and recessive gene What does it take to be a good scientist? pool. Visiting a temple and worshipping a Honestly, I think to be a good scientist, deity cannot cure a disease. Unless science is a you need to be a decent human being. You Submit your shirt design part of human life, it is di cult to tackle this. have to show empathy. You need broad-mind-  is education has to happen in school and edness and a liberal way of looking at things by Jan. 27. also at home in our microenvironment.  ere — you should be ready to accept that your has to be better scienti c communication hypothesis may not be correct. You need to across all spheres. We all have the tools — be curious about the world around you and For more details visit almost everyone has a smartphone — but we why things are the way they are. We need to do not use them to educate ourselves on issues have an inherent interest in the  eld of science asbmb.org/meeting2020/ like this. coupled with good communication skills to put our ideas across to everyone. tshirt/ What advice would you give to current and prospective women scientists? Isha Dey ([email protected]) is a Growing up, women are cautioned at dif- scientist at Thermo Fisher Scienti c ferent steps about what they can do in a world in India. run by men, and this a ects our thought pro- cess. We are constantly questioning ourselves: Can I have a family and do science? Can I

52 ASBMB TODAY OCTOBER 2019 T-SHIRT CONTEST

All ASBMB members are eligible to submit a T-shirt design related to biochemistry and molecular biology.

The winning T-shirt will be sold at the 2020 ASBMB Annual Meeting in San Diego.

Submit your shirt design by Jan. 27.

For more details visit asbmb.org/meeting2020/ tshirt/

OCTOBER 2019 ASBMB TODAY 53 ANNUAL MEETING

How science took over the town at the tip of California By Ana Maria Barral

San Diego’s lue skies touching the immense Area) and fth in the nation. e ranking history as a waters of the Pacic Ocean. Warm was based on factors such as National research hub sunshine bathing long stretches of Institutes of Health and venture capital Bsand. Surfers. Palm trees. Glorious funding, lab space, and job opportunities. makes it a sunsets. ese are the postcard images of Indeed, choices abound: From large great place for San Diego. public institutions such as the University of For scientists, particularly in biomedical California, San Diego, and San Diego State scientists to elds, San Diego can be a dierent kind of University to renowned private institutions gather. dream destination as a conference site or a such as Scripps Research and the San- place to complete postdoctoral training or ford–Burnham–Prebys Medical Discovery nd a biotech job. In Genetic Engineering Institute, from industrial behemoths such as and Biotechnology News’ 2018 list of the top Illumina to this year’s red-hot startups, plenty biopharma clusters, San Diego ranked second of opportunities exist for scientists looking in California (behind the San Francisco Bay for a new phase in their careers.

Aerial view of the pier at Scripps Institute of Oceanography.

54 ASBMB TODAY OCTOBER 2019 How science took over the town at the tip of California

San Diego’s Balboa Park at twilight.

However, it is not always sunny in San museums and events, Balboa Park is now a As home to the Diego; many coastal transplants experience popular destination for residents and visitors. San Diego Zoo and what’s known as the “May gray, June gloom” It began as City Park, 1,400 acres set aside by many museums period of fogginess due to the heavy marine San Diego civic leaders in 1868. layer. And the city only became a beacon for In the early 1900s, city o cials were and events, science after a long and winding history. San intensely courting the U.S. Navy to open Balboa Park is Diego’s status in the scientic community a base in San Diego and bring with it now a popular has as much to do with wars and cunning federal dollars that could boost urban destination for politicians as with visionaries and generous development. Capitalizing on excitement residents and philanthropists. about the 1914 opening of the Panama Much has been written about the many Canal, those o cials decided to showcase visitors. social paradoxes of Southern California, their city in what became the 1915 Panama- particularly San Diego, and it is not the goal California Exposition. Most of the arts of this article to discuss them. Instead, we organizations along Balboa Park’s famous will focus on some key moments that trans- El Prado pedestrian walkway are housed in formed the isolated village on a spectacular Spanish Renaissance-style buildings made bay into a booming science and technology especially for that occasion. e exposition powerhouse. contributed to San Diego’s success in becoming a military metropolis. Naval Base Balboa Park and the rise of the San Diego was founded in 1922, and with military metropolis military funding came other industries, As home to the San Diego Zoo and many including aerospace and engineering,

