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2 23 54 PRESIDENT’S MESSAGE MEET JEAN SCHAFFER ESSAY Are we more than biochemists Tracing the lipid path e recommendation letter conundrum and molecular biologists? from diabetes to heart disease 56 3 28 RESEARCH SPOTLIGHT NEWS FROM THE HILL ANNUAL MEETING Seeking to understand the rules of life — Raise the caps one last time 29 Award winner pro les and taking life lessons from dogs 43 Beyond federal funding 44 Professional development — 4 it’s not just for grad students NEWS 58 46 Scan and connect NIGHT SHIFT Member update 47 Carbs got you down? Struggle of choice 48 Welcome to Orlando 51 Getting around Orlando 7 52 Annual meeting round-up RETROSPECTIVE 60 Julian B. Marsh (1926 – 2018) OPEN CHANNELS 23 Credit for discovery and a patenting ga e 10 LIPID NEWS 54
PI(3,4)P2 : A versatile lipid second messenger 11 JOURNAL NEWS 11 A change in labs reveals a key to cataract formation 13 Proteogenomics researchers zero in on causes of immune disease 44 58 14 ‘Almost like a Velcro ball’ 15 J LR launches junior associate editors program 16 From the journals 21 A YEAR OF (BIO) CHEMICAL ELEMENTS For April, it’s copper — atomic No. 29 48 14
APRIL 2019 ASBMB TODAY 1 PRESIDENT’S MESSAGE
THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Are we more
OFFICERS COUNCIL MEMBERS Gerald Hart Squire J. Booker than biochemists President Victoria J. DeRose Blake Hill Jennifer DuBois Audrey Lamb Secretary James M. Ntambi Celia A. Shi er and molecular Toni M. Antalis Treasurer Takita Felder Sumter Kelly Ten-Hagen JoAnn Trejo EX-OFFICIO MEMBERS David Bernlohr biologists? ASBMB TODAY EDITORIAL Hao Wu ADVISORY BOARD Co-chairs, 2019 Annual By Gerald Hart Meeting Program Rajini Rao Committee Chair Cheryl Bailey Floyd “Ski” Chilton Chair, Education and Henrik Dohlman f you read the research interests of are working on. is creates a highly Professional Development Peter J. Kennelly a faculty member at any university interactive and intellectually stimulat- Committee Beronda Montgomery or medical school, it is nearly im- ing environment. A. Maureen Rouhi I Daniel Raben Melissa Vaught possible to tell whether the scientist is Fusing basic science departments Chair, Meetings Committee Binks W. Wattenberg a biochemist, molecular biologist, cell into one large unit can result in Sonia Flores Chair, Minority A airs ASBMB TODAY biologist or biophysicist. Some deans unexpected consequences. First, when Committee Angela Hopp have used this fact to justify fusing sta and faculty no longer enjoy close Susannna Greer Executive Editor basic science departments into single interactions, administrative support Chair, Public Outreach [email protected] large units. is is a huge mistake. su ers, making applying for grants Committee Comfort Dorn e topics might look similar, and dealing with paperwork more Matthew S. Gentry Managing Editor Chair, Public A airs [email protected] but a biochemist, cell biologist and di cult; the fusion of departments Advisory Committee John Arnst biophysicist all think di erently about does not save any money, but it does Sandra Weller Science Writer [email protected] biological problems. For example, a muddy the reporting lines and ac- Chair, Publications Committee Laurel Oldach biochemist studies biology at the mo- countability of the sta . Second, the Science Writter lecular level and tries to understand larger unit fractures into unpredict- Lila M. Gierasch [email protected] Editor-in-chief, JBC Ed Marklin the chemistry of living processes, able splinter groups, making it dif- A. L. Burlingame Web Editor whereas a cell biologist studies life cult to maintain collegiality and the Editor, MCP [email protected] processes typically at the organelle or overall intellectual environment. Allison Frick Nichilas O. Davidson Media Specialist more macroscopic level, and a bio- I believe it is best to maintain Editor-in-chief, JLR [email protected] physicist focuses on the atomic level. small, focused basic science depart- Kerry-Anne Rye Barbara Gordon At most universities and medical ments but create synergy with cross- Editor-in-chief, JLR Executive Director [email protected] schools, basic science departments are departmental centers and institutes small enough that all the faculty know in some detail what their colleagues CONTINUED ON PAGE 6
For information on advertising, contact Pharmaceutical Media Inc. at 212-904-0374 or [email protected]. Corrections In the March issue, the item title “Neuronal GIRK currents and blood cholesterol level” on page 17 should have stated that Anna Bukiya of the University of Tennessee Health Science Center and Avia Rosenhouse- Dantsker of the University of Illinois at Chicago led a team that published www.asbmb.org/asbmbtoday in the Journal of Lipid Research. PRINT ISSN 2372-0409 In the March issue, a pro le article on page 34 misstated Fan Liu’s Articles published in ASBMB Today re ect solely the authors’ views and not professional positon. She is a new faculty member at the Leibniz-Forsc- the ocial positions of the American Society for Biochemistry and Molecular Biology or the institutions with which the authors are aliated. Mentions of hungsinstitut für Molekulare Pharmakologie in Berlin. products or services are not endorsements.
2 ASBMB TODAY APRIL 2019 NEWS FROM THE HILL Raise the caps one last time By Benjamin Corb
e National Institutes of Health Congress immediately began talk- 10 percent cut would be devastating has seen a recent funding boom remi- ing about eliminating — or raising for all domestic priorities, including niscent of a period in the late 1990s — the caps on defense spending. In investments at the NIH and National and early 2000s when the agency’s response, thousands of organizations Science Foundation. budget doubled. e NIH budget representing constituencies supported e NIH has bene ted from the has increased by $9 billion since scal by nondefense discretionary, or Raise the Caps e ort. NDD United’s year 2015 (nearly 25 percent), and NDD, spending (investments in sci- latest letter to Congress (sent in the American Society for Biochemis- ence, for example), started a coalition March) made the case for a discretion- try and Molecular Biology, along with named NDD United. e ASBMB is ary caps increase, highlighting recent other scienti c societies, is calling for a leader in NDD United, and I am a investments in the NIH budget. a continuation of this growth in the national co-chair. NDD United’s op- “Previous bipartisan budget deals have coming year’s budget. erations currently are managed by the provided spending cap relief that has Remarkably, the recent period of ASBMB’s public a airs sta . allowed Congress to more adequately NIH budget increases has occurred For eight years, NDD United suc- fund services essential to Americans at a time when legislative budget caps cessfully has lobbied Congress to raise nationwide. For example, funding for limit the federal government’s annual spending caps on both defense and biomedical research has grown, allow- discretionary spending. nondefense priorities. anks to the ing scientists to conduct research and In 2011, in response to a balloon- coalition’s Raise the Caps advocacy discover life-saving treatments and ing federal debt and de cit, President e orts, Congress has passed bipartisan cures,” the letter states. Barack Obama formed a bipartisan budget agreements every two years e ASBMB urges Congress to super committee to develop scal for the past six years that resulted in work toward a plan to raise the caps policies that would restrain federal steadily increasing nondefense discre- for the nal two years of the BCA, spending. e e ort resulted in adop- tionary caps. allowing for sustained funding in tion of the Budget Control Act of e last budget agreement raised priorities such as biomedical research. 2011, or BCA, which limited both the caps for scal years 2018 and is deal would last through scal defense and nondefense discretion- 2019. e caps from the original 2021 and end the threat of spending ary spending for the next decade. 2011 law are back for scal 2020 cuts that will be mandatory if the caps e caps were intended to control and 2021, and without a plan to are not raised. spending and ensure limits on both raise them, continued increases to Republican and Democratic priorities the NIH budget are at risk. Spend- Benjamin Corb (bcorb@asbmb. (defense spending and social safety ing cap levels now in place for scal org) is director of public affairs net programs, respectively). 2020 represent a $55 billion cut to at the ASBMB. Follow him on e defense community criticized nondefense discretionary spending Twitter @bwcorb. these caps as draconian, and the U.S. from scal 2019 levels. is nearly
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APRIL 2019 ASBMB TODAY 3 MEMBER UPDATE Member update By Erik Chaulk
Weiss named Indiana U signi cant contributions to the eld support future research endeavors. of glycobiology. e foundation is honoring Schul- distinguished professor Taniguchi began his career on the man for her work in the elds of Indiana University has appointed faculty at Hokkaido University, where biochemistry and structural biology Michael A. Weiss, the Robert A. he rst focused his research in glyco- on the molecular mechanisms of the Harris professor of biochemistry and biology. In 1986, he was appointed ubiquitin system. molecular biology, professor and chair in the department Before joining the Max Planck as a distinguished of biochemistry at Osaka University Institute, Schulman served on the professor. School of Medicine, where his re- faculty at St. Jude Children’s Re- Weiss is one search group studied the structure and search Hospital and as an investigator of 10 IU faculty function of N-linked glycans. with the Howard Hughes Medical members who in After he retired from the univer- Institute. WEISS December received sity in 2006, Taniguchi continued In 2018, she was appointed an distinguished professorships, the his research as an endowed chair and honorary professor with the Technical university’s highest academic rank for professor emeritus. He also served University of Munich. educators or researchers. as director of the Distinguished professors are chosen systems glycobiol- In memoriam: for their outstanding achievement in ogy research group teaching, scholarship, innovation and at the RIKEN Laszlo Lorand leadership. research institute Laszlo Lorand, professor emeritus from 2007 to 2018. Weiss’ research focuses on two ar- TANIGUCHI at Northwestern University, died Dec. eas: insulin signaling with application He is now the 6. He was 95 years to diabetes mellitus and sex determi- director of the research center at the old. nation with application to genetic Osaka International Cancer Institute Born in Győr, infertility syndromes. and head of the department of glyco- Hungary, in 1923, In 2009, he founded ermalin oncology and medical biochemistry at Lorand attended Inc., a biotechnology company that the same institute. the University of LORAND designs and develops novel insulin Budapest, where analogs. Schulman wins he studied medicine. He earned a Weiss and the other distinguished Leibniz Prize Ph.D. in biomolecular structure at the professors were honored in March at University of Leeds in 1951. the university’s distinguished professor Brenda Schulman, director at the Lorand taught physiology and symposia. Max Planck Institute of Biochemistry, pharmacology at Wayne State Univer- is among the 10 re- sity School of Medicine before joining Glycobiology society cipients of the 2019 the Northwestern University faculty Leibniz Prize. in 1955. honors Taniguchi Established At Northwestern, he was a found- e Society for Glycobiology has in 1985 by the ing member of the department of cell German Research and molecular biology as well as the given the 2018 Karl Meyer Award to SCHULMAN Osaka University professor emeritus Foundation, the rst director of an National Institutes Naoyuki Taniguchi. Leibniz Prize recognizes outstanding of Health-funded biochemistry train- Established in 1990 in honor of achievement in the eld of research. ing program. German biochemist Karl Meyer, this Germany’s most prestigious An author on more than 200 sci- award recognizes a scientist with an research award, the prize comes with enti c publications, Lorand focused active research program who has made $2.85 million (2.5 million euros) to his research on thrombosis, protein
4 ASBMB TODAY APRIL 2019 associations and calcium ions. He was preceded in death by his In memoriam: Paul T. Englund wife, Joyce Bruner–Lorand, and is survived by his daughter, Michele Paul T. Englund, Johns Hopkins University professor emeritus, died Lorand. Jan. 12 of advanced Parkinson’s disease. He was 80 years old. Born in Worcester, Massachusetts, in 1938 to eodore and Mildred Englund, he studied chemistry at Hamilton College, receiving a bachelor’s In memoriam: Subir Bose degree in 1960. He earned a doctorate in biochemistry at Rockefeller Uni- Subir Kumar Bose, professor versity in 1966 before taking a postdoctoral position at Stanford Univer- emeritus of microbiology and internal sity with Nobel laureate Arthur Kornberg. medicine at St. Louis University, died Englund joined the faculty at Johns Hopkins as an associate professor July 25. He was 86 in the department of physiological chemistry in 1968 and remained there years old. until his retirement in 2010. He became a full professor in the department Born in Gaya, of biological chemistry in 1980. India, Bose earned He was known widely for his research on trypanosomes, parasitic undergraduate and organisms that cause African sleeping sickness. graduate degrees Among his positions, Englund served as a visiting scientist at the Inter- BOSE from the Univer- national Laboratory for Research on Animal Diseases in Nairobi, Kenya, sity of Lucknow. After moving to the in 1980. United States in 1958, he completed a He was highly esteemed as a teacher and mentor; in 2016, his former Ph.D. in molecular biology at Wash- trainees contributed funds toward an endowed ington University in 1963. professorship in his name. Bose joined the St. Louis Univer- Tamara Doering, endowed professor of mo- sity School of Medicine’s department lecular microbiology at Washington University of microbiology in 1965. He was School of Medicine in St. Louis and a former appointed associate professor in 1968 Englund trainee, was quoted in a Johns Hopkins and became a full professor in 1976. press release, saying, “Paul was a brilliant and He served as interim chair of the de- creative scientist whose excitement and enthusi- ENGLUND partment of microbiology from 1989 asm for research never agged … He was also an to 1991 and was appointed professor inspiring and supportive mentor, who taught generations of trainees to do of internal medicine in 1991. rigorous and collegial science.” Bose’s research focused on under- Englund was elected as a fellow of the American Association for the standing cell-to-cell interactions in Advancement of Science in 2000 and elected to the National Academy of intracellular infections, for which Sciences in 2012. he received the United States Public He is survived by his wife, Christine Schneyer Englund; his two broth- Health Service research career devel- ers, Robert J. Englund and Donald R. Englund; and his four children, opment award. Suzanne Elizabeth Pykosh, Maria Jean Englund, Jennifer Insley–Pruitt Highly regarded as an educator, and Peter Insley. Bose hosted many Indian students and postdoctoral fellows at his lab. After retiring in 1993, he moved to Athens, Greece, to live with his wife Send us your news and collaborator, Evangelia Vretou, re- search director at the Hellenic Pasteur Institute. Have you recently been promoted or honored? Erik Chaulk ([email protected]) Do you have good news to share is a peer-review coordinator and digital publications web specialist with your fellow ASBMB members? at the ASBMB. Email us at [email protected] — and don’t forget to include a photo!
APRIL 2019 ASBMB TODAY 5 CONTINUED FROM PAGE 2 begat focused societies such as the their governance structures. Perhaps American Society for Cell Biology, the it’s time for the ASBMB to consider and a joint umbrella graduate pro- Society for Neuroscience, the Protein creating, for example, the Omics and gram. us, each department main- Society and the RNA Society, some of Systems Biology Division, the Me- tains its culture, but cross-departmen- which are now larger than the tabolism Division, the Glycobiology tal interactions are encouraged. ASBMB. Many biochemists and and Extracellular Matrix Division, the Similarly, the American Society for molecular biologists now identify Enzymology Division, and so on. Of Biochemistry and Molecular Biology themselves by the biological problems course, the members of these groups sometimes grapples with the chal- they study. A hardcore biochemist and society leadership would need to lenge of representing broad areas of who works with lymphocytes might determine what each division should molecular science. call himself or herself an immunolo- be called and what its focus and mis- I’ve heard members complain that gist, or researchers working on bio- sion would be. the annual meetings are too large and chemical processes in neurons might Each division, along with ASBMB do not include enough sessions on call themselves neuroscientists, but, in journals, could play a direct role in whatever topic they are interested in. reality, they are still biochemists. programming the national meeting In past meetings, we highlighted spe- As science evolves, does the and/or small meetings so its interests ci c themes, sort of meetings within ASBMB need to rethink its organiza- are not forgotten. e national meet- the meeting. ese themes kept the tional structure to remain relevant? ing could retain major lectures and meeting interesting to subgroups Several years ago, to prevent the educational activities of interest to within the society, but people ended lipid community from leaving the all members, but we could give each up interacting mostly within their ASBMB and forming its own society, division a block of time in which to small areas of interest. is downside Greg Petsko, then the president of the organize activities of interest to mem- was o set by larger lectures and award ASBMB, together with Dan Raben, bers in their elds. presentations that cut across disci- a lipids researcher at Johns Hopkins Should the ASBMB create formal plines and were attended by most of University, helped create the Lipid divisions to make itself more attrac- the membership. Research Division, or LRD, of the tive to members? oughtful feedback e ASBMB is the victim of its ASBMB. is subgroup has been suc- is welcome. own success. It used to be that nearly cessful and active and has helped keep this eld among the strongest groups everyone in a biochemistry or mo- Gerald Hart (gerald.hart@uga. lecular biology department belonged within our society. However, to date, edu) is a professor and Georgia to the American Society of Biological the LRD is the only such division Research Alliance eminent Chemists (the society’s name prior within the ASBMB. scholar at the University of Most major scienti c societies have Georgia and president of the to ASBMB) and went to the annual ASBMB. meeting. With time, the ASBMB created formal divisions as part of
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6 ASBMB TODAY APRIL 2019 RETROSPECTIVE Julian B. Marsh (1926 – 2018) By Edward A. Fisher, Michael C. Phillips, Daniel J. Rader & Ernst J. Schaefer
ulian B. Marsh, a pioneer in lipid and lipoprotein metabolism Jresearch and a past editor-in- chief of the Journal of Lipid Research, died Nov. 16 at the age of 92. He was a beloved mentor and colleague to many investigators in the lipid eld, including the authors of this tribute. Born in New York City in 1926, Julian attended the High School of Music and Art in Harlem. He moved to Philadelphia to study chemistry as an undergraduate and then medicine at the University of Pennsylvania; he earned his M.D. at the age of 21. After postdoctoral work in biochem- istry in David Drabkin’s laboratory at Penn, he spent a year at the Walter Reed Army Research Institute. Julian joined the faculty of the school of medicine at the University of Pennsylvania in 1954 as an as- sistant professor of biochemistry. He was awarded a Guggenheim Fellow- PHOTOS COURTESY OF MICHAEL C. PHILLIPS ship in 1960 to study at the Medi- Julian B. Marsh, pictured here in 1983, served as editor-in-chief of the Journal of Lipid Research from 1983 to cal Research Council Laboratory in 1986. London, where he investigated fatty acid metabolism with Anthony James. Back at Penn, he became a professor lipoprotein metabolism, an interest in the Journal of Biological Chemistry in 1963 and was chairman of the bio- he maintained for much of his career. reported the rst measurement of the chemistry department at the dental Another longstanding interest was the rate of synthesis of cholesterol in se- school from 1965 to 1975. biosynthesis of lipoproteins, and, in creted lipoproteins. Julian also helped With Drabkin and other col- collaboration with Arthur Whereat, develop a simple charring method leagues, Julian published a series of he used rat liver slices and perfusates for rapid quantitation of lipids (for papers on the e ects of nephrosis on to investigate this topic. A 1959 paper example, in column chromatogra- phy fractions); this work with David Weinstein was published in 1966 in Julian was the true embodiment of a gentleman and a scholar. the Journal of Lipid Research. Julian moved to the Medical He leaves a legacy of groundbreaking scientific discovery College of Pennsylvania in 1975 to ‘‘ in lipid and lipoprotein metabolism and a community of scholars chair the department of physiology and biochemistry, a position he held around the world whom he trained, mentored and provided until 1984. He and George Rothblat recruited faculty to form what became with collaborative advice. well known as the Philadelphia Lipid ’’ Group, which was supported for 35 APRIL 2019 ASBMB TODAY 7 Julian B. Marsh stands front and center in this group photo taken at the 1982 Lipoprotein Metabolism Gordon Research Conference in New Hampshire, which he chaired.
