Biochemistry OF A Burger - THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY - asbmb
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Vol. 18 / No. 9 / October 2019
T H E M E M B E R M A G A Z I N E O F T H E A M E R I C A N S O C I E T Y F O R B I O C H E M I S T RY A N D M O L E C U L A R B I O L O G Y
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
FEATURES PERSPECTIVES
PERSPECTIVES
2 32 62
ASBMB ELECTS OFFICERS AND BIOCHEMISTRY OF A BURGER SERVICE BEYOND SCIENCE
COUNCIL MEMBERS A professor among prisoners
40 65
4 UNDER THE SKIN AND OUT
MEMBER UPDATE IN THE WORLD ESSAY
What I wish people understood
812 young scientists win PROLAB awards 46 about being a trans scientist
10
RETROSPECTIVE
MEET QI-QUN TANG
48
Q&A: SANDHYA VISWESWARIAH
32
Wolfgang Karl Joklik (1926 – 2019)
14
NEW MEMBERS
16
First tooth controls where and when
the rest come in
48
18
JOURNAL NEWS
18 Peptides to the rescue
20 Researchers link new protein
40
to Parkinson’s
21 JBC launches program
for early-career scientists
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?
26 58
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
ASBMB elects officers
THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY
FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY
and council members
OFFICERS COUNCIL MEMBERS
Gerald Hart Suzanne Barbour
President Joan Broderick
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 Staff
Joan Conaway JoAnn Trejo
Treasurer
M
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 and Molecular Biology have and section chief at the National
Meeting Program Committee Natasha Brooks elected new officers and council Institutes of Health, where her lab
Kelly Chaćon
Cheryl Bailey
Beronda Montgomery members, and the society’s commit- focuses on the structural characteri-
Chair, Education and
Professional Development Bill Sullivan tees have appointed new members zation of proteins involved in DNA
Melissa Vaught
Committee
Binks Wattenberg
and leaders. mismatch repair and translesion
Daniel Raben
Chair, Meetings Committee
DNA synthesis.
Sonia Flores
ASBMB TODAY Officers
Chair, Minority Affairs
Angela Hopp
Executive Editor Toni Antalis is Council members
Committee
ahopp@asbmb.org serving for one year, Three members have joined the
Nicole Woiowich Comfort Dorn
Chair, Science Outreach and starting in August, society’s governing council. Their
Managing Editor
Communication Committee
cdorn@asbmb.org as president-elect, three-year terms began in August.
Terri Goss Kinzy
Chair, Public Affairs
Lisa Schnabel followed by two
Graphic Designer
Advisory Committee Antalis years as president Suzanne
lschnabel@asbmb.org
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 jarnst@asbmb.org
Chair, Women in Biochemistry served two three-year terms as Education and
Laurel Oldach
and Molecular Biology Science Writter ASBMB treasurer and chaired the Professional
Committee loldach@asbmb.org
Publications Committee. Antalis Barbour Development
Sandra Weller Ed Marklin
Chair, Publications Web Editor is a professor of physiology at the Committee, is
Committee emarklin@asbmb.org 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
africk@asbmb.org 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
bgordon@asbmb.org program in molecular medicine and Barbour also has served on the
Editor-in-chief, JLR
the graduate program in life scienc- Minority Affairs 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 mperlowitz@pminy.com. 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 reflect solely the authors’ views and not Yang ciety’s Mildred Cohn spectroscopic and synthetic approaches
the official positions of the American Society for Biochemistry and Molecular
Biology or the institutions with which the authors are affiliated. Mentions of
Award in Biological to elucidate detailed chemical
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 Schiffer of the University of Massachusetts
the Public Affairs 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 Affairs 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 Affairs Committee.
ASBMB symposia program call for submissions
The ASBMB symposia program
aims to provide niche segments
of the scientific community with
opportunities to present unique,
cutting-edge science and engage
in active networking opportunities.
Help advance your field 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 Staff
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.”