OCTOBER 2019 ASBMB TODAY 55 ANNUAL MEETING

perman E.W. Scripps and his half-sister Ellen Scripps, established and supported multiple scientic and civic institutions from the 1890s to 1930s, including the Marine Biol- ogy Institute (later the SIO), the Metabolic Clinic (now Scripps Research), the San Diego Zoo and the Scripps Memorial Hospital. Anyone enjoying a hike in the Torrey Pines State Park can also thank Ellen Scripps. Other philanthropists followed her example A boat approaching the naval base in San Diego. of donating to scientic endeavors, including Joan and Irwin Jacobs, Debra Turner and providing the rst major reinvention of the Conrad Prebys and Malin Burnham. eir city’s character. names often appear in the names of institu- tions their generosity supports. War industries San Diego is a Navy town. In and around Postwar and UCSD the city are 14 major Navy and Marine Corps e city reinvented itself after World War installations, and San Diego is home to 60% II as a major center for advanced R&D. is of the ships in the U.S. Navy eet. More than development was largely tied to industries 100,000 active-duty members of the military closely aligned with the military, such as call the city home. San Diego can thank both aerospace and nuclear technologies, including its geography and the intense lobbying of major players General Dynamics Corp. and local politicians and civic leaders over the last General Atomics, respectively. century for its outsized military presence. e strength of the SIO’s research We may not think the defense industry is relationship with the Navy gave the institute related to the booming bioscience scene in San leverage to press for the creation of a new Diego, but federal investments in military in- general campus of the University of Califor- stallations, especially during World War II and nia in San Diego, something local leaders the Cold War, supported tremendous growth had been advocating for since the 1920s. in research and development. During World Planning of the campus was not devoid of War II, the federal government increased its controversies, however. Industry leaders such investments in basic research to support tech- as John Jay Hopkins of General Dynamics READ MORE nology development. e Scripps Institution wanted a technical research institute, while “Invention & Reinvention: of Oceanography, or SIO, started as a marine city voters preferred a broad-based school The Evolution of San biology research station at the turn of the 20th that included undergraduates as well. In Diego’s Innovation century. In 1938, Robert Gordon Sproul, pres- 1956, the regents approved a “graduate Economy” by Walshok, Mary ident of the University of California system, program in science and technology” that Lindenstein, and Shragge, created a UC Division of War Research that included undergraduate programs, a compro- Abraham J. Stanford, supported strong scientic and military collab- mise accepted by all. California: Stanford University orations. SIO scientists were instrumental in e new campus hired world-class experts, Press, 2014. the R&D of naval warfare technologies, and and by 1963, the 80 faculty (mostly scientists) after the war, Scripps became a powerhouse of included two Nobel laureates and 13 members “2017 Biocom California scientic research, playing an important role of the National Academy of Sciences. Luminar- Economic Impact Report in the establishment of UCSD. ies such as Harold Urey, David Bonner, Jim Ar- Databook” prepared by nold and Sol Penner were early UCSD recruits. TClower & Associates Philanthropists Excellent collaborative research brought fund- e Scripps name is ubiquitous in San ing and expansion of the university, including Diego. e family, particularly the newspa- the opening of its medical school in 1968.

56 ASBMB TODAY OCTOBER 2019 Biotech City While San Diego benetted enormously from military R&D, city leaders sought to diversify the economy after the Cold War. e Scripps Metabolic Clinic originally was founded by Ellen Scripps in 1924 to diag- nose, treat and research diabetes. Over time, the clinic became more focused on research, and in 1956 it was renamed the Scripps Clinic and Research Foundation. A number of high-prole researchers were hired in the 1950s, headed by Frank Dixon from the University of Pittsburgh. is development coincided with other advances in the biomed- ical sciences, including the founding of the Salk Institute and the opening of the UCSD School of Medicine. A sign at the University of California, San Diego Scripps Institution of Oceanography. All these institutions (and many more to come) settled in the Torrey Pines Mesa, part of pueblo lands that were acquired by the and San Diego Biotechnology Network, or city after the Mexican War and more than SDBN, for biotech. a century later were sold cheaply to institu- tions and companies to attract investment Still going strong in R&D. e city rezoned the area to attract San Diego’s life sciences engine still hums light industry, and San Diego’s rst biotech along. New institutions have joined the company, Hybritech, known for developing existing ones, among them the San Diego the prostate-specic antigen test for prostate Zoo Conservation Research Institute, the La cancer, also moved to the Mesa. After the sale Jolla Institute for Immunology, the Sanford of Hybritech in 1986, one of its founders, Consortium for Regenerative Medicine, the Howard Birndorf, helped found a string of J. Craig Venter Institute, and the UCSD biotech companies, including Neurocrine Clinical and Translational Research Institute. and Ligand, which are still in operation. Some biotech companies have expanded, oth- Many other companies in San Diego can ers have been bought, some have disappeared trace their origins to Hybritech alumni. and new ones keep springing up. e third reinvention of San Diego start- When attending the 2020 American ed in the mid-1980s as developers and in- Society for Biochemistry and Molecular Biol- vestors aimed to commercialize the products ogy annual meeting, you can look out from and services created by the R&D community. the convention center and see many signs Along with established institutions such of the city’s military past and present. If you as General Atomics, Scripps Research, the have a chance, visit the area of the SIO and Ana Maria Barral ([email protected]) is SIO and UCSD, new players arrived, both the Birch Aquarium; from there you can see an associate professor research institutions and biotech companies. both the magnicent beaches of the city and at National University in Costa Mesa, To help these organizations work together, a UCSD. Beyond lies the Torrey Pines Mesa, California, a member program called CONNECT was established the “Hispanic dowry” of 48,000 pueblo of the ASBMB’s in 1985. In addition to assisting startups, acres that helped San Diego to become a Science Outreach and Communication CONNECT is credited with developing San R&D success story. is convoluted and Committee, and a Diego’s business culture. A number of orga- fascinating history bets what was dubbed in member of the ASBMB Today editorial advisory nizations now support various technology 1972 by then-Mayor Pete Wilson “America’s board. Follow her on sectors, including BIOCOM for life sciences nest city.” Twitter @Bio_prof.