years by grants from the National mentored me and continued to col- the post-translational degradation of Heart, Lung and Blood Institute and laborate with me even after I moved to apolipoprotein B, or apoB. other institutes of the National Insti- New York, leaving a record of multiple tutes of Health. joint publications. Shortly after Julian Daniel J. Rader: As a rst-year medical At the Medical College of Penn- returned from a sabbatical with Paul student with no experience in bio- sylvania, Julian mentored three of the Nestel in Australia, a leader in the medical research, I fortuitously decided authors and promoted our interests in e ects of sh oils on very low-density to spend a summer working in the biomedical research in the lipoprotein lipoprotein production, he infected me laboratory of Julian and his collabora- eld. with his enthusiasm and helped get my tor Charles Sparks. A focus of their studies in this area o the ground. is research was the di erential metabo- Michael C. Phillips: Julian recruited me included both direct mentorship and lism of apoB100 and apoB48 (which from England and facilitated my entry sharing his wide network of scien- theyreferred to in conversation as big B into the U.S. lipoprotein research com- ti c colleagues; for example, I visited and little B) well before the discovery munity. We were members of the same Rochester to learn how to make primary of apoB mRNA editing. Julian was a research group, and I bene ted from rat hepatocytes and perform pulse- remarkably attentive mentor, ensuring many enriching discussions with Julian chase analyses of protein synthesis and that not only the scienti c concepts but about lipoprotein metabolism and also degradation from Charles and Janet also the methodologic details (in this from his insightful comments on draft Sparks. With characteristic generosity, case, of rat liver perfusion, endogenous manuscripts. Julian ceded leadership of his project on labeling, and separation of big B and a Philadelphia Lipid Group grant to little B) were taught e ectively and Edward A. Fisher: Julian recruited me me, resulting in a series of papers show- learned rmly. Julian permitted me as a junior faculty member, actively ing how fatty acids in sh oils regulated to continue working in his laboratory
8 ASBMB TODAY APRIL 2019 throughout medical school and without tenstein, Stefania Lamon-Fava and me the viola for many years in the Phila- a doubt prompted my entry into the in carrying out human apolipoprotein delphia Doctors Orchestra and, later, lipoprotein eld. metabolic studies. His former research in the Wellesley Symphony Orches- assistant Margaret Di enderfer took tra. He played tennis at a very high Julian also supervised M.D./Ph.D. over the responsibilty for the technical level, such that at many Lipoprotein candidate Joseph Bass on a nephrotic aspects of these studies. Gordon Research Conferences, much syndrome project that led to several younger opponents were seen to be publications on apoE and apoA-I in Colleagues marked Julian’s 80th losing while doing all the running. nephrosis. Bass is now a renowned birthday in 2006 when a symposium Julian was the true embodiment of molecular endocrinologist at North- on high-density lipoprotein me- a gentleman and a scholar. He leaves western University. tabolism was held at Tufts University. a legacy of groundbreaking scienti c In collaboration with Dennis During a special luncheon for his discovery in lipid and lipoprotein me- Cryer, Paul Coates and Jean Cortner 90th birthday in 2016, many former tabolism and a community of scholars at the Children’s Hospital of Philadel- colleagues called to congratulate him. around the world whom he trained, phia and Penn, Julian helped establish the methodology for studying human apolipoprotein metabolism using Julian was a man of character, warm and compassionate. His endogenous stable isotopic labeling, initially publishing this work in the advice was invariably wise and often leavened by humorous JLR in 1986. Endogenous label- ‘‘ puns. Always willing to help solve any problem, scientific or ing with stable isotopes allows for the simultaneous kinetic analyses of other, Julian was an oasis of calm and sage advice, focused on multiple apolipoproteins and permits pragmatic problem-solving. studies in children and women of child-bearing age. e methodology pioneered by Julian and his col- Julian was a man of character, mentored and provided with col- leagues was adopted rapidly by many warm and compassionate. His ’’laborative advice. He is remembered other investigators and has been used advice was invariably wise and often with great admiration and grateful extensively to understand lipoprotein leavened by humorous puns. Always a ection. metabolism in humans. willing to help solve any problem, He was predeceased by his wife, Soon after Julian retired from the scienti c or other, Julian was an oasis Priscilla, and is survived by a daugh- Medical College of Pennsylvania in of calm and sage advice, focused on ter, Gail, and two grandchildren. 1998, the Julian Marsh Faculty Schol- pragmatic problem-solving. After ar Award was created. Now an annual years of seeing a procession of people e authors thank Margaret Di end- award at Drexel University College of from graduate students to department erfer and Barbara Engle for valuable Medicine (which includes the legacy chairs come to his o ce, Peg Di end- research for this article. of the Medical College of Pennsylva- erfer commented he was truly a “Mr. nia), it has gone to 15 distinguished Fix-it.” winners to date. His over 100 publications, many Edward A. Fisher (Edward.Fisher@nyumc) is After he retired, Julian moved to of which have become points of the Leon Charney professor of cardiovascular Boston to be near his daughter and reference, reect Julian’s scienti c medicine at the New York University School of began a collaboration with the fourth abilities. He was editor-in-chief of the Medicine. author of this tribute. JLR from 1983 to 1986 and served as Michael C. Phillips (mcp3@pennmedicine. chair of the Lipoprotein Metabolism upenn.edu) is an adjunct professor of medicine Ernst J. Schaefer: Julian became a visit- Gordon Research Conference in 1982 at the Perelman School of Medicine, University of Pennsylvania. ing scientist in the lipid metabolism and chair of the American Heart laboratory at the Human Nutrition Association Arteriosclerosis Council Daniel J. Rader ([email protected]. from 1986 to 1988. His teaching was edu) is the Seymour Gray professor of molecular Research Center on Aging at Tufts Uni- medicine at the Perelman School of Medicine, versity. At weekly laboratory meetings of the highest quality, and in 1977 he University of Pennsylvania. and journal clubs, he never hesitated to won the Lindback Award for excel- lence in teaching. Ernst J. Schaefer ([email protected]) is provide his insights, to make presenta- a distinguished professor at the Tufts University tions and to provide suggestions with In addition to his scienti c prow- School of Medicine and the Friedman School of regard to our lipoprotein metabolic ess, Julian possessed exceptional musi- Nutrition Science and Policy at Tufts University. studies. He greatly helped Alice Lich- cal and athletic abilities. He played
APRIL 2019 ASBMB TODAY 9 LIPID NEWS
PI(3,4)P2: a versatile lipid second messenger By Hui Liu & Alex Toker
he phosphoinositide 3-kinase, or PI3K, signaling pathway has been Tstudied intensively since its dis- covery in the mid-1980s and has been found to play a critical role in the regulation of normal cellular physiol- ogy. e pathway is dysregulated in pathophysiologies such as cancer and diabetes. Much of this work focused on the lipid product of PI3K activity, PIP3, or PI(3,4,5)P3, derived from the phosphorylation of the membrane phosphoinositide PI(4,5)P2. PIP3 is a true lipid-derived second messenger: It is absent in unstimulated cells, it HUI LIU
is synthesized rapidly at sites of PI3K In phosphoinositide metabolism, PIP3, labeled PI(3,4,5)P3, is generated by phosphorylation of the precursor activation at the plasma membrane, it PI(4,5)P2 by the action of class I PI3-kinases, and the reverse reaction is generated by the phosphatase PTEN. is removed by the action of the lipid SHIP1/2 lipid phosphatases dephosphorylate PIP3 to generate PI(3,4)P2, which is degraded further by INPP4A/B to PI3P. Class II PI3-kinases also can generate PI(3,4)P by phosphorylating PI4P. phosphatase and tumor suppressor 2 PTEN, and it initiates PI3K signal re- lay by recruiting e ector proteins such PI(3,4)P2–binding proteins, ese discrete intracellular pools of as the serine/threonine protein kinase such as TAPP1/2 and lamellipodin, PI(3,4)P2 and PIP3 have remarkable Akt and downstream nodes such as link PI3K/PI(3,4)P2 to cytoskeletal consequences. In mammals, three Akt the mTOR pathway. remodeling. However, many proteins isoforms exist: Akt1, Akt2, and Akt3. By contrast, a separate lipid with modular domains that directly Genetic ablation studies have shown product of PI3K, PI(3,4)P2, remained bind to PIP3, including Akt, also that Akt isoforms play a non-redun- largely out of the limelight. Recent bind to PI(3,4)P2. is has hampered dant role both in normal develop- studies point to an important role identi cation of any potential unique ment and in diseases such as cancer. for this neglected lipid second mes- signaling roles for PI(3,4)P2. Ad- Although a few isoform-speci c senger, with some surprises. Unlike vanced high-resolution live cell imag- substrates have been identi ed, of the PIP3, PI(3,4)P2 can be generated by ing and microscopy show that PI(3,4) 200-plus Akt substrate proteins iden- ' more than one route of synthesis. 5 P2 is localized predominantly at early ti ed, most are not unique to any one phosphoinositide phosphatases can endosomes, although some plasma Akt. So how is speci city achieved? dephosphorylate PIP3 to generate membrane localization is also evident. Recent research shows that Akt1 and PI(3,4)P2. Alternatively, class II PI3- In growth factor signaling, this pool of Akt3 are activated speci cally by the kinases can use PI4P as a substrate PI(3,4)P2 seems to be generated pre- plasma membrane PIP3 pool, whereas to generate PI(3,4)P2. And PI(3,4)P2 dominantly by the action of phospha- Akt2 seems to be exclusively localized can be degraded by lipid phosphatases tases acting on PIP3. In contrast, PIP3 and activated by the endomembrane such as PTEN and INPP4B — tumor is localized exclusively at the plasma pool of PI(3,4)P2, at early endosomes suppressors frequently inactivated in membrane, where class I PI3-kinases human cancers. are activated. CONTINUED ON PAGE 12
10 ASBMB TODAY APRIL 2019 JOURNAL NEWS A change in labs reveals a key to cataract formation Researchers studying lens crystallin proteins describe how two types of damage interact By Laurel Oldach
esearchers working to understand the biochemistry of Rcataract formation have made a surprising nding: A protein that was long believed to be inert has an important chemical function that protects the lens of the eye from cataracts. e lens is made up of cells packed with structural proteins called crystallins that form a dense gel. e gel’s optical properties — such as its transparency and the way it refracts light — help focus light onto the retina. But when crystallin proteins clump together, they scatter incoming light, forming cloudy deposits known as cataracts. According to Harvard postdoctoral fellow Eugene Serebryany, lead author on a study in the Journal of Bio- logical Chemistry, researchers long ACELA 2038/WIKIPEDIA believed that crystallin proteins were chemically inert; except for aggregat- Though the labs where Eugene Serebryany did his graduate and postdoctoral research were just two stops ing over time, the proteins were not apart on the subway, he had trouble replicating his experiments when he moved. Figuring out what had changed led to a discovery in cataract formation. supposed to interact much with other proteins. As a graduate student at the who collaborated with Serebryany a protein everyone had thought was Massachusetts Institute of Technol- and his graduate adviser, Jonathan inert was causing a slightly damaged ogy, Serebryany used a mutant form King, on the earlier studies, described version to get much worse — and of gamma-crystallin to mimic the the nding as “fairly striking.” fast. Shakhnovich hired Serebryany damage ultraviolet light causes the “If you had these damaged proteins at Harvard to continue studying how protein. While studying how that in a test tube, they would not aggre- a supposedly inactive protein could mutation leads crystallin to clump up, gate for a while,” Shakhnovich said. cause this e ect. Serebryany found something surpris- “If you had the wild-type protein, But Serebryany had trouble ing: e mutant was more likely to it would not aggregate forever. But replicating the results of his own ex- aggregate if wild-type, or undamaged, then, when you mix the two, you see periments. “It’s a di erent place, it’s a protein was also present. rapid and precipitous aggregation.” Eugene Shakhnovich of Harvard, Somehow, the healthy version of CONTINUED ON PAGE 12
APRIL 2019 ASBMB TODAY 11 LIPID NEWS
CONTINUED FROM PAGE 10
and also early lysosomes. In the latter stream e ects, although this has yet case, upon nutrient deprivation, class to be demonstrated rigorously. ese Hui Liu ([email protected]. edu) is an instructor in pathol- II PI3-kinases produce PI(3,4)P2 at observations begin to ascribe a critical ogy and a researcher in the the lysosome, leading to suppressed role for PI(3,4)P2 in cell biology and Toker lab at Beth Israel Deacon- mTORC1 activity. Class II PI3- also explain the roles of Akt isoforms ess Medical Center. kinases also been have implicated in in phenotypes associated with disease. Alex Toker ([email protected] the formation of clathrin-mediated Questions remain about the vard.edu) is a professor in the endocytic cups leading to vesicle s- intracellular localization of PI3K lipid department of pathology and sion, a process shown to be mediated second messengers and their e ectors. chief of the division of signal transduction in the departments by PI34P2. e answers will come from contin- of medicine and pathology and A picture begins to emerge: ued advances in imaging technologies the cancer center at Beth Is- rael Deaconess Medical Center, Discrete pools of PIP3 and PI(3,4)P2 using live cells and tissues, giving a selectively activate Akt isoforms lead- more complete picture of how speci- Harvard Medical School, and a Journal of Biological Chemistry ing to presumably unique substrate city is achieved in this versatile lipid associate editor. Follow him on phosphorylation patterns and down- signaling pathway. Twitter @alex_toker.
CONTINUED FROM PAGE 11
di erent set of instruments, a slightly “Not only did the aggregation-prone protein molecules like a hot potato. di erent set of procedures. You see mutant acquire one internal disul de Given a whole population of where this is going,” he said. “All of a bond per molecule during the aggre- undamaged crystallin proteins, that sudden, experiments that were highly gation reaction, but the aggregation- could go on inde nitely. But if one reproducible before were giving a lot promoting wild-type protein lost its protein was already a little damaged, of variability.” disul de at the same time.” the authors showed, it caught the hot In the Harvard lab, the wild-type By mutating crystallin’s sulfur-con- potato with a di erent set of cyste- crystallin sometimes caused mutant taining cysteine amino acid residues ines, which were less able to pass it crystallin to aggregate, and sometimes one by one, Serebryany found that on. is drove the damaged protein it didn’t. two residues close together on the to aggregate. “Obviously, if there is suddenly surface of the protein acted as a kind According to Shakhnovich, the variability, there is a hidden variable of switch. When they bound, forming team is working on peptide treat- that we didn’t see before,” Serebryany a disul de bond, crystallin was able ments that might keep the hot potato said. He set up a series of experiments to push damaged molecules toward from reaching damaged proteins. to try to pinpoint that variable. aggregation. When each was bound to Serebryany hopes such peptides Close comparison of the molecular a hydrogen atom, wild-type crystallin “could actually soak up some of those weights of batches of the wild-type was inert. disul des and delay the time that it protein that caused or failed to cause How could one bond between takes to form the more aggregation- the mutant to clump revealed a dif- amino acids on the surface of this prone species.” ference equivalent to the weight of protein make it drive other proteins to at could lead to slower cataract two hydrogen atoms. is gave the aggregate? formation for patients. researchers a hint that the protein’s e team found that although the DOI: 10.1074/jbc.RA118.004551 redox state — whether two sulfur at- disul de bond forms easily, it strains oms were bound to one another or to the protein’s structure. is made each hydrogen atoms — made a di erence. molecule likely to pass along the disul- Laurel Oldach (loldach@asbmb. “By carrying out isotopically de bond to another nearby, receiving org) is a science writer for the resolved mass spectrometry ex- two protons in return. In this way, ASBMB. Follow her on Twitter @ LaurelOld. periments, we got more than we the disul de bond could be passed bargained for,” Serebryany said. constantly around among crystallin
12 ASBMB TODAY APRIL 2019 JOURNAL NEWS Proteogenomics researchers zero in on causes of immune disease By Laurel Oldach
Routine clinical sequencing has parts of the world — that’s another given doctors unprecedented insight unique challenge of working with rare into genetic disorders. However, diseases,” Klein said. “Sebastian ew genomics fails to diagnose up to half to Iran and Turkey, in a collabora- of patients who are tested. at’s the tive e ort with the pediatric hospitals problem that scientists at universi- there.” ties in Munich and Berlin tackled Back at home, after processing and in a recent study in the journal freezing the samples, Hesse handed Molecular & Cellular Proteomics. them o to Grabowski; the pro- With samples from patients in four teomics scientists repeated the analy- countries and a novel database on the ses to see what proteins had changed neutrophil proteome, Christoph Klein in the patients’ blood. and colleagues diagnosed two children e team used abnormal protein with severe congenital neutropenia pro les to guide the diagnosis of two using mass spectrometry-based pro- patients with inconclusive exome teomics when typical sequencing had sequencing results. failed. In one child’s case, a pseudogene “ ere are very few examples of made it di cult to identify mutations people who use multiple omics to in the protein-coding gene; in the sec- investigate rare diseases … (but) I ond, incomplete coverage by exome think this is the future of personalized GUY WATERVAL /WIKIMEDIA COMMONS sequencing had missed a key point medicine,” said Klein, a physician and Neutrophils, like the one in the center of this photo, mutation. Data on protein abundance director of the Children’s Hospital of are loaded with granules full of proteases that make in each patient led the researchers to them difficult to study. the University of Munich. run more speci c genetic tests that e patients’ disease a ects their proved conclusive. neutrophils, white blood cells packed bombers,” Klein said, explaining that “ is highlights (that) even if you with toxic proteins to deploy against the cells are full of granules loaded have highly controlled pipelines for bacteria. When neutrophil devel- with proteases that make retrieving genetic studies, there’s always a risk opment is disrupted, which Klein other proteins a challenge. Hesse that you are not 100 percent correct,” estimates happens to 1 in 200,000 painstakingly developed a protocol Klein said. newborns, every bacterial or fungal to collect intact proteins and mRNA e researchers did not set out to infection can become a life-threaten- from healthy neutrophils. make diagnoses from patient pro- ing medical emergency. Using mass spectrometry, scientists teomes, but the study highlights the Klein’s lab has studied rare genetic led by co- rst author Piotr Grabowski value proteomics data can add. causes of neutropenia for years, but in the Rappsilber lab at the Technical “Cellular proteome studies are not proteomics was a new eld for University of Berlin analyzed the cells’ in routine clinical use at this point,” the group. Postdoctoral researcher proteome. When they added tran- Klein said. “But … I think there will Sebastian Hesse met proteogenomics scriptomic data, they found strikingly be huge potential for proteome analy- expert Juri Rappsilber at a conference, little correlation with the proteome, sis at a very low cost down the road.” sparking a collaboration to study so they chose to focus on protein in e team plans to expand its stud- the proteome and transcriptome of patient samples. ies to other patients with immune neutrophil granulocytes. Next, Hesse collected neutrophils de ciencies, looking for new genetic Neutrophils are post-mitotic and from 16 patients with congenital mechanisms of disease. very fragile, which makes studying neutropenia. Some were in Germany; DOI: 10.1074/mcp.RA118.001141 them a challenge. to nd others, he had to travel. “You can think of them as suicide “ ese patients are from various
APRIL 2019 ASBMB TODAY 13 LIPID NEWS
‘Almost like a Velcro ball’ Proteome study illuminates eclectic nature of high-density lipoprotein By Laurel Oldach
Cholesterol carried in high-densi- ty lipoprotein, or HDL, particles is called the good cholesterol because people whose levels are high have a lower risk of developing heart dis- ease. at link, established in 1977, has been con rmed over and over. But in the last 15 years, a string of drug candidates that failed to raise HDL, along with genetic stud- ies that dispute a causal link, have led researchers, including Nathalie Pamir of the Oregon Health and Sciences University, to reexamine why HDL is a good predictor of cardiac mortality. “Around 2010, the belief was that HDL doesn’t matter with regard to cardiovascular disease risk,” Pamir e team measured some clinical in almost every strain, other compo- said. “But now, we understand that features of each healthy chow-fed nents varied among strains or even there’s more to HDL than HDL mouse, such as HDL’s ability to suc- among genetically identical individu- cholesterol level. Now, the more we tion cholesterol out of macrophages als. e team interpreted the latter dig, the more exciting biology we in the plaques in the blood vessel. group as responding to environmental discover.” “We interrogated as many traits and metabolic changes in each mouse. In the Journal of Lipid Research, as we could and treated each protein For Pamir, they con rm a new way of Pamir and colleagues report on their that gets associated with HDL as a thinking about HDL’s activity. work with an underappreciated HDL trait,” Pamir said. “It’s almost like a tiny Velcro ball component: its proteins. In a genetic In a process known as quantitative that is rolling on surfaces, in ltrating study of the HDL proteome, the team trait locus mapping, they correlated intercellular space … and sampling showed that a mixture of heritable each trait they measured to the known from the environments that it’s been and environmental factors drives genetic landscape of the hundreds of in,” she said. variation in protein makeup of HDL mice to reveal genetic loci that a ect Exposure to microinammations particles. e approach may help each protein or function. caused by changes as small as social unpack the lipoproteins’ puzzling rela- e team found single-nucleotide hierarchy within a cage of mice may tionship to cardiovascular mortality. polymorphisms linked to cholesterol change what HDL picks up. Pamir isolated and analyzed the eux capacity and several linked to e next step is to see whether the proteome of HDL particles from the the presence or abundance of certain team’s nding generalizes to human Hybrid Mouse Diversity Panel. e proteins. Correlation between pro- HDL, Pamir said. “At the end of the panel, developed in the University of teins hinted at complex interactions day, a mouse is a mouse is a mouse.” California, Los Angeles lab of senior within the HDL proteome. DOI: 10.1194/jlr.M090555 author Jake Lusis, includes both com- According to Lusis, this study is mon lab strains and hybrid strains, “the rst time where you can see how Laurel Oldach (loldach@asbmb. each inbred to homozygosity. e hy- genetics … could paint a really useful org) is a science writer for the brid strains remix the same core gene picture of how the di erent HDL ASBMB. Follow her on Twitter @ pool and o er an unlimited supply of components interact.” LaurelOld. genetically identical mice. While some proteins were present
14 ASBMB TODAY APRIL 2019 JOURNAL NEWS JLR launches junior associate editors program By Laurel Oldach
e Journal of Lipid Research welcomes its rst cohort of junior as- sociate editors. Junior associate editors of the JLR e four assistant professors, cho- sen from nominations made by the journal’s associate editors, are partner- ing with senior editors to learn how to Raymond Blind manage the peer-review process. Vanderbilt University School of Medicine “Engagement with the best and Research area: Nuclear lipid signaling and structure brightest young investigators in the Mentor: George Carman lipid eld is an investment in the future of JLR,” Co-Editor-in-Chief Kerry-Anne Rye said. Gissette Reyes-Sofer e new editors — two Ph.D.s and Columbia University Irving Medical Center two M.D.s — already have accrued Research area: Regulation and metabolism accolades and earned the community’s of Lipoprotein(a) trust. Two are recipients of the JLR Mentor: Henry Ginsberg Junior Investigator Award. One won the Journal of Biological Chemis- try/Herb Tabor Young Investigator Award. Another is on the Deuel Brandon Davies Conference board. University of Iowa Carver College of Medicine Co-Editor-in-Chief Nicholas Research area: Lipid metabolism in endothelial cells Davidson said the program’s mission Mentor: Jean Scha er is two-fold: “It’s demystifying the peer-review process and also teaching what we hope are going to be the next Rotonya Carr generation of full associate editors.” University of Pennsylvania Perelman School e new editors are serving a two- of Medicine year term from March 1, 2019, to Research area: Metabolism and lipid droplets Feb. 28, 2021. in liver disease ey also will contribute a new Mentor: Nick Davidson type of article to the journal — com- mentaries on exciting lipid research published elsewhere.
