CONTENTS

NEWS FEATURES PERSPECTIVES

2 24 50 EDITOR’S NOTE HOW TO PATENT AN ANTIBODY ESSAY On being well Advice from Charles Craik Why aren’t there quality controls 3 28 for antibody research? NEWS FROM THE HILL THE WELLNESS ISSUE 52 In 2019, advocacy will be all down hill 29 Finding the help you need EDUCATION 32 Leadership with a focus on wellness Catalyst conversation workshop 34 With a little help from my friends provides tools faculty can use 4 36 Grad students face MEMBER UPDATE mental wellness challenges 37 Career wellness: consider your strengths 54 6 39 Maternity in grad school — NIGHT SHIFT RETROSPECTIVE the best and worst of times Committing for more than one night 41 Holistic mentorship Thomas A. Steitz (1940 – 2018) 43 Refreshing my spirit 44 How I learned to stop worrying about 55 10 grad school and to love climbing rocks CARTOON A YEAR OF (BIO)CHEMICAL 46 For many college students, hunger can The 10 commandments of grantsmanship ELEMENTS ‘make it hard to focus in class’ 48 Chronic pain after trauma For January, it’s atomic No. 1 may depend on your stress gene 50 11 24 NEWS 11 ASBMB members elect six to council and other offices 12 Celebrating Herb Tabor 14 Student Chapter president sees value in campus groups

15 28 JOURNAL NEWS 15 The discovery of GABA in the brain 17 A molecular dance 54 of phospholipid synthesis 18 Researchers closer to gonorrhea vaccine after exhaustive analysis of proteins 19 A close-up of nascent HDL formation 20 From the journals 18

JANUARY 2019 ASBMB TODAY 1 EDITOR’S NOTE

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY On being well By Comfort Dorn OFFICERS COUNCIL MEMBERS Gerald Hart Squire J. Booker President Victoria J. DeRose Blake Hill et well soon. Jennifer DuBois Audrey Lamb We say that Secretary James M. Ntambi when someone Toni M. Antalis Celia A. Shiffer G Treasurer Takita Felder Sumter is sick. It’s a reflex, like Kelly Ten-Hagen saying “bless you” when JoAnn Trejo EX-OFFICIO MEMBERS you hear a sneeze. It’s the David Bernlohr ASBMB TODAY EDITORIAL sentiment emblazoned Hao Wu Co-chairs, 2019 Annual ADVISORY BOARD on cards, balloons and Meeting Program Rajini Rao teddy bears in hospital Chair Committee gift shops. Cheryl Bailey Floyd “Ski” Chilton Chair, Education and Henrik Dohlman But wellness is more Professional Development Peter J. Kennelly than the absence of dis- Committee Beronda Montgomery A. Maureen Rouhi ease. And we know this, Daniel Raben Melissa Vaught right? Even beyond the Chair, Meetings Committee Binks W. Wattenberg multi-billion dollar well- Sonia Flores Chair, Minority Affairs ASBMB TODAY ness industry with all its Committee Angela Hopp potions and pampering, Susannna Greer Executive Editor most of us know what it Chair, Public Outreach [email protected] is to feel unwell without Committee Comfort Dorn personal strengths. Matthew S. Gentry Managing Editor being diagnosed as ill. Wellness is a big-tent topic. In Chair, Public Affairs [email protected] Yet we’re ambivalent about work- this issue, we offer essays and articles Advisory Committee John Arnst ing at wellness — at taking steps to on everything from rock climbing to Enrique M. De La Cruz Science Writer [email protected] make ourselves (and others) feel our holistic mentorship. Some, like Paul Chair, Publications Committee Laurel Oldach best. That’s especially true of people Craig’s account of surviving failure, Science Writter Lila M. Gierasch [email protected] who take their careers very seriously, are deeply personal. Others, like Editor-in-chief, JBC Valery Masterson like (cough) scientists. Who has time Nathan Vanderford and Teresa Evan’s A. L. Burlingame Designer for yoga and counseling when you essay on leadership, offer step-by-step Editor, MCP [email protected] guidance and practical tools. And Ed Marklin have experiments to monitor, papers Nichilas O. Davidson Web Editor to write and breakthrough discoveries because we are science geeks at heart, Editor-in-chief, JLR [email protected] to make? we include an article on the genetic Kerry-Anne Rye Allison Frick cause of pain after trauma. Editor-in-chief, JLR Media Specialist This month, we want to remind [email protected] you that you can’t do any of those Have we covered all the bases? Barbara Gordon things well if you are not well. And Absolutely not. But if you find this Executive Director issue useful, thought-provoking or [email protected] beyond that, if you only get one shot at this mortal coil, you might as well even inspiring, let us know. I had such a great time working with all For information on advertising, contact Pharmaceutical feel your best — physically, spiritually Media Inc. at 212-904-0374 or [email protected]. and mentally. Maybe you can’t cure these authors and their wonderful words, I’d be happy to do this again your own cancer, but for sure you in January 2020. should be able to eke out eight hours Be well, and have a very happy of sleep and the occasional moment new year. of serenity. www.asbmb.org/asbmbtoday And because we don’t live on Comfort Dorn PRINT ISSN 2372-0409 private islands, we should look to the ([email protected]) is managing Articles published in ASBMB Today reflect solely the authors’ views and not wellness of others, whether it’s mak- editor of ASBMB Today. Follow her the official positions of the American Society for Biochemistry and Molecular ing sure undergrads get enough to eat on Twitter @cdorn56. Biology or the institutions with which the authors are affiliated. Mentions of products or services are not endorsements. or helping postdocs recognize their

2 ASBMB TODAY JANUARY 2019 NEWS FROM THE HILL In 2019, advocacy will be all down hill By Benjamin Corb

t is the job of the Public Affairs tweets to your elected representatives. activities that fall in this category. Advisory Committee to advo- Green circles are the bread and butter Not all members have the time or I cate for American Society for of an advocacy campaign. They are opportunity to organize such events, Biochemistry and Molecular Biol- an easy way for ASBMB members to but if you are willing to take up the ogy members by communicating get involved. When you do a green challenge, the public affairs office your needs to the U.S. Congress, the circle activity, it helps us contact as will provide you with support and White House and the federal agencies many elected officials from across the resources. that support your pursuit of scientific country as possible and allows you to The Public Affairs Advisory Com- discovery. However, studies show that be an advocate even if you’re busy. mittee will run several advocacy when individual constituents (that is, Tier two activities require a little campaigns in 2019; they will be voters) talk or write directly to their more effort, like “blue square” ski posted and updated at www.grass- representatives, those words have trails. These activities should take you roots.asbmb.org and also include greater impact than even the most a half-hour or less. A hand-written suggested activities at each of the dedicated advocacy group. letter to a member of Congress or a three levels. The first campaign, In other words — we need your letter to the editor of your local paper starting this month, is to educate the help. are examples of blue square advo- freshman class of Congress on the Your duties as a scientist may cacy opportunities. Your added time importance of robust federal invest- limit how much time you have for and attention will help you (and the ments in science. In the spring, we’ll advocacy. With that in mind, we’ve ASBMB) develop a stronger connec- highlight what ASBMB members designed a three-tiered approach to tion with your elected officials. And have been doing with increased communicating with government the public affairs staff will provide funding at the National Institutes of officials, and we’re offering a menu of sample text or topics and all the Health in recent years. We also plan actions to choose from depending on supporting information you need to to talk about immigration and STEM how much time you have. author a unique piece of writing for a education policies. If you have a topic Here on the East Coast, January blue square message. you think we should address, tell us at brings snow and skiing to mind, so Finally, in tier three “black dia- [email protected]. We look forward to working with we’re using common ski slope termi- mond” activities, passionate ASBMB you in 2019. nology to explain how this works. members can display their expert With tier one or “green circle” advocacy abilities. These opportuni- (think bunny slope) activities, you ties take significant effort but have Benjamin Corb ([email protected]) is director of can participate in one minute or less. great impact. Organizing a visit to public affairs at the ASBMB. These simple “click here to send a your representative’s office or a lab Follow him on Twitter @bwcorb. message” tools will direct emails or tour for government officials are

Interested in science policy? Follow our blog for news, analysis and commentary on policy issues affecting scientists, research funding and society. Visit policy.asbmb.org.

JANUARY 2019 ASBMB TODAY 3 MEMBER UPDATE Member update By Erik Chaulk

Hanson moves steroid hormones modify gene expres- Gentry receives sion, entering the cell and binding to to University of Michigan nuclear receptors, which modify gene Landis award Phyllis Hanson was appointed activity. Matthew Gentry is among the first chair of the department of biological He is the T.C. Thompson dis- recipients of the Landis Award for chemistry at the University of Michi- tinguished leadership professor of Outstanding Mentorship. gan Medical School molecular and cellular biology and Awarded by the in November. chancellor at Baylor College of National Institute Hanson previ- Medicine. of Neurological ously served on the The award, which O’Malley shares Disorders and faculty at the Wash- with Pierre Chambon and Ronald Stroke, the Landis ington University Evans, includes an honorarium and award will be HANSON GENTRY presented annually School of Medicine, a citation presented at a ceremony in to up to five faculty members who where she began as assistant professor October. have shown outstanding dedication to in 1997 and rose to hold the Gerty T. mentoring students and trainees. Cori professorship in the department ACS Bader award Gentry is a professor in the of cell biology and physiology. goes to Broderick department of molecular and cellular Hanson’s research focuses on biochemistry at the University of understanding intracellular mem- The American Chemical Society Kentucky College Of Medicine. He brane organization and trafficking. has presented the 2019 Alfred Bader serves as a mentor to students in his In addition to chairing the biologi- Award in Bioinorganic or Bioorganic lab, where the research focuses on cal chemistry department, she will Chemistry to Joan bothglycogen metabolism in humans hold a joint appointment with the Broderick. and starch metabolisms in plants University of Michigan’s department Established in and algae. of neurology. 1986, the annual Awardees receive $100,000 to sup- Hanson is an associate editor of the Bader award recog- port their efforts to develop and men- tor students and postdoctoral fellows Journal of Biological Chemistry. BRODERICK nizes outstanding contributions to in their laboratories. O’Malley shares bioorganic or bioinorganic chemistry research. In memoriam: Horwitz prize Broderick is a professor in the Bert W. O’Malley is one of three department of chemistry and bio- Gordon Shore recipients of the 2018 Louisa Gross chemistry at Montana State Uni- Gordon Shore passed away Sept. 7 Horwitz Prize for their work on hor- versity. She is being honored for her at the McGill University Health Cen- mone regulation of research on radical SAM enzymes and ter Palliative Care Unit. He was 73. distant cells. biological metal cluster assembly in Born July Presented by hydrogenases. 26, 1945, Shore Columbia Univer- In addition to her research received his Ph.D. sity since 1967, accomplishments, Broderick is highly from McGill Uni- O’MALLEY the Horwitz prize regarded for her excellence in teaching versity in 1974 and honors a scientific and mentorship of the students in her SHORE did postdoctoral investigator or a group of investiga- laboratory. work on mitochon- tors for outstanding basic research in She served on the faculties at dria in England with Jamshed Tata. biology or biochemistry. Amherst College and Michigan State Shore was a professor emeritus of O’Malley is being honored for University before moving to Montana biochemistry at McGill University, demonstrating in the 1960s that State University in 2005. where he taught and did research

4 ASBMB TODAY JANUARY 2019 ASBMB members elected as 2018 AAAS fellows The American Association for the Advancement of Science has elected 416 of its members as fellows, in recogni- tion of their extraordinary achievements in advancing science. Of those honored, the 31 listed below are members of the American Society for Biochemistry and Molecular Biology. The fellows will be recognized at the 2019 AAAS annual meeting in February. Section on chemistry Section on biological sciences Juan D. Alfonzo, The Ohio State University Wonhwa Cho, University of Illinois at Chicago Paul N. Black, University of Nebraska-Lincoln Neil K. Garg, University of California, Los Angeles Mary Dasso, National Institute for Child Health and Carlito B. Lebrilla, University of California, Davis Human Development/NIH Glenn D. Prestwich, University of Utah, College of Savithramma P. Dinesh–Kumar, University of Pharmacy California, Davis Joseph Jez, Washington University in St. Louis Section on medical sciences Kristen Marie Johansen, Iowa State University Eric R. Fearon, University of Michigan Megerditch (Mike) Kiledjian, Rutgers, The State University of New Jersey Isaac Ness Pessah, University of California, Davis Carla M. Koehler, University of California, Los Angeles Lawrence I. Rothblum, University of Oklahoma Health Iris Lindberg, University of Maryland, Baltimore Sciences Center Hua Lu, Tulane University Liangyou Rui, University of Michigan Neil Osheroff, Vanderbilt University School of Medicine L. David Sibley, Washington University School of Linda Joy Pike, Washington University School of Medicine in St. Louis Medicine in St. Louis Gary Arthur Silverman, Washington University School Kevin L. Schey, Vanderbilt University of Medicine in St. Louis Madeline A. Shea, University of Iowa Binghui Shen, Beckman Research Institute, City of Hope Section on neuroscience Holger Sondermann, Cornell University Jonathan Brewer Cohen, Harvard Medical School Allen Taylor, Tufts University Stephen Halley White, University of California, Irvine Section on pharmaceutical sciences Dong-Er Zhang, University of California, San Diego John L. Nitiss, University of Illinois at Chicago on cancer. His research focused on Hokin was born in Peoria, Illinois, school’s department of pharmacology, the regulation of oncogene-induced in 1924. He began his education a position he held from 1970 to his apoptosis. at the University of Chicago before retirement in 1993. He was also co-founder and chief enlisting in the scientific officer of Gemin X Bio- An accomplished researcher, Hokin U.S. Navy V-12 technologies, which develops small- is known for his discovery, along with molecule cancer therapeutics based on program to study his first wife Mabel Hokin, of the medicine at Dart- the regulation of apoptosis. phosphoinositide signaling system. He is survived by his wife, Alexan- mouth University. He also discovered the fundamental dra, and his children, Bobby, Michael, HOKIN He earned an biochemical features of sodium-potas- Dominique and Dylan. M.D. at the University Of Louisville Read a remembrance of Gordon School of Medicine and completed a sium ATPase. Shore by his friends and colleagues John residency at Michael Reese Hospital He is survived by his wife, Bergeron and Richard Rachubinski at Vivian, three children and three asbmb.org/asbmbtoday. in Chicago. Hokin then did doctoral research in biochemistry in England grandchildren. under Sir Hans Krebs. In memoriam: Hokin joined the faculty at the Erik Chaulk ([email protected]) is a peer-review coordinator and Lowell E. Hokin University of Wisconsin in 1957. He digital publications web specialist Biochemist Lowell Edward Hokin held several positions before being at the ASBMB. passed away in September. He was 93. named chairman of the medical

JANUARY 2019 ASBMB TODAY 5 RETROSPECTIVE Thomas A. Steitz (1940 – 2018) By Martin Schmeing

homas Arthur Steitz was a from then on they were the power remarkable person, scientist couple of molecular biology. Their T and mentor. He was a Sterling careers were independent, and they professor of molecular biophysics published together only rarely, but it and biochemistry at Yale University, is hard to imagine a more balanced, a Howard Hughes Medical Institute honored and impactful couple in investigator, a Nobel laureate and a modern science. giant in the field of structural biology. Tom joined David Blow’s lab at the His death on Oct. 9 left a void in the Laboratory of Molecular Biology in scientific community and for those Cambridge, England, as a postdoc- who knew him as well as a legacy of toral fellow and worked with then- fundamental discoveries. graduate student Richard Henderson Tom was born Aug. 23, 1940, in (Nobel laureate for chemistry, 2017) Milwaukee, Wisconsin. His child- on solving structures of chymotrypsin hood in a family of five siblings was bound to its substrates. These studies filled with classic Americana — ten- led to a mechanistic understanding nis and skating and summers spent of the serine protease family and of picking vegetables on his grandfather’s its substrate recognition. Tom often farm. In high school, Tom became PROLINESERVER/WIKIMEDIA COMMONS said the years in Cambridge were Tom Steitz at the Nobel Prize press conference at the a skilled saxophonist, developing Royal Swedish Academy of Sciences in 2009. his most scientifically fulfilling, and his lifelong love for music. He also they shaped his view of the optimal excelled academically, initially spurred scientific environment. He recalled myoglobin, the first atomic resolution on by his younger brother’s higher stimulating discourse, always about protein crystal structure, an achieve- grades. ment that had won Max a Nobel Prize science, with whichever world-leading Tom earned a scholarship to Law- in 1962. To Tom, seeing was believ- scientist (perhaps Fred Sanger, Francis rence College, where he majored in ing: Visualizing a macromolecule Crick or Sidney Brenner — Nobel chemistry and credited the humani- was clearly the way to understand its laureates all) was sitting next to him ties courses for maturing his world function. This was echoed throughout in the canteen for lunch. It was a view. Robert Rosenberg, a mentor at Tom’s career as generations of gradu- stress-free and wonderful time, he Lawrence, inspired him to pursue a ate students at Yale were asked, “Why said, with no worries, just exciting career in science. As a rising senior, don’t you just crystallize it?” science. Asked later about the pressure Tom attended a conference at the Upon learning that Bill Lipscomb to produce results to secure a faculty Massachusetts Institute of Technol- (Nobel laureate for chemistry, 1976) position, Tom replied, “Ah, yes, well. ogy held by the American Biophysical was using crystallography to study I did have a faculty position waiting Society to promote graduate study in proteins, Tom joined his group at for me at Berkeley.” biophysics; impressive talks by Alex Harvard. Working with five post- As it turns out, he was only at Rich and Paul Doty had the desired docs, and most closely with Martha Berkeley for two months. Starting effect. Tom enrolled at Harvard for Ludwig, Tom calculated progres- as an assistant professor in 1970, graduate studies in biophysics in sively higher electron density maps of Tom asked the department chair 1962. bovine carboxypeptidase A, culminat- to consider interviewing Joan for a Tom intended to study nucleic ing in a 2.0 Å structure of the protein. faculty position, as she had also done acids at Harvard until he was wowed At Harvard, Tom met Joan Arget- successful postdoc research in Cam- by lectures given by Max Perutz, singer, a fellow Midwesterner and a bridge. The chair told him promptly who was visiting from England. Max graduate student in Jim Watson’s lab. that females were best suited to be showed 3D slides of the structure of Tom and Joan married in 1966, and research assistants and that no female

6 ASBMB TODAY JANUARY 2019 COURTESY OF MARTIN SCHMEING Tom Steitz poses with his ribosome trainees in Stockholm after winning the 2009 Nobel Prize in chemistry. Pictured, from left, Poul Nissen, Tom Steitz, Martin Schmeing, Jeff Hansen and Nenad Ban. scientist would be considered for a tals were notoriously robust. In later biology. Starting in the late 1970s, faculty position. (This seems shock- years, if a trainee was short on crystals Tom and his lab made seminal ing now, when Berkeley is thought of for soaking experiments, Tom would discoveries that provided fundamen- as liberal, but Tom said back then, in recall that when more hexokinase tal understanding about every part general, the students were liberal and crystals were required, they would of the central dogma (see box: The the faculty members were conserva- simply saw them in half and, “Voila! discoveries). tive, which helped explain why it was Twice the crystals.” Most famously, in a collabora- a frequent site of protests.) Tom and Tom had been recruited to Yale by tion with Yale colleague Peter Moore Joan both received offers at Yale, so pioneering structural biologist Fred spearheaded by postdocs Nenad Ban they left California for New Haven. Richards. At about the same time, and Poul Nissen, Tom determined the At Yale, Tom started working on Don Engelman and Peter Moore were first structures of the large ribosomal the structure of hexokinase, the first hired, and together with Hal Wyck- subunit. The ribosome structures enzyme in the glycolysis pathway, off, they formed what became the provided insight into how proteins are a subject recommended to him by Yale Center for Structural Biology. By made and showed the ribosome to be Brian Hartley at Cambridge. Hexoki- the mid-1990s, this group included a ribozyme, making the logical link nase structures with and without sub- Jennifer Doudna, Paul Sigler and between the primordial “RNA world” strates were Tom’s first big success as Axel Brünger. This concentration of and the modern world dominated by an independent researcher. This work leading structural biologists made for protein enzymes. He also solved struc- with his postdoc Robert Fletterick an exciting and dynamic environment tures (with the author) representing visualized Dan Koshland’s induced fit that powered each group’s research. each chemical step of the ribosome model, according to which binding After hexokinase, Tom embarked linking amino acids together, and of the cognate substrate to an enzyme on a broad research scheme that (with Jeff Hansen) of the ribosome caused a conformational change to defined the rest of his career: studies bound by clinically important anti- enable activity. These hexokinase crys- of Crick’s central dogma of molecular biotics. For this ribosome work, he

JANUARY 2019 ASBMB TODAY 7 The discoveries These seminal discoveries made in Tom Steitz’s lab provided fundamental understanding of every part of Francis Crick’s central dogma of molecular biology.