OCTOBER 2019 ASBMB TODAY 57 ANNUAL MEETING Searching for drugs on the ocean oor

By Kerri Beth Slaughter

rowing up in New York City, Paul Jensen San Diego is a Jensen elected to take the position at watched the famous undersea explor- great location for Scripps and used his Harbor Branch experi- Ger Jacques Cousteau on television and the ASBMB annual ence to help Fenical establish a program in meeting because, dreamed of studying the ocean. marine microbial natural products. In 2003, as Ana Maria Barral “I wanted to explore the water even Jensen, Fenical and others discovered salino- points out in the though I couldn’t get in it very often,” Jensen preceding pages, sporamide A, a small molecule produced by said. it is home to so the marine microbe Salinispora tropica. After No one in Jensen’s family ever had grad- many life scientists. years of work by many scientists, the biophar- uated from college, but he was determined Here’s the story of maceutical company Celgene now is develop- to learn more about science and the sea. He how one researcher ing the discovery for cancer treatment. took a leap of faith after high school and some made his way to Jensen enjoyed making discoveries with community college, moving south to pursue “the town at the tip Fenical, but he quickly realized a graduate a bachelor’s degree in marine biology at the of California.” degree was key to advancing professionally in Florida Institute of Technology. marine science. Now, decades later, the rst-generation “If you have ambitions about exploring college student and East Coast city kid is a professor at your own ideas and doing creative science, then you have Scripps Institution of Oceanography in San Diego. Jen- to go to graduate school,” he said. sen’s nontraditional career path equipped him with tools Jensen earned a master’s from San Diego State Uni- to mentor future scientists and to study marine microbes versity and returned to Scripps to complete his doctorate for drug discovery. in marine biology. He worked at Scripps for 13 years as He initially thought earning an undergraduate degree a non-tenure track faculty member before becoming a was all that mattered, and he received little guidance professor. about what would come next. “I didn’t understand what was needed to advance in a Marathon training career in science,” he said. After many years doing research at Scripps, Jensen said the part of the work he most values is the students. Getting hooked “We get many of the brightest and most enthusiastic After graduation, he found a job at Harbor Branch, an minds from around the world that want to come here for oceanographic research institute in Florida. Around that graduate studies,” he said. “eir energy, dedication and time, Harbor Branch started Seapharm, one of the rst eort lead to discoveries that put our institution at the programs to search the ocean for potential drugs produced forefront of so many areas of marine science.” by microbes as biologically active secondary metabolites. Graduate school is about learning how to think inde- It was Jensen’s rst exposure to the eld of natural prod- pendently and solve problems, he said, and the students ucts, and he was hooked. e institute was small, so he who do the best at Scripps are the ones who embrace this was able to lead projects and publish rst-author papers. independence. Jensen encourages the students in his lab When an outside company withdrew funding for to decide the direction of their thesis research and oers Seapharm, Jensen faced a choice. He could take another them wisdom from his own career path. position within Harbor Branch or move to San Diego to “I tell my students it’s a marathon, not a sprint,” he work as a technician at Scripps under the organic chemist said. “If you’re doing research you really like, then there’s William Fenical. value in staying in it even if it takes some time for your

58 ASBMB TODAY OCTOBER 2019 GREG ROUSE COURTESY OF PAUL JENSEN Searching for drugs on the ocean oor

Paul Jensen and graduate student Nastassia Patin collect sediment samples in 2014 Paul Jensen, center, and members of his lab collect samples at at the Smithsonian field station in Carrie Bow Cay, Belize. the Channel Islands.