jlr.org/site/collections/vesicles/
APRIL 2019 ASBMB TODAY 15 JOURNAL NEWS From the journals By Nathalie Gerassimov, Jonathan Grin, Dawn Hayward & Sasha Mushegian
We o er a selection of recent papers which proteins in cerebrospinal uid, cause of gallstones. on a variety of topics from the Journal or CSF, samples change prior to the e stones develop when gall- of Biological Chemistry, the Journal onset of Alzheimer’s symptoms. eir bladder bile is supersaturated with of Lipid Research, and Molecular & results were published in the journal cholesterol, one of three major lipid Cellular Proteomics. Molecular & Cellular Proteomics. components in bile, with bile acids e researchers rst compared CSF and phospholipids being the other Blood and aggression proteins in Alzheimer’s patients to two. Traditionally, it is thought that those in people without the disease. excessive hepatic secretion of cho- in crayfish Next, they narrowed the set down lesterol is the main cause for such Transglutaminase is a cross-linking to CSF proteins from synapses, supersaturation. Rudling’s team used enzyme involved in diverse cellular identi ed by comparing the data set unpublished data from a previous functions including blood coagula- to synaptic proteins established in study to show that a shortage of bile tion and communication between the literature. Nine were chosen for acids is probably the major and most cells and the extracellular matrix. monitoring changes in expression common reason why gallbladder bile Di erent isoforms of the enzyme have levels in Alzheimer’s patients. is supersaturated with cholesterol di erent substrate speci cities and are Using a proteomics technique in gallstone patients. Furthermore, expressed di erentially across tissues called selected reaction monitoring, the researchers used 13 previously and cell types. Kingkamon Junkunlo the researchers found that while some published studies from 11 countries and colleagues at Uppsala University marker proteins were high throughout to corroborate their ndings. Future examined the role of transglutaminase the onset of disease, several proteins studies are needed to investigate the in hematopoiesis in cray sh. ey were lower in CSF from presymp- cause(s) of reduced bile acid levels. found that inhibiting transglutamin- tomatic patients than in healthy DOI: 10.1194/jlr.S091199 ase not only increased the number of individuals but then were elevated circulating blood cells but also unex- where neurodegeneration occurred. Discovering a new pool pectedly made cray sh move less and Lleo and colleagues described this as of iron display less aggressive behavior. is a “biphasic pro le” and concluded link between hematopoiesis and the that those decreased proteins could be Like many elements, iron is a nervous system controlling behavior early biomarkers of synapse loss that double-edged sword. It is an essential may provide insights into diseases could be used to identify individuals cofactor but can pose a danger to involving defects in motor functions. with Alzheimer’s disease before ir- cells by catalyzing the formation of e study was published in the Jour- reversible neurodegeneration becomes reactive oxygen species. In a paper in nal of Biological Chemistry. widespread. the Journal of Biological Chemistry, DOI: 10.1074/mcp.RA118.001290 Joshua Wo ord and colleagues at Early markers Texas A&M University describe how of Alzheimer’s disease The new old cause they revised previous estimates of iron of gallstones usage in cells by using multiple meth- Alzheimer’s disease is character- ods to inventory total iron content ized by neurodegeneration, including A person living in the U.S. has a and characterize the distribution of synapse loss, and preclinical markers 10 to 20 percent chance of developing di erent iron species in Escherichia of Alzheimer’s and other neuronal stones in their gallbladder. Yet up to coli. ey discovered a previously disorders have been elusive. ese 80 percent of a ected individuals will unknown low-molecular-mass Fe(II) markers someday could be used to have no symptoms. e remaining 20 pool in the cytosol and suggested that diagnose patients before symptoms percent may experience biliary pain or this pool might be prevented from start. other complications requiring costly reacting with oxygen by a shield of Alberto Lleo, Olivia Belbin and interventions. membrane-bound iron-rich respira- colleagues at the Hospital de la Santa In a paper in the Journal of tory complexes. Creu i Sant Pau in Barcelona, Spain, Lipid Research, Mats Rudling and DOI: 10.1074/jbc.RA118.005233 used a mass spectrometry-based colleagues at the Karolinska Institute, proteomic technique to determine Sweden, describe new insight into the
16 ASBMB TODAY APRIL 2019 JOURNAL NEWS
Distinguishing near-identical enzymes to help treat Cushing’s disease
BRIXIUS-ANDERKO ET AL. A structural comparison of CYP11B1 (cyan) and CYP11B2 (gray). Darker sticks represent nonidentical amino acids.
e stress hormone cortisol is produced in the ing drugs that will speci cally inhibit CYP11B1 adrenal glands but has important duties throughout and reduce cortisol levels without also disrupting the body, from nutrient metabolism to immune CYP11B2’s aldosterone-producing activities. suppression. Excessive production of this hormone Using an X-ray-based technique, the researchers can have devastating consequences, however, such found the crystal structure of each enzyme bound as Cushing’s disease, with symptoms that include to fadrozole, a breast cancer drug that inhibits the weakened immune responses, rapid weight gain and estrogen-producing CYP19A1. ey identi ed con- osteoporosis. siderable di erences between the orientation and In a study in the Journal of Biological Chem- placement of certain residues within the enzymes. istry, Simone Brixius–Anderko and Emily Scott at Because of these distinctions, the enzymes favored the University of Michigan shed light on unique mirrored shapes, or enantiomers, of the drug. structural features of the cortisol-producing enzyme CYP11B1’s structure accommodated the shape cytochrome P450 11B1, or CYP11B1, that could of the left-handed, or S, enantiomer of fadrozole, aid researchers in designing selective drugs for while CYP11B2 was a better t for the right-hand- Cushing’s disease treatment. ed version. For years, researchers have thought of CYP11B1 By identifying CYP11B1’s strong preference for as a prime drug target for Cushing’s; however, 93 the S enantiomer, this study could aid in the devel- percent of the enzyme’s amino acid sequence is opment of more selective inhibitors that would treat shared with CYP11B2, which is essential for the Cushing’s disease without causing unwanted e ects, production of aldosterone, a hormone central to such as reduced aldosterone, in patients. the regulation of blood pressure. Structural di er- DOI:10.1074/jbc.RA118.006214 ences between these close relatives have not been —Jonathan Grin determined, so researchers have di culty develop-
APRIL 2019 ASBMB TODAY 17 JOURNAL NEWS
DNA repair pathway Cellular Proteomics. relocalization to the capillary lumen Researchers found that without and cause hypertriglyceridemia. Fu- resolved the pglB protein, C. jejuni no longer ture studies may investigate why the DNA repair is a critical function, could recover from extreme cold or enhancer deletion had such strikingly and cells have multiple ways of car- heat as normal bacteria could. In di erent e ects in the liver versus the rying it out. One e cient method of addition, C. jejuni switched which heart and focus on other unknown DNA repair is transcription-coupled amino acids it used most, decreased players in the regulation of GPIHBP1 repair, which is carried out as DNA is levels of certain transport proteins expression. It is likely that other GPI- being transcribed. Previous research and could no longer migrate toward HBP1 enhancers were present, which provided conicting evidence as to some metabolic substrates. contributed to the tissue-speci c whether transcription-coupled repair Without glycosylation, certain changes in expression. worked on DNA sequences encoding proteins within the glycoproteome DOI: 10.1194/jlr.M091322 ribosomal RNA; this was unclear be- were downregulated, and an enzyme cause rRNA and protein-coding genes involved in utilization of nitrogen Finding ligands using are transcribed by di erent RNA was less active. is was speci c; a phage polymerases in eukaryotes. Yanyan strain without the pgl cluster had Yang and colleagues at the University restored activity of this enzyme when USP11 is a human deubiquitinase of North Carolina used excision repair researchers added the pgl cluster back. that regulates DNA double-strand sequencing with single-nucleotide Because protein glycosylation in C. break repair and cellular stress re- resolution to investigate this ques- jejuni was found to a ect many path- sponses; it is dysregulated in pan- tion. ey found that transcribed and ways, it could be a way to stop this creatic and ovarian cancers. Unlike non-transcribed sections of ribosomal gastrointestinal bacterium. other ubiquitin-speci c proteases, DNA are repaired at the same rates, DOI: 10.1074/mcp.RA118.001199 USP11’s peptide-binding sites were suggesting that ribosomal DNA is unknown. Anastasios Spiliotopoulos repaired by global repair mechanisms, How an upstream and colleagues at the University of not transcription-coupled repair. e enhancer regulates Nottingham combined phage display study was published in the Journal of library screening with next-generation Biological Chemistry. a protein’s expression sequencing to discover USP11-inter- acting peptide motifs. ey found a DOI: 10.1074/jbc.RA118.006121 GPIHBP1 is a protein that binding site that modulates USP11’s shuttles lipoprotein lipase, or LPL, DNA repair function and developed Glycoproteins from capillary endothelial cells to a ligand that could be used to arrest capillary lumen, where it can process and food poisoning the cell cycle. is strategy, published triglyceride-rich lipoproteins. Lack of in the Journal of Biological Chem- e gastrointestinal bacterium GPIHBP1 prevents LPL relocation to istry, could be used to develop new Campylobacter jejuni, a major cause the capillary lumen, impairing plasma biochemical tools. of food poisoning, causes abdominal triglyceride hydrolysis and leading DOI: 10.1074/jbc.RA118.004469 cramps and inammation and is to severe hypertriglyceridemia (high transmitted through contaminated blood levels of triglycerides — a risk water or poultry. C. jejuni uses factor for atherosclerosis). Selectivity hinges a sophisticated system to attach In a paper published in the on a hinge site oligosaccharide chains to the nitrogen Journal of Lipid Research, Chris- in some amino acids. e system topher Allan and colleagues at the Despite being structurally involves multiple steps carried out universities of California, Michigan similar, caspases are highly selective by the pgl cluster, which codes for and Arizona describe an upstream for speci c substrates. In a study proteins that act as a glycoprotein enhancer that regulates GPIHBP1 published in the Journal of assembly line. Researchers at the expression in a tissue-speci c man- Biological Chemistry, Derek University of Sydney generated C. ner. Deletion of the relevant DNA McPherson and colleagues at the jejuni bacteria without a key gene in segment using CRISPR/Cas9 genome University of Massachusetts searched this cluster and performed proteomic editing reduced GPIHBP1 expres- for secondary binding sites in caspases analysis to determine the importance sion by more than 90 percent in the that could help explain this selectivity. of N-glycosylation in pathogenesis. liver and by about 50 percent in the ey discovered an exosite in eir work was published heart and brown adipose tissue, but caspase-6 composed of a tri-arginine in the journal Molecular & that was wasn’t enough to block LPL patch in the hinge between the core
18 ASBMB TODAY APRIL 2019 JOURNAL NEWS
Is an over-the-counter sleep aid the next big diet fad?
MICHAEL C. BERCH/WIKIMEDIA COMMONS
The white fat running through red muscle, also known as intramuscular fat, or IMF, is made of lipids deposited in fat cells, called adipocytes, which affect the fl avor of animal meat as well as insulin sensitivity in humans.
Steak connoisseurs are familiar with the marble pig fat cells and mice, and they proposed a mecha- pattern of white fat running through raw red esh. nism for melatonin’s e ect on IMF deposition. e white fat inside the muscle, also known as intra- Speci cally, the researchers showed that melatonin muscular fat, or IMF, is inside adipose cells, called treatment inhibited pig intramuscular preadipocytes’ adipocytes, that are located between the skeletal proliferation by arresting the cell cycle in a way that muscle bers. In research published in the Journal varied according to dose and time. of Lipid Research, Kaiqaing Liu and colleagues at Furthermore, the size of deposited lipid droplets Nanjing Agricultural University, China, investigated in melatonin-treated preadipocytes was smaller while how melatonin, a circadian rhythm-regulating hor- the expression of lipolytic enzymes was increased. mone involved in sleep, a ects how IMF is deposited Additional experiments showed that melatonin likely and showed that long-term melatonin treatment re- acts via an increase in uptake through upregulation duces IMF deposition. ese results are relevant for of its receptor, MT2, and involves ERK1/2 and farm animal breeding where fat content a ects avor protein kinase A signaling pathway. Consistent with and for human “globesity” — the global epidemic of these observations in cultured cells, mice injected overweight and obesity. with melatonin had lower body weight and lower fat In humans, IMF content a ects insulin resistance deposition than control mice. and type 2 diabetes, with the reduction of IMF is research suggests that doctors and personal content improving insulin sensitivity of muscle tis- trainers may soon recommend melatonin supple- sue. Several previous studies using cells and labora- ments in addition to exercise and caloric restrictions tory animals also have shown that melatonin a ects to prevent and treat obesity and related diseases. fat deposition, but the observed e ects di ered by DOI: 10.1194/jlr.Mt087619 study. Liu and colleagues found consistent results in —Nathalie Gerassimov
APRIL 2019 ASBMB TODAY 19 How a gut pathogen sidesteps antibiotic treatment
Hospital-acquired antibiotic-resistant infections occur in hospitals and clinics worldwide. Klebsiella pneumoniae is a Gram-negative bacterium that invades the gastrointestinal and respiratory tracts, causing a range of diseases. e ability to cling to medical devices JOURNALmakes it especially NEWS harmful in those hospital settings where antibiotic resistance is common. Sarah L. Keasey and colleagues at the U.S. Army Medical Research Institute of Infectious Diseases exam- ined the gastrointestinal pathogen K. pneumoniae from a lethal outbreak in laboratory monkeys to determine which pathways were altered when standard antibiot- ics were used. ey published their work in the journal Molecular & Cellular Proteomics. When the researchers used a panel of antibiotics on bacterial cultures isolated from the infected monkeys, they found di ering growth patterns depending on the treatment used. ey then did a proteomics study using streptomycin and doxycycline alone and in combina- tion. ese two antibiotics both target the ribosome but WIKIMEDIA COMMONS have very di erent chemical structures, and research- Klebsiella pneumoniae, shown with an immune cell, evades antibiotic treatment by altering its proteome. ers found di erences in bacterial enzymes involved in biosynthesis. Next, since antibiotics must rst cross the bacterial cell wall, the researchers examined changes in biotics were combined, researchers found that treated transport protein levels, some of which decreased with cells had lowered transport of certain molecules and treatment, indicating that bacteria could change their increased levels of membrane proteins. After repeated proteome to prevent antibiotic entry. doses, as in a clinic, K. pneumoniae recovered and its As transport protein changes also meant certain sug- growth rate increased over time, signaling resistance to ars couldn’t enter cells, researchers found that the bacte- the combination. ria altered their fuel sources to compensate. In addition, Knowing which pathways bacteria use to evade the capsule that surrounds K. pneumoniae increased its antibiotics is therefore key to developing e ective treat- composition in cells treated with doxycycline but not ments for these pathogens. those treated with streptomycin, indicating they have DOI: 10.1074/mcp.RA118.000739 di erent mechanisms of resistance. When these anti- —Dawn Hayward
caspase domain and a disordered Nathalie Gerassimov (nathalie. Dawn Hayward (dhaywar5@ N-terminal domain. Since caspase-6 [email protected]) is jhmi.edu) is a graduate student plays a unique role among apoptotic a Ph.D. student at the Johns at the Johns Hopkins University caspases in neurodegeneration, Hopkins University School of School of Medicine. Medicine. modulating this substrate-binding site could be therapeutically valuable for Jonathan Griffin (jgriffin@ Sasha Mushegian (amushe- conditions such as Alzheimer’s and asbmb.org) is a science [email protected]) is a post- communicator for all ASBMB Huntington’s disease. doctoral fellow at Georgetown journals. Follow him on Twitter University. Follow her on Twitter DOI: 10.1074/jbc.RA118.005914 @spelledjon. @sash_mu.
20 ASBMB TODAY APRIL 2019 A YEAR OF (BIO) CHEMICAL ELEMENTS For April, it’s copper — atomic No. 29 By Quira Zeidan
019 marks the 150th anniversary tory chain, a binuclear copper center of the rst publication of Dimi- in cytochrome c oxidase transfers elec- 2tri Mendeleev’s periodic table trons from cytochrome c to molecular of chemical elements. To honor the oxygen in the nal redox step of the occasion, each month we are focusing oxidative phosphorylation pathway. on elements important in biochemis- Similarly, a copper-containing protein try. In January and February, we fea- called plastocyanin in the thylakoid tured hydrogen and iron, respectively, lumen of chloroplasts carries elec- and in March, we tripled down with trons between two membrane-bound sodium, potassium and chlorine. proteins — cytochrome f and P700+ For April, we have selected copper, — during photosynthesis. a transition metal with chemical sym- Like hemoglobin in vertebrates, bol Cu and atomic number 29. Cop- a copper-containing protein called per participates in chemical reactions hemocyanin transports oxygen in the via a wide range of oxidation numbers hemolymph of invertebrates, such as from -2 to +4 but most commonly is mollusks and some arthropods. When found in organic cuprous and cupric JAWAHAR SWAMINATHAN & MSD STAFF / a molecule of oxygen binds two cop- EUROPEAN BIOINFORMATICS INSTITUTE complexes with oxidation states of +1 per atoms in hemocyanin, copper is and +2, respectively. Oxygen-bound copper, represented by the two oxidized from Cu+1 to Cu+2, and the Ancient civilizations used copper orange spheres in the center of the structure of the energy associated with this electron protein hemocyanin, gives arthropod hemolymph a extensively in the manufacture of blue color. transfer changes the light-absorbing ornaments, weapons and tools, and properties of copper. is causes the late fth millennium BC is the oxygen-rich hemolymph in these archeological period known as the in trace amounts, but it can produce animals to appear blue in contrast to Copper Age. highly reactive toxic species when the bright red color of oxygen-bound Copper most likely forms during found in excess inside cells. Microor- iron in hemoglobin. the expansion of supergiant stars and ganisms can mobilize solid copper by In eukaryotes, the antioxidant en- makes up about 0.0068 percent of the incorporating it into cyanide com- zyme superoxide dismutase uses cop- Earth’s crust. In nature, it occurs in its pounds, and copper-binding proteins per to catalyze the decomposition of pure metallic form as native copper or in the periplasmic space allow bacteria the superoxide radical into molecular in combination with other elements to trap copper to avoid intracellular oxygen and hydrogen peroxide, which in minerals containing copper oxides, toxicity. In yeast, cell surface metal- are less toxic to the cell. copper sul des or copper carbonates. loreductases render copper available to us, from the heart of volcanoes ese minerals form when volcanic high-a nity transporter proteins by to the relay of electrons inside cells, activity separates copper from magma reducing Cu+2 to Cu+1. Fungi that col- copper is critical to the survival of all and the copper reacts explosively with onize the roots of host plants protect aerobic organisms. ascending sulfurous gases, precipitat- them from toxicity by trapping soiled ing beneath the surface as copper-rich or soluble copper in compounds with ores. other metals. Quira Zeidan (qzeidan@asbmb. After iron and zinc, copper is the Once in cells, copper binds to org) is the ASBMB’s education third most abundant metallic element proteins that participate in electron and public outreach coordina- in biological systems. Copper is in- transfer reactions or oxygen transpor- tor. Follow her on Twitter @ quirazeidan. dispensable for most living organisms tation. In the mitochondrial respira-
APRIL 2019 ASBMB TODAY 21 GRANT WRITING WORKSHOP June 13–15 • Washington, D.C.