DNA to DNA • The first structure of HIV reverse transcriptase, • The first structure of a DNA-binding protein (the the key polymerase in the AIDS-causing virus, in catabolite gene activator protein), solved first in the complex with a non-nucleotide inhibitor, revealing its absence and then later in the presence of DNA mechanism of inhibition • The first structure of a DNA polymerase and structures of many DNA polymerases at RNA to protein mechanistically important states, which together • The first structure of a tRNA synthetase bound allowed the proposal of the two-metal ion mechanism to tRNA, explaining the tRNA recognition that is for phosphoryl transfer reaction, with universal important for ligating the right amino acid on the implications for polymerases and ribozymes right tRNA, and other tRNA synthetase structures • Structures of the homologous recombination illuminating an important proofreading mechanism enzyme RecA • Structures of the site-specific recombinase gamma • Structures of enzymes required to add the last three delta resolvase nucleotides in a nontemplated fashion onto some tRNAs so they can be used in protein synthesis DNA to (and from) RNA • Pioneering ribosome structural biology, including • A comprehensive series of structures of the RNA the first structure of the large ribosomal subunit, polymerase from phage T7, visualizing initiation, and co-complexes of the ribosome with substrates, elongation and termination of transcription antibiotics and translation factors

Remembrances These are excerpts from remembrances written by scientists who worked with Tom Steitz. Read the complete texts at asbmb.org/asbmbtoday.

The group that Tom established was like a family; we spent me well today: He taught crystallography in a mathemati- so much time together immersed in the science, learning cally rigorous but intuitively logical way, he always kept the from each other and helping each other grow under the biological “big picture” in mind, he taught us how make watchful gaze of our fearless leader. We will never forget the clear figures, and he never treated female trainees differently phrase, “just because it’s more interesting doesn’t mean it’s than male ones. more difficult.” — Phoebe A. Rice — Andrea Berman and Satwik Kamtekar One time, someone wanted an inside scoop on a yet-to-be Tom would come down to C10 (a room in the basement published structure and asked Tom what the bending angle of Kline Tower at Yale) almost every afternoon and half- of a bound DNA was. Tom hesitated for a hundredth of a teasingly ask whether you had solved your structure yet. For second and said, “Larger than 0 and less than 90 degrees.” lunch, everyone would decamp to the cafeteria on top of That person wrote a review predicting a 45-degree bending Kline, often to discuss what was going on in science at Yale angle. The actual bend is 60 degrees. We all had a good and elsewhere. It was during one of those lunchtime con- laugh. versations that I first heard Tom and Peter (Moore) discuss — Wei Yang how to approach solving the structure of the ribosome. — Lorena Beese I remember when we named the RNA motif where exposed adenosines pack into the minor groove of another RNA I was first exposed to Tom Steitz’s enthusiasm for structural helix. I presented a range of suggestions for names; he was biology when I visited Yale as a prospective graduate stu- not very impressed with any of them but then was delighted dent in 1986, and he showed us the very first structure of a with one of his own: A minor. Music-based puns ensued. DNA polymerase. Many aspects of his mentorship still serve — Poul Nissen

8 ASBMB TODAY JANUARY 2019 COURTESY OF MARTIN SCHMEING Tom Steitz and his family in Stockholm for Nobel week in early December 2009. Pictured from left, daughter-in-law Katherine, son Jon, wife Joan and Tom. shared the Nobel Prize in 2009 with are skiing” and “if your crystallization including Tom Cech, Jim Dahlberg, Venki Ramakrishnan and Ada Yonath. drop doesn’t have precipitate in it, John Abelson and Olke Uhlenbeck; Tom trained generations of out- you haven’t done the experiment.” and trips with his son, Jon. Tom was standing students at Yale. He had Complementing his no-nonsense a loving and proud father to Jon, who a reputation for bluntness but was attitude to science, Tom had an ear- was born in 1980. Tom and Joan a supportive mentor. He effectively nest sense of humor, full of dad jokes hosted memorable lab picnics and conveyed his excitement for impor- and puns, often made with a pause Halloween parties, sometimes serving tant fundamental science and knowl- and a telling smile. The antibiot- bottles from Tom’s prized wine collec- edge for the sake of knowledge. Con- ics that blocked peptide movement tion. He was a keen gardener, at times tinuing the advocacy that inspired through the ribosomal tunnel caused battling the local Stony Creek rabbits him to leave Berkeley, he believed “molecular constipation.” The so- that talent and drive, not gender, called “thumb” domain in polymer- and deer. He also enjoyed hiking in should be determinants of success ases structures that resemble a right the mountains and sailing among the and embodied this with egalitarian hand had to be coloured green in Thimble Islands. mentoring. He fostered a rigorous reference to gardening. In his Nobel Tom was at his home overlooking attitude to performing science where autobiography, he referred to a spank- these Thimble Islands when he died the most direct route to a clear answer ing as an application of the “board of from pancreatic cancer. He will be was prized, a virtue visible in many of education” to his “seat of knowledge.” dearly missed. his lab alumni. And he would start serious advice in Some information for this article All his trainees fondly recall go-to the style of Yogi Berra, “The hardest was sourced from the Thomas A. Steitz Tomisms such as “if it doesn’t crystal- thing to predict is the future …” Biographical Essay, nobelprize.org. lize, add another component to the Outside the lab, Tom loved skiing, complex,” “always set up crystal trays which led to the annual Steitz-Engel- Martin Schmeing ([email protected]) before you go on vacation so experi- man lab ski trip; the annual “Riboski” is an associate professor of biochemistry and ments are still happening while you trip with RNA-loving colleagues Canada research chair at McGill University.

JANUARY 2019 ASBMB TODAY 9 A YEAR OF (BIO) CHEMICAL ELEMENTS For January, it’s atomic No. 1 By Quira Zeidan

ollowing a proposal used for cellular metabolism initiated by the Inter- such as synthesis of molecules, F national Union of Pure cell movement and solute and Applied Chemistry and transport. other global scientific organi- Cells also use H+ to gener- zations, the United Nations ate energy from the break- has declared 2019 the Inter- down of foods such as sugars, national Year of the Periodic fats and amino acids in a Table of Chemical Elements, process called cellular respira- or IYPT2019. tion. In a cascade of metabolic The designation commemo- reactions, nutrients like glu- rates the 150th anniversary of cose are oxidized and split into the first publication of Russian smaller molecules, yielding chemist Dmitri Mendeleev’s reduced nicotinamide adenine periodic table in 1869. Men- dinucleotide, or NADH, deleev’s table was not the first and reduced flavin adenine dinucleotide, or FADH as attempt to arrange the just over 2 60 chemical elements known biochemical intermediates. at the time, but it was the first Under aerobic conditions, a version to predict the existence series of proteins that comprise the electron transport chain of unidentified elements based WIKIPEDIA transfer electrons from NADH on the periodicity of the ele- High-energy electrons (from the oxidation of food, for example) passed and FADH to cellular oxygen ments’ physical and chemical along the electron-transport chain release energy that is used to 2 pump H+ across the membrane. The resulting electrochemical proton while pumping H+ across a properties in relation to their gradient serves as an energy store used to drive adenosine triphosphate membrane. This process gener- atomic mass. synthesis by the adenosine triphosphate synthase. ates a strong H+ electrochemical Today’s periodic table con- gradient with enough force to tains at least 118 confirmed 1 indicates the presence of a single drive the activity of the adenos- elements; of these, only about 30 are proton in its nucleus. Hydrogen can ine triphosphate synthase, resulting in essential to living organisms. Bulk occur as a single atom designated as biochemical energy production as the elements such as hydrogen, carbon, gradient dissipates. H, as diatomic gas, or H2, in mol- nitrogen and oxygen are abundant The potential energy in +H gradi- structural components of cells and ecules such as water or natural organic compounds (such as carbohydrates, ents can be used to generate heat for tissues, whereas trace elements (iron, thermogenesis in the brown fat tissue zinc, copper and magnesium, for lipids and amino acids) or as negative or positive ions — H- or H+, respec- of hibernating mammals, to power example) occur in minute amounts flagellar motors in bacteria, to trans- as enzyme cofactors and stabilizing tively — in ionic compounds. Living organisms use hydrogen in port nutrients into cells or to gener- centers for protein complexes. ate low pH inside vacuoles. These oxidation-reduction, or redox, reac- To celebrate IYPT2019, we are examples highlight the ubiquitous tions and electrochemical gradients to launching a yearlong series that role of a single element — hydrogen derive energy for growth and work. features at least one monthly element — in essential-for-life biochemical Microbes can uptake H from the with an important role in the molecu- 2 reactions across multiple kingdoms. lar life sciences. environment and use it as a source of electrons in redox interconversions catalyzed by enzymes called hydrog- Quira Zeidan (qzeidan@asbmb) Hydrogen is the American Society for Bio- enases. The transfer of electrons chemistry and Molecular Biology’s For January, we selected the between H2 and acceptor molecules education and public outreach first element of the periodic table, generates H+, and it’s accompanied by coordinator. Follow her on Twitter hydrogen, whose atomic number substantial energy changes that can be @quirazeidan.

10 ASBMB TODAY JANUARY 2019 NEWS ASBMB members elect six to council and other offices By Comfort Dorn

embers of the American CoA desaturase genes in lipid and and the finance and meetings com- Society for Biochemistry carbohydrate metabolism of obesity, mittees. M and Molecular Biology have diabetes and fatty liver disease. He Kim Orth was elected some new and some familiar won the 2013 ASBMB Award for elected to the faces to leadership positions in the Exemplary Contributions to Educa- Nominating Com- society. tion. mittee. She is the Three new members of the Kelly Ten Caruth scholar in ORTH ASBMB Council were elected to Hagen is a senior biomedical research three-year terms; they will serve from investigator and and holds the Forsythe chair in bio- 2019 to 2022. section chief in the medical science at the University of Audrey Lamb National Institute Texas Southwestern Medical Center. TEN HAGEN is a professor in of Dental and Orth works to elucidate the activity the department of Craniofacial Research at the National of bacterial virulence factors on the molecular biosci- Institutes of Health. Her lab studies molecular level, providing insights ences, University of the biochemistry and biological roles into how bacteria cause disease and LAMB Kansas. She studies of the enzyme family responsible for how eukaryotic host cells signal in structural and functional analysis of the initiation of a conserved protein response to infection. She serves on modification (mucin-type O-linked enzymes associated with iron uptake the ASBMB Awards Committee and glycosylation) to better understand and the goal of her lab is to under- won the 2018 ASBMB-Merck Award. how aberrations in glycosylation may stand the structure-function relation- Evette Radisky contribute to disease susceptibility ships that drive the biosynthesis of was elected to the and progression. She is a member of siderophores, compounds linked to Publications Com- the ASBMB Meetings committee. virulence and pathogenesis in a vari- mittee. She is a ety of deadly bacteria. professor of cancer RADISKY James Ntambi Other offices biology at the is a professor of Treasurer-elect Mayo Clinic. Her long-term research biochemistry and Joan Conaway focus is on the molecular recogni- Steenbock profes- is an investiga- tion between proteases and protein sor of nutritional tor and holds the protease inhibitors, and her research NTAMBI sciences at the Helen Nelson interests include many aspects of University of Wisconsin–Madison. CONAWAY distinguished chair cancer biology, including the role of His research interest lies in the genetic at the Stowers Institute for Medical proteases in tumor progression and regulation of metabolism in health Research. She studies the mecha- metastasis. She previously served on and disease. He researches, adipocyte nisms of gene transcription and her the ASBMB Meetings Committee. biology, differentiation, hormonal and work helped define mechanisms that dietary regulation of gene expres- regulate initiation and elongation of Comfort Dorn ([email protected]) is managing sion. In recent years, he has used a mRNA transcripts by the enzyme editor of ASBMB Today. Follow her multidisciplinary approach to unravel RNA polymerase II. She has previ- on Twitter @cdorn56. the physiological role of the stearoyl- ously served on the ASBMB Council

JANUARY 2019 ASBMB TODAY 11 NEWS Celebrating Herb Tabor Longtime Journal of Biological Chemistry editor Herbert Tabor turned 100 on Nov. 28. As part of the journal’s celebration in Tabor’s honor, friends and colleagues shared their best wishes and appreciation for him on the journal website. Below are some of the snapshots they contributed to the virtual scrapbook. See more at jbc.org.

Officially ‘Herb Tabor Day’ The Montgomery County (Md.) Council recognized Herb Tabor’s contributions to science, the scientific Big cake on the big day community and the world by designating Nov. 28 American Society for Biochemistry and Molecular Biology Executive Director Barbara Gordon and Senior Director Herb Tabor Day in an official proclamation (above). for Publications Nancy Rodnan paid Herb Tabor a visit at his home on the National Institutes of Health campus The state of Maryland, meanwhile, provided a in Bethesda, Maryland on Nov. 28. The cake they brought with them was tastefully decorated; it was also tasty, governor’s citation to honor Tabor. Download them according to ASBMB staffers who sampled the leftovers. both at jbc.org.

Grand opening ‘You tutored me on how to be an outstanding journal editor’ Anthony Pegg, Laurence Marton, Shin-ichi Hayashi and Herb and Celia Tabor Three ASBMB journal editors — Ralph Bradshaw (Molecular & Cellular prepare for a sake barrel opening ceremony at the 1996 Tokyo International Proteomics), Herb Tabor (JBC) and Edward Dennis (Journal of Lipid Research) Symposium on Polyamines in Shonan Village Center. The picture was taken — celebrate Tabor’s 40 years of JBC service on April 26, 2010. The snapshot “just before the big splash,” according to Olle Heby of Umeå University and was shared by Dennis, who said, in part, that Tabor tutored him Lo Persson of Lund University, who submitted it. Heby and Persson wrote: “on how to be an outstanding journal editor.” Read Dennis' full “Dear Herb, Many congratulations on your 100th birthday! Thank you submission and Bradshaw’s at jbc.org. for your great contributions to the polyamine field!”

12 ASBMB TODAY JANUARY 2019 ‘What a wonderful human being you are’ Norma Allewell wrote of Tabor, in part: “Because of JBC’s stellar reputation and the role that you have had in building it, I was in awe of you for many years. It was only when I had the opportunity to interact with you regularly as an associate editor, that I came to They’ve got his genes understand what a wonderful human being you are and how much Herb Tabor’s children, all of whom were raised on the National Institutes of Health campus, where your personal integrity, wisdom and warmth have contributed to the family lived, joined the JBC associate editors in toasting Tabor’s service to the journal in 2011. JBC’s success.” Read more at jbc.org. Here are Tabor and his sons, from left, Ed, Richard and Stan.

Here for the polyamines From left: Jim Coward, Peter McCann, Herb Tabor, Celia Tabor, Erkii Holta, Tony Pegg, and an unidentified scientist from Finland. This photo was taken by K.-Y. Chen at the Phoenix Temple, Nara, Japan on July 19, 1986, after the International Symposium on Polyamines in the Life Sciences held at Lake Yamanaka, Japan, from July 14 to 18, 1986. Photo courtesy of James K. Coward.