career path to develop.” e resins are buried in ocean sediments to capture His students’ research today looks very dierent from molecules made by microbes in the environment. In the the work Jensen did when he started at Scripps. Advances lab, the molecules are removed from the resin with an in molecular genetics have transformed the way scientists organic solvent and analyzed to learn about how and why study natural product synthesis. they are made. Jensen believes these techniques will lead Random isolation and culturing of marine microbes to ndings about marine microbe interactions with hosts has been streamlined with high-throughput DNA and chemical competition among bacteria. sequencing to identify strains of bacteria with new or Changes in the eld have broadened the scope of interesting gene patterns. is method, known as genome Jensen’s research. With access to DNA sequence data, his mining, helps Jensen and other scientists understand what researchers can study the evolution of natural products in genes look like and how they make enzymes to build marine microbes. Jensen’s lab looks at closely related mi- natural products. crobial species to see how they make dierent versions of Jensen does less hands-on work now than when he similar molecules. eir analysis gives his team a chance rst came to Scripps, but he still loves getting in the water to see how nature works to generate chemical diversity. for eld work. About twice a year, he and members of his “We could identify the microbes before,” Jensen said, lab visit marine labs in places such as California’s Channel “but we could never understand the relationships between Islands, Fiji, Belize and the island of Moorea in French the microbes and the molecules they produced.” Polynesia to collect samples for research. Jensen’s work has evolved with time to harness the “Two weeks in the eld can generate two years’ worth wealth of microbes produced beneath the ocean’s surface. of work in the lab,” he said. His career path, though unclear early on, taught him the importance of running the slow and steady race for Buried resins science. Today, he continues to use what he learned along Back on shore, Jensen’s lab screens samples from the way to make breakthroughs in marine microbiology. various habitats to identify genes that appear relevant for making natural products. With advances in sequencing,

they can examine ocean environments at a DNA level and Kerri Beth Slaughter ([email protected]) is a predict where interesting natural products are synthesized. graduate student in the biochemistry department His lab also uses absorbent resins to study natural at the University of Kentucky. Follow her on Twitter @KB_Slaughter. product synthesis at its source. “We are looking to see if we can detect molecules di- rectly in the habitats in which they are produced,” he said.

OCTOBER 2019 ASBMB TODAY 59 MCPcover_SpecialCover_AD2_color8.5x11.pdf 1 8/27/2019 5:46:27 PM

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The journal Molecular & Cellular Proteomics (MCP) fosters the development and applications of proteomics in both basic and translational research. It showcases cutting-edge advances in proteomics, metabolomics and informatics. The American Society for Biochemistry and Molecular Biology publishes MCP. The artwork above is from the MCP Special Collection: Multi-Omics Data Integration.

60 ASBMB TODAY OCTOBER 2019 NEW! ASBMB Today call for submissions

ASBMB Today is publishing a new essay series in 2020 SERVICE BEYOND SCIENCE A career in the life sciences is demanding, but some researchers fi nd time to give back to their communities — often in surprising ways. Do you do volunteer work that is unrelated to your life in the lab? Tell us about what you do and why. Email [email protected] for more information, or submit at asbmb.org/asbmbtoday. Want to see an example? Read Ruma Banerjee’s essay, “A professor among prisoners,” on page 62 of this issue.

STIMULATING ANALYSES DEFINING NEW DIRECTIONS IN SCIENCE Save yourself from a landslide of literature. Read JBC Reviews to get expert insights into recent ndings, ongoing controversies and unsolved questions in biological chemistry.

Use JBC Reviews in the classroom and at journal club.