The ASBMB Interactive Mentoring Activities for Grantsmanship Enhancement (IMAGE) grant-writing workshop is designed to help early-career scientists and senior postdoctoral fellows write winning research proposals.
ASBMB.ORG/GRANTWRITING
22 ASBMB TODAY APRIL 2019 FEATURE Meet Jean Schaffer Tracing the lipid path from diabetes to heart disease By Laurel Oldach
ardiologist Jean Scha er realized early that she wanted to pursue Cresearch. She was an undergrad- uate biochemistry major at Harvard University, working with molecular biologist Richard Morimoto. “ at experience told me I wanted research to be a central focus of my career,” Scha er said. “But I also knew I wanted to study human disease.” She opted for medical school and completed a residency in medicine and a fellowship in cardiology before returning to the lab as a postdoctoral fellow with cell biologist Harvey Lodish at the Massachusetts Institute of Technology. e two aspects of her training progressed in parallel, Scha er said. “I began to see relationships between TIM PARKER/TIM PARKER PHOTOGRAPHY what I was studying in the laboratory, Jean Schaffer, director of the Diabetes Research Center at Washington University at St. Louis, is also an which was very interesting at a basic associate editor of the Journal of Lipid Research. biological level, and fundamental questions about the kinds of patho- physiology that we commonly see in professional roles. is interview has the clinic.” been condensed and edited. Scha er began her own program of investigation when she took a job as How did you start working on an assistant professor at the Washing- the molecular mechanisms ton University School of Medicine in linking metabolic stress and St. Louis. She since has become a full cardiovascular disease? professor and director of the univer- sity’s Diabetes Research Center. Her I began studying fatty acid trans- lab seeks to understand the molecular port as a postdoc in the Lodish lab. I basis of diabetes complications includ- was very interested in testing the hy- ing heart failure. e research focuses pothesis that speci c proteins regulate on lipotoxicity, which occurs when fatty acid import into tissues, given fatty acid accumulation damages cells both the importance of this metabolic and tissues. substrate and the potential toxicity of Scha er became an associate editor lipid overload. I used an expression at the Journal of Lipid Research in cloning strategy to identify the rst 2017. ASBMB Today writer Laurel fatty acid transport protein and long- Oldach caught up with her over the chain acyl CoA synthetase 1 as key phone about her research and her regulators of fatty acid transport.
APRIL 2019 ASBMB TODAY 23 TIM PARKER/TIM PARKER PHOTOGRAPHY Jean Schaffer (right) with staff scientist Robert Crowder, who works in her lab at Washington University at St. Louis.
As I studied these molecules, I to hyperglycemia-induced oxida- observed that overexpression of these tive stress, and enhanced oxidative proteins in the heart in a mouse mod- metabolism of both glucose and fatty el led to excessive lipid uptake that re- acids at the level of the mitochondria sulted in cell death, tissue damage and produces reactive oxygen species. So heart failure. And I was struck by the both of these metabolites clearly can parallels with the heart disease that I cause problems for tissues. treated in my patients with diabetes. Another way tissues respond to the is led me to pursue my current excess fatty acid supply is to seques- interests in metabolic stress responses ter that lipid in cellular triglyceride and diabetes complications. stores. We found that this initially helps protect against lipotoxicity, but Broadly, how can diabetes the storage function is limited in non- lead to heart disease? adipose tissues, and triglycerides can eventually be hydrolyzed to release Dysregulation of both glucose and free fatty acids. fatty acid metabolism in diabetes Metabolite-induced oxidative stress leads to excess delivery of metabolic damages the endothelium, and it can substrates to tissues throughout the also cause dysfunction of monocytes, body. One way that cells in di er- macrophages and foam cells. So in ent organs compensate initially is by these ways, the abnormal substrate upregulating metabolic pathways to environment of diabetes can lead to dispose of these substrates. initiation and progression of athero- Excess glucose increases ux sclerosis. But I think it’s important to through pathways that can contribute also remember that there are direct
24 ASBMB TODAY APRIL 2019 untoward e ects of hyperglycemia tion of proteins involved in snoRNA and hyperlipidemia on the cardiac biogenesis and tra cking also led to myocytes themselves that contribute resistance. at suggested to us that to heart failure. we had identi ed several components of an important metabolic stress Some of your recent articles pathway. focus on how noncoding RNAs As we further studied these affect mitochondrial function. snoRNAs, an important step was Tell me about that research. to con rm we had the right gene identi cations. It’s important to show We wanted to identify novel regu- that that the knockout phenotype can lators of lipid-induced cell death, or be complemented by restoring the lipotoxicity, so we used a cell culture disrupted genetic elements. In this model of lipotoxicity and carried out case, the Rpl13a locus encodes four a genetic screen. rough this e ort, snoRNAs and the RpL13a protein. my lab discovered that small nucleolar We found that genetic comple- RNAs, or snoRNAs, encoded within mentation only occurred when the the introns of the ribosomal protein snoRNAs were restored. L13A gene are critical for lipotoxic cell death. What research questions or For a long time, we’ve known that directions are most exciting snoRNAs form ribonucleoprotein for you right now? particles that reside in the nucleus and direct epigenetic modi cations Obviously, we’re interested in the on newly synthesized ribosomal physiological function of these snoR- RNAs. But a new role for snoRNAs NAs. Our studies suggest that they in metabolic stress really intrigued may have important roles in regulat- us. We discovered that disruption of ing metabolism. Mice with loss of the gene that hosted these snoRNAs the Rpl13a snoRNAs have evidence conferred resistance to lipotoxicity, of metabolism that is uncoupled at and our screen showed that disrup- the level of mitochondria, and this
TIM PARKER/TIM PARKER PHOTOGRAPHY Jessie Zhang, McKenna Feltes and Sammy Moores (left to right) work together in the Schaffer lab’s tissue culture room.
APRIL 2019 ASBMB TODAY 25 COURTESY OF JEAN SCHAFFER Members of the Schaffer lab enjoy a lunch outing.
alteration is likely to have important outstanding investigators studying e ects on whole-body metabolic ef- metabolism and diabetes. Washing- ciency. at’s an area we are excited ton University has a long and rich to pursue. tradition of contributions to metabo- Another really important direc- lism science. It is also an incredibly tion for us is to determine whether supportive institution for career loss of the Rpl13a snoRNAs actually development for physician-scientists. protects against lipotoxicity in vivo in It seemed like the right place. diabetes complications — which was the motivation for originally pursuing In addition to running your lab, these studies. you also direct the Diabetes ere are about 400 well-character- ized snoRNAs throughout the human Research Center at Washington genome. ere’s an intriguing possi- University. Do running a center bility that other snoRNAs could have and heading a lab inform each noncanonical functions that impact other in any way? cellular metabolism. at’s an area for future studies. ese two roles actually involve many of the same skills. One needs You spent a long time in Boston. to be always looking for new op- Was it a big move to go out portunities: new science to pursue, to St. Louis? new faculty to recruit, new areas for development of a center to provide Yes. I spent a good number of resources for the research community. years getting educated and trained in Learning how to listen to others and Boston. But as I embarked upon my how to build consensus, how to make independent career, I looked for an decisions, and how to engage others environment with a critical mass of to pursue common goals — these are
26 ASBMB TODAY APRIL 2019 important skills both in the laboratory a scientist, and together we raised our and for leading a research center. You two children during the early stages of really need to strike a proper balance. our careers. We bene ted immensely from mentors who trusted us to work How did you first get involved with hard and gave us the exibility to the Journal of Lipid Research? design our own schedules. I also have a great love for music — I play the I published my rst paper in the piano and attend concerts as much as JLR, in 1999. is journal reaches a my schedule allows. broad audience with interest in many In the end, to be able to spend di erent aspects of lipid metabolism time with family and music — or and physiology, so it’s a great place to whatever else interests the scientist showcase our work. Along the way, outside of their work — the most im- I’ve been asked to review many pa- portant skill for success is good time pers. I suppose because I was diligent management. as a reviewer and turned my reviews in on time, I was rewarded with being asked to serve as an associate editor.
What do you like to do when you’re not thinking about snoRNAs, metabolism and Laurel Oldach (loldach@asbmb. org) is a science writer for the diabetes? ASBMB. Follow her on Twitter @ My passions outside the lab are LaurelOld. family and music. My husband is also
TIM PARKER/TIM PARKER PHOTOGRAPHY Sasha Medvedeva (left) and Sarah Gale hard at work in the Schaffer lab.
APRIL 2019 ASBMB TODAY 27 28 ASBMB TODAY APRIL 2019 ANNUAL MEETING
MILDRED COHN AWARD IN BIOLOGICAL CHEMISTRY Gronenborn honored for advances in NMR spectroscopy By Kerri Beth Slaughter
Angela Gronenborn, a professor at mining complexes of viral and cellular the University of Pittsburgh, has won proteins. She combines computational the 2019 Mildred Cohn Award in tools from chemistry and physics with Biological Chemistry from the Ameri- her expertise in NMR spectroscopy can Society for Biochemistry and and X-ray crystallography to analyze Molecular Biology for her work in HIV biology. nuclear magnetic resonance spectros- Robert Gri n, a professor at the copy. is award recognizes scientists Massachusetts Institute of Technol- who have developed innovative physi- ogy, wrote in his letter supporting cal approaches to advance the eld of Gronenborn’s nomination, “Her re- biological chemistry. search continues to push the techno- Tatyana Polenova, a professor at logical boundaries for determination the University of Delaware, nomi- of structure and dynamics of large nated Gronenborn for the award, “I am deeply grateful and very complexes of HIV assemblies with pleased to have been nominated writing, “Professor Gronenborn’s human proteins.” and selected for the 2019 Mildred pioneering contributions to the eld Cohn Award from the ASBMB. In addition to her research achieve- of biological chemistry are remarkable Mildred Cohn was one of the ments, Gronenborn has been honored in their vision, creativity and intellec- rst women in NMR and pio- for her devotion to the scienti c tual depth.” neered its use to study enzymatic community. She has trained more Gronenborn chairs the department reactions. She was daring and than 60 Ph.D. students, postdoc- of structural biology at the University undeterred, overcoming countless toral researchers and undergraduate of Pittsburgh School of Medicine. obstacles during her long life. It’s students during her academic career. Her research group combines NMR an honor to receive this award She also has chaired multiple interna- spectroscopy with biophysics, bio- named after such a tremendous tional scienti c conferences, and she chemistry and chemistry to investigate scientist.” serves in editorial roles for a number cellular processes at the molecular and ANGELA GRONENBORN of journals. In 2007, Gronenborn was atomic levels to understand human elected to the National Academy of disease. Major focuses of her lab Sciences for her outstanding contribu- include protein-carbohydrate recogni- tions to research. tion, HIV pathogenesis and protein in HIV-targeted antiviral program. Gronenborn will receive her award deposition diseases. She pushed the boundaries of NMR at the ASBMB annual meeting dur- Gronenborn became interested spectroscopy by developing new tech- ing the Experimental Biology 2019 in NMR spectroscopy during her nologies to determine the structures conference in Orlando, where she graduate training at the University of of proteins and protein complexes will deliver an award lecture on “ e Cologne. roughout her career, she larger than 20 kilodaltons, a feat the awesome power of Fluorine NMR” at has transformed and expanded the scienti c community considered 9 a.m. April 17 in Valencia Ballroom applications of NMR spectroscopy to impossible at the time. A at the Orange County Convention determine the structure of biological Bax wrote in his letter of support Center. macromolecules. Her work includes for Gronenborn’s nomination, “Her nearly 500 peer-reviewed articles, in- work, both in quantity and depth, Kerri Beth Slaughter (kerri. cluding several landmark publications continues to de ne and extend the [email protected]) is a gradu- that opened the door for modern limit of macromolecular NMR.” ate student in the biochemistry triple-resonance NMR experiments. Gronenborn’s current work aims to department at the University of Kentucky. Follow her on Twitter @ In 1988, Gronenborn joined the understand how HIV hijacks host cell KB_Slaughter. National Institutes of Health to work machinery for replication by deter-
APRIL 2019 ASBMB TODAY 29 DELANO AWARD FOR COMPUTATIONAL BIOSCIENCES Kuhlman solves protein puzzles with a modeling program By Elizabeth Stivison
e American Society for Bio- important applications.” chemistry and Molecular Biology has Kuhlman’s group has worked to given the 2019 DeLano Award for solve the longstanding problem of Computational Biosciences to Brian creating bispeci c antibodies, anti- Kuhlman, a professor of biochemistry bodies that bind two di erent anti- and biophysics at the University of gens, by creating a novel protocol for North Carolina School of Medicine. multi-state protein design. ey gen- e award recognizes scientists whose erated two di erent light and heavy work excels in two key elements: chains with orthogonal interfaces that “more productive use of computers can be assembled with high delity. to accelerate and facilitate research, is has signi cant potential in any and ready access of these programs eld where two cellular structures for the scienti c community.” need to be brought in close proximity, Kuhlman’s studies have done “What a fantastic honor! Warren including cancer immunotherapy. exactly that; Ruth Nussinov of the DeLano’s software, PyMOL, is a e lab is also working on creating terri c example of what can be National Cancer Institute wrote in protein switches that can be turned achieved by making research tools her nomination letter, “I cannot think easily accessible. It has been very on or o using light with high spatial of a more deserving recipient than rewarding to contribute to the and temporal resolution. ey are Prof. Kuhlman.” Rosetta software and community designing these switches to control Kuhlman’s work can be described in the same way, and it is exciting intracellular localization, gene expres- broadly as using computers and to see all of the wonderful pro- sion and di erentiation. computational biology to design new teins that are being designed with Kuhlman is known among his col- protein structures and functions. As a Rosetta.” leagues as an innovative and reliable postdoc in David Baker’s laboratory, — BRIAN KUHLMAN scientist, an e ective and wise col- Kuhlman created a protein design laborator, and a superb speaker. is module in the molecular modeling is shown in his high (and increasing) software Rosetta. As a professor, he interfaces that allow previously number of citations, his many papers has continued to advance the uses nonbinding proteins to bind each written in collaboration with other of Rosetta in several forms: protein other or other substrates they would labs and the many talks he gives interface design, antibody assembly not typically bind. is has achieved around the world. and engineering binding with micro to nanomolar Kuhlman will receive his award photoactivatable a nities, and the experimentally during the ASBMB annual meeting proteins. He determined structures of his designed at the Experimental Biology 2019 makes the interfaces typically were quite similar conference in Orlando, where he modules to his models, showing how e ec- will deliver an award lecture titled available to tive his modeling techniques are. “Designing novel protein structures all research- is work and his freely available and interactions with Rosetta” at 1:45 ers. Rosetta modules open the doors for p.m. April 9 in Valencia Ballroom A In the many researchers to use these ideas in at the Orange County Convention eld of pro- countless other elds. Center. tein interface Gideon Schreiber of the Weizmann Elizabeth Stivison (elizabeth. design, Kuhlman’s Institute of Science wrote in support [email protected]) is a Ph.D. lab has redesigned of the nomination that Kuhlman student at Columbia University proteins to increase their a nity to “is known for driving technology studying mechanisms of DNA binding partners and has designed as well as using it in biologically repair.
30 ASBMB TODAY APRIL 2019 ASBMB AWARD FOR EXEMPLARY CONTRIBUTIONS TO EDUCATION Garg made organic chemistry one of UCLA’s most popular classes By Adriana Bankston
Neil Garg is a chemistry profes- classes as an undergraduate, sup- sor with a mission to change the ported the award nomination with a way organic chemistry is taught. For letter. “Dr. Garg has a unique teach- his classroom innovations, he has ing style that sets him apart from won the 2019 American Society for other professors,” Bañaga wrote. “He Biochemistry and Molecular Biology inspires and captivates his students Award for Exemplary Contributions with his highly entertaining and en- to Education. joyable lectures and devises ingenious Organic chemistry is not a class methods of combining fun facts with that people typically think of as notable information to help his stu- being fun. But Garg’s Chemistry dents learn the depth and immense 14D: Organic Reactions and Phar- amount of material that he covers.” maceuticals is a popular course at the In another letter of nomination, University of California, Los Angeles. “It is a tremendous honor to receive Robert Grubbs, a chemistry professor the ASBMB Award for Exem- Garg describes real-life applications at the California Institute of Tech- plary Contributions to Education. in his classes, and students say that Organic chemistry has been viewed nology, wrote, “Garg has also done he makes a personal connection with as a weed-out class for decades, amazing things in undergraduate edu- every one of his nearly 400 individu- but at UCLA, we are challeng- cation and is clearly one of the best als in the classroom, according to ing our students to overcome such university educators in the country.” an article on the UCLA Newsroom preconceived notions.We want our Garg has won numerous honors, website. students to appreciate how organic including UCLA’s Harvey L. Eby Catherine Clarke, a professor and chemistry relates to biology and Award for the Art of Teaching. He chair of chemistry and biochemistry modern medicine.We also use the also competed for and won the Rob- at UCLA, nominated Garg for the class as a vehicle for students to ert Foster Cherry Award, which is the award, explaining that he has suc- learn impeccable problem solving largest university teaching prize and skills that will bene t them in all ceeded with Chem 14D because he spans all elds of academia. of their future endeavors.” can explain concepts clearly and teach Garg will receive his award during problem-solving skills. He also is able — NEIL GARG the ASBMB annual meeting at the to integrate established and innova- Experimental Biology 2019 confer- tive teaching methods — for example, ence in Orlando, where he will deliver with an assignment in which students in Larry Overman’s lab at the Uni- an award lecture titled “How organic can produce chemistry music videos. versity of California, Irvine, where he chemistry became one of UCLA’s “Simply put, Neil has been an completed the total synthesis of the most popular classes” at 3 p.m. April amazing teacher and his impact on bioactive alkaloid sarain A. 7 in Valencia Ballroom A at the Or- chemical and biochemical education Since joining the UCLA faculty in ange County Convention Center. has been transformative,” Clarke 2007, Garg has helped develop many wrote in her nomination letter. educational tools to help students, Adriana Bankston ([email protected]) is Garg earned his undergraduate including an app called Backside At- a former bench scientist with a degree in chemistry from New York tack, an online tool called QR Chem passion for improving training University and a Ph.D. from the and an online tutorial, BACON, and policies for junior scientists. California Institute of Technology, short for Biology and Chemistry She is a policy and advocacy fellow at the Society for Neurosci- where, in Brian Stoltz’s lab, he syn- Online Notes. He also wrote and ence and a policy activist at the thesized several dragmacidin alkaloids self-published an organic chemistry nonprofit organization Future of possessing anti-viral and anti-cancer coloring book for children. Research. Follow her on Twitter activities. He did postdoctoral work Justin Bañaga, who took Garg’s @AdrianaBankston.