JANUARY 2019 ASBMB TODAY 13 NEWS Student Chapter president sees value in campus groups By Elizabeth Stivison

hen Victoria Mak joined high schoolers also can get advice the American Society for from Doisy College of Health Sci- W Biochemistry and Molecular ences faculty on college applications Biology Student Chapter during her and other learning opportunities for freshman year at St. Louis Univer- area students interested in scientific sity, the group had been active for a careers. few years but was small, unchartered Mak is an investigative and medical by the university and limited to the sciences major, which she hopes will medical campus. prepare her well for medical school. Thanks to the work of Mak and She loves the problem solving and others, the chapter now has more troubleshooting required in research and gets satisfaction from figuring than 50 members and a presence on out why a protocol didn’t work as the main campus. The group is char- expected. tered by SLU and hosts numerous Outside of biology, Mak loves speakers, workshops, and outreach COURTESY OF VICTORIA MAK languages and the way they allow her and social events. Victoria Mak, president of the ASBMB Student Chapter at St. Louis University, says balancing to interact more deeply with people Mak is now a senior, and she academics and extracurricular activities has she meets when traveling. At home enriched her college experience. doesn’t like to sit around. She’s in Hawaii she speaks English and involved with multiple honor societ- Cantonese. In school she has become ies and student groups at SLU, and students and the group’s faculty advi- fluent in French, Mandarin and Japa- she studies ballet. As she looks back sor, Dr. Uthayashanker Ezekiel, began nese as well. She co-founded a Hawaii over her undergraduate career, one of the process. They started by dem- student club at SLU. the things she’s most proud of is her onstrating that the ASBMB chapter These days, you’ll likely find Mak role in the thriving ASBMB Student was unique, had members and really on the move somewhere on campus Chapter. offered something. More than a year — dancing, pipetting, organizing an As a freshman, Mak was drawn and several committee votes later, event for ASBMB members, starting a to the chapter because of its basic they were fully chartered and had new group to fill a need on campus or science focus and the friendliness and the resources of SLU behind them. maybe even studying for her classes. approachability of its members, she Such groups on campus are impor- The best part of college so far for said. She wanted to get the chapter tant, Mak said, because they “allow Mak? chartered because she could see the the attendees to bring out the best in “Being able to balance academics value ASBMB provided. themselves.” and extracurriculars,” she said. “I love “I thought we offered more to the The SLU ASBMB chapter hosts an using them interchangeably to make students than we could really show,” annual Day in the Clinical Labora- my experience richer.” she said. If the chapter was chartered, tory when local high school stu- “so many more students would be dents visit to learn and perform lab Elizabeth Stivison ( elizabeth. [email protected]) is a Ph.D. interested; if we were chartered, then techniques to complete a case study. student at Columbia University we could reach (them).” SLU students and faculty volunteers studying mechanisms of DNA repair. So Mak, a few other motivated run the free event, Mak said, and the

14 ASBMB TODAY JANUARY 2019 JOURNAL NEWS The discovery of GABA in the brain By Martin J. Spiering

Some scientific discoveries land with a boom only to fizzle out and become a small blip — but there are times when this order is reversed. Such was the case with the discovery of gamma-aminobutyric acid, or GABA, in the brain. In a study published in 1950 in the Journal of Biological Chemistry preceded by a brief conference report, Eugene Roberts and Sam Frankel not only identified GABA as a major amine in the brain but also reported that it is produced and preferentially accumulates in that organ. The initial response to the dis- covery was rather muted. In the five years following Roberts and Frankel’s report, which was accompanied by two other articles on GABA in the brain in the same JBC issue, accord- ing to PubMed only four additional SCHOLARPEDIA studies of GABA in the brain were Eugene Roberts first reported in 1950 that GABA is a major amino compound in the brain. published. Whether the research commu- Frankel’s discovery marked a major inhalation section at the University nity was stunned into silence or this milestone in the quest to unravel of Rochester in New York, where he lackluster reaction simply reflected how neurotransmitters control brain worked on the toxicology of uranium a lack of methods to quickly test activity. dusts, Roberts moved to Washing- GABA’s function is difficult to tell Roberts’ research career and the ton University in St. Louis in 1946. as we approach the 70-year mark of story of GABA in many ways exem- There, he became interested in amino this finding. But we do know that at plify how discoveries and careers can acids in the brain, studying them in first no one seemed to have an inkling be molded from humble and obscure normal and neoplastic brain tissues. what GABA might be doing in the beginnings. This was at a time when “metabo- brain. Roberts’ personal history as a first- lomics” and “proteomics” would have GABA’s activity in the brain was generation immigrant mirrors that of been considered bizarre, futuristic clarified in 1957 when researchers in legions of researchers working in the terms, when even mass spectrom- Canada reported that an unknown United States. Born Evgeny Rabi- etry and other tools now considered compound having inhibitory activ- nowitch in 1920 in southern Russia, standard in analytical chemistry were ity on crayfish neurons was, in fact, Roberts arrived in the U.S. in 1922, far off on the horizon or too labori- GABA. settling with his parents in Detroit. ous and time-intensive for the task Baruch Kanner of Hebrew Uni- Awarded a scholarship from Wayne at hand. Instead, Roberts used paper versity Hadassah Medical School State University when he was only 16, chromatography and ninhydrin, a in Israel is a member of the JBC Roberts graduated magna cum laude chemical dye that reacts with and editorial board who studies GABA with a bachelor’s degree in chemistry stains primary amines, to isolate and transporters. in 1940. He went on to study bio- identify free amino acids in mouse “The GABA receptors mostly have chemistry, earning a master’s in 1941 brain extracts. an inhibitory input,” Kanner said, and a Ph.D. in 1943 from the Univer- As he meticulously analyzed “and they are the major inhibitory sity of Michigan in Ann Arbor. these extracts, Roberts came across a receptors in the brain.” After a short stint as an assistant ninhydrin-reactive compound whose It is now clear that Roberts and head of the Manhattan Project’s migration on paper chromatograms

JANUARY 2019 ASBMB TODAY 15 did not match any known amine- GABA inhibits the firing of action effects, Kanner said. containing compounds. What’s more, potentials in neurons presented These snags notwithstanding, this mysterious amino acid–like another novelty. Other amine- GABA’s discovery has spurred many metabolite apparently accumulated containing neurotransmitters whose research activities; as of this writing, at much higher levels in the brain activities were known at the time, a search of PubMed for “gamma-ami- than in other tissues. Acid treatments such as norepinephrine and acetylcho- nobutyric acid” and “brain” returns of brain tissues didn’t increase these line, are activating (excitatory) ones. about 30,000 papers on the topic. levels, suggesting that this amine The amino acid glycine also can These efforts include those of Kan- exclusively occurs in the free form inhibit brain neurotransmission, but ner, who is studying the mechanism in the brain. Luckily, it was a lone Kanner pointed out, “GABA is clearly by which the GABA transporter oper- wanderer, migrating far enough from the most abundant one.” ates. Kanner said he recalls meeting other ninhydrin-staining compounds Accordingly, researchers are inter- Roberts some 40 years ago and talk- that Roberts and Frankel were able ested in targeting the GABA system ing with him about his own research to extract it from strips cut from the to manage epilepsy, which arises from plans and findings on GABA. chromatograms. over-excitation of the brain’s neu- “I think it must have been quite The researchers ran the strip- rons. An initially promising avenue gratifying for him to see how (impor- extracted compound along with has been to prevent or slow reuptake tant) this molecule that he discovered carefully prepared reference stan- of GABA once it is released into in the brain is and how all the aspects dards in different solvent systems. A synapses by targeting its transporter, of its action are being investigated,” technique called the isotope deriva- a strategy that has been successful Kanner said. “I think it’s wonderful that his central contribution will be tive method developed by a colleague for several brain neurotransmitters to remembered.” at Washington University, Sidney manage other disorders. Roberts died in 2016; he would Udenfriend, helped them to home in “By inhibiting the GABA trans- have turned 100 in 2020. on the unknown amine. Through this porter, GABA is staying around (at This article originally appeared in multipronged approach, Roberts and the synapse) for a longer time,” Kan- the Journal of Biological Chemistry as Frankel concluded that the brain- ner said. “Then you get more inhibi- a JBC Classic. It has been edited for associated amine was GABA. Taking tion, and that could be potentially ASBMB Today. Read more JBC Classics it a step further, using radioactive an anti-epileptic drug because the at jbc.org. labeling of potential GABA precur- inhibitory input becomes bigger.” sors, the research duo demonstrated However, although they show Martin J. Spiering (mspiering@ that brain tissues can convert another promise, compounds that prevent asbmb.org) is the technical common cerebral amino acid, glu- GABA reuptake or stimulate its editor at the Journal of Biological tamic acid, to GABA. receptor have not yet made it beyond Chemistry. Follow him on Twitter The 1957 finding revealing that clinical trials, probably because of side @Spieringmj.

Upcoming ASBMB events and deadlines

22: ASBMB–DEUEL Conference on Lipids abstract deadline and registration closes

JAN 30: Annual meeting late-breaking abstract and early registration deadline 31: Honor Society nominations due

4: Communications Winter Course begins

FEB 16: Annual meeting outstanding Student Chapters award deadline

5–8: ASBMB–Deuel Conference on Lipids MARCH

16 ASBMB TODAY JANUARY 2019 JOURNAL NEWS A molecular dance of phospholipid synthesis By Sasha Mushegian

The most abundant mol- time once we got the data just ecule in cell membranes is the looking on the screen at these lipid phosphatidylcholine, or dancing molecules.” PC, commonly known as leci- The simulated dance of thin; accordingly, the enzymes the CCT molecule showed responsible for synthesiz- that when the M-domain, ing it are essential. Research the section of the enzyme published in the Journal of that typically binds to the Biological Chemistry used membrane, detaches from a computer simulations to membrane, it snags the active gain insights into how one of site of the enzyme, prevent- these enzymes activates and ing it from carrying out its reaction. When the snagging shuts off PC production. The segment was removed from results could help researchers the simulation, the team saw understand why small changes a dramatic bending motion in in this enzyme can lead to the docking site for the snag- conditions like blindness and ging element and speculated dwarfism. that this bending would create Rosemary Cornell, a a better enzyme active site for professor of molecular biol- MOHSEN RAMEZANPOUR AND JAEYONG LEE catalyzing the reaction when ogy and biochemistry at CCT is a key enzyme that maintains a balanced composition of cell attached to a membrane. They Simon Fraser University in membrane phospholipids. This image highlights the dynamics of a portion confirmed these mechanisms Canada, studies the enzyme of the enzyme CCT that is essential for regulation of its functions. with biochemical laboratory CTP:phosphocholine cytidy- experiments. lyltransferase, or CCT. CCT the answer must have to do with the Previous genetic studies had sets the rate of PC production in enzyme’s dynamic changes in shape shown that mutations in the gene cells by binding to cell membranes when it binds to a membrane. But encoding CCT are responsible for with low PC content. When bound these changes are difficult to capture rare conditions like spondylometaph- to membranes, the CCT enzyme with traditional structural biology yseal dysplasia with cone-rod dystro- changes shape in a way that allows it methods such as X-ray crystallogra- phy, which causes severe impairments to carry out the key rate-limiting step phy, which take a static snapshot of in bone growth and vision, but it was in PC synthesis. When the amount molecules. Instead, the team used not known how these changes in the of PC making up the membrane computational simulations of molecu- enzyme could lead to such dramatic increases, the CCT falls off the mem- lar dynamics, which use information consequences. Cornell hopes that brane, and PC production ceases. about the forces between every indi- understanding how the enzyme works “The membrane is this big macro- vidual atom in a molecule to calcu- could help researchers find the causes molecular array with lots of different late the trajectories of the enzyme’s of these conditions. molecules in it,” Cornell said. “How moving parts. “If you have just one small change in CCT, then how is that going to does this enzyme recognize that ‘Oh, “What it looks like (when you make this whole process of synthesiz- I should slow down because the PC visualize the output) is your big mol- ing PC defective?” she asked. “That’s content of the membrane is getting ecule dancing in front of your eyes,” what we’re studying right now.” Cornell said. “We set up the molecu- too high?’” DOI: 10.1074/jbc.RA118.002053 Cornell and her project team — a lar dynamics simulation not once, not collaboration with Peter Tieleman and twice, but 40 different (times). It took Sasha Mushegian (amushegian@ graduate student Mohsen Rameza- months and months just to do the gmail.com) is a postdoctoral npour at the University of Calgary computational parts and even more fellow at Georgetown University. and Jaeyong Lee and Svetla Taneva, months trying to analyze the data Follow her on Twitter @sash_mu. research associates at SFU — thought afterward. We actually spent a lot of

JANUARY 2019 ASBMB TODAY 17 JOURNAL NEWS

Researchers closer to gonorrhea vaccine after exhaustive analysis of proteins By Steven Lundeberg

In a study of drug-resistant studying the proteins revealed; gonorrhea strains historic they found seven matching in its scope, researchers at phenotype clusters between Oregon State University have already-known signatures pushed closer to a vaccine for and the ones uncovered by gonorrhea and toward under- proteomic analysis. standing why the bacteria that Together, the findings rep- cause the disease are so good resent a key step toward new at fending off antimicrobial weapons in the fight against drugs. a relentless and ever-evolving The findings, published pathogen. “We created a refer- in the journal Molecular & ence proteomics databank Cellular Proteomics, are for researchers looking at especially important since the gonococcal vaccines and also microbe Neisseria gonorrhoeae NIAID antimicrobial resistance,” is considered a “superbug” Neisseria gonorrhoeae, the bacterium that causes gonorrhea, is shown here said Sikora, co-corresponding because of its resistance to all in a scanning electron micrograph. author on the study. “This classes of antibiotics available was the first such large-scale for treating infections. that show all known profiles of gono- proteomic survey to identify Gonorrhea, a sexually transmitted coccal antimicrobial resistance. new vaccine candidates and potential disease that results in 78 million new For each strain, researchers divided resistance signatures. It’s very cases worldwide each year, is highly the proteins into those found on the exciting.” damaging if untreated or improperly cell envelope and those in the cyto- The findings add new momentum treated. It can lead to endometritis, plasm. More than 1,600 proteins — to a vaccine quest that also received a pelvic inflammatory disease, ecto- 904 from the cell envelopes and 723 boost in summer 2017, when a study pic pregnancy, epididymitis and from the cytoplasm — were found to in New Zealand showed that patients infertility. be common among all 15 strains, and receiving the outer membrane vesicle Babies born to infected mothers from those, nine new potential vac- meningococcal B vaccine to prevent are at increased risk of blindness. cine candidates were identified. Neisseria meningitis were 30 percent Up to 50 percent of infected women A vaccine works by introducing an less likely to contract gonorrhea than don’t show any symptoms, but those “invader” protein known as an anti- those who didn’t get the vaccine. asymptomatic cases still can lead to gen that triggers the body’s immune “All previous vaccine trials had failed,” Sikora said. severe consequences for the patient’s system and subsequently helps it Gonorrhea and meningococcal reproductive health, miscarriage or quickly recognize and attack the meningitis have different means of premature delivery. organism that produced the antigen. transmission, and they cause different Aleksandra Sikora, a researcher Researchers also found six new pro- problems in the body, but their source with the OSU College of Pharmacy teins that were expressed distinctively pathogens are close genetic relatives. and Oregon Health and Science Uni- in all of the strains, suggesting they’re DOI:10.1074/mcp.RA118.001125 versity’s Vaccine and Gene Therapy markers for or play roles in drug This article is republished from the Institute, helped lead an international resistance and thus might be effective EurekAlert website (eurekalert.org). collaboration that performed pro- targets for new antimicrobials. teomic profiling on 15 gonococcal In addition, scientists looked at Steven Lundeberg (steve. strains. the connection between bacterial [email protected]) is Among the isolates in the study phenotype — the microbes’ observ- a news writer at Oregon State were the reference strains maintained able characteristics and behavior University. by the World Health Organization — and the resistance signatures that

18 ASBMB TODAY JANUARY 2019 JOURNAL NEWS

A close-up of nascent HDL formation By Laurel Oldach

Oil and water don’t mix. But our aqueous blood is full of hydrophobic lipids — including cholesterol. To travel via the bloodstream, those lip- ids must hitch a ride on an amphipa- thic carrier. In a paper in the Journal of Lipid Research, scientists at Boston University report an advance in our mechanistic understanding of how one such carrier forms. “Lipoproteins are like boats that deliver and remove cargoes of fatty substances to and from our cells,” said David Atkinson, chair of the physiol- ogy and biophysics department at WU ET AL/JBC 2009 Boston University School of Medicine A model of a high-density lipoprotein particle shows apolipoprotein A-I in pink, phospholipids in gray and and senior author on the JLR paper. cholesterol in yellow. The subset of those “boats” that carry cholesterol and other lipids to cholesterol from the inner to the the formation of nascent HDL. The the liver from other parts of the body outer leaflet of the cell membrane. team has not yet tested whether the are called high-density lipoproteins, Because the cholesterol that ABCA1 extra-flexible mutant binds to ABCA1 or HDL, aka “good cholesterol.” transfers usually ends up bound to better or whether binding of either HDL can remove cholesterol from apoA-I, some researchers suspected a form of apoA-I activates ABCA1. distal cells — such as macrophages in physical interaction between apoA- But about one thing Atkinson is the walls of arteries, where choles- I and ABCA1. Others argued that certain: “It’s the apoA-I/ABCA1 inter- terol accumulation can lead to heart cholesterol and phospholipids could action which then enables the nascent attacks — and deliver it to liver cells, diffuse passively and bind to apoA-I. HDL particle formation to happen as a process known as reverse cholesterol “Even if you demonstrate that the membrane components are being transport. The liver disposes of excess apoA-I binds to the cell surface, you transported out by ABCA1.” cholesterol by converting it into bile don’t actually know that it’s bound Increasing reverse cholesterol trans- acids secreted into the small intestine. to ABCA1. It’s just bound to the cell port may be a way to reduce athero- According to Atkinson, a biophysi- surface,” Atkinson said. So he asked sclerosis and heart disease. Atkinson cist, most of what is known about his team to see if they could “demon- is optimistic about the promise of HDL formation comes from experi- strate that interaction actually hap- understanding the physiological pro- ments that take a cell biological tack. pening in the isolated components.” cesses better. In such studies, he said, “You can see The team, led by graduate stu- “Translational research might be in (HDL formation) happening, and dent Minjing Liu and supported by vogue,” he said, “but remember that you can quantitate what happens, Xiaohu Mei and Haya Herscovitz, if you don’t do foundational basic but you don’t understand the driving used isolated apoA-I and ABCA1 to discovery research, you will not have interactions that cause it to happen.” test for a physical interaction. They anything to translate.” HDL is built on a scaffold protein, were able to show immunoprecipita- DOI: 10.1194/jlr.M084376 apolipoprotein A-I. This apoA-I is tion of apoA-I with purified ABCA1. thought to collect cholesterol and The lab earlier had designed a Laurel Oldach (loldach@asbmb. phospholipids from the cell mem- mutant apoA-I with a little extra org) is a science communicator for the Journal of Lipid Research brane. Atkinson’s team wanted to wiggle in an already flexible hinge and Molecular & Cellular better understand that process. region. For this study, they used the Proteomics and a staff writer for ApoA-I depends on a lipid trans- mutant to show that higher flexibil- ASBMB Today. Follow her on porter protein, ABCA1, that pumps ity increased apoA-I lipidation, or Twitter at @LaurelOld.

JANUARY 2019 ASBMB TODAY 19 JOURNAL NEWS

From the journals By Nathalie Gerassimov, Dawn Hayward & Sasha Mushegian

We offer a selection of recent encoding Cas9, which subsequently Polyunsaturated fatty papers on a variety of topics from the are translated in the cell. Deliver- Journal of Biological Chemistry, ing already synthesized Cas9 protein acids in dividing T cells the Journal of Lipid Research, and and guide RNA into cells would be As cells grow and prepare for cell Molecular & Cellular Proteomics. a more direct approach. Yuefei Shen division, they also synthesize the lipid and colleagues at University of Mas- components of the cell membrane, Fresh CRISPR-Cas delivery sachusetts Medical School developed some of which do double duty as CRISPR delivery particles built on signaling molecules. However, mam- The bacterial CRISPR-Cas9 amphipathic peptides to do just that. mals cannot synthesize from scratch system can be used to edit genes As proof of concept in the Journal all the fatty acids they need, such as with single-nucleotide precision, but of Biological Chemistry, they used most polyunsaturated fatty acids, or current methods of delivering the these particles to edit a gene in fat PUFAs. The initial building block for system remain inefficient in real- cells to convert white adipocytes into omega-3 and omega-6 PUFA is an world therapeutic settings. Currently, energy-burning brown adipocytes. 18-carbon fatty acid with two or three most methods deliver nucleic acids DOI: 10.1074/jbc.RA118.004554 double bonds derived from the diet.