The pair, who were honored with the American The 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. “Their 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 The 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
The 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
fluorescence indicates aggregation. The 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 The program allows undergraduate
Clinical Biochemistry. and graduate students in science, engineer-
The award was established in 1993 to recognize those ing, technology and math fields to spend 10 weeks learn-
who have made “unique contributions in laboratory medi- ing the ropes of scientific 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
certificate 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 The 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. The 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 COURTESY OF DAN DRIES
combine an ecologically respon-
sible product with outreach to
their community. Rinku Chewy
is a homemade organic chewing
gum that, when returned to the
company, is repurposed as filler
for shoe soles. These 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 Koffler, president emeritus of the Univer- John Tymoczko, an emeritus professor at
sity of Arizona, died March 10 at age 95. Carleton College in Northfield, Minnesota, died
Koffler fled 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, Koffler 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.”
flagella, structures important for bacterial motility. His teaching extended beyond the Carleton
In one line of inquiry, Koffler and colleagues showed campus; along with Jeremy Berg and Gregory
that flagellar enzymes from thermophilic bacteria are Gatto, Tymoczko co-authored five editions of the
more heat-stable than flagella from their less classic textbook “Biochemistry” by Lubert Stryer
heat-resistant relatives. used by college students across the country.
Beginning in 1975, Koffler 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 Koffler’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.
asbmbtoday@asbmb.org.
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
Solving the enigma
tions and information systems.
When his military service ended, Sauer
of the sphinx, one
attended Cornell University and then earned his
medical degree at the University of Rochester
sphingolipid
and his Ph.D. from the Rockefeller Institute in
New York. He spent several years doing research
at Yale University before joining Bassett in 1975.
During his career at Bassett, a teaching at a time
hospital now affiliated 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/
fly fishing 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
T
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
Latin American Biochemists program to advance Biology have given 71 biochemists these travel awards.
their research by working directly with collaborators in This 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.
The 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
affiliated 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. “This 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 significance
and physicians,” Barrachina said. of our project and nourish an important collaboration to
help unveil the effects 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 Thomas 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. The identification 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.” field 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 Scientific 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. “This 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 affects tRNA repertoire
8 ASBMB TODAY OCTOBER 2019and 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 different 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 inflammatory/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 Pontifical 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 offset 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 9RETROSPECTIVE
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 “The Influence
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-
There, he and his younger brother Günther assumed the berra, where he remained until 1962. There 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 first 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 2019Research 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 defined 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 modifica- hensive Cancer Center in 1971 and founder and first
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 purifica- 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 purification 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 finally 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. These 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.
DUKE UNIVERSITY
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
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 findings in both loca-
tions were characterization of the reovirus segmented dou-
ble-stranded RNA genome and its transcripts, identifica-
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 11RETROSPECTIVE
“Zinsser’s Microbiology,” for several years a leading text-
DUKE UNIVERSITY
book for medical students.
Bill was elected to the National Academy of Sciences
in 1981 and the Institute of Medicine of the NAS in
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.
The 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
The 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 (jack.keene@duke.edu) is the James B. Duke
professor of molecular genetics and microbiology at the Duke
University School of Medicine.
Charles E. Samuel (samuel@lifesci.ucsb.edu) 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, Helene,talks with Johns Hopkins colleague Yadong Wei at his apartment in
Tom August
in 1943, when both boys were students at Cranbrook Academy.Baltimore,
Bill, bornabout a month
Johnbefore his death.
J. Skehel August kept workingisonanhisemeritus
(John.Skehel@crick.ac.uk) 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 project
Nationaluntil the very
Institute for end. When
Medical he couldMill
Research, no longer go to
Hill, London.
born in 1928, was elected to the National Academy of Engineering at Wei would stop by the apartment a few times each week.
his lab,
approximately the same time. Frank presented a eulogy at Bill’s funeral.