OCTOBER 2019 ASBMB TODAY 61 SERVICE BEYOND SCIENCE

A professor among prisoners

By Ruma Banerjee

t was 1981. As a student at Delhi dreams into rugs and volunteered at remember wishing that my daughter University, I had spent the fall lick- a nonprot that delivered ophthal- would direct her activism to a safer Iing postage stamps and envelopes mic care to the indigent. In contrast, issue, I admired her for her interest and mailing applications, pregnant my interest in social causes found in a marginalized community and with expectations for admission to only limited expression. In those ear- her commitment to criminal justice graduate schools in the U.S. Across ly years, we occasionally volunteered reform long before it had started to oceans, A.B. (whose initials have as a family at a soup kitchen that was percolate up into political and media been changed to protect her privacy) a stone’s throw from my lab. consciousness. had entered prison in Michigan, sen- Fast forward to 2013. I had As a novice, I have struggled to tenced to serve the balance of her life relocated to the University of grapple with our criminal justice without the possibility of parole. We Michigan, where, reading a campus system. With less than 5% of the were both 20 years old. Our paths rag one day, I found myself drawn world’s population, the U.S. is home were to cross many decades later. to a story about a colleague who to about 20% of the world’s incar- Since that time, my life has had introduced the Inside-Out cerated, according to 2018 statistics unfolded in a kaleidoscope of oppor- Prison Exchange Program, in which from the online World Prison Brief tunities and experiences. I mean- students from the outside study hosted by the Institute for Criminal dered through institutions of higher with inmates serving time inside Policy Research. Over 2.1 million learning, itting from botany to correctional facilities. On a whim, I of our citizens languish behind bars. biochemistry to biophysics, and then reached out to her. at, in turn, led Our imprisonment rate (655 per settled into a life of scholarship at a me to the National Lifers of Amer- 100,000) surpasses that of repressive land-grant institution in the prairies. I ica chapter at the Women’s Huron regimes like the Russian Federation upped the ante on the academic stress Valley Correctional Facility, the (402) and China (118, though track by having children pretenure only women’s prison in the state of numbers for China are incomplete), in a departmental home where for a Michigan, where prisons outnumber and is staggering compared to that long time I was the lone woman. My public universities 2 to 1. e NLA of India (33), the world’s largest growing academic family added to my is an advocacy group comprising democracy. personal one with two children and a prisoners serving long indeterminate Prison demographics reveal that spouse who was a fellow biochemist. or life sentences and volunteers who we disproportionately punish people Yet something was missing. support their work. of color and the poor. As Michelle Before stepping into the Alexander notes in “e New Jim Advocating for criminal justice WHVCF for the rst time, I had no Crow,” it was projected in the 1970s reform prior experience with prisons and that investments in U.S. prisons When I was growing up, my generally subscribed to the stereo- would decline, as research indicated mother deftly modeled community typical view that they held danger- that punitive approaches were less service in our family. She found ous individuals who needed to be eective for reducing crime than causes to champion and institutions separated from society. In retrospect, providing economic and educational to serve, even as she relocated con- I had been prepared subconscious- opportunities and access to health stantly as the wife of an army o cer ly by my daughter’s activism as an care. Few people anticipated that the who rose to be a lieutenant general. undergraduate with Students Or- politicization of crime to monger She assembled bandages for veterans, ganizing Against Prisons to abolish fear and fuel mass incarceration helped Mother Teresa’s Missionar- the prison industrial complex and would prove to be a hugely successful ies of Charity, supported a cottage with a nonprot to help the formerly campaign strategy used by everyone industry for rural women who wove incarcerated with reentry. Although I from all-powerful county prosecutors

62 ASBMB TODAY OCTOBER 2019 DWIGHT BURDETTE/WIKIMEDIA COMMONS

The Women’s Huron Valley Correctional Facility near Ypsilanti is the only women’s prison in the state of Michigan. to presidential candidates. distance from the main entrance such as domestic violence scholars, Crossing the sally port across a central yard, which I cross as legislators, or advocates of prison Barbed wire curls around the vigilant eyes stare down from watch- reform working for nonprots. At perimeter fences, and a sense of deso- towers that have been radioed about other times, they organize workshops lation hangs over the WHVCF. Its my presence. I have been instruct- for writing or parole readiness. As overcrowded interior, however, bus- ed to walk but never run. Double volunteers, we support and enable tles with life. After checking in with doors open into a corridor lined by these activities. (usually burly) armed guards and rooms and lead to a large auditorium I am deeply touched by the surrendering my driver’s license, I designed for reverberation and to resilience of women who are locked traverse the sally port where security drown out communication. One of up for life. In them, I see altruism, guards, in addition to the routine pat the rooms is an often-busy library. At humanity and hope despite the down, inspect the nape of my neck the end of the corridor sits another dehumanizing circumstances that and beneath my tongue and feet for guard. I must check in with him too conspire constantly to instill despair. contraband. It is an uncomfortable before I can nally turn to my work I also see their largesse; many earn experience that invariably imbues me as a volunteer. about 84 cents a day yet contribute with a sense of foreboding, although On the rst Monday of each generously to breast cancer research I always enter with nothing but the month, we meet in one of the or to shelters by organizing walks in authorized notebook (without metal drab rooms with the NLA leaders the prison yard. ring binders) and a pen with a clear who run the various committees I have had powerful experiences barrel. I gure that the guards are advocating for sentencing reform, with the women at the WHVCF trained to be expressionless. ough medical commutations for the frail, using the restorative justice practice I have been a regular visitor to the changes in aiding and abetting laws, of peace circles for learning and facility for half a dozen years and and other initiatives, and we plan healing through a collective process. more, it is the rare person who ad- programs for the larger NLA meet- e circle-keeping approach is one mits familiarity. ings, whimsically referred to as the of several that we use to help women e program building is a short Saturday soirees. ey invite speakers articulate personal responsibility