Linking diabetes to cognitive decline

Chronic diabetes has a well-known yet little under- stood effect called cognitive decline. In fact, patients with diabetes are more likely to develop cognitive disor- ders such as dementia than those without. To determine the link between the two, Liangcai Zhao and colleagues at Wenzhou Medical University performed a metabolo- mics study on the brains of diabetic rats. This work was published in Molecular & Cellular Proteomics. First, the researchers treated rats with the drug strep- tozotocin, which selectively attacks pancreatic beta cells, causing hyperglycemia and other symptoms associated with diabetes. After observing the cognitive decline in these rats using behavioral tests and brain scans, they

looked at which metabolites changed with diabetes, WIKIMEDIA specifically in the hippocampus. Lactate, a metabolite in Astrocytes in the brain can accumulate the metabolite lactate between cells the glycolysis pathway, was higher in the diabetic rats’ during chronic diabetes in rats, contributing to cognitive decline. brains than control animals, especially when the disease became chronic. in the transcription of genes in learning and memory, While glycolysis generates some energy, cells usually thus providing a link between diabetes and cognitive move to the next step, the tricarboxylic acid cycle, to decline. To alleviate lactate’s hold on cognitive decline, make even more energy. In chronic diabetic rats’ brains, researchers blocked its production with an inhibitor. however, cells use glycolysis for energy exclusively, and Diabetic rats showed improvement on behavioral tests, the enzyme used to make lactate had higher activity in which indicated better memory, and brain scans showed these animals. less atrophy than previously observed. Not all of this lactate was utilized, however. Lactate The authors suggest that blocking the production of transporter levels decreased during the chronic stage lactate in diabetic patients may be a way to limit cogni- such that excess lactate accumulated between astrocytes, tive decline. a type of brain cell with a range of important roles. The DOI: 10.1074/mcp.RA118.000690 excess dysregulated a specific signaling pathway involved — Dawn Hayward

20 ASBMB TODAY JANUARY 2019 Protecting the liver — a full-body job To survive fasting, humans and other mammals can shift their metabolism from reliance on glucose and fat derived from food to reliance on fat stores. Peroxisome proliferator-activated receptor alpha, or PPARA, is a major regulator of lipid homeostasis and is critical for surviving fasting and starvation. PPARA, a transcription factor found in the liver and some other tissues, upregu- lates genes that contribute to the catabolism of free fatty BROCKER ET AL./JLR acids, or FFAs. Mice lacking PPARA in the entire body develop abnormal lipid accumulation in In a paper published in the Journal of Lipid the liver during fasting, pictured in the center, which makes the liver appear Research paler than a normal liver, at left. When PPAR is missing only in the liver, at , Frank Gonzalez and his team at the National right, this phenotype is ameliorated. Cancer Institute together with collaborators in China demonstrated that PPARA in tissues outside the liver can protect a liver that lacks PPARA during fasting. The matically redced. PPARA activity from outside the liver investigators compared the liver phenotype of normal boosted fatty acid oxidation and lipase activity, reduced mice and mice lacking PPARA either in the entire body the systemic lipid load and reduced lipid accumulation or only in the liver after one day of fasting. in the liver. Food deprivation is associated with elevated fat- PPARA function is decreased in several diseases derived FFAs circulating in the blood, which are taken affecting the liver such as nonalcoholic fatty liver disease up by the liver. In normal mice, these FFAs are broken and hepatitis C. This research suggests that PPARA down to generate energy and are used in gluconeogen- from outside the liver could compensate for low hepatic esis. Mice completely lacking PPARA still can uptake PPARA, which may help develop novel approaches to FFAs into the liver but cannot catabolize them, leading treat these diseases. to an abnormal lipid accumulation in the liver called DOI: 10.1194/jlr.M088419 hepatosteatosis. In mice lacking PPARA in only the — Nathalie Gerassimov liver, the researchers found that this phenotype was dra-

Once in cells, enzymes elongate and and how PUFA misregulation con- extracellular matrix doesn’t just hold desaturate these 18-carbon PUFAs tributes to diseases with proliferation cells in place but plays an active role to generate even longer and more defects, such as cancers. in cellular metabolism. unsaturated PUFAs. While several DOI: 10.1194/jlr.M090050 DOI: 10.1074/jbc.RA118.004563 enzymes have been shown to catalyze these reactions, which of them play a The call is coming significant role in proliferating cells A new way to quantify is unknown. In a paper published in from outside the house your favorite protein the Journal of Lipid Research, Marc During nutrient shortages, cells’ Tracking where a protein is inside Surette and colleagues at the universi- nutrient sensors can trigger autophagy ties of Mancton and Quebec, Canada, a cell and exactly how much there characterized the PUFA profiles and to recycle cellular components. This is isn’t trivial. Scientists use mass the responsible enzymes in resting process is dysregulated in cancer and spectrometry, antibodies, tags and and proliferating primary human T metabolic diseases. Maria Gubbiotti other means to find and follow their cells and in the Jurkat cell line. The and colleagues at Thomas Jefferson favorite protein, but these methods investigators found that both primary University showed that an important cannot be used for real-time intra- cellular imaging. Chromobodies and cultured cells had a greater nutrient sensor is located outside the (nanobodies with a fluorescent tag) capacity to incorporate, elongate and cell, in the extracellular matrix. The desaturate exogenous PUFA when can be injected into cells and bind extracellular proteoglycan decorin proliferating. Furthermore, they iden- endogenous proteins. Bettina-Maria tified ELOVL5 as the key elongase in was required to induce autophagy in Keller and colleagues at the University this process. Future studies will show cardiomyocytes in fasting mice. This of Tuebingen in Germany optimized a whether changes in PUFA profiles are study, published in the Journal of chromobody to improve its sensitivity necessary for successful cell division Biological Chemistry, hints that the in tracking endogenous proteins. The

JANUARY 2019 ASBMB TODAY 21 Why a pain drug failed in humans Everyone knows that humans aren’t rats, but in the context of preclinical laboratory studies, we’ve got to do our best with what we’ve got. Many drugs show promise during rodent trials and subsequently fail in humans. To make such studies more efficient, it’s important to understand how humans differ from model species at the molecular sites that potential drugs target. Neuropathic pain is caused by the nervous system misfiring rather than by stimulation of typical pain receptors. Potential drug targets for neuropathic pain are the nicotinic acetylcholine receptors, or nAChRs, in the

dorsal root ganglia. However, the sensitivity of recep- WIKIPEDIA tors such as nAChRs differs in rodents and humans. The five subunits of nicotinic receptors are arranged symmetrically around a In a recent example, a conotoxin peptide — a venom central pore, and each subunit comprises four transmembrane domains with produced by carnivorous marine snails — alleviated both the N- and C-terminus located extracellularly. neuropathic pain in mice but not in people. In a study published in the Journal of Biological Chemistry, Arik J. Hone and colleagues at the Uni- reduced potency. Changing the same amino acid in the versity of Utah investigated the molecular basis of this rat receptor did not affect its potency, suggesting that difference in effectiveness between conotoxin inhibition differences elsewhere in the receptor also affected how of human and rat nAChRs. They found that, on the the receptor and ligand interacted. whole, the pocket on the receptor that binds ligands like Understanding the molecular details of species-spe- conotoxins looked very similar in the two species. cific drug targets may help researchers to better predict But three amino acids were different, and one of which pharmacological findings will be translatable these differences was critical: The substituted amino from animal models to humans. acid slightly changed the orientation of the conotoxin DOI: 10.1074/jbc.RA118.005649 as it attempted to bind the human receptor, resulting in — Sasha Mushegian

work, published in Molecular & Cel- biological processes. Toshitaka Matsui Cholesterol-lowering lular Proteomics, introduces these and colleagues at Tohoku University destabilized chromobodies. To make report a new reaction pathway in drug target discovered the chromobody sensitive to time- which hydrogen sulfide induces heme About a quarter of deaths in the dependent changes in concentration, oxygenase to produce new isomers of United States are caused by heart dis- researchers altered its N-terminal sulfur-containing biliverdin, or SBV, ease, according to the Centers for Dis- sequence so it was degraded immedi- and describe the mechanism of the ease Control and Prevention. Hyper- ately by the cell if it did not specifi- cholesterolemia, or high cholesterol, is cally bind its antigen. After pathway formation of these catabolites. Biliver- dins, the bile pigments responsible for a major risk factor for cardiovascular induction or drug treatment, the disease. However, cholesterol, a com- amount of chromobody, and therefore the greenish color of bruises, increas- ponent of lipid bylayers, is essential fluorescence, tracked the increases and ingly are recognized as antioxidants. for life. Mammals can either synthe- decreases in protein concentration The new SBV-producing pathway was size cholesterol or absorb it from food in real time. This new and improved less dependent on oxygen concentra- using the intestinal transmembrane chromobody now can be used instead tion than canonical heme oxygenase protein Niemann–Pick C1-like 1, of traditional methods to track a sci- activation, leading the authors to or NPC1L1. This transporter resides entist’s favorite protein sensitively. speculate that it allows mammalian DOI: 10.1074/mcp.TIR118.000914 in lipid rafts, which are membrane cells to degrade heme and produce microdomains used for cell–cell antioxidants under hypoxic condi- interaction and cell signaling that A new heme catabolite tions. The study was published in the are enriched in cholesterol as well as Hydrogen sulfide is a gaseous sig- Journal of Biological Chemistry. gangliosides — a group of galactose- naling molecule important for many DOI: 10.1074/jbc.RA118.004641 containing glycolipids. In a paper in

22 ASBMB TODAY JANUARY 2019 the Journal of Lipid Research, Jin- Biological Chemistry, B. McKay alteration of intracellular pathways ichi Inokuchi from Tohoku University Wood and colleagues at Harvard and increasing cellular stress. The in Japan and colleagues show that Medical School write that they devel- authors say that these pathways, NPC1L1-dependent intestinal choles- oped a suite of assays, including a though harmful to the placenta and terol uptake requires the ganglioside partially reconstituted model system, fetus, could be used as markers in the GM3 and the enzyme that synthe- to examine steps in the teichoic acid clinic, making it easier to detect the sizes it, GM3S. Cholesterol uptake D-alanylation pathway. They found effects of malaria in pregnancy. is decreased in GM3S-deficient cells, that a previously uncharacterized DOI: 10.1074/mcp.RA118.000907 and GM3S-deficient mice fed a high- membrane protein in the pathway cholesterol diet show a lower suscep- attaches alanine onto lipotechoic acid, tibility to hypercholesterolemia. This defining one new step and setting the Regulation by research proposes a new viable target stage for further investigations. membrane curvature for cholesterol reducing therapies. DOI: 10.1074/jbc.RA118.004561 DOI: 10.1194/jlr.M089201 Some proteins can be found in Negative effects both the plasma membrane and the Crystals, cataracts endoplasmic reticulum membrane. of controlled malaria One example is diacylglycerol kinase and hot potatoes in pregnancy epsilon, or DGK-epsilon, which car- Highly stable crystallin proteins in ries out important functions in the the lens of the human eye are never Malaria during pregnancy can phosphatidylinositol cycle. José Carlos result in detrimental fetal effects, such replaced over a lifetime. With age, Bozelli and colleagues at McMas- as low birth weight. After parasite though, they accumulate oxidation- ter University investigated whether infection, the mother’s immune induced disulfide bonds, which can DGK-epsilon activity is affected by response restricts parasitic growth to lead to formation of protein aggre- the properties of the membranes in gates and cataract disease. Eugene the placenta, but chemokines and which they can be embedded. They Serebryany and colleagues at Harvard other immune cells can infiltrate found that, when embedded in a University examined disulfide bond and prevent nutrient flow to the formation in mixtures of wild-type fetus. Clearance by drug treatment, locally flat membrane, the kinase and cataract-associated human while helpful, does not reverse all had low activity and broad acyl γD-crystallin. They identify a “redox fetal effects. Rebeca Kawahara and chain specificity; curved membranes, hot potato competition” wherein colleagues at the University of Sao in contrast, improved activity and the disulfide bonds are exchanged Paulo in Brazil did a proteomics study specificity by allosterically regulat- dynamically between molecules and on placental tissues from uninfected ing DGK-epsilon activity. Thus, can be trapped in aggregation-prone and previously infected mothers and membrane shape, in addition to lipid intermediates. This study, published used a mouse model to look at cel- composition, may be an important Journal of Biological Chem- in the lular changes in controlled placental regulator of lipid signaling. The study istry, thus reveals a new enzyme malaria. This work was published in was published in the Journal of function for crystallins and provides Molecular & Cellular Proteomics. Biological Chemistry. potential insights into the evolution Using mass spectrometry and statisti- of exceptionally long-lived proteins. DOI: 10.1074/jbc.RA118.005293 cal analysis, they identified proteins DOI: 10.1074/jbc.RA118.004551 with altered expression levels, their Nathalie Gerassimov (nathalie. associated cellular processes and post- [email protected]) is a Decorating bacterial walls translational modifications indicative Ph.D. student at the Johns Hop- kins University School of Medicine. The teichoic acids in the cell of changes in regulation. Mapping the walls of Gram-positive bacteria are resultant networks revealed that in Dawn Hayward (dhaywar5@jhmi. modified frequently, altering bacterial the placenta of the previously infected edu) is a graduate student at the Johns Hopkins University School growth, aggregation and resistance to mothers, processes such as apoptosis, of Medicine. antibiotics. Understanding how these cell signaling and oxidative stress were modifications are introduced is there- dysregulated, an observation also seen Sasha Mushegian (amushegian@ gmail.com) is a postdoctoral fore important for combating these in the mouse model. This means that, fellow at Georgetown University. bacteria, but the pathways are difficult although the infection was cleared, Follow her on Twitter @sash_mu. to characterize. In the Journal of placental cells could face cell death,

JANUARY 2019 ASBMB TODAY 23 FEATURE How to patent an antibody Advice from Charles Craik By Laurel Oldach

harles Craik knows a lot about I definitely believe that it’s good to patenting research findings. patent things, because in my opinion, C The University of California, if pharmaceutical companies are going San Francisco, professor of pharma- to invest their money in developing a ceutical chemistry and protease expert drug, they need to have it protected is named as an inventor on 16 patents so they can try to recoup some of with six under review, most recently those costs. a series of antibodies targeting the I don’t think everything should be urokinase-type plasminogen activator patented, and I don’t spend all my receptor pathway to both image and time just thinking about patents, but treat aggressive and recurring cancers. when there is something that can be He also has taught in a course involv- a practical invention, I enjoy going ing intellectual property at UCSF for through the process of figuring out several years. Craik sat down with how to get it protected so someone ASBMB Today writer Laurel Oldach can make money off it and the cycle to talk about Amgen Inc. v. Sanofi et can continue for the development of al., a lawsuit over antibody patents future drugs. that has generated a lot of buzz in And I’ve been told multiple times biotechnology. Their conversation has by companies, big and small, “If you been edited for length and clarity. don’t get a patent, Charly, we will not be able to work with you.” Do you think a lot about patents and patenting? Of all of the monoclonal I definitely think about it a lot. I’m antibodies patented last year, an academic professor, so that’s my about a quarter came out of job 100 percent of the time. But in academic research institutions. A my spare time, I have started compa- nies, and I’ve learned certain things in large subset of those worked with the lab that have been very practical. a commercial co-applicant. How I’m still learning. Perhaps more than does that process work? an average person, I think about the It’s very hard to make one gener- practical applications of my work. alization about the whole process. As an assistant professor, I helped validate HIV protease as a therapeutic But imagine yourself running a lab. target in 1990. I don’t have the patent You’re in a university; you’re making on HIV protease — we got the crystal discoveries. You’re pushing the edge of structure, and we made it available the field, really trying to do some- — but I did work with companies so thing completely novel that no one’s they could develop compounds that ever thought of or done before. That’s could target the enzyme and provide what drives us. the basis for making a If you come across something that pharmaceutical. could be of practical interest, one of

24 ASBMB TODAY JANUARY 2019 CINDY CHEW/UCSF Charly Craik, pictured here in his office at the University of California, San Francisco, says he enjoys figuring out how to protect an invention “so someone can make money off it and the cycle can continue." the first things you usually do is file a So the cost is for a lawyer to disclosure. A disclosure means going make the patent watertight? to your university and saying, “I think That’s a way to put it. But it is I have something that’s of value here.” a judgment call — no one knows You write down the information asso- exactly how to write a patent. In the ciated with why you think it’s valu- Sanofi-Amgen case, there were highly able, what the concept is, when the qualified lawyers. In one case, you experiments occurred that reduced it could say that he or she failed. On the to practice — that really showed that other hand, the patent was upheld. So it happened. That’s filing a disclosure. it’s divining tea leaves in some cases. It doesn’t cost anything, just filling When a lawyer talks to you, they’re out a form. But it puts it on record at charging by the hour; if they write the university. stuff up, they charge you for that. I’ve The university evaluates whether got ways of keeping those costs down: it’s worth filing a patent. Now, it costs I write a lot of the stuff myself, and money to file a patent. Depending they turn it into legalese; that saves on the lawyer, it can be very inexpen- a huge amount of time. If I’m about sive and not very good, or it can cost to publish something, a lot of it is between $10,000 and $15,000. Let’s already written. say it’s roughly that amount of money. The university has to decide whether they’re going to pay those If every university filed on every idea, costs. Sometimes they say, “Well, they’d break the bank really fast. So we don’t think this is of interest; can there’s an evaluation process. you do some more work?” or they go As a professor, particularly in a out and market it, speaking in very university that doesn’t have a com- vague terms. They can say, “We have pany behind it, these filings can really a potential cure for cancer,” and they drain the bank. The hope is there will haven’t told anything. Or they say, be some big winners and there’ll be a “We’ve targeted this particular path- jackpot, and that supports the whole way, and we’ve found this particular thing. But it can be pretty risky. enzyme,” and that’s still not giving a

JANUARY 2019 ASBMB TODAY 25 a good patent. He took the time to teach me 30 years of his life in a few weekends. That was extremely valuable. So I started a course at UCSF to introduce students to the process of intellectual property and how to develop their ideas beyond publishing impor- tant papers. If they want to start a company, what are the fundamental points about the whole process? I bring in experts to teach that sort of thing. If you’ve ever seen a patent, it can be 15 pages. It can be 60 pages. It’s an intimidating document. The language is somewhere between Shakespeare and science, and it’s just not easy reading. Not to say that all that prose isn’t important, but to keep things simple, CHARLES CRAIK go straight to the claims. They are the The first five claims from a patent Craik and two colleagues filed in 2010 describe their invention of antibod- essence of the patent. And the claims ies that bind to urokinase-type plasminogen activator receptor, blocking its interaction with integrins. This are also prioritized. The No. 1 claim application listed 39 claims in total. is the most important thing to read. If you’re writing a patent, make sure whole lot away. that first claim is really substantive. Companies will sometimes reach Everything flows from there. out to the university and say, “Oh, It’s like trying to write a research we’re interested in this area; we’ll paper. I teach my students to focus on sign a confidentiality disclosure the data. Just tell me what the story agreement.” And now the researcher is on the data, and then the paper is is allowed to go and talk to that going to come. It’s the same on a pat- company. ent. Get your claims. Sometimes a company is just gathering information. They have You’ve applied for a lot of patents, no intention of ever licensing your and a good number have been patent. As you get into this, you can smell that pretty quickly. If they’re awarded or licensed out and are genuinely interested, they might say, in commercial development. ‘OK, we’ll co-develop this with you.” If it was all done at the university, What’s the ratio of hits to misses? they say, “We’ll license it.” There are That’s hard to generalize. Some- lots of ways. But that disclosure is the times I think if I were better, they’d beginning. all be licensed out. That’s always the thought that haunts you as a scientist: Do you wish someone had told you “God, I wish I were better at this.” about the patent process when I think I’ve gotten better as time goes on. At the very beginning, HIV you were starting out? protease was a pretty big hit. But I was fortunate enough to have like I said, we initially published that exactly that. When I was an assistant freely. We did file for some inhibi- professor, when we had HIV protease, tors, but it’s the job of pharmaceutical a lawyer worked with us. He and I got companies to make drugs. So once along really well, and he taught me a they had the target, it was a free-for- lot off the clock about how to write all; they were off and running. My lab