A ASBMB
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OCTOBER 2019 ASBMB TODAY 13NEW MEMBERS
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Lipoprotein (a): Many
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strides made, yet there is
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OCTOBER 2019 ASBMB TODAY 15NEWS
First tooth controls where
and when the rest come in
By Karen Bascom
W
hether it’s a baby human, baby Bowdoin College in Maine studying dow passed, they were able to induce
zebrafish or anything else with tooth formation in these tiny fish. the growth of a 4V1 –like tooth,
teeth, those first pearly whites “It’s more difficult to study which was followed by 3V1 and
form in an orderly fashion. They 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, zebrafish 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 five days.” a 4V1 tooth form in an area of the
This timing of teeth wasn’t lost Zebrafish embryos start to grow throat where it doesn’t usually grow.
on A. Gordon Edmund, a paleontol- their first tooth, called 4V1 for its The 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 fish’s throat, about 48 hours ifying the formation of the initiator
why: that the first 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 first tooth’s timing, fibroblast 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
WILLIAM JACKMAN, BOWDOIN COLLEGE
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 first tooth was both
the Cancer Institute and Research necessary and sufficient for the other
Center in 2018. teeth to form but didn’t think we
In his research, Gibert uses would fully show that FGF is the
zebrafish primarily to study new likely transmitter.”
therapeutics for cancer and meta- “The 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 2019College who studies organ formation UMMC
in animals. “There’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. The
same is true for other aspects of anat-
omy, physiology and biochemistry.
“If you look at a zebrafish pancreas,
you will see the same molecular and
cellular mechanisms as a mammal
pancreas.”
This 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 fishes
and reptiles is very efficient. Think for ways to regrow teeth, using they would be a billionaire,” Gibert
of sharks, who can replace teeth techniques including gum line-de- said. “This 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 confirm Edmund’s idea.
evolutionary time, “humans and terms of genetic instruction in order That’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 This 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 (kbascom@umc.edu)
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 finned friends. the Office of Institutional
Advancement, University
and they break. Scientists at oth- “If someone could figure out a of Mississippi Medical
er universities are already looking way to regenerate teeth in humans, Center.
OCTOBER 2019 ASBMB TODAY 17JOURNAL NEWS
Peptides to the rescue
By Martin J. Spiering
I
nsulin and glucagon are well- venting or managing type 2 diabetes,
LUNENFELD–TANENBAUM RESEARCH INSTITUTE
known peptide hormones that in which beta-cell apoptosis may
keep our glucose levels within a contribute to insufficient 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-
beta cells against stresses that lead to ta-cell death, in the presence and ab-
dysfunction or cell death. sence of the specific GLP-1R agonist
One of these protective regu- exendin-4. The authors then assessed
lators is glucagonlike peptide 1, or the effect 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 find 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 findings, JBC reached out to
peptides that mediate the incretin Drucker, now at the Lunenfeld– discoveries. First, pharmacological
effect, 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. This 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. Specifically, 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
The incretin effect 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 Third, 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 purified rat beta
incretin effect by showing that GLP- cells exposed to cytotoxic cytokines,
1R signaling protects beta cells from What were your main findings? a model of tissue inflammation.
cell death. This is significant for pre- We made several interesting We also discovered that GLP-1’s
18 ASBMB TODAY OCTOBER 2019anti-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- This 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. The first 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 field continues to grow.
and became the first 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 field 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 This is a little difficult to appre-
receptor as is sometimes the case overlapping functions with other ciate. The 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 first
activation by agonists downregulates Both GLP-1 and another pep- studies to highlight a cytoprotective
this receptor. This fortuitous finding 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 findings expected, and high clinical relevance.
how has your own work and the Drucker and Li’s paper was nomi-
field progressed since your paper’s nated as a JBC Classic by JBC Associ-
publication? ate Editor Eric Fearon at the Univer-
SWEDBERG ET AL./JBC
Before our study, I don’t think sity of Michigan Medical School. This
anyone had clearly addressed the article originally appeared in JBC. It
question of whether GLP-1R sig- has been edited for ASBMB Today.
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 (mspiering@asbmb.org)
is the technical editor at
The small peptide GLP-1 (green ribbon) binds 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 field, research into on Twitter @spieringmj.
them against injury and death. both the basic science and clinical
OCTOBER 2019 ASBMB TODAY 19You can also read