OCTOBER 2019 ASBMB TODAY 63 SERVICE BEYOND SCIENCE

Another approach is and empathy to repair harm and to was interested in felons like her who writing. The NLA newsletter prepare for parole hearings, which had been sentenced under the state’s is the only one authorized can be a brutal experience. common law felony murder rule, Another approach is writing. which broadened the crime such for circulation outside the e NLA newsletter is the only one that accomplices and co-conspirators walls of the WHVCF. As authorized for circulation outside the could be found guilty of murder. its volunteer editor, I help walls of the WHVCF. As its volunteer Six weeks after A.B.’s 1981 sentenc- women use the newsletter editor, I help women use the newslet- ing, the state’s Supreme Court, in ter as an instrument of self-expression. People v. Aaron had deemed the rule as an instrument of self- Some articles are newsy and describe “fundamentally unfair.” e ruling expression. visitors (such as Abdul El-Sayed, who was applied to trials in progress but ran for governor) or bills that the was not grandfathered. A.B.’s life NLA supports. Others are introspec- sentence was thus unaected. tive, with titles like “What would I I was in the prison on Dec. 21, like my victim to know.” and A.B. seemed despondent as we talked. e governor’s term would Parallel paths run out at the end of the year, and A.B.’s path and mine crossed a there had been no word on her few years ago when she decided to appeal. Later that evening, we heard rejoin the NLA chapter, which she that Snyder had signed her commu- had, in fact, founded at the WHVCF. tation order. Entering prison with a fourth-grade On Feb. 12, 2019, A.B. was education, A.B. picked up the broken released on a 48-month parole. A thread from a childhood stamped by week before her release, A.B. penned poverty and instability. She earned her nal article for the newsletter, her GED in prison and later trained “My praise report.” As a volunteer, as a paralegal. A.B. is quiet and has a I am forbidden to maintain contact matriarchal air. I noticed that peers with her. I have heard through the looked to her for her legal expertise grapevine that she is thriving and and historical knowledge about NLA has enrolled in a graduate program procedural issues. in criminology. I smile as I realize As the years passed, I worried that we remain connected on parallel that A.B. looked pu er and more ashen every time I saw her. On a diet that is estimated to cost less than $2 Ruma Banerjee (rbanerje@ umich.edu) is the Vincent per person per day for three meals, Massey collegiate professor healthy eating is not an option. Obe- of biological chemistry at the University of Michigan sity is rampant at the WHVCF. and a Journal of Biological At a soiree that we organized last Chemistry associate editor. She received the 2019 fall, A.B. learned that Rick Snyder, ASBMB–Merck Award. the outgoing governor of Michigan,

64 ASBMB TODAY OCTOBER 2019 ESSAY What I wish people understood about being a trans scientist

By TL Jordan

very morning I wake up won- for many marginalized communities, my chest, but then some days I have dering: How many times will I but there is a particular isolation that to stay home because my body is sore E be misgendered today? How many comes with being a trans nonbinary from binding my chest, and it is too times will people call me something scientist. I look around my institu- dysphoric for me to go out in public I am not? How many times will I be tion and I don’t think I can name without wearing my binder. I’m not called a girl? How many times will I more than one other transgender trying to skip out on being produc- have to correct people awkwardly when individual working as a scientist. I tive, but this is di cult for me to they say “she” instead of using “they”? certainly can’t name a trans member explain to my colleagues. I feel tired How many times will my identity of the faculty. In my entire Ph.D. and degraded, and all of this aects be invalidated today? training, I will never have a mentor my ability to do science. While I’ve been out as a queer, non- who shares my identity and my most graduate students are worrying binary trans person for almost two experiences. about their Western blots or their years. I realized I was nonbinary my And that is one of the most qualifying exams, I’m also worrying senior year of undergrad and came isolating truths that I have to endure about whether insurance will cover out my rst year of graduate school every day. the services I need, gritting my teeth in a place where there were no other Most of the faculty and students at having to gender myself on forms trans people for support and very I work with still struggle to use my and struggling to breathe in my chest few LGBTQ people. My entire life pronouns (they/them) on a regular binder. I have dreamed of being a scientist, basis. On top of my normal lab I also question my safety. In exploring the world and spending duties, grant writing and planning bathrooms I get yelled at or catch my time learning. Being nonbinary for qualifying exams, I have to go people giving me side eye. I have to has changed many of my interac- through each day being beaten down remember where the nearest gen- tions within science and academia. and invalidated. People I’ve met der-neutral bathroom is on campus; Coming out as a trans scientist many times refer to me in emails as there isn’t one on any of the research immediately isolated me and made “she” and “her.” On an average day, oors in my building. Walking the simplest tasks hostile and full at least ve people will misgender around the city or in the halls of my of fear. A day in the lab wasn’t just me (if not more). I don’t always have institution, people stare at me. I hear spent learning and working but also enough energy to correct them. If cat calls and slurs from passing cars. questioning how much invalidation I my day is lled with meetings, by Every time I reach out to some- would endure. afternoon I’ve had to a rm my gen- one to start a new collaboration or Questions of identity and identi- der in my head about 30 times after get advice on a project, I wonder if ty invalidation plague many mem- others have projected an incorrect they will refuse to work with me be- bers of the trans community. I know gender on me. I try to spend most of cause I am trans. Will my science be I’m not alone. Many of us are scared my time in the safe haven of my lab impeded because someone believes and have to spend time assessing if a or my desk. At least the cells I’m cul- that I shouldn’t exist? It’s a fear that space is safe before we enter it, trying turing won’t misgender me; at least I have to live with constantly, every to determine if we are welcome. But the few people in my lab understand time that I branch out and meet being a trans scientist seems to make and make an eort to use my correct someone new. I have yet to experi- these questions more common. pronouns. ence this level of discrimination, but Academia lags far behind in I experience gender dysphoria if when I see headlines every day about becoming an inclusive environment I go out in public without binding another trans person being shot or