26 ASBMB TODAY JANUARY 2019 was academic; we had a few chemists still want the broad claims. making some molecules compared to For example, I tried in the 1990s 350 chemists at Merck. And Merck to get a patent for an antibody developed some good inhibitors. inhibiting any protease. No one had So back to your question; maybe done it, no one had filed; there were 10 percent of the things we file no examples where an antibody could disclosures on actually make it into a trap a protease in its active state versus patent that’s then awarded, that then an inactive state. It was a big idea, is licensed out. right? The examiner came back and said, “No. Too broad.” And in the end And then is perhaps considered they gave me any antibody that would for development? inhibit this particular protease. That Yes. And it’s sometimes said that a was a disappointment. patent is only as good as its ability to But now, reading this Amgen v. be defended. Sanofi case, I wouldn’t even get that. Some patents never are contested. They would only give me that particu- CINDY CHEW/ UCSF A lot of money can be made from lar antibody inhibiting that particular Charly Craik, pictured here in his lab at University of them, and they run out before there’s protease, just like PCSK9. That’s all California, San Francisco, worked early in his career a problem. But usually, if a patent is you’re getting: just one particular with an attorney who taught him how to write a good effective, valid, licensed and valu- antibody. So if someone gets another patent. “He took the time to teach me 30 years of his life in a few weekends,” Craik said. able, when it starts making money it’s antibody with a different sequence, going to be tested. it’s not protected. That’s exactly what happened in The pendulum swings, and in my Amgen v. Sanofi. Statins were going opinion it’s getting too specific. To off patent, and so this whole market have any value to a patent, so that was wide open for something new. someone would go through the whole This PCSK9 antibody potentially process, it should cover more space. could keep your cholesterol levels below what a statin could, particu- You sound pessimistic. larly for people who aren’t responsive to statins, and this was a pretty cool I don’t think this is the end of thing. There was a big race, and a lot getting good patents in the antibody of money was involved that drove space. There’s still a lot of meat on some exciting new science. those bones. There are so many opportunities What do you think about the in the antibody space right now; appeals court’s decision in immunotherapy has taken over, but More on antibodies the Amgen v. Sanofi case — you can do other things with antibod- When ASBMB Today science that knowing about a newly ies. They can translate into the clinic as diagnostics, as imaging agents, as writer Laurel Oldach interviewed characterized antigen is not therapeutics at the margins of tumor Charly Craik for her December enough to give an inventor environment, and the list goes on and feature, “The antibody patent a patent on a whole class of on and on. question,” their conversation antibodies that bind to it? I can’t say Amgen v. Sanofi is just a about patenting one’s academic speed bump, but the road isn’t com- discoveries went beyond the I have to choose my words on this pletely washed out. We just have to scope of that article, so we one. figure out how to navigate around it. decided to offer this extended I find it very disappointing that version of his comments. And this is the direction patents are going if you haven’t yet read enough Laurel Oldach (loldach@asbmb. with antibodies, because it’s slicing about antibodies, check out the salami so thin that you can’t get a org) is a science communicator for the Journal of Lipid Research Daniel Bojar’s essay, “Why meal off of it. So that’s a disappoint- and Molecular & Cellular aren’t there quality controls for ment. Proteomics and a staff writer for antibody research?” on page 50 ASBMB Today. Follow her on In the law, it always comes down to of this issue. a particular unique situation. But you Twitter at @LaurelOld.

JANUARY 2019 ASBMB TODAY 27 THE WELLNESS ISSUE

To start the new year right, we offer here a collection of articles, essays and tips on taking care of yourself and others. And to start the collection off right, we offer you this page to color. Studies have shown that coloring can reduce anxiety and stress while improving mood and enhancing mindfulness. So get out your crayons and improve your wellness. You’re welcome.

28 ASBMB TODAY JANUARY 2019 THE WELLNESS ISSUE Finding the help you need By Paul A. Craig

ailure. None of us want to encounter it or admit it has F happened, but it’s a part of the career of every successful scientist. This article is written specifically for students who hope to embark on that career, to help you deal with and overcome failure wherever you are on your path. My story When I was an undergraduate student, I experienced the faculty as people who challenged me but in a supportive way. They expected everyone to succeed and graduate. My teachers encouraged me, and I received lots of positive feedback. Graduate school was different.

I was the first person in my fam- COURTESY OF PAUL CRAIG ily to pursue a graduate degree. I In a photo from the early 1980s, Paul Craig, second from left, is shown with his research adviser, Eugene E. was so naive that I appeared for my Dekker, left, and Prasanta Datta, Harry Winter and Thomas Riggs at the University of Michigan. grad school interview in a suit — I thought that was how it was done. I publish and win grants. I soon real- second year but was able to pass my had a strong undergraduate record, so ized that I was part of a larger system qualifying exams to become a Ph.D. I had been a big fish in a small pond. that was expected to be successful. I candidate the following June. That When I arrived at graduate school, I saw that a significant number of stu- was when the real struggles began. found that I was an average student, dents did not complete their degrees. I had picked up a project that and it seemed to me that others in my I went home for Christmas break involved characterizing an enzyme class had arrived with much better after my first semester uncertain that a previous graduate student from preparation. whether I would return. It had been my lab had purified. The procedure The pressure of grad school was a difficult term — for the first time, was clearly written out, and the prior new to me and not comfortable at all. I did not have any family nearby, so I student had repeated the purification Up to that point, going to school was was quite lonely. successfully a number of times. It all about getting good grades. Now I I did return, and I remember one should have worked on the first try had started on a path for which the event from the following summer if I followed the directions properly, roadmap was unclear. (This is one rea- very well. My aunt and uncle visited but it didn’t. It also didn’t work on son I am such a strong supporter of Michigan in August, and they invited multiple attempts over the next twelve undergraduate research — I want my me to go with them to Greenfield Vil- months, and I grew despondent. My students to learn early in their careers lage and the Henry Ford Museum in advisor was on sabbatical. I kept send- how to respond when the answer to a Dearborn. It had been a tough sum- ing him reports about my failures, question is not known.) mer — research was new to me, and I and he wrote back long letters that The faculty members were all good was making very little progress. When were encouraging but also questioned people, but they were driven by the I went to meet them, I wasn’t sure if my motivation. I still have those let- need for success and productivity in I would laugh or burst into tears. We ters, but I have been unable to read terms of papers, grants and reputa- ended up having a wonderful time. them again. tion. I sensed the pressure they felt to I struggled a bit with classes in my I needed help to deal with the

JANUARY 2019 ASBMB TODAY 29 Five things you need I’d like to share a few things I’ve learned about surviving and thriving. 1. Have a sense of personal well-being and 3. Find a support group and stick with it. My fulfillment. This is discussed at length in Great support group was my faith community, but there Jobs, Great Lives, a study by Purdue University are many other choices. One of my friends in and Gallup. This survey of 30,000 college graduate school practiced aikido, which for him graduates measured the impact of different factors combined physical and spiritual well-being. on preparing undergraduates to become fully Unfortunately, some of us find ourselves drawn to engaged in their careers. They identified five the dangerous excesses of addiction. The January elements of well-being (quoted here) and found a 2017 issue of ASBMB Today contains a wonderful direct correlation between engagement at work essay about ongoing recovery from addiction titled and the number of elements found to be present “A Journey to Sobriety” by Dr. 24hours. If you are in the life of the graduates, according to the drawn to abuse alcohol or other substances or find Gallup-Healthways Well-Being Index. yourself involved in compulsive gambling or sexual • Purpose well-being: Liking what you do each behavior, you may be able to seek help from a day and being motivated to achieve your goals 12-step group, such as Alcoholics Anonymous. • Social well-being: Having strong and 4. Stay connected to your family. My move to supportive relationships and love in your life graduate school left me isolated from family. I finally became desperate enough to look up some • Financial well-being: Effectively more-distant relatives. Eventually, I met a second managing your economic life to reduce stress and cousin, and we became fast friends. His farm increase security became a weekend retreat for me while I was • Community well-being: The sense of finishing my Ph.D. and completing my postdoc. engagement you have with the areas where you 5. Be open to real connections from unexpected live, liking where you live, and feeling safe and sources. During my last year of graduate school, having pride in your community I was asked to host a biochemistry graduate • Physical well-being: Having good health and student from North Carolina who was visiting a enough energy to get things done on a daily basis Christian fellowship that I had joined. Bob While not foolproof, asking ourselves whether Bateman and I quickly became fast friends, and these elements are present in our lives provides a he has stood beside me in many challenging and good test to assess where we stand each day. joyful situations. I remember calling him when 2. Get honest with someone, particularly your I was awaiting my tenure decision. He urged me to advisor. Over time, I found that the more honest stop talking so fast. Then he pointed out that I I was with my advisor, the better things went for would have my family and friends no matter how me. If things were not working, I needed to assess that decision turned out. We have shared many the failure, try some solutions and present my wonderful moments together with our families findings without excuse or justification. We could over the last 34 years. I continue to be grateful for then look together at the cold, hard facts and his friendship, advocacy and advice, even though I decide the best next steps. never expected to meet him.

emotional impact of failure. of the house leaders asked me why I pointed me in a new direction for Fortunately, I was not isolated. As was so quiet at suppertime. I told him purifying the enzyme. It took about a practicing Christian, I looked for it was because I had no successes to two months of methodical effort to fellowship with other believers. That report. He challenged me to share my work out a new purification scheme summer I was living in a training/dis- failures and to ask the others for help and another two months to convince cipleship house with about 30 young and prayer. So I did the next night. my professor that this was the right men led by a few older men. Perhaps My friends surrounded me, encour- thing to do. it was the testosterone in the air, but aged me and promised to continue every night as we ate supper together, praying for me. From that point, it took another people talked about their personal Things did not change immedi- two-and-half years to complete my and professional successes. I was ately, but I lost my hopeless feeling graduate work, but that was more heartbroken because I had none to and started looking for solutions. I about learning persistence than fear share. I remember the night when one found a recently published paper that of failure.

30 ASBMB TODAY JANUARY 2019 What I’ve learned Each of us has unique experiences in our careers. In my story, I empha- size the role of my faith because it was central to my experience. I hope that aspect of my story doesn’t lead you to dismiss the discouragement, loneliness and challenges I faced for the first time when I entered graduate school. I believe these are common experiences for people in all walks of life and certainly for those pursuing scientific careers. I also experienced encouragement, voices of wisdom and love. In graduate school, you will be surrounded by lots of talented people: established investigators who have been publishing and overseeing funded research for decades; the new stars — assistant professors who just completed postdocs with famous sci- entists and are on a path to greatness; COURTESY OF PAUL CRAIG talented postdocs; and more senior Paul Craig, right, is pictured with Eugene E. Dekker, his research adviser at the University of Michigan, in the grad students. They all know more early 1980s. than you do, and many of them have what you want — a life as a scientist, As you engage in a scientific career, learn how to cope so that it is only a including the pursuit of knowledge in your life will be filled with ups and temporary state. a stable career that, perhaps, one day downs. In academia, papers are If you enjoyed reading this article, will include recognition at the local or accepted or rejected. For most of us, please feel free to reach out to Paul at even national level. You will start out [email protected]. with other new and talented students grants are rejected more often than who share your dreams. To reach they are funded. We face anxiety as those dreams, you need to work hard. we seek tenure (in academia) and Paul A. Craig ([email protected]) promotion (everywhere). is a professor of biochemistry and You will encounter frequent chal- head of the School of Chemistry lenges, and sometimes they will be Our lives have great potential for and Materials Science at the more than challenges. I hope my story joy, but here I am focused on the Rochester Institute of Technology. will encourage you to find the help challenges the scientific life brings. He won the 2018 ASBMB Award you need as you pursue those dreams. Failure is part of our lives. We must for Exemplary Contributions to Education.

Pulse points: Out of the dark From their labs to their personal lives, scientists now are addressing wellness and working to raise awareness about mental health issues. Throughout this issue of ASBMB Today, you will find short summaries of work in this area, including a study on how sleep deprivation can lead to loneliness, an initiative to improve heart health and research on worms under extreme stress. Check out our website (asbmb.org/asbmbtoday) for links to more information.

Susanna Harris is a graduate student studying with depression after failing an exam in graduate school microbiology at the University of North Carolina and how she came through the other side of what she School of Medicine. Last summer, she gave a talk for described as “months of crushing darkness.” Watch her The Monti, a series of live shows in which guests share talk: vimeo.com/286214085. Follow her on Twitter at personal stories. In her talk, she shared her experience @susannalharris.

JANUARY 2019 ASBMB TODAY 31 THE WELLNESS ISSUE Leadership with a focus on wellness By Teresa M. Evans & Nathan L. Vanderford

“Nothing in life is to be feared, it is trainees. We suggest that scientists tor stopped with the “yes” response, only to be understood. Now is the time take advantage of what is known they might assign a task beyond to understand more, so that we may fear about leadership both from the aca- the scope of the student’s ability less.” demic sector and the business world rather than listening to the student — Marie Curie and work to be transformational and understanding their needs and leaders. concerns. The answer to the second eaders often portray themselves question is very telling. as confident and fearless, but as Transformational A2: I have used a pipette in my L leaders we are often the opposite. introduction to biology course, but Confused leaders, misunderstood leadership my professor said that I needed more practice. leaders, overwhelmed leaders and Transformational leaders are dedi- This answer shows a clear need for sometimes even scared leaders is more cated to incorporating the ideas and additional training to ensure that the like it. taking into account the needs of all student is confident and capable. As Whether as a graduate student members of their organization, work- leaders, we need to make sure to set mentoring an undergrad in the lab, a ing to build a team that can achieve our teams up for success; sometimes faculty member overseeing a research its goals efficiently and effectively. that means taking a step backward to team or a department chair leading a We all know that being a good ensure that everyone is trained and group of faculty, we all question our leader is not about wearing a tie, prepared. leadership ability and are unsure of having a title or giving instructions. ourselves at times. Therefore, we need A leader should embrace transforma- to reflect on our own leadership styles tional leadership, support the needs of Emotional intelligence to better understand the critical role the team and incorporate new ideas to Another way to ensure that we are they play in our health and well-being ensure the team’s needs are being met. working to understand the needs of as well as the health and well-being of Transformational leaders work to those we lead. our team members is to engage our reduce fear in their teams through own emotional intelligence. This EI As scientists, we often are influ- increasing understanding. As we is essential for managing our own enced first by the leadership styles know from the fundamentals of neu- emotions and for ensuring that we we see in graduate school. We see roscience, experiencing fear hinders are aware of the emotions within our how our laboratory advisor reacts to our ability to think critically and team. successes and failures in research, and make rational choices. To ensure that we begin to adapt to these reactions. the team can function at its fullest The EI of their leaders is what Over time, we become conditioned potential, we must determine our motivates 87 percent of millennials to to react one way when our advi- team members’ needs. For example, help their employers succeed, accord- sor congratulates us on successfully as a mentor in the lab, we should ing to a 2017 survey by the Lenovo completing our qualifying exam and determine a new student’s knowledge Institute. EI is defined in three ways: another when this same advisor scolds level before assigning tasks. This often 1. Notice, label and define what us about a failed or incorrectly con- requires asking more than yes-or-no YOU are feeling. trolled experiment. questions. 2. Notice, label and define what As leaders in the sciences, we have Q1: Have you used a pipette OTHERS are feeling. plenty of room to improve how we before? 3. Use this information to GUIDE lead; in particular, scientific leaders A1: Yes. your thinking and behavior. should work to put more focus on Q2: Can you tell me about your Mastery of EI will help us under- ensuring that wellness is considered as experiences doing so? stand not only our own emotions but a key variable in the success of their If, in the scenario above, the men- also the emotions of our teams so that

32 ASBMB TODAY JANUARY 2019 we can respond effectively. We all have known leaders with varying degrees of EI and can reflect on how that made us feel. To promote the well-being of a team, leaders should work to understand the impact that actions and words have on them as well as how to communicate effec- tively about emotions. The ABC model To understand the impact of our actions on our own emotions and those of others, we can use the ABC model. This model is designed to help us understand the interactions among thoughts, emotions and behaviors. Think about the last time you did not handle your emo- tions well. Now go through the steps below. You should have a new way of looking at the initial event that allows you, in the future, to react in a more emotionally intelligent way. This colorful wheel, designed in 1980 by Robert Plutchik, a psychologist, identifies eight basic emotions and their combinations. A: Activating event — Something happens to you or within the environment By regularly using the ABC model, called emotional literacy. around you. Example: “Someone we can train our behaviors and work When leading a team that struggles turned off my experiment while I was to align better with those of a trans- with emotional literacy, consider away.” formational leader. The ABC model is using this wheel to guide the conver- B: Beliefs — You have a belief or also a great tool for discussing tough sation and ensure accurate percep- interpretation regarding the activating situations and reactions with a team tion of each person’s emotions. For event. Example: “They are trying to to ensure that we are building strong example, a leader might perceive that ruin my results.” communication. a team member is showing rage after C: Consequences — Your belief being asked why they were late for has consequences that include feelings a meeting, but in reality that team and behaviors. Example: “I believe Wheel of emotions member is simply annoyed by the they are out to get me.” A leader needs a robust and traffic that made them late. D: Disputations of beliefs — nuanced emotional vocabulary to Challenge your beliefs to create new communicate effectively and to consequences. Example: “Maybe they promote open communication of Be a role model just made a mistake.” emotions by team members. A leader should be a role model E: Effective new beliefs— Adop- in their organization, laboratory or tion and implementation of new Plutchik’s wheel of emotions department. A good leader should, adaptive beliefs. Example: “I will turn identifies eight basic emotions and therefore, be aware of the need for it back on and assume the best until combinations of those basic emo- I have a definite reason to believe tions within a colored wheel. This can wellness in the organization and work otherwise. I will talk to them and ask help promote the effective and clear to embrace wellness programs that that they be more cautious next time.” communication of emotions, which is CONTINUED ON PAGE 35

JANUARY 2019 ASBMB TODAY 33 THE WELLNESS ISSUE With a little help from my friends By Mark Zbinden