APRIL 2019 ASBMB TODAY 31 FASEB EXCELLENCE IN SCIENCE AWARD Kahn honored for research, mentoring By George Van Den Driessche
Barbara Kahn is the recipient of provide a new therapeutic treatment the Federation of American Societ- for Type 2 diabetes. ies for Experimental Biology’s 2019 Kahn’s contributions go beyond Excellence in Science Award. groundbreaking research. She has FASEB is honoring Kahn, the mentored 100 postdocs and students, George R. Minot endowed chair and and she has played a leadership role in professor of medicine at Harvard mentoring programs that help junior Medical School and vice chair for re- faculty, especially underrepresented search strategy in the Beth Israel Dea- minorities and women, gain high- coness Medical Center department visibility positions in the research of medicine, for her contributions to community. diabetes research and the scienti c As a physician–researcher, Kahn community. Kahn is a member of the has served as a consultant for the National Academy of Sciences and “It is an honor to receive this National Diabetes Advisory Board the National Academy of Medicine award on behalf of the talented at the National Institutes of Health postdoctoral fellows, students and a fellow of the American Associa- and is on the Advisory Council for and junior faculty who have tion for the Advancement of Science. catalyzed the discoveries in my lab, the National Institute of Diabetes, Gerald I. Shulman, a professor at and our collaborators who have Digestive and Kidney Diseases. She Yale University, wrote in his nomi- expanded our scienti c horizons. has served on numerous American nation letter that Kahn “has made e inspiration and skills of this Diabetes Association committees and pioneering discoveries throughout team deserve this award. As a as an editor for several academic jour- the past 30 years that elucidate the physician-scientist, my vision is to nals. Kahn is also a leader within the molecular mechanisms underlying leverage emerging technologies to Beth Israel Deaconess Medical Center obesity, insulin resistance and type 2 better understand metabolism and where she was chief of the Diabetes diabetes, with a particular emphasis discover new approaches to prevent Unit and the Division of Endocrinol- on the role of the adipocyte in regu- and treat metabolic diseases.” ogy, Diabetes, and Metabolism. She lating glucose homeostasis.” — BARBARA KAHN also co-chairs the Unconscious Bias In the 1990s, Kahn discovered Awareness committee for the depart- that obese and diabetic people had ment’s Committee on the Advance- downregulation of the major insulin- a pro-inammatory state. In 2012, ment of Women. regulated glucose transporter protein, Kahn’s lab found that increasing Kahn will receive her award at the GLUT4, in fat cells, causing insulin GLUT4 protein expression induces ASBMB annual meeting during the resistance. is discovery fueled a carbohydrate-response element- Experimental Biology 2019 con- research career studying insulin action binding protein (ChREBP) which ference in Orlando, where she will de- and the pathogenesis of type 2 dia- regulates fatty acid synthesis. Kahn’s liver an award lecture titled “Glucose betes. Kahn’s work regarding the cel- lab discovered ChREBP is necessary transport, adipose biology and novel lular and molecular e ects of altered in adipocytes to maintain whole-body mechanisms for regulating systemic GLUT4 levels resulted in identi ca- insulin sensitivity. insulin sensitivity” at 8 a.m. April 8 tion of novel mechanisms that cause e insights gained from these in Valencia Ballroom A at the Orange insulin resistance and increase the risk studies led to the discovery of a new County Convention Center. of developing diabetes. In the early class of lipids called branched fatty 2000s, her lab determined that the acid hydroxy fatty acids, or FAHFAs. fat-secreted retinol binding protein Insulin-resistant people have low George Van Den Driessche 4, RBP4, is increased in adipose biological concentrations of FAHFAs. ([email protected]) is a Ph.D. tissue and blood in obesity and If these lipids are restored to normal student in chemistry at North type 2 diabetes in humans, and this healthy levels in diabetic mice, insulin Carolina State University. Follow him on Twitter @George_V14. causes insulin resistance by creating sensitivity improves. ese lipids may
32 ASBMB TODAY APRIL 2019 RUTH KIRSCHSTEIN DIVERSITY IN SCIENCE AWARD Torres honored for decades dedicated to diversity in science By Alyson Smith
Jorge Torres, an associate profes- arrived he has served as an extraor- sor in the department of chemistry dinary role model for our diverse and biochemistry at University of student body. He has proven to be California, Los Angeles, has won the a great colleague and has shared our Ruth Kirschstein Diversity in Science campus’ vision for improving the Award. With this award, the Minority diversity of the academy.” A airs Committee of the American Torres shares his discoveries and Society for Biochemistry and Mo- mentorship experience with a variety lecular Biology honors an outstand- of audiences. He has spoken at ing scientist who has contributed minority-targeted conferences and signi cantly to increased participation participated in multiple campus and and e ective mentorship of under- statewide diversity initiatives, includ- represented minorities in the sciences. ing the National Science Foundation- Torres studies proteins that direct “I am deeply honored to be Louis Stokes California Alliance for the recipient of the 2019 Ruth the assembly and function of the Minority Participation. He has given Kirschstein Diversity in Science mitotic spindle and uses multidisci- Award. It is imperative that the Spanish-language interviews about his plinary approaches to develop new scienti c workforce represent the research on Univision and CNN en anti-cancer drugs. He has authored diversity of our society. A diverse Español. over 30 publications in his nine years and inclusive scienti c workforce Torres’ colleagues commend his as a principal investigator, and his can harness the creativity, thought contributions in research, mentor- discoveries have led to two provi- and experience that can spur in- ship, teaching and advocacy. In her sional patents. He also has developed novation and the advancement of nomination letter, Sabeeha Merchant, a compound target identi cation science. I commend all that strive formerly of UCLA and now a distin- database and other resources, which for true diversity in STEM!” guished professor of biochemistry, he has posted online to bene t other — JORGE TORRES biophysics and structural biology at researchers in his eld. His the University of California, Berkeley, contributions to un- describes Torres as “an all-around derstanding mitotic ties as a graduate student at Princeton outstanding individual — a creative spindle function University and postdoctoral fellow at scientist, an inspired teacher and a and pathology Stanford University and Genentech. dedicated citizen of the diverse com- have earned him As a principal investigator, he has munity around him.” multiple honors, mentored more than 20 minority Torres will receive his award during including the Basil undergraduates, graduate students the ASBMB annual meeting at the O’Connor Award and postdoctoral fellows. Most of his Experimental Biology 2019 confer- from the March of undergraduate students become co- ence in Orlando, where he will deliver Dimes Foundation and the authors on a publication before leav- an award lecture titled “Dissecting the American Cancer Society Research ing his lab, and three have won the mechanisms of cell division” at 8:30 Scholar Award. UCLA Dean’s Research Prize. Torres a.m. April 8 in Valencia Ballroom A When he was an undergraduate also mentors students in the class- at the Orange County Convention at the University of California, Santa room, developing new curricula and Center. Barbara, Torres helped found an orga- guest lecturing in multiple courses. Alyson Smith is a recent Ph.D. nization to recruit minority students In her nomination letter for the graduate from Scripps Research to the university and provide peer award, Tama Hasson, assistant vice in La Jolla, California. Follow her mentoring and tutoring. He partici- provost for undergraduate research on Twitter @cellbionerd. pated in similar programs and activi- at UCLA, wrote, “From the day he
APRIL 2019 ASBMB TODAY 33 ASBMB–MERCK AWARD Banerjee honored for discoveries in vitamin B12 and H2S signaling By Dawn Hayward
e complicated makeup and and master’s degrees from Delhi chemistry of the cofactor vitamin B12 University in India and her Ph.D. have intrigued researchers for decades. in biochemistry from the Rens- Ruma Banerjee, Vincent Massey col- selaer Polytechnic Institute in New legiate professor and associate chair of York and was a postdoctoral fellow biological chemistry at the University in biophysics at the University of of Michigan, has unraveled much Michigan. She served on the faculty of the mystery behind this vitamin, at the University of Nebraska-Lincoln including transport to other proteins before moving back to the University and the kinetics of a related sulfur of Michigan. signaling pathway. For her work, she Banerjee is an associate editor for has won the American Society for Chemical Reviews and the Journal Biochemistry and Molecular Biology’s of Biological Chemistry. She also has 2019 ASBMB–Merck Award. “I saw that Natalie Ahn was call- chaired and started two new sections Also known as cobalamin, vitamin ing and wondered what ASBMB for the Gordon Research Confer- committee she was going to ask me B12 is a cofactor for two mammalian ence. Squire J. Booker, a professor at to serve on. I was oored when I enzymes, but how the cobalt atom is realized she was calling about the Pennsylvania State University, wrote prepped to reach its nal destinations Merck award!” in his letter supporting the nomina- had eluded researchers. Banerjee’s tion, “She cares deeply about our — RUMA BANERJEE laboratory discovered dual func- scienti c discipline, and gives of her tionalities for a protein, CblC, that time unsel shly to make it better.” partitions cobalamin to the cytoplasm Banerjee has authored more than and the mitochondrion to gener- the chaperone in this process. 230 publications. She received the ate methionine and succinyl-CoA, Banerjee investigated hydrogen P zer award early in her career, and respectively. sul de production where substrate this is noteworthy, according to In the mitochondrion, cobalamin homocysteine is used in the methio- Judith P. Klinman, a professor at the is transferred to the active site of a nine arm of vitamin B12 chemistry. University of California, Berkeley, di erent enzyme to generate succinyl- Cystathionine beta-synthase, or CBS, because the P zer “has been a very CoA from methyl-CoA. Inactivating produces H2S along with cystathio- signi cant predictor of future ad- the enzyme, however, can lead to nine. Banerjee determined the speci c vances by the awardee. Her progress buildup of a radical. Banerjee showed residues in CBS that di erentiate and contributions have con rmed that turnover can be regulated by the these functions and identi ed a this expectation.” substrate to prevent metabolic switch whereby iron helps Banerjee will receive her award at high radical levels. determine activity. the ASBMB annual meeting dur- Collaborat- Her University of Michigan col- ing the Experimental Biology 2019 ing with league James Bardwell, who nomi- conference in Orlando, where she will Catherine nated Banerjee for the award, wrote deliver an award lecture titled “Signal- Drennan at in his nomination letter, “ is insight ing through sul de” at 8 a.m. April 9 the Mas- explains why previous clinical trials in Valencia Ballroom A at the Orange sachusetts for lowering homocysteine have failed County Convention Center. Institute to increase cardiovascular disease bur- Dawn Hayward (dhaywar5@jhmi. of Technol- den and suggests … that a strategy for edu) is a graduate student at the ogy, Banerjee modulating H2S might be e ective Johns Hopkins University School determined the instead.” of Medicine. crystal structure of Banerjee received her bachelor’s
34 ASBMB TODAY APRIL 2019 WILLIAM C. ROSE AWARD Shippen mentors students, breaks new ground in telomere and plant science By Kelsey Hughes
Dorothy Shippen, a professor and scienti c experience.” interim head of the department of Shippen’s dedication to the biochemistry and biophysics at Texas development of young scientists A&M University, has won the Ameri- extends far beyond her own group. can Society for Biochemistry and In collaboration with Texas A&M Molecular Biology’s 2019 William C. business professor Daria Panina, she Rose Award for her contributions to developed a course, Building Scien- both molecular biology and the train- ti c Relationships, that focuses on ing of younger scientists. equipping students and postdocs with Shippen has made numerous often overlooked skills in leadership signi cant contributions to telomere and management. As chair of the biology and plant science. Andrew university’s interdisciplinary graduate Nelson and Mark Beilstein, research- program in genetics, she has worked ers at the University of Arizona, sub- “ e ASBMB Rose Award is espe- to expand career development op- cially meaningful for its recogni- mitted a joint letter in support of her portunities for trainees by creating an tion of collaborative research. e nomination, writing, “While plant vast majority of scienti c discover- administrative postdoctoral fellow po- biologists proudly proclaim her one ies, even the most exciting, end up sition, a summer biotech internship of our own, she is equally a member as a thin sedimentary layer in the program and a summer fellowship of the biochemistry, telomere biology, rising mountain of new knowl- program. Shippen is also active in and molecular genetics communities.” edge. What lasts is our impact on programs supporting the recruitment Also supporting the nomination young scientists. Sharing with my and retention of women and under- was Virginia Zakian of Princeton students the scienti c enterprise — represented minorities in science. University. “Research from the Ship- its empowerment, disappointments, Sarah Bondos, a colleague at Texas pen lab has had a major impact on and ultimately, illumination — A&M, nominated Shippen for the the telomere community, especially in has been one of the greatest joys of Rose Award, writing, “Her research is my life.” the area of telomerase regulation,” Za- outstanding, and her deep commit- kian wrote. “She has made important — DOROTHY SHIPPEN ment to training younger scientists contributions to the telomere eld has helped a variety of students across in two di erent organisms, ciliated the university.” protozoa and plants.” been linked to devastating stem cell Shippen will receive her award Shippen’s early contributions to disorders. during the ASBMB annual meeting telomere biology include discovery Shippen has mentored 126 stu- at the Experimental Biology 2019 of a Euplotes crassus telomerase dents at all levels and is invested in conference in Orlando, where she will RNA template and determination of their success as independent scien- deliver an award lecture titled “Break- the mechanism and regulation of E. tists. “Dorothy allows researchers in ing new ground: the emergence of crassus de novo telomere formation. her group to engage in side projects, non-canonical functions for telom- Most importantly, she established permitting exploration of the eld erase subunits in plants” at 8:30 a.m. Arabidopsis thaliana as a model of telomere biology,” Nelson and April 9 in Valencia Ballroom A at the system for the study of telomere func- Beilstein wrote in their letter. “She Orange County Convention Center. tion. is work paved the way for was always available to talk, and she signi cant ndings, including identi- encouraged brainstorming sessions Kelsey Hughes (kelsey.hughes9@ cation of A. thaliana CST complex to esh out models and plan future gmail.com) is a writer and RNA homologues and, in collaboration experiments. ese sessions … pro- scientist living in Austin, Texas. with Carolyn Price, the identi cation vided us with an invaluable model of of human CTC1, which has now an e ective researcher engaged in the
APRIL 2019 ASBMB TODAY 35 WALTER A. SHAW YOUNG INVESTIGATOR AWARD Chng a ‘rising star’ in bacterial membrane lipid research By Courtney Chandler
Shu-Sin Chng, a professor in port in mycobacteria could lay the the department of chemistry at the groundwork for improved therapies National University of Singapore, has against mycobacterial infection. been awarded the American Society Jean-Francois Collet of the Univer- for Biochemistry and Molecular sité catholique de Louvain nominated Biology’s 2019 Walter A. Shaw Young Chng for the award. “ e importance Investigator Award. e award recog- of his work is greatly ampli ed given nizes Chng’s work on outer mem- that the bacterial (outer membrane) brane biogenesis in Gram-negative is a prime target for the development bacteria and mycobacteria. of novel antibiotics, especially in the In her letter supporting Chng’s context of combat against multidrug nomination for the award, Tracy resistant ‘superbugs,’” Collet wrote in Palmer of Newcastle University wrote his nomination letter. that his research has made “an out- “I am extremely excited and Hiroshi Nikaido, of the Univer- standing contribution to our under- honored to receive the Walter Shaw sity of California, Berkeley, wrote in Young Investigator Award in Lipid standing of bacterial lipid tra cking” support of the nomination that he Research. I am deeply indebted to and that Chng “has already cemented my mentors Daniel Kahne and “was struck by both the range of Dr. himself as a world leader in his eld.” Jonathan Beckwith for providing Chng’s work as well as the creativity e outer membrane of Gram- exceptional training, friendship and originality in his studies,” while negative bacteria has a unique and support throughout my career. Stephen Trent of the University of composition compared to the inner I am also very grateful to my post- Georgia called Chng “a rising star.” membrane. While mechanisms docs and students past and present Chng received his Ph.D. in for outer membrane protein and for their commitment, patience chemistry at Harvard University in glycolipid transport and assembly and hard work — this success also 2010, and he remained at Harvard have been well de ned, how glycero- belongs to them!” as a postdoctoral fellow. In 2011, he phospholipids are transported to and — SHU-SIN CHNG joined the department of chemistry at from the outer membrane was largely the National University of Singapore. unknown. Chng has investigated He is also a visiting professor at the how phospholipids are transported transport of phospholipids from Singapore Center on Environmental by the OmpC-Mla system, which the outer to inner membrane and is Life Sciences and Engineering. is important for the maintenance of thus required for outer membrane Chng will receive his award during outer membrane lipid asymmetry in lipid homeostasis in Gram-negative the ASBMB annual meeting at the Escherichia coli. e Mla system had bacteria. Experimental Biology 2019 confer- been described previously, but Chng Chng also investigates mycobac- ence in Orlando, where he will deliver identi ed a new component OmpC, teria, which have evolved an outer an award lecture titled “Bacterial de ned the biochemical mechanisms membrane rich in mycolic acids. lipid tra cking and outer membrane of this system and demonstrated Mycobacteria are notoriously hard to homeostasis” at 1:45 p.m. April 8 in that it did in fact transport lipids. work with, yet Chng was able to de- Valencia Ballroom A at the Orange e Chng lab also reported that the scribe how mycolic acids are ipped County Convention Center. Tol-Pal complex, rst de ned over 50 by a protein called MmpL3, as well as years ago, is involved in phospholipid how MmpL3 is the direct target for Courtney Chandler is a Ph.D. transport. In what Palmer described small molecule inhibitors. Mycolic student in biochemistry at the as a “profound discovery,” Chng’s acid synthesis is an important path- University of Maryland, Balti- more. Follow her on Twitter @ group demonstrated that this com- way for targeted antibiotic therapies. CourtneyEChan. plex is important for the retrograde us, Chng’s research on lipid trans-
36 ASBMB TODAY APRIL 2019 EARL AND THRESSA STADTMAN DISTINGUISHED SCIENTIST AWARD Tonks honored for seminal work on protein tyrosine phosphatases By Nathalie Gerassimov
Nicholas Tonks, the Caryl Boies signaling molecule with membrane professor of cancer research at Cold permeability, regulates PTP func- Spring Harbor Laboratory, has won tion as part of the unfolded protein the American Society for Biochemis- response to endoplasmic reticulum try and Molecular Biology’s 2019 Earl stress, an essential process implicated and ressa Stadtman Distinguished in many diseases. ey also discov- Scientist Award for his three decades ered that PTPs can be inactivated of outstanding research in the eld reversibly by oxidation and developed of protein tyrosine phosphatases, methods to assay PTP redox state. or PTPs, enzymes that regulate the is mechanism plays a role in insu- signal transduction cascades of many lin signaling, providing a therapeutic cellular processes. target for diabetes. Bruce Stillman, president and Tonks has pursued the therapeutic CEO of Cold Spring Harbor Labora- “I am honored to receive this potential of his discoveries. His lab award, which I hope will help to tory, nominated Tonks, calling him “a showed that small molecule inhibi- draw attention to all of the out- pioneer and a consistent leader in the standing research being performed tors of PTP1B could have therapeutic eld.” David Barford of the Medical on the PTP family of enzymes. use for Rett syndrome, and he led an Research Council Laboratory of Mo- ese are exciting times as new early-stage human trial to show that lecular Biology wrote in support of biological functions and links to PTP1B allosteric inhibitor MSI-1436 the nomination, “Tonks is a member disease are being de ned for the (trodusquemine) is a therapeutic tar- of a select group of scientists respon- PTPs. Hopefully, we will soon wit- get for HER2-positive breast cancer. sible for establishing and develop- ness the rst drugs that target these “Nick Tonks has been a major ing a new research eld of immense enzymes for the treatment of major gure in biochemistry and signal importance and signi cance.” human diseases.” transduction for nearly 30 years,” Tonks received a bachelor’s degree — NICHOLAS TONKS Benjamin Neel of New York Univer- in biochemistry from Oxford Uni- sity wrote in a letter supporting the versity in 1981 and a Ph.D. from the award nomination. “He shows no University of Dundee in 1985, work- characterized further the importance sign of slowing down, and indeed, his ing with Sir Philip Cohen. of its lipid and protein phosphatase most important work may yet be to Little was known about tyrosine function. roughout his indepen- come.” dephosphorylation when Tonks dent career, Tonks has advanced the Tonks will receive his award dur- started his postdoctoral work with PTP eld in diverse cellular pathways. ing the ASBMB annual meeting Edmond Fischer at the University His lab helped lay the groundwork at the Experimental Biology 2019 of Washington, where Tonks dis- for PTP1B as a therapeutic target for conference in Orlando, where he will covered and characterized the rst a range of human diseases. In collabo- deliver an award lecture titled “30 PTP, known as PTP1B. Tonks and ration with others, they determined years of protein tyrosine phosphatases collaborators also showed that the the crystal structure of PTP1B, — basic research to novel therapeu- membrane-spanning lymphocyte deciphering the mechanisms of PTP tics” at 1:15 p.m. April 9 in Valencia common antigen CD45 was a PTP, catalysis and substrate recognition, Ballroom A at the Orange County advancing the eld of immunology. and then designed substrate-trapping Convention Center. After Tonks joined the faculty at mutants that other researchers used to Nathalie Gerassimov (nathalie. Cold Spring Harbor in 1990, his lab identify physiological PTP substrates. [email protected]) is showed that PTEN, the major tumor In their second decade, Tonks’ a Ph.D. student at the Johns suppressor protein mutated in many team discovered how PTP1B is regu- Hopkins University School of cancers, had PTP activity, and he lated: Hydrogen sul de, a gaseous Medicine.