OCTOBER 2019 ASBMB TODAY 65 ESSAY

With the confidence of feeling comfortable in my own skin, I have improved my speaking skills, and I am more willing to be a champion and speak for those LGBTQ people who aren’t out or aren’t comfortable speaking out against the injustices in STEM.

courtrooms determining whether my outspoken about being nonbinary discussed what it’s like to have to identity exists, it keeps the fear alive and trans. Coming out turned me come out every time I meet someone in the back of my head. into a more condent person, and new in school — or decide whether e idea of presenting my work I really enjoy the person that I have coming out is the smart thing to do. at a conference is both thrilling and become. I am more comfortable in In addition to relating to another terrifying, because there’s a good my own skin than I have ever been. trans person about day-to-day strug- chance I’ll be the only trans person I can dress in the way that I feel gles, it’s incredible to be a rmed there — the only person who has comfortable, and I have become less and see that other trans scientists are scratched their pronouns on their apologetic about doing so. I like to doing wonderful work. I don’t get name badge. I wonder if people will wear T-shirts that say things like to see them doing their science in judge my science dierently because “Nonbinary Icon” or “No TERFs” person, but Twitter helps me feel less of my identity. (trans-exclusionary radical feminists) isolated. Existing as a trans scientist because I feel a rmed in my gender I am proud to be a trans nonbi- means compartmentalizing that fear and my beliefs. Unfortunately, being nary scientist. Despite the di culty whenever I meet new people, hoping out and proud as a trans person and isolation, I will continue to be and praying that I won’t have to comes with the baggage of misgen- myself in every way. Some days are answer dehumanizing questions like dering and discrimination. at’s the better than others; I don’t always “When is the surgery?” or “Are you a price I have to pay to be myself. have the support of allies around me. boy or a girl?” or “Why does it mat- With the condence of feeling But I will never be able to do science ter if I use they/them when referring comfortable in my own skin, I have successfully if I don’t put every ounce to you?” improved my speaking skills, and I of my own identity forward. To push Being a trans person in science am more willing to be a champion the forefront of science to be more means bearing the weight of igno- and speak for those LGBTQ people inclusive and diverse, I must make rance. I work overtime to advocate who aren’t out or aren’t comfortable academia a better place for up-and- for myself at my institution. I’m speaking out against the injustices coming trans scientists. trying to teach my department and in STEM. Being isolated from my My name is TL Jordan. I am institution how to create an environ- graduate school peers makes me trans. I am nonbinary. And I am ment that is safe for me and other want to work harder to be the non- proud of who I am. trans people. I nd myself doing an binary mentor in science that I’ve incredible amount of uncompensat- never had. ed work with the diversity depart- I am connected to many ments in my institution just because LGBTQ scientists through Twitter.

of my trans identity. ey have helped me navigate some TL Jordan (Jordan.Torri@ Some days, being a trans Ph.D. of the ins and outs of being trans mayo.edu) is a predoctoral student at the Mayo Clinic student feels like getting an educa- in science and commiserated with and an ASBMB Advocacy tion in hard mode. me about identity-related pressures Training Program delegate. Despite all this, I am incredibly that pile up on my already stressful Follow them on Twitter @TLJordanScience. proud of my identity. I am loud and plate as a Ph.D. candidate. We’ve

66 ASBMB TODAY OCTOBER 2019 2020 ASBMB–Deuel Conference on Lipids Fat in Liver and Beyond

MARCH 3 – 6, Hotel del Coronado, Coronado, Calif. Learn more, register and submit your abstract at www.asbmb.org/deuelconference/ Dec. 5: Early registration deadline Feb. 4: Abstract submission deadline

PROMOTING RESEARCH OPPORTUNITIES FOR LATIN AMERICAN BIOCHEMISTS PROLAB

The Promoting Research Opportunities for Latin American Biochemists (PROLAB) program allows Latin American graduate students and postdoctoral fellows to spend up to six months in U.S. or Canadian laboratories.