“He is going to be so upset.” That was my first thought when the head nurse in the emergency psychiatric ward told me they needed to notify my emergency contact of my situation. “He” wasn’t my PI. Nor was he my father or any other blood relative. He was my friend. It was my fourth year of graduate school, and things were not going well. My project refused to cooper- ate, my relationship with my PI was strained, and I simply couldn’t handle it. I had made an appointment to speak with a therapist, and within half an hour of our meeting, she was escorting me to the hospital across the street. I was terrified. But as traumatic

as the whole ordeal seemed, I was RISA BURR most concerned how my best friend, Mark Zbinden, right, and Jarrett, the friend who helped Zbinden after his hospitalization, at the Cherry Blossom now an objectively successful postdoc Festival in Washington, D.C., in 2014. at MIT, would react to the news. A recent report in the journal an unfamiliar place, crippling what- apartment. I was waiting outside on Nature Biotechnology shows that ever local support system they had the stoop, and he sat down next to my story is not uncommon among before starting the pursuit of their me. What followed was a long silence, my peers. Around 40 percent of advanced degree. More is expected of which I broke: students surveyed reported experienc- them than ever before, and they try “Thanks, man.” ing depression, and a similar number to meet those expectations with as After his laughter subsided, he reported anxiety. The study also small a support structure as they’ve responded, “No problem.” suggests that these experiences are ever had. We talked for a long time, and correlated with students having nega- So what can graduate students do after a while, it dawned on me just tive feelings about relationships with to overcome this common and unten- how much I appreciated this person. their mentors. able situation? In addition to oth- He, along with the rest of the friends Graduate students also experience ers detailed in this issue of ASBMB I made in graduate school, meant an inordinate amount of stress. I Today, I’d like to put forth a resource more to me than I knew — until that know plenty of students who report that rarely is talked about in any very moment. working 50-plus hours in a week, depth: friendship. Throughout the next few weeks, and many take on additional debt to When I was released from the I made it a point to talk to each make ends meet when their stipends hospital the next morning, I was one, telling them what I was going fall short. Often, they’ve entered their greeted by some very concerned text through and that I appreciated program right after college, and this is messages from my friend. After I told them. I was dumbfounded by their their first full-time job experience. On him I was home, he dropped his lab responses: offers of support and love, top of that, they likely have moved to work and came to meet me at my without fail or hesitation. My story

34 ASBMB TODAY JANUARY 2019 wound up having a happy ending, to introduce yourself to someone new, That said … and I’ve compiled some advice here remember: they’re in the same posi- • Make special plans together. on friendship so that yours can too. tion you are. Planning and taking vacations • Don’t be afraid to tell your together cuts down on costs and friends how you feel. The strongest promotes a healthy work-life balance, Advice foundation of any relationship is and it is a more concrete commitment Before I continue, I’d like to plead honesty, and friendships are no differ- to time away from the lab than “I’ll with anyone who is having thoughts ent. When things are going well, tell try not to go to the lab this weekend.” of self-harm to talk to someone about them. And when things aren’t great? Additionally, spending time with it immediately. There are people who Tell them. Your friends care about people you care about will reinforce want to help and care about you. you, and they’ll help you if they can. the bonds between you, and all Which brings me to my first bullet • It’s a two-way street. Your involved will be better for it. point: friends will need you as you will need No one is an island, and no one • Psychiatrists, therapists and them; be sure to listen to and care for can do this alone. Make friends, care mental health counselors can help them, if doing so doesn’t overly tax for them and build on each other’s you. And a psychiatrist can work with you. It’s always OK to say no if you’re strengths. Lean on them and offer you to treat any neurochemical imbal- uncomfortable, but reciprocal effort your hand when they need it. ances you may have. If you have an in any relationship is critical. Even though graduate school opportunity to see a professional, and • Friendship doesn’t have to mean threatened to capsize me, my friends you think you need to, I urge you to hanging out. Time and money are were my bulwark. take advantage of it. short in graduate school, but luck- And they still are. • We’re all in this together. ily, friendship doesn’t require either Your classmates and older graduate of those things. Coffee breaks taken Mark Zbinden ([email protected]) students have some understand- together and exchanged text messages is a scientific project coordinator at a small ing, at least, of what you are feeling. are great ways to catch up and remind biotech company in Boston. Follow him on Twitter @_PhDnD. Although it can be anxiety-inducing yourself that you are not alone in this.

CONTINUED FROM PAGE 33 Conclusion members. We must model positive EI and wellness for those we lead to pro- promote the well-being of the team. As scientists, we focus on collecting mote a culture that embraces leading As leaders, we should educate our- data, publications and grants, hop- through wellness. selves and our team members about ing that one day we will accumulate enough to be rewarded in our work EI and emotional literacy. Teresa M. Evans (evanstm@ We can cultivate EI in our teams lives, and only then will we allow ourselves to start enjoying life. With uthscsa.edu) is an assistant by encouraging emotional responsibil- professor in the department of this mindset, we can find ourselves ity through promoting team service pharmacology at the University dedicating most of our time to work projects. A leader who wishes to of Texas Health Science Center at and neglecting our wellness. San Antonio. promote EI also should aim to create As researchers, we spend most an honest work environment where of our time in the laboratory or Nathan L. Vanderford (nathan. transparency is held in the highest our offices, so it is imperative that [email protected]) is an assis- regard. Most importantly, we must faculty, academic leaders and mentors tant professor in the department lead by example and develop our embrace the importance of wellness of toxicology and cancer biology at the University of Kentucky. personal EI as leaders. both in themselves and in their team

Pulse points: Stressed worms

Researchers funded by the National Institutes of Health such as starvation, they stop developing temporarily and investigated the impact that environmental stress can then continue growing after the stressful situation has have on the nervous systems of roundworms called passed. Researchers studying worms before and after a Caenorhabditis elegans. A news release from the NIH period of stress concluded that stress rewired the worms’ explained that when C. elegans are exposed to a stressor, nervous systems.

JANUARY 2019 ASBMB TODAY 35 THE WELLNESS ISSUE

36 ASBMB TODAY JANUARY 2019 THE WELLNESS ISSUE Career wellness: consider your strengths By Natalie Lundsteen

hruba Deb began his postdoc- toral training at the University D of Texas Southwestern Medical Center with mixed feelings. He was confident in his scientific training and knowledge, and he felt prepared to begin work on a project developing novel lung cancer therapeutic strate- gies. He knew he could succeed at the bench, but he was wary of taking on senior lab leadership responsibilities in this new phase of life. He came from a large city in India but found the culture of Dallas a challenge, and he knew that postdoctoral research is often solitary and sometimes isolating. Starting his postdoc, Deb immedi- often don’t consider consciously those From the start, Deb became ately picked up on a crucial aspect of aspects of self where they are naturally involved in postdoctoral leadership workplace wellness and happiness — accomplished. They rarely work to activities, which presented him with self-awareness makes you a stronger identify strengths. opportunities for self-assessment, individual contributor and a better One of my favorite resources for finding camaraderie and feeling like team member. personal/professional development part of a team. Increasing his knowl- is specifically focused on strengths edge of his own talents, skills and Why strengths matter — the CliftonStrengths Assessment values had a profound impact on his (formerly known as the Strengths- personal development and well-being. I advise biomedical science trainees Finder), created by the Gallup He learned about successful teams on career development, and I’ve consulting company. I first took this and how to thrive in them, seeing that found that a process of self-reflection assessment about 15 years ago when everyone contributes something to can move a trainee forward if he or I was a university consultant and the group work settings. she feels stuck in any way, whether dean wanted to see how I would fit in “Till this moment of my life, it’s setbacks at the bench, indecision with the rest of our working group. everything was about me,” he said. about next career steps or a general I learned that my love of building “My studies, my grades, my papers, lack of confidence. relationships and helping other people my grants. For the first time, I real- Postdocs and graduate students directly correlates to a few of my top ized now the priority is shifting. It are probably familiar with individual strengths, including communication, is about the paper of the graduate development plans; trainees create positivity and “WOO” (winning student training with me, the poster these personal road maps as a tool to others over). I like motivating people of the summer student I taught, the strategize their professional choices and helping them see possibilities, so collaborative multi-PI grant that I’m and skills development, which can I’m happy that I get to use my natural writing with four other postdocs. help determine career preferences and strengths in my job every day. It Suddenly, it is not about just me values. But so much of a scientist’s makes my work seem less like work. anymore. It is more about how others training is about learning new things. I’ve seen CliftonStrengths make a around me perform, and their states While building skills and identify- difference for many grad students and of mind and wellness as well.” ing areas for improvement, scientists postdocs who are finding their way as

JANUARY 2019 ASBMB TODAY 37 scientists, learning about professional online assessment takes about 20-30 options and making choices about minutes to complete and asks you Resources what to do after their scientific train- to make choices between pairs of ing. But CliftonStrengths is not about words in order to produce a Signa- You can find the StrengthsFinder choosing a particular career path. ture Themes Report of your top five at gallupstrengthscenter.com. Instead, the tool helps you see aspects talents and how to maximize them. Pair it with other resources: of yourself that can help you make There are a total of 34 strengths • the MyIDP tool at better career decisions and choices organized into four domains (execut- sciencecareers.org about activities and settings where ing, influencing, relationship-building • the occupational path explo- you can thrive, including working in and strategic thinking). The odds of ration tools at biocareers.org teams or groups. two people having the same top five and versatilephd.com Gallup has found that people strengths in the same order is one in Often, taking even a small step in who spend more of their day using 33 million, so your results are truly learning about yourself and your their strengths are less likely to be personalized and individual. options can put you in a better stressed, worried and sad — and I Cost to identify your top five frame of mind to get past feeling agree. It makes sense to choose, if talents is $20. It’s definitely worth stuck and start thinking about possible, a career path where you will the price, in my opinion, but since it your future. be naturally adept. You spend most is a popular tool in higher education of your waking hours at work; how settings, you should be able to take you make a living and the people with recent program retreat. Faculty, staff, CliftonStrengths through a workshop postdocs and students all took the whom you work certainly affect your or course at your institution. You quality of life. Career setbacks, career CliftonStrengths assessment before do not need a coach or counselor to the off-campus event and then used activities and even thinking about review CliftonStrengths results, which career choices cause stress and anxiety, their personal results during retreat is one of the great things about it, but activities to spark conversations about especially for scientists in training or I’ve found that it helps my trainees to lab and team dynamics, getting the professional transition. debrief and discuss their strengths in I like the CliftonStrengths assess- most from collaborative activities and groups or one-on-one. I also recom- ment because it gives immediately interactions, and developing under- mend that non-native English speak- useful results that can have a positive standing of individual work styles. ers take the version in their first lan- impact on someone who feels stuck in Having the common language of guage, if possible; CliftonStrengths is a work or personal situation or who the CliftonStrengths assessment “was available in more than 25 languages. is uncertain about making choices. a positive, morale-building way to Being reminded of the things you are strengthen our academic community,” naturally good at is a powerful con- Team-building Banaszynski said. “Everyone felt good fidence boost, and I think everyone with strengths about it. It helped our group be more makes better choices when minimiz- personal and to understand each ing stress and tension. (Do you see Once you know your own other while also having fun.” my positivity at work?) strengths, it’s also useful to know Postdoc Dhru Deb was happy To give some examples of identi- the strengths and talents of oth- to discover not only his top five fying what strengths you naturally ers in your immediate circle. Most strengths but also those of his col- might possess, consider these ques- activities, whether in your personal or leagues, he said. “This training gave tions: Have you been told that you are professional life, involve interacting a great listener? Do you have a knack me confidence to talk about my own with others, so knowing more about for sizing up people or seeing the strengths in job interviews, and also what motivates or discourages others big picture? Are you great at finding made me aware of a ‘magic list’ of patterns and analyzing data? Those are in your team, lab or organization talents for the people who I can col- strengths. If you find a career where can result in better harmony and a laborate with to execute tasks requir- you regularly can use your strengths, smoother path toward accomplishing ing certain skills that I lack.” you will probably enjoy your work goals. almost every day, and knowing your Laura Banaszynski, assistant profes- Natalie Lundsteen (natalie. strengths is also powerful in day-to- sor of obstetrics and gynecology in [email protected]) day interactions and situations with the Green Center for Reproductive is assistant dean for career and professional development in the family and friends. Biology Sciences at the University Graduate School of Biomedical CliftonStrengths results outline of Texas Southwestern Medical Sciences and assistant professor your natural talents and how they Center, incorporated understand- of psychiatry at the University of Texas Southwest- influence the way you live. The ing of strengths when planning a ern Medical Center.

38 ASBMB TODAY JANUARY 2019 THE WELLNESS ISSUE Maternity in grad school — the best and worst of times By Nathalie Gerassimov

he doctor placed my tiny, naked daughter on my chest. It was Jan. T 15, 2018, and I was in the sixth year of my Ph.D. graduate studies. The timing was perfect. At the same time, there is never a perfect time to have a baby. I agonized and analyzed the timing of my potential pregnancy for years, hoping my family planning would not interfere with my career. Turning 30 pushed this issue to the forefront, especially since I’d just married the wonderful man I’d been dating for many years. A female PI said once that having a baby while you are writ- ing your thesis works well, so that was my goal. Like most Ph.D. journeys, mine was a series of ups and downs. Just as I started to gain confidence as a scientist, my graduate lab decided to move to a different state, and I knew I wouldn’t go with them. Luckily, my graduate advisor arranged for me to continue my project with her but to do my work in a new lab. This COURTESY OF NATHALIE GERASSIMOV Nathalie Gerassimov and her daughter, age one month, who was born while Nathalie was working on her Ph.D. arrangement was supposed to last for one year, and I decided to postpone starting a family. When the arrange- myself. I was relieved to learn I was inhale into right nostril, exhale from ment was extended for another year, I pregnant. Now I understood why I’d left nostril … Miraculously, breath decided it was time to get pregnant. been having such a hard time. control calmed me in less than two To be completely honest, I had Determined not to be the emo- minutes. reason to believe that I might have tional pregnant woman in the lab, I In the second trimester, I was full difficulty conceiving. If I waited until focused on controlling my thoughts, of energy, and I channeled all of it I was 35 to start trying and then had and through that I was able to hold toward my research (I had arranged fertility problems, I would be furious my feelings in check. Previous dab- all things pertinent to baby — such as with myself for not starting sooner. bling in yoga and meditation helped. registry — during my first trimester). I was pregnant three months later. I’m an anxious person, excellent at Being pregnant put a tangible clock § worrying about what could hap- on my time in grad school, and I The first month, when I still didn’t pen. After more than a decade of became better at prioritizing. know I was pregnant, I was incredibly self-created emotional pain, I finally Sleeping became a challenge as my tired and emotional. The science was learned how to breathe: inhale into belly got bigger. I credit my sanity not going as I’d hoped; I felt sorry for left nostril, exhale from right nostril, to the Snoogle — a large C-shaped

JANUARY 2019 ASBMB TODAY 39 pillow that supported my entire body. side of my body. about being gone for long hours. However, no pillow could help with Countless times I had imagined the I’d heard that mothers always feel the urgent need to empty my bladder moment I would meet her, gazing at guilty. I worked at focusing on what at least once a night. my baby through a rosy mist of love. I was doing when I was doing it and During my third trimester, I Instead, all I cared about was stopping reminding myself that I was only became a master time planner. I was the pain. human, with limited time and energy. diagnosed with gestational diabetes, § I also felt less guilty because I was able and my life circled around manage- Someone said once that uncondi- to breast feed my baby (I am grateful ment of the disease. I had to inject tional love comes from selfless actions for the breast pump and maternity insulin three times a day and measure repeated over and over again. I had room at my school). I abandoned my my blood sugar four times a day. My a chance to test that hypothesis dur- yoga and meditation practice at this meals were calculated precisely, and ing the eight weeks allocated by the point (due to what I called mother I had to walk 30 minutes after each Johns Hopkins University School of interference syndrome — both meal to help regulate my blood sugar. Medicine’s new extended maternal from being a mother and having my At that point, I was doing a lot of leave policy. mother there), but Mom and I went imaging, and I walked miles in the The first two weeks, I slept on to the gym several times a week, hall outside the microscope room average two hours a day and func- which helped me sleep and regulate while the images were being acquired. tioned whenever my baby needed my stress. I also had lengthy appointments twice me, despite being sick, hurt and tired I managed to finish my graduate a week during which I could see my beyond imagining. Every day, I was work and secure two internships to baby hiccup in my belly. reduced to tears of exhaustion. I kept help me figure out what I want to do Sleeping got even more challeng- reminding myself that nothing is as professionally. I am now an intern in ing. Instead of having to pee once or intense or painful as giving birth. the biotech industry, and I love it. twice per night, I was usually up four My meditation and yoga practice did My mom had to leave, but we times. This is clearly nature’s joke on help me through this period. It was found a wonderful nonprofit child- women; getting out of bed with a also crucial to talk to people I trusted care center that awes me with its qual- large belly is ridiculously hard. about my fears and anxieties — like ity of care, even though it costs my Despite all that, I was better at my need to check every 30 minutes entire graduate stipend (my husband balancing life and work. I constantly that my baby was breathing. The first pays the rest of our living expenses). I reminded myself what really mattered: month was incredibly hard, but my still work long hours and use breast- Yes, I needed to do due diligence in heart melted in those moments when feeding and my supportive husband my research, but these nine months she slept peacefully in my arms. to feel less guilty about being gone so would affect my baby’s whole life. So When it came time for me to much. My daughter just got her first when I could, I worked hard for long return to grad school, my daughter tooth and cries “Mama” when she hours, which was 80 percent of the was sleeping though most nights. My is hungry or upset. Most nights she time. And when I couldn’t, I went mother was able to come and stay sleeps well, and so do we. home and cuddled with my husband. with us for six months, and my hus- Maternity transformed me; I am My water broke to announce my band was fully involved in our baby’s stronger, more determined and less baby girl’s arrival. What followed was care. All I have accomplished rests afraid. I am also consumed by the hands down the most terrifying and on their support of my goals and the desire to make this world — the painful experience of my life. As they sacrifices they made for me. world that my daughter will be living say, it’s called labor for a reason. I’d I had four months to finish my in — better in whatever way I can. tried to prepare myself with more fre- experiments, write my thesis and quent meditation and yoga practice, figure out what to do next. I had Nathalie Gerassimov (Nathalie.gerassimov@ but in the end I opted for the pain to work like crazy. With my mom gmail.com) is a Ph.D. student at the Johns meds — which only worked on one watching my baby, I felt less guilty Hopkins University School of Medicine.

Pulse points: Shunned and sleepless Researchers at the University of California, Berkeley, you as more socially repulsive, further increasing the demonstrated that sleep-deprived people not only feel grave social-isolation impact of sleep loss.” The team lonelier, but also alienate others. Matthew Walker told used brain imaging, simulations and other tools to mea- Berkeley News: “The less sleep you get, the less you sure the social implications of poor sleep. Visit asbmb. want to socially interact. In turn, other people perceive org/asbmbtoday to learn more and see the simulations.

40 ASBMB TODAY JANUARY 2019 THE WELLNESS ISSUE Holistic mentorship Tips for supporting graduate students and postdoctoral fellows By Kelly Edwards, Ziyan Bai & Bill Mahoney

Holistic: relating to or concerned with wholes or with complete systems rather than with the analysis of, treat- ment of, or dissection into parts — Merriam−Webster Unabridged Dictionary

raduate students in the sciences work to understand or create G something novel and present these findings to the larger commu- nity, with the goal of moving on to an independent career solving bigger and more complex problems. Postdoctoral fellows feel added pressure to own a piece of the work and to be seen as the creator and keeper of this knowl- edge as they explore careers inside and outside of academia. Graduate students and postdocs advice, if we show genuine interest • The pressures experienced by are more than their work in the lab. and listen, we can better align guid- graduate students and post- They have complex lives. They may be ance with where the mentee actually docs are often overwhelming: responsible for a family or be living • Will there be enough funding? is. For example, either before or after far from their family (or both). Per- • Will my experiments work? a research-focused conversation, ask sonal commitments beyond current • Will anyone be interested in how the grad student is feeling about research projects may provide the fuel my findings? the work and check in about other and fire for their further training; • Will someone beat me to things (interests and stressors) going perhaps they bear the expectations, on in their lives. them? or assumptions, of others. They have • Do I have what it takes to be financial stresses and feel self-doubt successful? about how they choose to invest in Set clear expectations As faculty members working to their future. Many students enter graduate support graduate students and post- Here are some suggestions for school or a postdoctoral fellowship docs in an uncertain and high-stakes mentors to holistically support the knowing little about the unique environment, we have developed a set development and success of graduate milestones of academic progress — of approaches that serve us and other students and postdocs. mentors in the academic community. qualifying exams, masters’ theses, We advocate for building a mentor- finding a primary faculty advisor or ing team; a single primary research Ask open-ended questions developing a line of independent advisor has difficulty meeting all the Instead of assuming we know research. Demystifying these steps can needs and interests of a trainee. A what’s going on with a mentee, be helpful, especially for students who team can provide support on all sides, we should be curious. We can be may be the first in their families to and feeling supported goes a long way surprised to learn what’s happening earn a college degree or international to enhancing a trainee’s productivity, in their lives and with their thinking. students who have experienced a dif- resilience and overall satisfaction. Before we start lecturing or offering ferent educational system.