APRIL 2019 ASBMB TODAY 37 HERBERT TABOR RESEARCH AWARD Thorner stands as a giant in the golden age of yeast research By Gelareh Abulwerdi
Saccharomyces cerevisiae is a spe- Using yeast, orner studied G- cies of yeast, a unicellular organism protein coupled receptors, or GPCRs, long used by bakers and brewers. As and their downstream signaling a eukaryotic single-cell microbe, yeast cascades. He cloned the rst MAP is also a great organism for research. kinase, Kss1, and showed that these Among the pioneers in studying yeast kinases are downstream of GPCRs. is Jeremy orner, who has increased is work helped illuminate certain understanding of signal transduction pathways that are important in cancer in several diseases, using yeast as a treatment. research model. Michael Hall of the University For his breakthrough research of Basel nominated orner for the and other contributions to science, award, calling him “one of the giants orner, a professor of biochemistry, of the golden age of yeast research.” biophysics and structural biology at “I feel very honored to be the most Hall wrote in his nomination letter the University of California, Berkeley, recent (2019) recipient of the that orner “has continually made ASBMB Herbert Tabor Research has won the American Society for groundbreaking contributions of Award. e year (1971) Herb Biochemistry and Molecular Biology’s ascended to editor-in-chief of the great importance to our understand- 2019 Herbert Tabor Research Award, JBC coincided with my rst sci- ing of hormone action, signal trans- which honors excellence in biologi- enti c publication (in the JBC, of duction and cellular morphogenesis at cal chemistry and molecular biology course!) and his superb stewardship the biochemical level.” and contributions to the community of the journal over the next four orner is an outstanding men- of scientists. decades is legendary among bio- tor, according to Hall, “with at least orner grew up in Quincy, Mas- chemists. Having the opportunity seven former Ph.D. students and sachusetts. He received his Ph.D. in to be a scientist and do research has fteen postdocs in faculty positions at biochemistry from Harvard Uni- been an enormous privilege.” distinguished universities.” He is also versity in 1972 under the guidance — JEREMY THORNER a longtime journal editor who “tire- of Henry Paulus, studying a model lessly writes lengthy emails to authors allosteric enzyme, E. coli glycerol to ensure a fair, constructive review kinase. As a postdoctoral fellow under Along with an early student, David process,” Hall wrote. I. Robert Lehman at Stanford Univer- Julius, orner published seminal orner will receive his award sity, he studied T4 phage and E. coli papers describing the mechanisms during the ASBMB annual meeting DNA replication. by which the peptide mating phero- at the Experimental Biology 2019 At a Lake Arrowhead Genetics mones of yeast are produced. One of conference in Orlando, where he will Conference in Los Angeles, orner these factors is pheromone precursor deliver an award lecture titled “Regu- ran into Ira Herskowitz, an acquain- prepro-alpha-factor, which is pro- lation of plasma membrane homeo- tance from graduate school, who was cessed to its active form through the stasis: Dissecting TORC2 signaling” studying mating-type switching in secretory pathway. Julius and orner at 8:15 a.m. April 7 in Valencia yeast. At Herskowitz’s suggestion, discovered Kex2, a prohormone- Ballroom A at the Orange County orner enrolled in the Cold Spring processing endoprotease whose Convention Center. Harbor yeast genetics course, which mammalian orthologs are important in maturation of proinsulin and other Gelareh Abulwerdi (gelareab@ led him to establish projects working umaryland.edu) is a Ph.D. with yeast in his own lab when he bioactive peptides. ese discoveries candidate at the University of joined the faculty at UC Berkeley in contributed to making recombinant Maryland, Baltimore. Follow her 1974. insulin for treating diabetes. on Twitter @ Gelareh_science.
38 ASBMB TODAY APRIL 2019 BERT AND NATALIE VALLEE AWARD IN BIOMEDICAL SCIENCE Thompson honored as ‘exemplary scientist’ in cancer biology By Isha Dey
Craig B. ompson, president and and microbiology and immunology CEO of Memorial Sloan Kettering at the University of Michigan. He Cancer Center, is the recipient of the went on to become a professor in the American Society for Biochemistry departments of medicine and mo- and Molecular Biology’s 2019 Bert lecular genetics and cell biology at the and Natalie Vallee Award in Bio- University of Chicago, an investigator medical Science. e award honors an at the Howard Hughes Medical Insti- established scientist for outstanding tute, and then a professor and chair accomplishments in basic biomedical of the department of cancer biology research. ompson’s lab focuses on at the University of Pennsylvania. In studying cancer cell metabolism. 2010, he was appointed president and ompson is a pioneer in the eld CEO of Memorial Sloan Kettering of cancer biology. His ndings have Cancer Center. challenged existing notions about “I am honored to receive this recog- ompson has co-authored more nition from the American Society mammalian cell metabolism and its than 400 peer-reviewed articles, has for Biochemistry and Molecular regulation. Contrary to earlier nd- Biology and to be recognized been cited more than 93,000 times ings that mammalian cells take up among those who have previously and holds 30 patents. He also serves nutrients autonomously, ompson won this award. I wish to thank in leadership positions at various demonstrated that growth factor the Vallee Foundation for their scienti c organizations. signaling is essential for glucose and commitment to championing basic As the Vallee award recognizes amino acid uptake by cells for ATP biomedical science, and the Society outstanding achievements synthesis. Without growth factors and for recognizing my lab’s work on in sciences basic to hormones, cells ultimately undergo cancer metabolism.” medicine, omp- apoptosis. However, oncogenic trans- — CRAIG B. THOMPSON son ts the bill as a formation of mammalian cells alters “champion of cancer the regulation of cellular metabolism. research,” Massagué Due to activation of the oncogene Sloan Kettering Institute, nomi- wrote in his nomina- Myc, cancer cells switch to using glu- nated ompson for the award. “Dr. tion letter. tamine instead of glucose as an energy ompson’s research elucidating ompson will source. is allows glucose metabo- cancer cell metabolism is pioneering, receive his award during lites to be directed to nucleotide visionary and of outstanding quality,” the ASBMB annual meet- synthesis, which aids in uncontrolled Massagué wrote in his nomination ing at the Experimental Biology cell proliferation. letter. “He has established a reputa- 2019 conference in Orlando, where ompson’s group showed how tion as one of the most thoughtful he will deliver an award lecture titled mutations in genes coding for meta- and accomplished investigators in the “ e role of metabolites in regulat- bolic enzymes lead to several forms of eld of cancer research.” ing cellular di erentiation and gene cancer. Over the years, his work has ompson received his under- expression” at 1:15 p.m. April 8 in established beautifully how cellular graduate degree in biochemistry from Valencia Ballroom A at the Orange metabolism regulates signal transduc- Dartmouth College in 1974, followed County Convention Center. tion and gene expression and how by a medical degree at the University oncogenic transformation alters these of Pennsylvania in 1977. He served Isha Dey ([email protected]) mechanisms. He also has contributed as medical o cer at the Naval Blood is a scientist at Thermo Fisher to the development of treatment for Research Institute and National Naval Scientific in India. autoimmune diseases. Medical Center before being appoint- Joan Massagué, director of the ed an assistant professor of medicine
APRIL 2019 ASBMB TODAY 39 ALICE AND C.C. WANG AWARD IN MOLECULAR PARASITOLOGY Soldati–Favre honored for research on Toxoplasma gondii By Kerri Beth Slaughter
Dominique Soldati–Favre, a mechanism of organelles biogenesis professor at the University of Geneva, and inheritance as well as on cell–cell has won the American Society for communication. Biochemistry and Molecular Biology’s In addition to her research con- 2019 Alice and C.C. Wang Award in tributions, Soldati–Favre has served Molecular Parasitology. Soldati-Favre in editorial roles for several major is honored for her outstanding work journals in her eld, including PLoS in Toxoplasma gondii invasion and Pathogens and Cell Host & Microbe, egress. and as editor of parasitology in Soldati–Favre’s research group Molecular Microbiology. Among her studies intracellular parasites, speci - many awards and honors, Soldati- cally members of Apicomplexa, to Favre was a Howard Hughes Medical understand how they cross biological Institute junior and senior Interna- barriers during invasion. Apicom- “Alice and C.C. Wang paved the tional Research Scholar, nominated plexan parasites cause a number of way of my education in parasitol- as a European Molecular Biology ogy through the insightful Bay diseases in humans and animals, such Organization member in 2011 and Area Parasitology Clubs at the as malaria, toxoplasmosis, cryptospo- time of my postdoctoral training elected in 2014 as a member of the ridiosis and coccidiosis. To address at Stanford. I am deeply honored Swiss Academy of Medical Sciences. this disease burden, Soldati–Favre’s and grateful to receive this award She currently serves as the vice dean group investigates Toxoplasma to that I wish to share with all the for basic research of the faculty of discover the mechanisms involved in talented collaborators who have medicine at the University of Geneva. host cell attachment, invasion and built fantastic teams around me Henri Bounameaux, dean of the intracellular survival. over the years. In sweet memory of faculty of medicine at the University After obtaining her Ph.D. in 1990 C.C.’s big smile.” of Geneva, nominated Soldati–Favre from the University of Zurich, Sol- —DOMINIQUE SOLDATI-FAVRE for the award, writing, “Dominique dati–Favre worked as a postdoctoral is unanimously recognized among her fellow in John Boothroyd’s labora- peers as one of the most gifted Swiss tory at Stanford University School of inducible system to study the func- scientists of her generation.” Medicine. While studying Toxoplas- tion of essential genes in apicomplex- Soldati–Favre will receive her ma there, she was the rst researcher an parasites and the characterization award during the ASBMB annual to develop methodologies to apply of the molecular machine termed meeting at the Experimental Biology reverse genetics in this parasite. “the glideosome” that powers motility 2019 conference in Orlando, where “Dr. Soldati–Favre is an out- and invasion. she will deliver an award lecture titled standing scientist whose work has Recently her group has unraveled “ e ins and outs of Toxoplasma in- consistently broken new ground,” the central roles played by aspartyl vasion and egress” at 2:30 p.m. April Boothroyd wrote in a letter of sup- proteases that act as key maturases for 8 in room W307AB at the Orange port for the award nomination. “ e secreted proteins involved in subver- County Convention Center. eld of parasitology would not look sion of host cellular functions or in the way it does were it not for her and invasion and egress. Her laboratory her lab’s key contributions.” also contributed to some studies on Kerri Beth Slaughter (kerri. Soldati–Favre returned to Switzer- the metabolic pathways hosted by two [email protected]) is a gradu- land in 2004 to build her laboratory endosymbiotic organelles, the mito- ate student in the biochemistry at the University of Geneva. Seminal chondrion and the relic of a plastid department at the University of Kentucky. Follow her on Twitter @ contributions from her research career called the apicoplast, and conducted KB_Slaughter. include the establishment of a tight exciting cell biology projects on the
40 ASBMB TODAY APRIL 2019 ASBMB YOUNG INVESTIGATOR AWARD Dunham recognized for ribosome regulation insights By Kelsey Hughes
In recognition of her contributions impact of basic, fundamental studies to the elds of biochemistry and mo- of the utmost creativity and quality.” lecular biology, Christine Dunham, Christopher Lima of the Sloan an associate professor of biochemistry Kettering Institute, wrote a letter in at Emory University, has been se- support of the nomination, highlight- lected to receive the American Society ing the importance of Dunham’s for Biochemistry and Molecular Biol- work. “Her investigations are funda- ogy’s 2019 ASBMB Young Investiga- mental to our biological understand- tor Award. ing of the ribosome and its roles In the 17 years since her rst pub- decoding the genome, and perhaps lication examining hammerhead ribo- more intriguing, its unanticipated zyme biology, Dunham has published importance in adaptive processes such more than 30 original research papers. as bacterial persistence,” he wrote. Dunham consistently has been recog- “It is an incredible honor to have Dunham’s work is recognized our work on the regulation of nized as a superb scientist, beginning widely and has garnered awards from protein synthesis recognized by with her graduate work with William our ASBMB colleagues. I have numerous scienti c organizations and Scott at the University of California, been honored to mentor and work funding agencies. She has received a Santa Cruz, and continuing through alongside a diverse group of bright National Science Foundation Faculty her postdoctoral work with Nobel and creative researchers in my lab Early Career Development, or CA- laureate Venki Ramakrishnan at the and this award is a recognition of REER, award, as well as recognition Medical Research Council Laboratory their accomplishments. Science as a Pew Scholar in the Biomedical of Molecular Biology in Cambridge, is challenging but working with Sciences, a Burroughs Wellcome England. Dunham’s recognition has such inspiring colleagues towards Investigator in the Pathogenesis of only grown since she started her own unexpected discoveries has been the Infectious Disease and the 2017 group in 2008 at Emory. greatest privilege of this wonderful American Crystallographic Associa- career.” Writing in support of the award tion’s Etter Early Career Award. One nomination, Johns Hopkins Univer- — CHRISTINE DUNHAM of her lab’s recent papers was a Jour- sity professor Rachel Green described nal of Biological Chemistry Editor’s Dunham as “an outstanding early Pick and a 2018 paper in PNAS won investigator who has established a translation and antibiotic resistance. the Cozzarelli Prize. program focused on interesting Anita Corbett, an Emory col- Dunham will receive her award and important (medically relevant) league, nominated Dunham for the during the ASBMB annual meeting problems. Her early work at Emory award, noting her far-reaching impact at the Experimental Biology 2019 has made substantial contributions to as a researcher. “Her work exploits her conference in Orlando, where she the eld and is taking her in new and expertise in structural biology of the will deliver an award lecture titled compelling directions.” ribosome and touches on fundamen- “Mechanisms of RNA-mediated Dunham’s work has provided sig- tal aspects of biochemistry and mo- translational control” at 2:15 p.m., ni cant insight into the structural ba- lecular biology,” Corbett wrote in her April 7 in Valencia Ballroom A at the sis of ribosomal decoding and frame nomination letter. “Notably, her work Orange County Convention Center. shifting, the bacterial toxin-antitoxin highlights how focused mechanistic system and mechanisms of antibiotic studies that employ biochemistry and Kelsey Hughes (kelsey.hughes9@ resistance. Her work has touched on molecular biology approaches can gmail.com) is a writer and RNA numerous aspects of translation, in provide critically important insights scientist living in Austin, Texas. particular the impact of tRNA and to broad areas of biology. Her work rRNA modi cations on bacterial gives perspective and highlights the
APRIL 2019 ASBMB TODAY 41 AVANTI AWARD IN LIPIDS Bankaitis a ‘tour de force’ in the field of lipid biology By Courtney Chandler
Vytas Bankaitis, a distinguished how we think about the regulation, professor at the Texas A&M Univer- physical organization, and diversi ca- sity College of Medicine, has been tion of lipid signaling, and it promises awarded the Avanti Award in Lipids to rewrite the textbooks” on these by the American Society for Bio- subjects. chemistry and Molecular Biology. He Of Bankaitis’ collective research is being recognized for his work on contributions to the eld of lipid sci- elucidating the role of lipid transfer ence, Johnson wrote that his “creative, and phosphatidylinositol exchange thorough, and comprehensive elucida- proteins in cell biology. tion of the structure and function of Arthur Johnson, also of Texas PITPs and of their integration into A&M, wrote in his letter supporting the metabolic signaling pathways of the award nomination that Bankaitis’ the cell constitutes a tour de force.” contributions to the eld of lipid sci- “I am deeply honored to be Bankaitis earned his Ph.D. in recognized as recipient of the ence “have profoundly inuenced our microbiology at the University of Avanti Award in Lipids. is understanding of the importance of award belongs to the talented and North Carolina and then worked in lipids to so many areas.” dedicated students, postdoctoral cell biology as a Helen Hay Whitney For 25 years, Bankaitis and his fellows and technicians who drove Foundation postdoctoral fellow at the laboratory have focused on the our research over the years. I stand California Institute of Technology. He regulation and organization of lipid on their shoulders. It also serves subsequently joined the faculty at the signaling in eukaryotic cells. His as testimony to my mentors and University of Illinois, Urbana–Cham- laboratory described the rst biologi- insightful colleagues, and to the paign, followed by positions at the cal function for what had previously lipid community who embraced University of Alabama at Birmingham been a functionally enigmatic group our science, that their interest and and the University of North Carolina. of proteins, the phosphatidylinositol investment was worthwhile. I In 2012, he joined the department of thank them all.” transfer proteins, called PITPs. ese molecular and cellular medicine at the proteins bind and exchange speci c — VYTAS BANKAITIS Texas A&M Health Sciences Center, phospholipids, the phosphatidylinosi- where he is the E.L. Wehner-Welch tols, between membranes in vitro. His foundation chair in chemistry. early research described an important signaling. In this way, PITPs act Bankaitis will receive his award at and novel link between lipid metabo- as highly regulated coordinators of the ASBMB annual meeting dur- lism and cellular tra cking when phosphatidylinositol kinase signaling ing the Experimental Biology 2019 he discovered that a yeast protein in eukaryotic cells, which channels conference in Orlando, where he will called Sec14 had PITP activity. is lipid kinase activities toward speci c deliver an award lecture titled “In- launched a new research area at the biological outcomes. When the in- structive regulation of phosphoinosit- interface of vesicle tra cking and terfaces are regulated inappropriately, ide signaling by lipid transfer pro- lipid metabolism. He discovered that it can a ect membrane tra cking, teins” at 1:45 p.m. April 7 in Valencia vesicle tra cking is, in fact, depen- growth factor receptors, cell growth Ballroom A at the Orange County dent on lipids, and he went on to and developmental pathways. Convention Center. elucidate the structure and mecha- William Dowhan of the McGov- nism of Sec14. ern Medical School at the University Bankaitis’ recent research indicates of Texas Health Science Center at Courtney Chandler is a Ph.D. student in biochemistry at the that PITPs are crucial for coordinat- Houston wrote in his nomination University of Maryland, ing the interfaces of lipid-driven letter that Bankaitis’ recent research Baltimore. Follow her on Twitter metabolic reactions and intracellular is entirely novel and “is reshaping @CourtneyEChan.
42 ASBMB TODAY APRIL 2019 ANNUAL MEETING Beyond federal funding PAAC workshop to explore nontraditional sources for research grants By Benjamin Corb
For many American Society for professor at the Cold Spring Biochemistry and Molecular Biology Harbor Laboratory; and Town hall at EB members who run independent labs, the search for research funding is an • Janet Hieshetter, executive direc- For the third consecutive year, ongoing challenge. tor of the Dys- the ASBMB PAAC will hold e ASBMB’s Public A airs Ad- tonia Medical an advocacy town hall event at visory Committee started an alterna- Research Experimental Biology. tive funding working group in 2017 Foundation. e event, at 12:15 p.m. Sun- tasked with creating tools to help day, April 7, in room W307CD, members nd funding from sources e panel will be is an open-format brie ng from HIESHETTER other than federal science agen- chaired by ASBMB PAAC chair Matt Gentry of the cies such as the National Institutes PAAC member Terri University of Kentucky and Ben- of Health or the National Science Kinzy, vice president for research at jamin Corb, the ASBMB’s public Foundation. Western Michigan University. a airs director. Matt and Ben will e working group will host its All ASBMB members are invited update attendees on the commit- rst major event during the annual to attend. Greer tee’s activities over the past year meeting at 5:30 p.m. Sunday, and Hieshetter and discuss the policy agenda that April 7, in room W205A. is panel will describe the the public a airs team is advocat- discussion will explore alternative funding mecha- ing for in Washington on behalf funding options available to nisms o ered by of ASBMB members and the biochemists and molecular biologists. their organizations research community. ey also e panelists will include: and share tips for KINZY will answer your questions about submitting successful science policy and your research • Susanna Greer, applications. ey also will talk about experience. ASBMB similarities and di erences between Topics for dis- member and grants from large and small founda- cussion include director of the tions. Tonks will share his experience the NIH’s clinical cancer as a recipient of several grants from Next Genera- research, nutri- foundations. tion Research GREER GENTRY tion and immu- is panel is one of several events Initiative, how nology program planned by the PAAC’s alternative science funding in the extramural grants depart- funding working group to help AS- agencies are working to combat ment of the American Cancer BMB members learn about innova- sexual harassment and scal poli- Society; tive ways to nd funding for their cies in Capitol Hill that might research. If you want to see more of impact investments in research. • Nick Tonks, these events highlighting alternative Ben Corb and policy special- recipient of funding opportunities, please contact ist Daniel Pham will be at the the ASBMB’s us at publica [email protected]. meeting representing the ASBMB 2019 Earl and public a airs team, and they will ressa Stadt- be happy to arrange one-on-one man Distin- Benjamin Corb (bcorb@asbmb. meetings with you to discuss poli- org) is director of public affairs guished Scientist TONKS cy questions, concerns or strategy. at the ASBMB. Follow him on Just visit the ASBMB booth and Award (read his Twitter @bwcorb. pro le on page 37) and a they’ll help you connect.