Sign up for updates at asbmb.org/pabmb/

OCTOBER 2019 ASBMB TODAY 67 ASBMB Student Chapters

The American Society for Biochemistry and Molecular Biology Student Chapters program is a national network of more than 100 chapters representing more than 2,000 undergraduate students and faculty members dedicated to the advancement of research, education and science outreach. The program provides networking and career-development opportunities at regional and national conferences and resources for research and science outreach, as well as funding and awards.

Reasons why you should start a chapter • Exclusive research and travel awards • Funding for outreach and undergraduate research projects • Funding for on-campus research symposia • Exclusive networking events with other faculty advisers • Student eligibility for the ASBMB Honor Society

Register your chapter by Nov. 20 to take advantage of these benefits. www.asbmb.org/studentchapters [email protected] CLASSIFIEDS

Drake University: Assistant Professor Perelman School of Medicine at the University of Pennsylvania: Faculty Position Department of Biochemistry and Biophysics -Junior Rank

The Chemistry Department at Drake University invites applications for The Department of Biochemistry and Biophysics at the Perelman a tenure-track assistant professor position, beginning August 2020, School of Medicine at the University of Pennsylvania seeks candi- in the area of biochemistry. Required: a PhD or ABD in Biochemistry dates for an Assistant Professor position in the tenure track, with or related eld. Applicants are expected to demonstrate a strong rank commensurate with the experience of the candidate. Expertise is interest in teaching undergraduates and the potential to establish required in the area of biophysics, including computational approach- es in biophysics and structural biology. We are particularly interested an active research program that engages undergraduate students. in investigators with a strong track record of outstanding accom- Teaching duties will include an introductory chemistry class as well as plishments. Applicants must have an M.D. and/or Ph.D. or equivalent courses in biochemistry. Drake University has an ACS-certi ed chem- degree. Teaching responsibilities may include contributing to graduate istry major, a biochemistry, cell and molecular biology major (BCMB), and medical school education of the University. and a biophysics concentration. Successful applicant will be highly creative, and must have demon- https://www.asbmb.org/Careers/Jobs/81360/ strated exceptional scholarly success in their eld. It is expected that the candidate chosen will establish an independent, extramurally funded research program. https://www.asbmb.org/Careers/Jobs/81188/

UC Davis: Assistant Professor Genentech, Inc.: Scientist, Early Discovery Biochemistry - Peptide Discovery, Protein Engineering, Biochemistry

The Department of Molecular and Cellular Biology, in the College of An opportunity for a creative, talented and highly motivated Scientist Biological Sciences, University of California, Davis, invites applications is available in the Department of Early Discovery Biochemistry. The for a tenure-track faculty position at the ASSISTANT PROFESSOR level. successful candidate will join a dynamic group pursuing cutting-edge The Department seeks outstanding candidates investigating funda- research in peptide drug discovery and development, and will inter- mental questions in modern biology that will add to or complement face with diverse therapeutic functions across Genentech including existing strengths in structural biology and biochemistry. oncology, ophthalmology and immunology. The successful candidate Competitive applicants must have a Ph.D. (or equivalent) in biological is expected to contribute to the discovery of peptides of therapeutic sciences-related elds and have demonstrated outstanding potential interest to modulate protein - protein interactions and understand in their eld. Candidates will be expected to develop a strong dynamic their mechanism of action by biochemical, biophysical and struc- independent research program and to share our commitment to tural biology methods. They will also contribute to the research and scholarly undergraduate and graduate education. We are especially interested in candidates who demonstrate an ability to integrate development of cutting-edge peptide discovery platform technologies multi-disciplinary approaches into their proposed research, including to enable the identi cation of new leads to support the Genentech cryo-electron microscopy. pipeline. Working with display technology experts, the individual will be expected to implement robust screening or selection methods https://www.asbmb.org/Careers/Jobs/81142/ coupled with next generation sequencing data analysis work’ ows as well as structural understanding to engineer peptides with speci c cellular functions. https://www.asbmb.org/Careers/Jobs/81369/ ANNUAL MEETING SAN DIEGO | APRIL 4-7, 2020

Community Binds Us Take your place among a diverse network at the 2020 ASBMB Annual Meeting. Attend high-caliber lectures, participate in hands-on workshops and team up with the best minds in your field to strengthen your life’s most important work. Discover your common bond. Priority consideration abstract deadline: Oct. 15 Regular abstract deadline: Nov. 14 Submit your abstract today! asbmb.org/meeting2020