JANUARY 2019 ASBMB TODAY 41 Create connections departmental, professional or com- Help broaden their networks: munity meetings that are important None of us knows everything about We sometimes assume that stu- to the work — this helps expand the dents just will figure out how to seek all potential employment sectors. circle of belonging within the profes- We need to connect our mentees to the things they need or are interested sional community. in. We who have worked in university people within our own networks or settings for decades can forget easily those of our colleagues and friends if that these things are not all obvious. Show that being their interests align. When we share Isolation — from peers or faculty — vulnerable is OK our network, our trainees can build can be a risk, particularly for students more relationships as collaborators, who see asking for help as a weak- As mentors, we need to talk about mentees, friends or future colleagues. ness or who believe it is not safe to our own support structures and self- If we are lucky, each of us is both be vulnerable. It’s helpful to schedule care practices. The more honest we mentor and mentee throughout our regular advising meetings as a routine are, the more students can trust us career. Mentorship, peer connections check-in. This setting can help nor- with their concerns and needs. Failure malize feedback so it becomes routine is part of our academic lives — we and access to support, whether for to talk about what’s going well so all have missteps, and we need to academic skills or emotional health, trainees can build confidence in their recharge and refuel. Demonstrating can help our mentees shift from sur- strengths. Regular feedback also cre- how we seek support can be our best viving to thriving. ates a safe opportunity for trainees to gift to a trainee (and by practicing self-care, we can offer our best selves learn what they might do differently Kelly Edwards ([email protected]) to do better in the future. as mentors without burning out). is the associate dean for student We suggest sharing a true story from and postdoctoral affairs at the when you were a graduate student or University of Washington graduate Create a culture postdoc about having a paper rejected school and a professor of bioeth- by a journal or being questioned ics in the UW School of Medicine. of belonging She has focused her research and leadership on about research methodology at a We have heard from some students how educational environments shape people both national conference; talk about your personally and professionally. that others make them feel that they feelings and how you reached out for were admitted to graduate school help. Explain how you were able to Ziyan Bai ([email protected]) only because of diversity priorities. draw upon these experiences the next is a doctoral candidate in the They experience micro- or macroag- time you hit a tough patch. University of Washington College gressions from classmates, faculty of Education and graduate staff or staff — hurtful comments that assistant in the office of post- Stay focused on the why doctoral affairs. She is interested question whether someone who is not in graduate education policy, practice and the from the dominant culture can really Tapping into a trainee’s passion financing of higher education. fit in. What can we as mentors do to and purpose — the why of why they highlight the unique contributions are in graduate school or pursuing a Bill Mahoney (wmahoney@ every person brings to a program or postdoctoral fellowship — is key to uw.edu) is co-director of the training environment? We need to helping them sustain energy and com- University of Washington Office stress that diversity in backgrounds of Postdoctoral Affairs and is an mitment for the long haul. Here too, associate professor in pathology and training is best for advancing any we can get curious, ask questions and at the UW School of Medicine. He field. The unique gifts and experi- then, as allies, remind them of their has a longstanding interest in STEM professional ences of each team member should be passion and purpose when the going development, focusing on graduate students, celebrated. Invite trainees to attend gets tough. postdoctoral fellows and junior faculty.

Pulse points: Feel like a fraud?

Julia Omotade, Jamie King and Richard A. Kahn outcomes.” Have you experienced these feelings in your wrote in this magazine in February 2017 that the term educational or professional career? If so, you’re not alone “imposter syndrome” is used “to describe the chronic and there are ways to overcome them. Elizabeth Cox and potentially lifelong feelings of inadequacy and answers the question “What is imposter syndrome and self-doubt that affect performance and professional how can you combat it?” in a TED-Ed animation.

42 ASBMB TODAY JANUARY 2019 THE WELLNESS ISSUE Refreshing my spirit By Edward Eisenstein

ilence. You may be S skimming this issue of ASBMB Today rather quickly before turning back to the rapid pace of your everyday life. As we become absorbed by today’s increasing demands of science and teaching, with informa- tion bombarding us through every medium, it is a wonder that we find any time to pause and reflect on our men- tal, physical or spiritual well-being. Although many of us enjoy and even thrive on ED EISENSTEIN the excitingly rapid pace Ed Eisenstein attends meeting at the meetinghouse at Sandy Spring, Maryland, where Quakers have gathered since 1770. Initially, a log house was used for worship; this current brick structure was built in 1817. of science and discovery, teaching and counsel- my smartphone, scroll through email ing, and contributing to our local Then there is the silence or even listen to the radio. Instead, and global communities, how do we When I am able to settle myself I try to clear my mind and avoid restore ourselves and reconnect with anything that might distract me from fully, first my body and then my our values in order to persevere when experiencing meeting for worship. mind, I am able to open myself to life events are overwhelming? Once I arrive, I sit on a simple silent prayer. I begin by meditating There is now greater appreciation bench in an old, unadorned building. on the gratitude I feel for all the joy for the importance of wellness in our Our meetinghouse was built in 1817 in my life, for my family and com- lives, and accordingly, many avenues — though Quakers have gathered on munity, for the ability to discern my are available to us for physical rejuve- the site since 1753 — and it hasn’t direction so that, as a way opens in nation. But how does one revive the changed much since then. The hand- my search for truth, I can meet the spirit? For me, I restore and nourish hewn pews face one another with no challenges ahead of me more readily. I my spirit at a meeting among Friends. altar or pulpit but simply an open ask for faith, forgiveness, equality and space in the center of the room. peace. And I do this silently. So, what do I do at a Although there aren’t many distrac- The silence is important. Not tions, it isn’t always easy to center simply for reflection but so I can Quaker meeting? myself — for life reasons or because listen, carefully, to the “still, small My Quaker meeting is held in of the sounds of traffic or someone voice” that Quakers believe dwells in silence. Deep silence. Before I arrive coughing. But being in a sacred everyone’s heart. The silence enables at the meetinghouse, I don’t review a place with so much history helps me me to be more receptive to revelation to-do list, read the newspaper, look at become still. CONTINUED ON PAGE 45

JANUARY 2019 ASBMB TODAY 43 THE WELLNESS ISSUE How I learned to stop worrying about grad school* and to love climbing rocks *at least for a little while By Richard Sima

very Tuesday, I find myself sweating and holding onto a E wall for dear life. I recently started bouldering, which is rock climbing without the rope or associated safety gear. As the name implies, the sport historically involved climbers attempting to conquer boulders outdoors. Nowa- days, there is an indoor option with human-designed walls, artificial lights and padded floors. My previous forays into building an exercise regime inevitably petered out. The touted benefits of an aerobic workout did little to outweigh the pain and boredom of running; though my mood was heightened in the hours and days after a good run, the anticipated wheezing, groaning and misery meant I never looked forward to lacing up my running shoes. In the face of this dread, I stopped putting on my running shoes at all. Climbing was different from the start. I have to be mentally pres- ent every time I’m on the rock wall

because inattention has immediate HANNAH AHN consequences. Not checking the Richard Sima nearly slips off a rock wall at an EarthTreks gym in Baltimore but manages to catch himself. placement of my feet before shifting my entire body weight will lead to a about experiments and analyses wait- ing even a few feet off the ground is fall. Not judging clearly the distances ing back at the lab also will lead to a enough to focus my attention on the between two handholds will lead to a fall. In this way, climbing has a medi- task at hand as opposed to the myriad fall. Becoming distracted by thoughts tative quality. The danger I feel hang- ideas, internal monologues and latent

44 ASBMB TODAY JANUARY 2019 anxieties I would otherwise occupy ting over the fear of failure through success that much sweeter. myself with. what amounts to exposure therapy in The climbing gym I frequent is The climbing routes are distin- a low-risk setting; by being repeatedly well-suited for those keeping typical guished from one another by color, exposed to something that provokes graduate student hours: it opens early each assigned a difficulty and quirk- anxiety in a low-stakes environment, and closes at 11 p.m. Unlike tennis, ily named — “Long Way Home,” I can habituate myself to that stress my previous sport of choice, boul- dering does not require a partner, so “Time for Coffee,” “You Have Feet.” of failure. Research shows this to be there is no need to wrangle conflicting The beginner routes include many a benefit of hobbies outside the lab. schedules or deal with dropped plans platforms, called holds, that are large Bouldering gives me a chance to fail due to an experiment that took longer or have hand-conforming edges, often and publicly. If you aren’t failing than expected. making them easy to grab or stand at climbing, then you aren’t trying to Climbing is a social activity, on. Five months in, I’m climbing at a push yourself to improve. however, and the community has V3 level, which is solidly intermedi- This is something I’ve had to get been very open and welcoming. We ate. The routes I now climb feature used to. It’s easy to feel self-conscious all learn from watching one another, smaller holds, tougher transitions and approaching a new problem or climb- and we sometimes share pointers on increased soreness post-climb. ing route, getting my hands on the different approaches to a route we’re Each step up the wall is gratifying, starting holds and then immediately struggling with. As a neophyte, I find mentally and physically. Bouldering realizing I have no idea what to do it inspiring to see children a fifth my age and a third my height scramble forces me to move and sense my body next. I contort my body in various up routes I have not yet dared to in ways I’ve never done before. My angles and directions, trying to find attempt. I see how far I have to go fingers and hands are more sensitive purchase on the next step, which in improving my physical strength to the weight and pressure I put on initially seemed so easy and obvious. and skill. But I also see how far I’ve them, even as the skin on my palms No doubt I look very silly. come, and I take pride in what I have becomes increasingly calloused with I notice, however, that climbers learned thus far. use. I’ve learned to move my feet and with years of experience go through I’m not sure where I’ll be when I legs with greater precision and to trust this same awkward dance on diffi- (fingers crossed) finish my thesis later the weight I can put on even just the cult problems that are new to them. this year. But I know many more toe of my shoe as I reach for a higher There’s nothing wrong or embarrass- routes will be left to climb, and I’ll hold. Feeling the pull of gravity is ing about it. They also have to drop take each of them one step at a time. thrilling as I let go with one hand and down as their strength gives way or rebalance myself. When I’m clinging they lose their balance. Even the sea- Richard Sima (rsima1@jhu. to a wall some ten feet off the ground, soned veterans fall. The key is to then edu) is a Ph.D. candidate in the neuroscience department at the my lab experiments are far from my brush oneself off, take a deep breath Johns Hopkins University School of mind. and try again. Each attempt decreases Medicine. Follow him on Twitter For me, climbing is a way of get- my anxiety and makes the eventual @richardsima.

CONTINUED FROM PAGE 43 share with the meeting. When I am have questions about the hour that led by spirit so strongly that I must just passed. We connect with one and to connect with the others who share with the meeting, I recall, as a another, our spiritual community, are worshipping at the meeting. strengthened by the mystical bonds good rule of thumb, a quote attrib- we have nurtured, and prepare to face Often, in deeply gathered meet- uted to Albert Einstein: “I like to the world and let our lives speak. ings, nothing breaks the silence. But keep things as simple as possible. But sometimes a Friend will receive a not any simpler.” Edward Eisenstein (eisenstein@ message that requires vocal ministry umd.edu) is an investigator at The meeting is over when one the Institute of Bioscience and and will feel that it must be shared member, appointed as clerk, stands Biotechnology Research and a with those present. Do I ever receive and shakes the hand of another. We faculty member of the Fischell Department of Bioengineering a message? Certainly. But sometimes then gather in friendship, sharing at the University of Maryland. He is a member of I think it is meant only for me, and updates in our lives and hearts, and Sandy Spring Monthly Meeting of the Religious sometimes I think it isn’t ready to talk to newcomers who doubtless Society of Friends.

JANUARY 2019 ASBMB TODAY 45 THE WELLNESS ISSUE For many college students, hunger can ‘make it hard to focus in class’ By Michelle Andrews Kaiser Health News

s students return to campus this winter, many will hunger for A more than knowledge. Up to half of college students report that they were either not getting enough to eat or were worried about it, according to published studies. “Food insecurity,” as it’s called, is most prevalent at community col- leges, but it’s common at public and private four-year schools as well. Stu- dent activists and advocates in the education community have drawn attention to the problem in recent years, and the food pantries that have sprung up at hundreds of schools are perhaps the most visible sign. Some schools are also using College, Community and Justice. “I find, are working and receiving finan- the Swipe Out Hunger pro- want to know that they’re address- cial aid, but still struggling with food gram, which allows students to donate ing high food prices on campus and insecurity,” Broton said. their unused meal plan vouchers, or taking steps to ensure no student goes Adding to the stress is the fact swipes, to other students to use at hungry.” that while tuition and fees continue campus dining halls or food pantries. Part of the disconnect may stem to rise, financial aid hasn’t kept pace. Those “free dining passes have from a misperception about what In the 2017-18 school year, after given me chances to eat when I today’s students are really like, said accounting for grant aid and tax ben- thought I wouldn’t be able to,” one Katharine Broton, an assistant efits, full-time students at two-year student wrote to the program. “I used professor in educational policy and colleges had to cover $8,070 in room to go hungry and that would make it leadership studies at the University and board on average, while those hard to focus in class or study. [The of Iowa who has published research at four-year public institutions faced passes] really helped my studying and on food and housing insecurity in an average $14,940 in room, board, may have helped me get my GPA up.” colleges. Many of them don’t fit the tuition and fees. Pantries and food passes are good profile of a “typical” student who Anti-hunger advocates credit stu- band-aids, but more systemwide solu- attends a four-year institution full dents with both sounding the alarm tions are needed, advocates say. time and doesn’t have a job, Broton about hunger on campus and in some “If I’m sending my kid to college, said. Rather, about 40 percent of stu- cases offering ingenious solutions. I want more than a food pantry,” dents today are working in addition Rachel Sumekh, who founded the said Sara Goldrick-Rab, professor of to going to school, and nearly 1 in 4 Swipe Out Hunger program with higher education policy and sociology are parents. friends at UCLA several years ago, at Temple University in Philadelphia, The juggling act can be hard to said they wanted to do something who founded the Hope Center for maintain. “Most of the students, we useful with the unused credits from

46 ASBMB TODAY JANUARY 2019 the meal plans that they were required Canedo said a key focus last fall regular cooking demonstrations. But to buy. The program now counts 48 was to enroll eligible students in what Canedo said he’s particularly schools as participants, and Sumekh CalFresh, the California version of proud of is a 15-week nutritional said in the past year they’ve seen a the federal Supplemental Nutrition science course that students can take “dramatic” increase in the number of Assistance Program(SNAP), formerly that teaches them about healthy colleges that are reaching out to them known as food stamps. eating, prepping food, budgeting about getting involved. Under federal rules, students gen- and grocery shopping, among other The University of California, erally must work at least 20 hours a things. Some of those skills can help Berkeley, is part of Swipes, as the week to qualify for SNAP, something students learn to manage their money program is known. It’s one element many cannot manage. But states have and food to get them through their in a multipronged effort that targets flexibility to designate what counts as time at school without running short. students who may need extra support employment and training programs, This article was originally published to meet their basic housing, food and said Elizabeth Lower-Basch, direc- on Kaiser Health News, a nonprofit other needs, said Ruben Canedo, a tor of income and work supports at news service covering health issues. It is university employee who chairs the CLASP, an anti-poverty advocacy an editorially independent program of campus’s basic needs committee. (He organization. In California, for the Kaiser Family Foundation, which is also co-chairs a similar committee for example, students who participate not affiliated with Kaiser Permanente. all 10 UC campuses.) in certain educational programs at According to a survey of Berke- school are eligible for CalFresh. ley students, 38 percent of under- “That’s our first line of defense,” graduates and 23 percent of graduate Canedo said. “Students are being students deal with food insecurity awarded about $192 per month.” at some point during the academic For students who don’t qualify for Michelle Andrews (andrews.khn@ year, Canedo said. The school targets CalFresh, the school sponsors a paral- gmail.com) is a writer for Kaiser particular types of students, including lel food assistance program that also Health News. Follow her on Twitter those who are first-generation college- provides benefits. @mandrews110. goers, parents, low-income or LGBT. There’s a food pantry that offers

Pulse points: Healthy hearts Researchers at the Centers for Disease Control and not implemented. For those reasons and others, the Prevention and Agency for Healthcare Research and CDC and Centers for Medicare & Medicaid Services Quality project that there will be about 16.3 million launded the Million Hearts initiative. The initiative cardiovascular events and upwards of $173.7 billion brings together state and federal agencies and private- in hospitalization costs between 2017 and 2021 if sector partners to prevent 1 million cardiovascular interventions in clinical settings and communities are events by 2022.

JANUARY 2019 ASBMB TODAY 47 THE WELLNESS ISSUE Chronic pain after trauma may depend on your stress gene By Sarah Linnstaedt

lmost every person in because cortisol and another the world will expe- stress hormone called A rience at least one adrenaline have been shown traumatic event, such as a car to sensitize peripheral nerves crash, an assault, war combat directly, which enables or a natural disaster, during cortisol to signal pain in the their lifetime. Many will absence of nerve injury. For endure more than one. this reason, it is vital for our Most people recover bodies to regulate cortisol lev- from a traumatic incident, els carefully and to resolve the but a substantial percentage stress response quickly and develop chronic problems, PUBLIC DOMAIN effectively. including post-traumatic This ball-and-stick model represents a molecule of cortisol, known as the stress symptoms, depression “stress hormone.” Cortisol and adrenaline have been shown to sensitize and chronic pain. peripheral nerves directly, which enables cortisol to signal pain in the absence Regulating Chronic pain? Isn’t pain of nerve injury. the stress hormone caused by nerve injury? Not always. Chronic pain can collision. We collected blood samples Our bodies have natural develop and is quite common after from more than 1,500 such individu- regulators of blood cortisol levels. Typically, a protein called the glu- trauma exposure. This might seem als and assessed their DNA and their cocorticoid receptor, or GR, binds surprising given the fact that many pain levels six weeks after the car to cortisol that is released after stress traumas involve little or no tissue crash. exposure and causes cells to alter damage. activities of the immune system and I am a geneticist and molecular Trauma, then pain brain. But another protein called biologist studying predictors and FKBP5 also can manipulate cortisol mediators of chronic pain and other Before I go into details about this study, let’s brainstorm how chronic levels by binding GR and preventing chronic neuropsychiatric conditions it from binding cortisol. pain might develop after trauma. that develop after a traumatic experi- If FKBP5 levels are high, that If we know how pain develops, we ence. I am particularly interested in sequesters the GR and prevents the can find treatments to prevent its understanding the biological reasons GR from binding and lowering blood onset. And by preventing the onset why some individuals are more vul- cortisol levels. Consequently, levels nerable to chronic pain than others. of chronic pain, we eliminate the of cortisol in the blood can rise and Based on previous findings from need to use addictive and potentially potentially cause harm by binding our research group and others, my deadly opioids. nerve endings and causing pain. colleagues and I hypothesized that Exposure to traumatic events Previous studies have shown that a individual genetic variation affects causes our stress system to activate. person’s genes can influence relative who develops pain and who recovers This stress system sends signals levels of these proteins. after trauma exposure. To test this between the hypothalamus in the Based on this knowledge, our hypothesis, our group at the Institute brain, the pituitary gland and the group hypothesized that the ability for Trauma Recovery, led by Samuel adrenal gland, ultimately resulting of FKBP5 to regulate cortisol and McLean, enrolled individuals in a in the release of cortisol, commonly potentially affect pain levels might study of European-Americans and known as the “stress hormone.” originate in our DNA. We tested African-Americans who had been Cortisol is a critical link between this hypothesis using data from our involved in a traumatic motor vehicle trauma and chronic pain. This is more than 1,500 car crash survivors.