APRIL 2019 ASBMB TODAY 43 ANNUAL MEETING
Professional development — it’s not just for grad students By Danielle Snow ack
Each year, the American Society for Biochemistry and Molecular Biology invites top researchers from around the world to inspire the next generation of scienti c discoveries with their talks at the ASBMB annual meeting. is year, I o er a challenge to all annual meeting attendees: Step away from the science and take time to in- vigorate your professional life outside the lab. Career development e ASBMB 2019 annual meeting ASBMB has career development for researchers at all career stages. In addition to the let you share your science story. At the end of the workshop, you’ll grad student/postdoc career develop- Want to see science communi- have time to pitch your ideas to our ment sessions and the undergraduate cators in action? is year, we are panelists and the audience to get speed-networking opportunities, we hosting the inaugural Science in a feedback on how to take your science will focus on “Transitions at the Flash communication contest. is to the public. Mid-Career Point.” ese talks, high- event features 10 speakers, each of lighting career transitions in teaching, whom will share their science in just Education industry and university leadership, four minutes with only one slide. In will help midcareer faculty think addition to distilling their research Looking for inspiration to shake about their next professional steps. down to its essence, presenters must up your teaching practices? Start with work to eliminate scienti c jargon so the ASBMB Award for Exemplary Science communication that their presentation is understood Contributions to Education lecture; by specialists and non specialists alike. 2019 award winner Neil Garg (see Writing a grant to fund your e audience will play a major role in his pro le on page 31) will talk about research? Emailing a member of Con- selecting winners, so join us and vote how he made Chem 14D, an organic gress to advocate for funding? Talking for your favorite. chemistry class, into one of UCLA’s to your neighbor about your work? most popular undergraduate courses. ese are all moments when you Outreach After the award lecture, the educa- need science communication skills. tion spotlight sessions will help you One secret to good communication is After being inspired by the work explore biochemistry and molecular creating a compelling narrative about presented in the science outreach biology teaching in the lab and in the your science through storytelling. In poster session, join us to learn strate- lecture hall. our interactive workshop “Storytelling gies to take your science beyond the and the art of giving a great presenta- bench and into the public sphere. In Danielle Snowflack (dsnow- tion,” experienced science storytellers the “Transforming science research fl[email protected]) is the share strategies to help you think into science outreach” workshop, ASBMB’s director of education, about your research in a new way to speakers will talk about how they suc- professional development and engage and excite your audience. cessfully translated their research into outreach. Follow her on Twitter @drsnowflack. At the end, we open the oor to outreach and engagement programs.
44 ASBMB TODAY APRIL 2019 ANNUAL MEETING
CAREER DEVELOPMENT OUTREACH / ADVOCACY Workshop / Alternate Funding: Driving Philanthropic EB Welcome Reception Support for Basic Science with Science Outreach Poster Session 5:30–7 p.m. Sunday, April 7 7–8:30 p.m. Saturday, April 6 Convention Center W205A Convention Center Valencia Ballroom ABCD
Transitions at the Mid-Career Point Advocacy Town Hall Meeting 9:30–11:30 a.m. Monday, April 8 12:15–1:45 p.m. Sunday, April 7 Convention Center W306AB Convention Center W307CD
Micro-learning hub / How to Develop a Comprehensive Workshop / Transforming Science Research Job-Search Strategy into Science Outreach Part 1: 3:30–4:30 p.m. Monday April 8 5:30–7 p.m. Monday, April 8 Part 2: 9–9:30 a.m. Tuesday April 9 Convention Center W307CD EB Career Central
Workshop / Navigating Difficult Conversations 5:30–7 p.m. Monday, April 8 Convention Center W306AB
SCIENCE COMMUNICATION Constructing your Elevator Pitch 1:15–2:45 p.m. Saturday, April 6
Convention Center W306AB ASBMB Workshop / Storytelling and the Art of Giving a Great Presentation EDUCATION 5:30–7 p.m. Sunday, April 7 Using Large Sets of Data with Students Convention Center W207B 10 a.m.–noon Sunday, April 7 Convention Center W306B Micro-learning hub / How to Get Started with Science Writing and Build a Portfolio ASBMB Award for Exemplary Contributions 3–3:30 p.m. Monday, April 8 to Education Lecture EB Career Central “How organic chemistry became one of UCLA’s most popular classes” — Neil Garg, UCLA ASBMB Student Flash Talk Science Communication 3–4 p.m. Sunday, April 7 Competition and Reception Valencia Ballroom A 7–8:30 p.m. Monday, April 8 Rosen Centre Grand Ballroom C Exploring Biochemistry Teaching and Learning 4:15–5:15 p.m. Sunday, April 7 Convention Center W305A
Workshop / Integrating Research into the Classroom: Developing an Engaging CURE with Big Data 5:30–7 p.m. Sunday, April 7 Convention Center W306AB
Exploring Experimentation in Biochemistry Lab and Non-Lab Settings 2:30–3:45 p.m. Monday, April 8 ASBMB Convention Center W306AB
APRIL 2019 ASBMB TODAY 45 INSTAGRAM
SNAPCHAT SPOTIFY
46 ASBMB TODAY APRIL 2019 ANNUAL MEETING Carbs got you down? Come get friendly with glycans By Catherine Grimes & Natasha Zachara
Glycans are everywhere. to create, test and disseminate new your eld? If so, we’re here to help. INSTAGRAM Development, the immune system, tools, reagents and methods to help A workshop to highlight recent the de nition of self, protection of all scientists do research under the advances from the glycoscience com- surfaces, adhesion of cells, signal glycoscience umbrella. Four years munity and assist you in tackling transduction and metabolism. What in, the program’s investigators have your glyco needs will be held Sunday, do they have in common? progressed toward the NAS goal of April 7, at the American Society for All are regulated by glycans and a glycoscience tool kit and now seek Biochemistry and Molecular Biol- their conjugates (glycoproteins, collaborating partners from the broad- ogy annual meeting in Orlando. is glycosaminoglycans and glycolipids). er scienti c community — researchers low-key networking event is designed Perhaps you’ve encountered glycans with an interest in glycans and their to facilitate discussions tailored to in your research: milk oligosaccah- binding partners — to use these tools. all levels of your research needs. e designers of new tools, standards, methods and syntheses will be waiting Emerging Technologies in the Glycosciences to talk with you at tables labeled “Ask a Glycoscientist.” Academic investiga- SUNDAY, APRIL 7 n 5:30 – 7 p.m. tors Catherine Grimes, Will York, SNAPCHAT SPOTIFY Lance Wells, and Natasha Zachara Room W307CD, Orange County Convention Center and industry representatives from Presented by Catherine Grimes, University of Delaware, and Natasha Zachara, Lectenz Bio and Glycan erapeutics Johns Hopkins University LLC will be available to answer such questions as: • How do I determine if my pro- rides that play a critical role in innate Funded projects must cross-validate tein is glycosylated? immunity, the ABO blood group their e orts, highlighting the utility • How do you approach a glycom- antigens, hyaluronic acid (in our of tools and reagents while promoting ics project? knees and in cosmetics), and the car- fruitful collaborations. For example, • What bioinformatics tools are bohydrates that often form the ligands Catherine Grimes’ laboratory at the there? critical to vaccines. University of Delaware has developed • What reagents are available to Discovering a glycan associated a method to label the bacterial cell help me label my glycans? with your favorite research question wall metabolically with modi able We hope this interactive night of can be daunting. What do you do? sugar building blocks. ese reagents programing will lower any barriers Call a friend who knows about gly- have been shared with numerous labo- between you and working on sugars cans? Stop working on the problem? ratories. Nina Salama’s laboratory at in your research. Dealing with anything glyco tradi- the Fred Hutchinson Cancer Research Indulge your sweet tooth in tionally has been reserved for special- Center in Seattle used Grimes’ tools Orlando. ists. Yet, given their prevalence in to study the role of the glycan coat in biology, everyone should get to know the pathogenesis of Helicobacter py- Catherine Grimes (cgrimes@ these molecules. lori, the bacteria that causes stomach udel.edu) is an assistant profes- sor of chemistry and biochemistry In response to the National Acad- cancer. is non-glycobiologist has at the University of Delaware. emy of Sciences’ 2012 report “Trans- streamlined the methodology into her forming glycoscience: A roadmap for microbiology-based research program. Natasha Zachara (nzachara@ the future,” the National Institutes of is is just one example of how the jhmi.edu) is an associate profes- Health is investing about $120 mil- common fund is working across dis- sor in the biological chemistry lion in the Common Fund Glyco- ciplines to assure that new approaches and oncology departments at the science Program. An NIH working to studying glyco are inclusive. Johns Hopkins University School group designed a seven-year program Do you have glycans questions in of Medicine.
APRIL 2019 ASBMB TODAY 47 ANNUAL MEETING
WELCOME TO ORLANDO By Haley Davenport, Haley Lehew, Jessica Krogh, Matthew Caldwell & Andy Nguyen
ere will be plenty to do and see inside the Orange County Convention Center during Experimental Biol- ogy 2019. Even so, you’ll want to get outside to see some of the sites of Orlando. e following guide was created by o cers of the University of Central Florida’s American Society for Biochemistry and Molecular Biol- ogy Student Chapter. is guide includes some of Orlando’s most notable tourist destinations as well as some local favorites. Op- tions range from short evening events to activities that may take all day. Distances listed are from the conven- tion center. For advice on how to get around, check out
our transportation guide on p. 51) COURTESY OF KEN TETER/UCF All activities listed — from arcades to Disneyworld These officers of the newly chartered University of Central Florida ASBMB Student — are suitable for all ages and have been experienced Chapter assembled this guide. In back are Haley Davenport (president), Andy Nguyen by one or more of our members, so we guarantee that (treasurer) and Matthew Caldwell (historian). In front are Haley Lehew (vice president) every activity is enjoyable. and Jessica Krogh (secretary). THINGS TO DO IN ORLANDO INTERNATIONAL DRIVE Yard House, Shake Shack, Sugar are not. More a ordable than the big Factory and many other restaurants parks such as Disney or Universal. ICON Orlando 360 are located here. (1.5 miles) (4 miles) (iconorlando.com). e Orlando Eye, Madame Tussauds wax muse- Fun Spot Orlando Dave and Buster’s um, the SEA LIFE Orlando Aquar- (fun-spot.com/orlando). is theme (daveandbusters.com/locations/ ium, Arcade City and the Orlando park has go-karting, roller coasters orlando). A full-service sports bar and StarFlyer are among the attractions and many other fairlike activities. restaurant as well as a large arcade of this entertainment complex. Admission is free, but the attractions with many games. Great for families. (1.7 miles)
Andretti Indoor Karting & Games (andrettikarting.com). A large indoor arcade and indoor go-karting venue. Also o ers food and drink, bowling, VR games and simulators, and more. (0.8 miles)
Topgolf (topgolf.com/us/orlando). Large multi-story gol ng venue with over 100 individual hitting bays. Includes a full-service restaurant and bar. Great for families and parties. $15 per bay and up. (1 mile)
AARON CLAUSEN Fun Spot America Orlando Freedom Flyer Coaster
48 ASBMB TODAY APRIL 2019 ANNUAL MEETING
The Escape Game Orlando (theescapegame.com/orlando). You have 60 minutes to solve puzzles and nd a way to escape from one of four rooms with themes including Mission: Mars and Gold Rush. Great for par- ties of up to 8 people. $35/person. (2 miles) Wonderworks (wonderworksonline.com/orlando). If you don’t get enough science inside the convention hall, this amusement park features more than 100 hands-on science exhibits in six zones, including natural disasters and physical chal- lenges. $34/adult, $25/child. (1.7 miles) Titanic: The Artifact Exhibition (premierexhibitions.com). Self-guided BRIAN MARSHALL Drops of Taumata Racer in Aquatica, Florida tours of objects and displays from the Titanic or a guided tour with an actor portraying an individual linked to the SPORTS SHOPPING MALLS Titanic. Interesting for all ages. $22/ adult, $15.75/child. (2.5 miles) Orlando Magic (nba.com/magic) The Florida Mall (simon.com/ host the Atlanta Hawks for Classic mall/the-orida-mall). is large Pointe Orlando (pointeorlando. Night and Fan Appreciation Night, 7 enclosed mall features many depart- com). is outdoor shopping center p.m., April 5, at Amway Center. $18 ment stores, smaller stores and a food includes a movie theater, restaurants, and up. (11 miles) court. (6 miles) live entertainment and other activities for adults and children. (1 mile) Orlando City Soccer Club The Mall at Millenia (mallatmil- (orlandocitysc.com) host the Colo- lenia.com). is indoor mall includes SEAWORLD rado Rapids, 7:30 pm, April 6, at department stores, high-end designer Camping World Stadium. $23 and stores, smaller stores and a food court. SeaWorld (seaworld.com/orlando). up. (10 miles) (6.2 miles) is theme park is on International Drive, close to the convention center. Orlando Vineland Premium It has multiple exhibits, aquatic shows Outlets (premiumoutlets.com/ and thrill rides. is is a full-day activ- outlet/orlando-vineland). is large ity. $80. (3 miles) outdoor outlet mall contains multiple stores as well as a food court. Aquatica (aquatica.com/seaworld). (5.5 miles) is water park is across the street from SeaWorld on International Orlando International Drive. It has multiple slides and wave Premium Outlets pools. is is a full-day activity. $40. (premiumoutlets.com/outlet/orlando- (2 miles) international). Another large outdoor outlet mall with many stores and a food court. (4.5 miles)
BOB LINSDELL Universal Studios CONTINUED ON NEXT PAGE
APRIL 2019 ASBMB TODAY 49 ANNUAL MEETING
CHAD SPARKES Disney’s Typhoon Lagoon
UNIVERSAL Universal Studios. is mov- Animal Kingdom. is theme universalorlando.com (4 miles) ie- and TV-based theme park has park is continent based and features multiple rides, restaurants and shows. animals, rides, dining and shows. CityWalk. is location features is is a full-day activity. $114/adult, is is a full-day activity. ($109 age mini-golf, clubs, a movie theater, and $109/child. 10 and up) many gift shops and dining oppor- tunities. It directly connects to the Islands of Adventure. is Epcot. is theme park is a world theme parks. ere is a $25/day park- theme park has multiple rides, res- showcase featuring food, drinks and ing fee for park visitors. taurants and shows. is is a full-day performances representative of regions activity. $114/adult, $109/child. of the world. is is a full-day activity. ($109 age 10 and up) Volcano Bay. is water park has a surf pool, an arti cial volcano and Hollywood Studios. is theme multiple slides. is is a full-day activ- park is mostly movie-based, featuring ity. $80/adult, $75/child. rides, shows and dining. is is a full- day activity. ($109 age 10 and up)
WALT DISNEY WORLD Blizzard Beach/Typhoon disneyworld.disney.go.com (7miles) Lagoon. ese water parks feature lazy rivers, slides and wave pools. ($65 Disney Springs. is location age 10 and up) features multiple restaurants, shops, shows and other activities such as a Winter Summerland/Fantasia movie theater and bowling alley. Gardens. ese 18-hole themed mini-golf courses are located at the Magic Kingdom. is theme park Disney World and Epcot resorts. ($14 contains multiple areas, each with age 10 and up) a unique theme, as well as dining, IVAN CURRA shows and rides. is is a full-day Epcot Center activity. ($109 age 10 and up)
50 ASBMB TODAY APRIL 2019 ANNUAL MEETING Getting around Orlando Welcome to the sunshine sprawl By John Arnst
Congratulations. If you’re heading for the American Society for Bio- chemistry and Molecular Biology’s annual meeting, then you’ll be in Orlando in April. As a former Florid- ian, I can state authoritatively that’s a pretty good month to visit — the weather is likely to be hot but not yet sweltering — so you might want to see some sights outside the big Experimental Biology meeting in the Orange County Convention Center. What’s the best way to do that? Most of Orlando isn’t especially hospitable to foot tra c; the heat, humidity and asphalt can render more than a few minutes outside sweaty VISITOR 7/ WIKIMEDIA and unpleasant. However, the shop- Orange County Convention Center ping centers and restaurants around the convention center are surprisingly or Uber will save you from a running bridges. If you aren’t inclined to eat walkable, given the sprawling nature meter if you wind up stuck in traf- at the hotel restaurants, a short walk of the city and state, so you’re in c, but both will carry a $5 airport on International Drive takes you to luck if you want to get through the surcharge. a Denny’s, Red Lobster and Dunkin’ meeting without renting a car. If you If you aren’t pressed for time, the Donuts, and just northward lie the decide to rent a vehicle, buckle in and westbound route 42 of the local Lynx bars and upscale chain restaurants of drive carefully — the combination of bus system, which runs between the the Pointe Orlando. congested roadways and tourists unfa- airport and Destination Parkway near If you want to explore a bit farther miliar with them can be harrowing. the convention center with minimal a eld, consider the I-RIDE Trolley. If you’re reading this before you’ve stops, is the most a ordable option at is a ordable transportation service arrived at either the Rosen Centre $2. However, the ride takes an aver- operates from 8 a.m. to 10:30 p.m. Hotel or the Hyatt Regency Orlando, age of 80 minutes and requires exact in the International Drive area. Cost your nonrental options for getting change. is $2 per adult and $1 per child. from the airport to your hotel are to Between these extremes of cost and Unlimited day passes also can be take a taxi, one of the local Lynx buses convenience are the paid shuttle bus purchased online. More information, or a paid shuttle. If you’ve already services Mears Transportation and including the route map and real- made it to your hotel, consider these SuperShuttle, which respectively cost time trolley tracking, can be found on as options for your return trip. $22 and $19 for a one-way trip from the website. A taxi’s a taxi, and the hotels are the airport and can be scheduled in nearly 13 miles from the airport; with advance. minimal tra c, the drive takes about Once you’ve gotten to your hotel, John Arnst (jarnst@asbmb. 20 minutes, but with springtime it’s a breeze to get to the conven- org) is an ASBMB Today science tourism, it may take the better part of tion center; both the Hyatt Regency writer. Follow him on Twitter @ arnstjohn. an hour, and the cost averages $30 to Orlando and the Rosen Centre Hotel $60. A rideshare service such as Lyft connect to the center through indoor
APRIL 2019 ASBMB TODAY 51 ANNUAL MEETING
SPEAK YOUR MIND Will you be at #ASBMB2019 in Orlando? If so, drop by ASBMB headquarters for an on-camera interview. We invite you to share • career advice • your thoughts on wellness for scientists • inspiring personal experiences • opinions on other topics e edited videos will be paired with online editions of upcoming ASBMB Today articles. MAYBE YOUR NEW FAVORITE T-SHIRT? Please contact our media specialist, Allison Frick, at [email protected] or is year’s American Society for Hughes drew up the nal design and on Twitter, @AllisonFrick, to schedule Biochemistry and Molecular Biology thought of the phrase “these are a few your interview or ask questions. annual meeting T-shirt design comes of my favorite things.” from the ASBMB Student Chapter at e Otterbein University ASBMB Otterbein University in Westerville, Student Chapter is a decentralized Follow #ASBMB’s Ohio. student chapter that prides itself on o§ cial meeting tweeter “We came up with this idea one allowing everyone to be involved, day while in the research lab,” Erin Hughes said. “We focus on making Guillaume ibault is an assistant Hughes, the chapter’s president, said. connections between the members professor in the School of Biological “A few chapter members were trying and talking about science in new and Sciences at the Nanyang Technologi- to brainstorm what ASBMB and fun ways.” cal University in Singapore. In his lab, BMB meant to us.” is year’s T-shirt will be sold at he uses his multidisciplinary training Chapter member Katie Dodds the ASBMB booth at Experimental to tackle biologi- came up with the idea to use some Biology 2019 in Orlando, April 6–9. cal key questions common research techniques to spell — Stephanie Paxson on endoplasmic out ASBMB and created the design. reticulum stress, lipid regulation and homeostasis using the model organ- THIBAULT DOWNLOAD THE EB APP isms yeast, cell culture and C. elegans. He won the highly 1. Search “EB Annual Meetings” in your app competitive Elite Nanyang Assistant store. Professorship Award in 2013. ibault was previously a research 2. Select “Experimental Biology 2019.” fellow in Davis Ng’s laboratory at 3. Browse sessions and abstracts. Temasek Life Sciences Laboratory, Singapore. He received his Ph.D. 4. Build your schedule. under the supervision of Walid Houry 5. Get ready to enjoy #ASBMB2019 at EB! in the department of biochemistry, University of Toronto, Canada. is is ibault’s rst Experimental Biology conference. Follow him on Twitter @Guillou76 or @ThibaultLab.
52 ASBMB TODAY APRIL 2019 APRIL 2019 ASBMB TODAY 53 ESSAY The recommendation letter conundrum Should the trainee write their own rst draft? By Kamalika Saha
magine this: You are well on your way to graduating or nearing the Iend of your postdoctoral stint, and it’s time for the pivotal transition to- ward that coveted postdoc or industry position. You’ve done the groundwork by successfully clearing the rst two interview rounds. e key factor is now the letter of recommendation. You approach your mentor, who tells you to start by drafting the letter yourself. What’s your reaction? Are you surprised at the request, or do you readily comply? What are the ethical guidelines surrounding this? Are mentors shirking their responsibilities by having students write their own letters? Richard Eckert, a professor of I ask for a draft from trainees I do not A letter of recommendation is an biochemistry and molecular biology directly mentor, it is solely informa- important piece of the application at the University of Maryland, Bal- tional,” she said. “I’m looking for puzzle, and the opinions reected in timore, believes that writing a draft data that I can polish, elevate with this letter can sway the outcome. A letter can be educational. “I prefer to language and context, and provide my well-written letter succinctly high- have students and postdocs draft their perspective. e labor is not lessened, lights and analyzes the candidate’s recommendation letters to help them but the content is enhanced.” strengths in an unbiased manner. And understand how to encapsulate their In other instances, the quantity a letter with a personal touch provides achievements,” Eckert said. “I then of requests is an issue. Application an added advantage. rewrite them to a nal form season for graduate and professional Having a student or postdoc write and share the copy with candidates schools brings a surge of recommen- the rst draft may provide a platform as an additional part of the learning dation letter requests, and it might the mentor can build upon. It gives experience.” not be feasible for the mentor to them the pertinent facts to create the When a mentor has limited remember and highlight exact nu- nal version. At times, drafting this contact with a student who was a ances for each trainee’s letter without letter helps candidates rethink their summer intern or short-term research assistance. A draft from the student strengths and weaknesses from the trainee, a draft letter listing achieve- makes the process more e cient and employer’s perspective and impels ments or experiences can provide a helps a professor draft a personalized them to evaluate their career path. more targeted approach than basing letter. A mentor’s feedback on a draft letter the recommendation on a CV. Mayuri Rege, faculty at Ramnarain can help a candidate gain valuable in- at’s the view of Rajini Rao, Ruia Autonomous College in India, sights into how they should represent a professor of physiology at Johns sees the bene ts in this approach themselves to the employer. Hopkins School of Medicine. “When but also limitations. “One of the
54 ASBMB TODAY APRIL 2019 reasons that professors, especially in universities, will ask students to write their own LORs is because they are simply overwhelmed with writing them for almost 20-30 students in one application season,” she said. “However, these impersonal letters written by inexperienced writers make for little impact and show how little the professor cares for the student. A good alternative is to ask the student to provide a list of career highlights and circumstances that were special moments shared with that professor.” A candidate might be applying for a position outside academia that re- quires strengths and skills unlike those needed at a university. In such cases, it is useful for the student to provide a template highlighting the job-speci c qualities. Priyanka Subrahmanyam, a post- doctoral fellow at Stanford, recognizes this. “ e tendency to let students write their own letters stems from the PI wanting to make sure the right the University of New South Wales in professor and not by the student/post- qualities are highlighted, especially Sydney, believes that trainees may not doc,” she said. “If the professor asks for jobs outside academia,” she said. have the bigger picture in mind and the applicant to write his or her own “For grant applications or academic are ill-equipped to elaborate honestly LOR, I would believe that either the jobs, they will almost certainly write on their strengths and weaknesses. professor isn’t very keen on spending the letters themselves, with minimal “I write every single LOR for my time on the applicant or he/she could involvement from the student.” In students,” he said. “I deliberately keep care less.” either case, Priyanka believes it is it factual and honest so that the reader e recommendation letter fair to assume that the mentor has gets a true picture of the student’s conundrum has multiple solutions. thoroughly reviewed the letter and time in my lab. I believe as group Arguments exist both for and against will stand by its contents. So having a leaders, we owe it to the students having students and trainees author student or postdoc draft a letter may and future employers who value our a draft of their own letters. A rec- stimulate ideas for the mentor, who words, to put these facts and opinions ommendation letter needs to have can then reword, edit and review the in our own words rather than entrust just the right blend of thoughts and nal version before signing o on it. it with the students. In cases where perceptions to propel a trainee to the One professor who asked to remain the student’s growth has been positive, next rung of the career ladder. Getting anonymous believes, however, that I believe it matters that the group some insight from the mentee may mentors are passing o a fundamen- leaders take the time to do justice to aid the process of writing a letter that tal responsibility by having students their hard work.” is factually accurate and has a personal or trainees draft their own letters. “I From a trainee’s perspective, touch. On the other hand, writing a would personally never ask my train- choosing the right person to write a well-crafted letter is an art, and if a ees to do the job for me and write a reference is of utmost importance for mentor readily writes one unassisted, grant application in my name,” the their career path. Sreemoyee Acharya, the mentee can’t ask for more. professor said. “Although this could a graduate student in the University be construed as part of the training, of Iowa, believes a professor or men- Kamalika Saha (kamalika.saha@ it is, in my opinion, way outside of tor who has worked closely with them gmail.com) is a medical writer the job description for any research and is familiar with their work ethic is at Sanofi. trainees.” a natural choice. “ e recommenda- Senthil Arumugam, group leader at tion letters should be written by the
APRIL 2019 ASBMB TODAY 55 RESEARCH SPOTLIGHT Seeking to understand the rules of life — and taking life lessons from dogs
s an assistant professor of biochemistry and biomedical Ainformatics at Vanderbilt Univer- sity, Carlos F. Lopez works to develop numerical methods to understand signal transduction cascades in cells and their dysregulation in cancer. He is also the Vanderbilt liaison to Oak Ridge National Laboratory. Lopez earned his Bachelor of Sci- ence in chemistry and biochemistry (double major) and Bachelor of Lib- eral Arts at the University of Miami and his Ph.D. in physical chemistry at the University of Pennsylvania. He did postdoctoral work at University of Texas at Austin in biophysics and then in systems biology at Harvard Medical School. In this month’s Research Spotlight, Lopez talks about the value of strong mentors and his need for alone time. His answers have been edited for length and clarity.
What key experiences and decisions have enabled you to COURTESY OF CARLOS LOPEZ reach your current position? Carlos F. Lopez has had many supportive mentors in his life and says, “Your adviser’s trust is fundamental to building your own confidence as a scientist.” Excellent mentorship has shaped my career. I was lucky to nd mentors who guided me toward excellence nervous about talking to my mentor, interface of chemistry, physics and and encouraged me to search for the but he was very matter-of-fact about biology in a way that would not have answers to big questions — mentors it and taught me simply to own it, been possible otherwise. who were willing to trust that I could correct it and move on. I learned that deliver what I promised. it was OK to make mistakes as long as How did you first become During my graduate work with we can correct them. interested in science? Michael Klein, I once gave him Support from mentors at the some slides with incorrect results for undergraduate, graduate, postdoctoral I learned to read when I was very a presentation. I found out a week and even faculty levels has shaped young, and I asked many “why” ques- later that I had made a mistake. I was my multidisciplinary interests at the tions. My mother found all kinds of
56 ASBMB TODAY APRIL 2019 child-friendly books about science with this failure, I embraced my skills, to nd as your career evolves, so I topics, and I devoured them. My embraced multidisciplinary research try to be mindful about these times. father later encouraged my interest in in biology, and never looked back. is alone time spurs creativity. My science, and I enjoyed chemistry and creative process is nurtured by good physics. However, it was not until I What advice would you movies, good music, conversations, took biochemistry as an undergradu- give to young persons from walks (preferably with a dog) and ate that I found a connection between underrepresented backgrounds playing with my children. the physical and biological sciences. who want to pursue a career in ere was a component of luck when What was the last book you read? I once stayed after organic chemistry science? I read two at once. “ is Is How class a bit too long and the instructor Find advisers who believe in you You Lose Her” by Junot Diaz is a col- recommended I explore undergradu- — advisers who understand your lection of short stories about relation- ate research. I found an undergradu- talents and where you need to im- ships among individuals with mixed ate mentor, Je Evanseck, and that prove. You need advisers with whom ethnic and socioeconomic back- experience completely changed my you can build a relationship based on grounds. e book’s themes revolve career focus. trust and who are willing to give you around what it means to be human, opportunities to learn from failure. what it means to be male and the roles ey may not tell you what you want Were there times when you failed we play in society. “A Field Guide to hear, but they will help you grow, at something critical to your to Getting Lost” by Rebecca Solnit focus your work on the areas that reminded me that being lost is how path? If so, how did you get back excite you and achieve your goals. we nd ourselves. on track? I tell my students that a mentor- Many times! I think the constant mentee relationship goes beyond Do you have any heroes, heroines, in science is failure. guiding their project. Many emotions are involved in this process, and you mentors or role models? If so, I worked as a postdoctoral fellow how have they influenced you? with Peter Rossky studying water- need to have a mentor with whom protein interactions at UT-Austin. I you can express your frustrations and I do not have a speci c hero, but thought quantum dynamics sounded celebrate your achievements. I always I nd qualities in many people that cool, and I wanted to pursue this joke with Peter Sorger, my postdoc I would like to emulate. I have taken topic. Prof. Rossky explained that this advisor, that we have a mostly loving many lessons from my dogs: live the was not a good idea: I did not have a relationship. He helped me to take moment, fear can be overcome with strong foundation in quantum me- a deep breath during the hard times love and good company, forgive and chanics, and I struggled with some as- and, most importantly, always showed forget, enjoy the journey — and cud- pects of mathematics. He pointed out that he believed in me. Your adviser’s dling with your loved ones is perhaps that I was talented with statistics and trust is fundamental to building your the most important thing you can do had an understanding of biology that own con dence as a scientist. every day. others in my program simply did not have. But I was not good at quantum What are your hobbies? What keeps you working hard dynamics. It was a hard conversation. Despite enjoying other people’s every day? My ego was bruised, but I realized he company, I nd that I need long pe- was correct, and I decided to nour- riods of solitude to think and process e desire to understand how life ish my talents. After coming to terms my ideas. Alone time becomes harder works! We know that we have DNA, RNA, proteins and so forth; that these make cells; and that cells talk to each ABOUT THE RESEARCH SPOTLIGHT other to make organs — and suddenly we have a human being. But how does e American Society for Biochemistry and Molecular Biology’s Re- it all come together? How do we un- search Spotlight highlights distinguished biomolecular and biomedical derstand this parts list to explain how scientists from diverse backgrounds as a way to inspire up-and-coming life works? ese questions keep me scientists to pursue careers in the molecular life sciences. Eligible candi- coming to work and writing grants on dates include Ph.D. students, postdoctoral fellows and new or estab- a regular basis. lished faculty and researchers. To nominate someone for this feature, contact [email protected].
APRIL 2019 ASBMB TODAY 57 Struggle of choice Letter from a chronic night owl By Len Sprague
As I leave the o ce for the day, I sail over to my desk to wake my night … maybe best for tomorrow if I exhausted after hours tethered to the computer. I press the space key, and wish to get any shuteye this evening. computer screen struggling through a loud clack resonates in the silence Perhaps a few more edits on that articles and code, I begin fantasizing as my keyboard ares to life, cours- manuscript? Pro: close in on nishing about dinner and an early bedtime. ing with a myriad of colors. Bright this current paper. Con: I spent all Sweet relief from the endless typing, light bursts from the monitors and day on the paper already and may do pondering, calculating, analyzing washes over the room, reinforcing my more harm than good by looking at it tasks that consume my daily routines, re-invigorated state. again without a fresh perspective. soon to be granted as I return home. Ideas begin to cascade over one Brainstorming a new clip? Pro: Dinner is prepared in a haze. My another — should I begin that litera- builds my portfolio. Con: article was eyes close slowly, kept open only by ture review? Review a few more edits deeply technical, so it might take a heat from the stove top’s ames as I on my nearly complete manuscript? while just to sort through the jargon. carefully warm last night’s leftovers. I Brainstorm a new clip about that Na- Emails? … Just, no. can feel my mind fog and my eyelids ture article? Emails? (Yuck.) Options A bubble of an idea begins to sag, begging me to rest. abound, and I struggle to sort through form amid the tangle of thoughts, Soon, I promise myself. Soon. them for the best choice. breaching the chaos, an idea that is But then, a familiar sensation I convince myself that this will be a dismissed more often than I would passes through me — as the clock simple task. like: What about spending time with strikes 8 p.m., I get my second wind. “All right, not a problem. Just need friends? My magni cent mattress no longer to compare my options a bit. Easy As if on cue, my phone buzzes. A seems appealing as my eyes open wide enough!” group message has come alive, fellow and my limbs shake o the heaviness What if I start that literature chronic night owls reaching out for of near slumber. review? Pro: new paper in the works. companionship and camaraderie. I Night has begun. Con: likely to consume the entire notice that everyone else is available
58 ASBMB TODAY APRIL 2019 this evening. Epilogue: ing bonds among kindred individuals I struggle again. How do I choose? My work as a graduate student and reveling with them in those in- How can I choose? brings many challenges, likely shared between moments (our beloved night I reach for my phone, forming a by others traversing similar paths. I hours) ful lls my desire for support, message of regret in my mind: “Sorry must rapidly digest information and re-motivating me faster than anything everyone, but maybe next time.” reconstitute it for peers, instructors, else can. I can rest when I’m done with my mentors, editors, committees … only As I barrel through the turbulent work. to restart the process from a di er- waters of graduate school and career A feeling halts me — loneliness. ent angle. I scramble to pursue my hunting, I know I bene t from It’s been weeks since I’ve been able to passions (climate advocacy, renew- keeping my friends at the top of my speak with everyone. I’ve begun to able energy, writing and teaching), priority list — even if, sometimes, my feel out of place, burned out by the to identify and claim who I am and academic passions end up ghting constant struggle. where I want to go, all while trying them for attention. I reach my phone and reply: “I’ll not to forget the simple things — be there!” like dinner (or, more often, lunch) Len Sprague (leonard_ Night is a special opportunity; the sprague@ brown.edu) is a and paying rent. I love the battle chemistry graduate student, silence makes it easier to see every for understanding, the tension of summer instructor and writing possibility that could be embarked projects coming to a crescendo, the consultant at Brown University. upon. In the plethora of choices, a joy of collaboration; I equally fear the He is pursuing science writing rare chance to be with friends is not a as a way of sharing knowledge evaluations, worry about the possible and experiences with a global choice to be overlooked. failures and struggle to accept it all. audience. Len also enjoys cook- Yet none of this entirely nourishes ing and snowboarding, albeit Sincerely, my spirit, my drive or my motivation. not at the same time. Follow him on Twitter @ lensprague. Chronic Night Owl Sharing time with close friends, forg-
APRIL 2019 ASBMB TODAY 59 OPEN CHANNELS Credit for discovery and a patenting gaffe
n page 32 of the December 2018 issue of ASBMB better served without patenting of their invention. I Today, there is a half-page box that includes a believe that the likely truth is di erent. Neither Milstein Opicture of Nobel laureate César Milstein who, as the nor anybody else could have guessed in 1975 the impact article explains, invented an e cient method to develop of monoclonal antibodies in diagnostics and therapeutics. monoclonal antibodies. In the same issue, on page 27, Most academics, even today, are not familiar with patents you have a picture of Nobel laureates Michael Brown and the regulatory/disclosure issues associated with them. and Joseph Goldstein, who invented critical pathways of When they have a discovery, they usually try to publish cholesterol metabolism. Unfortunately, in the aforemen- it as soon as possible, for the fear of being scooped, and tioned box, you did they lose sleep until not credit Georges J. their paper is accepted F. Köhler, who was in Nature or a similar the rst author of the journal. If my suspicion 1975 paper in the is true, this incident journal Nature on was likely a ga e due to monoclonal antibod- ignorance of patenting ies and co-winner of practices as well as the 1984 Nobel Prize impatience. Based on its with Milstein (and estimated value (around Niels Jerne). Köhler’s $100 billion), this name is not men- discovery likely quali es tioned even once. as the biggest nancial Since both Köhler CELIA MILSTEIN/MRC LABORATORY OF MOLECULAR BIOLOGY ga e in the history of and Milstein are now This photo of César Milstein and Georges Köhler was taken in 1982, two years before they, scienti c discovery. dead, I do not believe along with Niels Jerne, won the Nobel Prize in physiology or medicine. Regarding claims that this mishap will of inventorship, the bring up any im- Nobel prizes and Nobel mediate complaints. But I believe it would be instructive laureates: I published a 2013 paper in the journal Clinical to your audience, especially trainees, to publish a picture Chemistry and Laboratory Medicine on Nobelitis, a portraying both Köhler and Milstein and give them equal common disease among Nobelists, and I recently argued, credit in the caption. with Clare Fiala, in the same journal that the Nobel Prize On the question as to who contributed more to the should be abandoned. ere are many reasons, one being discovery, Köhler or Milstein or others, I would say, Who that credit is impossible to assign fairly among those who knows? But if I have to guess, I would pick Köhler, the contributed to the inventions. Controversies as to who postdoc who likely conducted all the experiments. should get the prize are almost as many as the awarded On the issue of not patenting the invention, you report prizes themselves. that Milstein blamed the bureaucracy of his institution. — Eleftherios Diamandis I read elsewhere (but do not recall the speci c reference) ([email protected]), that Milstein believed that humanity would have been University of Toronto
60 ASBMB TODAY APRIL 2019 Scripps Institution of Oceanography, Western New England University UC San Diego: Marine Aquaculture/ Assistant Professor or Professional Educator Marine Omics of Forensic Science Assistant/Associate/Full Researcher (Biology Section)
The Scripps Institution of Oceanography (http://scripps.ucsd.edu) at The Department of Physical & Biological Sciences at Western New the University of California San Diego invites applications for a full- England University seeks applications for a full-time faculty position in Forensic Science beginning in September 2019. Depending on time Researcher position to be funded largely by extramural research the education and background, the nalist will be hired either as a grants and contracts in the research areas of marine aquaculture and tenure-track Assistant Professor or as a Professional Educator with a marine omics. The Researcher series at SIO parallels the Professor three-year renewable contract. series in terms of expectations for research and service but carries no Responsibilities include teaching lecture and laboratory sections of fo- teaching requirements. Researchers receive nine-month appointments rensic science courses on Scientic Evidence, Crime Scene Processing, with 25% salary support from institutional sources. Externally funded and advanced Forensic Science courses and laboratories, and guiding research programs are expected to provide the remaining salary student research projects and internships in support of the B.S. in Forensic Biology and B.S. in Forensic Chemistry programs. support, including an opportunity for summer salary. Researchers at SIO often obtain lecturer appointments in the SIO department, which To be considered for a tenure-track position, candidates should have a Ph.D. in forensic science, molecular biology, or analytical chemistry. provides a mechanism to serve as a graduate student advisor. Professional work experience in a forensic science laboratory or in http://www.asbmb.org/Careers/Jobs/79457/ molecular biology/analytical chemistry with applications to forensic science is required. http://www.asbmb.org/Careers/Jobs/79417/
National Institute of Environmental Alabama College Health Sciences of Osteopathic Medicine Sta Scientist Assistant or Associate Professor in the Biomedical Sciences
We are seeking an experienced scientist with a proven track record in The Alabama College of Osteopathic Medicine (ACOM) is now metabolomics utilizing mass spectrometry. The Metabolomics Lead is recruiting for an Assistant/Associate Professor in the Biomedical Sci- to recommend, develop and/or implement innovative mass spectrome- ences. This is a new full-time position to add to our existing faculty try-based metabolomic analysis methods to support the research needs to teach rst and second-year medical students. The successful ap- of the investigators of the NIEHS. A demonstrated mastery of mass plicant must have a Ph.D. or equivalent degree in Molecular Sciences, spectrometry is required; an expert understanding of cellular metabo- Biomedical Sciences or other related eld. We are looking for a lism is highly preferred. The Metabolomics Lead will work in conjunc- candidate whose training and experiences will enhance our existing tion with the existing MSRSG sta to import and implement novel small faculty’s basic sciences areas of expertise. Prior teaching experience molecule mass spectrometry approaches. The Metabolomics Lead must in a medical or biomedical program is a plus. The faculty member is also maintain state-of-the-art knowledge of the eld and be skilled in expected to contribute to the development of scholarly programs preparing scientic presentations and publications. in areas of their choosing. The review of applications will begin im- mediately and continue until the position is lled. http://www.asbmb.org/Careers/Jobs/79705/ http://www.asbmb.org/Careers/Jobs/79458/ www.mcponline.org
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