48 ASBMB TODAY JANUARY 2019 Importantly, these individuals experi- to FKBP5 levels than the cortisol lev- The exact folding of the RNA sec- enced trauma but did not have bone els of individuals carrying the FKBP5- ondary structure differed depending fractures or tissue injury. TT variant, who have less pain. on whether the FKBP5 gene con- We chose motor vehicle collision The common TT gene variant tained the TT variant or the TG/GG as our trauma exposure because it is causes less cortisol to build up in the variant. Using RNA structural model- common and highly traumatic, and blood and less pain. The rare TG and ing called SHAPE, we showed that we can capture data in the immediate GG variants cause cortisol levels to the RNA structure varied significantly aftermath of the traumatic incident. surge, and this can trigger chronic in the region of the miR-320a bind- Physicians in emergency departments pain. ing site, such that miR-320a could across the country helped us enroll bind in the presence of the protective individuals and collect blood from variant but could not bind efficiently them so that we could measure DNA, The effect in the presence of the risk variant. RNA, microRNA and hormone on microRNA binding Therefore, in people with the TG levels. This was important because for or GG genetic variants, the variant We wanted to find the molecu- this study we wanted to understand causes the FKBP5 RNA to fold into a lar mechanism through which this how all of these types of molecules secondary structure that inhibits miR- genetic variant alters FKBP5 and are related and how their composition 320a silencing of FKBP5. This dis- related cortisol levels. Our first can vary from one individual to the inhibition leads to increased FKBP5 next. clue was that the gene variant we levels and increased post-traumatic were studying is located in the chronic pain. 3ˈuntranslated region, or UTR, of the Overall, this recent discovery by Our pain and our genes FKBP5 messenger RNA. The 3ˈUTR our group suggests a way that humans Our group discovered that which contains many regulatory elements can develop chronic pain following genetic variant of the FKBP5 gene that control the amount of protein trauma exposure without experienc- a person carries is predictive of how produced from a gene. One such type ing tissue injury. It also highlights much post-traumatic chronic pain of regulatory element is a microRNA a gene involved in the development that individual will experience follow- binding site. of post-traumatic chronic pain that ing motor vehicle collision. microRNAs bind to mRNA, usu- could be a promising new target for Our study of car crash survivors ally in the 3ˈUTR region, and silence drug therapies. And it proposes a showed that rare variants TG and GG the bound genetic message. Humans mechanism through which this gene in the stress response gene FKBP5 have more than 2,000 different is regulated naturally. increase vulnerability to developing microRNAs, which bind to mRNA This last point can help us in our chronic pain. through specific base pairing. Our quest to discover specific types of Both African-American and Euro- group and others have shown that therapeutics, because, for instance, if pean-American individuals carrying microRNAs such as miR-320a and we didn’t want to try to target FKBP5 at least one copy of the less common miR-15 can bind FKBP5. Therefore, directly, we could mimic the action variants FKBP5-TG or FKBP5-GG we examined the genetic sequence of this naturally occurring regulatory experienced more pain than the indi- surrounding the FKBP5 gene variant mechanism. Our work suggests that viduals carrying only the more com- we had shown to be associated with with such a potential therapeutic, we mon FKBP5-TT variant. (We all have post-traumatic chronic pain and could preferentially treat individu- two copies of every chromosome, so found a predicted miR-320a site just als with the DNA variant that causes we can carry two different versions or over 100 nucleotides upstream of the more pain. variants of the same gene.) variant. A version of this article was We then wanted to know how With more than 100 nucleotides published in The Conversation these variations affect the stress separating the genetic variant and website under a Creative Commons response and subsequent chronic the potential miR-320a binding site, license. Read the original article at pain. it was clear that the genetic variant theconversation.com. We knew that individuals with the did not influence microRNA bind- less common variants FKBP5-TG or ing directly in the same way seen in a FKBP5-GG are more likely to experi- previous study. However, in collabora- ence pain after trauma exposure. We tion with Alain Laederach’s group at predicted that in these individuals, the University of North Carolina at Sarah Linnstaedt (Sarah_ FKBP5 regulation of cortisol would Chapel Hill, we determined that the [email protected]) is be abnormal. We measured cortisol in genetic variant influenced the ability an assistant professor of anesthe- these individuals and found that their of the FKBP5 RNA to fold into a siology at the University of North cortisol levels were higher with respect secondary structure. Carolina at Chapel Hill.

JANUARY 2019 ASBMB TODAY 49 ESSAY Why aren’t there quality controls for antibody research? One of science’s most helpful tools gives an alarming number of false results By Daniel Bojar

any people know antibod- M ies as our bodies’ safeguard against infections. They keep us healthy by recognizing surface features on bacteria or viruses and alerting the immune system: attack! But they also play a crucial role in life science research. Their ability to recognize exactly one protein makes them ideal precision tools for detection, quantification and, in some cases, even treatments. Of course, that’s only true if the anti- bodies do what they’re supposed to. Bad biological substances such as poor-quality antibodies are major gering $28 billion wasted every year ity of commercially available antibod- drivers of scientific studies that can’t due to irreproducible preclinical ies or evaluations by third-party insti- be reproduced. research. tutions before commercial availability. Reproducibility is one of the gold standards of sound science — to be The quality of everyday research As these unreliable preclinical studies, considered trustworthy, a lab’s results substances — an issue that seems partly caused by poor-quality anti- have to be repeatable by others. But fundamentally mundane — impedes bodies, distort entire scientific fields around 36 percent of all research that the progress of medicine and costs and endanger the lives of citizens rely- has been flagged as irreproducible is every one of us dearly, financially as ing on future health care, distributors caused by bad biological substances, well as personally. Currently, there of commercial antibodies have to take making up a good third of the stag- are no official standards for the qual- action by imposing stricter quality

50 ASBMB TODAY JANUARY 2019 tioned their results, an obvious next A good third of the staggering $28 billion wasted each step would have been a clinical trial year on irreproducible preclinical research is caused by bad to test whether early detection with this novel biomarker led to a better biological substances. patient outcome. People could have died from the error, as the detection of cancer wouldn’t have happened standards. protein from the pancreas, CUB and at an early stage but at a later stage Two studies that comprehensively zona pellucida-like domains protein when the cancer protein CA125 was investigated the quality of commonly 1, or CUZD1, which seemed to reli- present. used antibodies tell a disconcerting ably indicate the presence of pancre- Tackling an abstract problem such story. In the first, published in 2010 atic cancer. as the reproducibility of preclinical in the journal Nature Structural & To determine elevated levels of research is notoriously hard, as action- Molecular Biology by the group of CUZD1, they used a commer- able procedures are not immediately Jason D. Lieb located at the Uni- cial testing kit, an enzyme-linked obvious. One approach is to apply versity of North Carolina at Chapel immunosorbent assay, or ELISA. practical solutions to the much more Hill, all 246 of the commonly used Briefly put, in an ELISA, an antibody tangible root causes of this prob- antibodies in the field of DNA-bind- specific for the target protein, such as lem. Poor-quality antibodies are one ing protein modifications were tested. CUZD1, binds to the target protein, of these root causes. So what can we do about it? Of these, 25 percent bound multiple and then a second antibody (specific Every link in the chain of the great targets instead of the one that they for the first antibody) coupled to human endeavor of research has to were supposed to do. Four antibod- an enzyme is added. The amount of play its part to achieve improvement. ies were perfectly specific — to the enzyme then is measured by, say, a Manufacturers of antibodies need to wrong protein. In the second study, color change induced by an enzy- implement more stringent quality published in 2008 in Molecular & matic reaction. From this the initial standards, testing their antibodies Cellular Proteomics by the labora- amount of CUZD1 can be inferred. with multiple methods. These quality tory of Mathias Uhlén at the Royal Commercial availability from a major standards ideally should be set by an Institute of Technology in Stockholm, distributor of laboratory substances independent organization (at least Sweden, researchers tested the quality typically indicates standardization and partly consisting of scientists) that of around 6,000 of the most com- reliability, which is why it usually is would certify the antibodies prior to monly used commercial antibodies. preferred to a self-made solution. their usage. Funding organizations The results were dismal; less than But something was rotten in the should demand this antibody quality half of the antibodies were sufficiently state of biomarker detection. When standard prior to the start of a project, specific for their supposed target Diamandis and his team investigated and editors as well as reviewers of sci- protein. whether their ELISA truly recognized entific journals should demand them Eleftherios Diamandis, a can- their protein of interest (something after the end of a project. cer researcher at the Mount Sinai most researchers would never attempt We should demand an improve- Hospital in Toronto, Canada, is to do with a purportedly reliable ment in the groundwork for clinical one researcher who fell prey to this commercial product), they found trials, starting with mandatory quality widespread issue. He just wanted the horrible truth: Their expensive controls of commercial antibodies. to contribute to the fight against product did not detect CUZD1 at We all entrust our lives and health to pancreatic cancer. As in practically all. Instead, it measured the cancer these quality standards. every type of cancer, early detection protein CA125. This essay was originally published in is key, as it can increase the five-year No wonder it presented a good August on Massive Science survival rate from 5 percent up to 20 biomarker for cancer — it liter- (massivesci.com). percent. What better way to detect ally was cancer. A poor-quality cancer early than by a biomarker, a antibody in the commercial ELISA Daniel Bojar (daniel.bojar@bsse. molecule whose presence in unusual kit cost the Diamandis lab around ethz.ch) is a doctoral student in the department of biosystems amounts indicates cancer, measur- $500,000 and many months of hard science and engineering at ETH able by a quick blood test? He and work. And worst of all, only a hair’s Zurich. Follow him on Twitter his collaborators found a promising breadth away: If they hadn’t ques- @daniel_bojar.

JANUARY 2019 ASBMB TODAY 51 EDUCATION Catalyst conversation workshop provides tools faculty can use By Ann Aguanno

never liked workshops. Starting in graduate Feedback I school and continuing Participants in the March workshop were asked to describe something they through my postdoc and early learned and, if they were presenters, something they hoped others learned from faculty positions, I attended their presentations. workshops on lab techniques, I learned some important strategies Scientific literacy is an important and for improving student learning, such mentoring undergraduates and integrated part of critical thinking skills, as how to strategically use pre-lecture including interpretation and representa- teaching strategies. The goal or pre-lab quizzes, as well as using tion of scientific data; problem solving was often unclear or not aligned augmented reality as another way to using quantitative skills; evaluation of with the workshop’s title, the study protein structure. We also discussed scientific information and sources; recog- how to work on math skills in our classes participants were unengaged, nition of evidence to support hypothesis; and how to encourage crossover between the activities lacked guidance biology and chemistry topics to enhance understanding of research design; and and direction and, in the end, I learning. making justifications, predictions and took very little home with me. I hope that the workshop participants conclusions based on quantitative data. This began to change when came away from my presentation with —Yufeng Wei, Seton Hall University I joined the American Society some new ideas about how to present the links between DNA and protein struc- for Biochemistry and Molecular ture, as well as the impact of mutation I enjoyed hearing about the innova- Biology and got involved in a on protein structure and human disease. tive practices other faculty were using series of workshops organized I presented some possible lab exercises in their classrooms. Since lots of us are by the Educational and Profes- that could be used as a substitute for finding similar challenges as we try to “wet lab” exercises. sional Development Committee employ active learning practices, it is —Tricia Melloy, and held over a five-year period Fairleigh Dickinson University good to have a chance to hear about that focused on concept-driven some works in progress to get suggestions teaching strategies in biochem- I learned that ideas and reflections and share ideas. I have been developing a course-based istry and molecular biology. As take on more pixels and color when they are shared with others. It helped me undergraduate research, or CURE, a participant and eventually to explain more fully my thoughts and project for a nonmajor’s lab and talked a host and organizer, I finally ideas when I shared with colleagues. about some aspects of this that have been saw what a workshop could be My presentation was on a pre- and rewarding and some that have been — an engaged group of faculty post-test on threshold concepts in challenging. I hope that for other faculty biochemistry, and I have students with from diverse institutions work- who are developing or plan to develop varying chemical backgrounds in my CUREs, it gave them ideas for things ing together to improve student class. I hope people saw that student to try and things to avoid, and also the learning in the molecular life learning is not just about how many willingness to try a good idea that will sciences. previous classes a student has taken but engage students even if there are some When those workshops how deeply they learned about these abstract topics. kinks still to work out. concluded a few years back, —Kelly Keenan, —Amy Springer, University of the steering committee of the Stockton University Massachusetts Amherst ASBMB Student Chapters, of

52 ASBMB TODAY JANUARY 2019 which I was member, recognized that faculty still looked to the society for More conversations a collaborative experience where best The ASBMB and La Sierra University will host a Catalyst Conversations teaching practices could be explored. for Undergraduate Educators on Feb. 24 in the Troesh Conference Center The steering committee decided to on the La Sierra campus in Riverside, California. offer a new series of education work- Educators will exchange ideas about teaching practices in biochemistry shops that would build on the model and molecular biology and navigating the research landscape in the under- and success of those organized by the graduate environment. EPD Committee. In March, we hosted the first in The session themes are as follows: this new series of faculty development • Research at a PUI: Challenges, opportunities and funding, led by Jessica Bell, University of San Diego workshops called Catalyst Conversa- • BMB for a new generation: Concepts and assessment, led by tions for Undergraduate Educators. Marvin Payne, La Sierra University Hosted by Montclair State University • Developing NSF funding for your undergraduate research, a in New Jersey and funded by the working lunch and discussion led by Christopher Meyer, Califor- ASBMB, the event included a dozen nia State University, Fresno chalkboard talks, each focusing on a • CURE: Theory and implementation, presented by Ellis Bell class activity or pedagogy approach, and Joseph Provost, both from the University of San Diego followed by general discussion. Pam Mertz of St. Mary’s College of Participants will also have an opportunity to give short chalk talks, share instructional materials, and discuss implementing new ideas into Maryland, Celeste Peterson of Suffolk their own teaching and research. University, Quinn Vega of Montclair State University and I organized the To register or submit an abstract for a chalk talk (you do not need to workshop. Both ASBMB members submit an abstract to participate), go to asbmb.org/catalystconversion. and nonmembers were invited, with a maximum of 25 participants to ensure n ease of collaboration and networking. Participating faculty, mainly from The ASBMB and the University of Wisconsin−La Crosse will host a East Coast colleges and universi- Catalyst Conversation for Undergraduate Educators within the North Central Region on March 16 at the Myrick Park Center in La Crosse, ties, explored the use of the primary Wisconsin. literature in the classroom, innovative approaches to lab activities, strategies The session themes are as follows: for teaching core concepts and the • Best practices in science lab building design, led by Todd use of computational and bioin- Weaver and John May formatics sources as teaching tools. • Career planning for the molecular life science major, led by With handouts to help synthesize Basudeb Bhattacharyya each presentation — including the • Strategies to develop an inclusive undergraduate research lab, led by Daniel Grilley and Kelly Gorres activity’s objective, implementation, • Applying to graduate school for the molecular life science assessments and potential challenges major, led by Basudeb Bhattacharyya and Todd Weaver — each participant walked out of the workshop with tools in hand. The final session will give faculty at primarily undergraduate institu- tions an opportunity to share teaching materials and discuss best practices

Ann Aguanno (aaguanno@mmm. in biochemistry and molecular biology education. edu) is a professor of biology, chair of the department of natural Both workshops are free and include a continental breakfast and catered sciences and a recruiter at Mary- lunch. Email questions to Stephanie Paxson at [email protected]. mount Manhattan College.

JANUARY 2019 ASBMB TODAY 53 Committing for more than one night By Adriana Bankston

often have many things on my mind — and I I usually do my best work — at odd late-night hours. Snuggled on the couch with familiar music or a movie in the background, I can focus on detailed tasks and big questions. Work defines me, brings me joy, fulfills me and is often my refuge from the rest of the world. So it’s no surprise that when I found work that I enjoyed and could pursue freely, I jumped on it. I was volunteering at the Future of Research, a nonprofit, on a proj- ect researching postdoc salaries, which grew into and likely already felt bad that I was raining. I was tired; it had been a long an interest in studying the postdoc working as a volunteer — somewhat day, and I could barely keep my eyes position as a whole. I happily could ironic, since we were advocating for open at times. I drank lots of coffee. pursue this topic no matter the time better postdoc pay. We used the postdoc salary work as of day (or night). I frequently found But I could see the potential for a case study, and as I wrote about it, myself reading, just for fun, National this book chapter to increase transpar- I realized how much this work meant Academies’ reports on postdocs and ency around the postdoc position. So, to me. I remember thinking how other publications on the state of the instead of having the intended effect, valuable volunteer work can be. I felt research enterprise. Gary’s statement made me realize how validated; the book chapter symbol- Realizing that this was more than a committed I was already becoming to ized the larger potential to create fleeting interest, I decided to ask our postdoc advocacy. I didn’t care what change by volunteering, by just show- executive director, Gary McDowell, if time it was; I just knew I had to work ing up and committing to a cause. I could contribute to a book chapter on this book chapter. If someone like The more I wrote, the more fun it he was writing on postdoc reforms. me, who had been through postdoc became. I never felt any writer’s block, When I asked him on a Friday training, didn’t advocate for postdocs, and I just continued writing without afternoon, he replied, “I don’t want to who would do it? realizing what time it was. I enjoyed commit you.” I remember sitting the following the tremendous teamwork and com- We would need to work intensely Thursday night at the desk in my mitment we both had to this crazy on the chapter to submit it before office, covered by a blanket as I often deadline. the deadline. Gary is a nice person am when writing. It was probably We divided up the work pretty

54 ASBMB TODAY JANUARY 2019 much 50-50, and while Gary would going, and I kept writing. I gained I went to bed utterly exhausted say I had the harder task (a detailed new appreciation for the work’s but elated. This night elicited a lot section about our data), I watched in importance as well as for Gary’s abil- of emotions. I felt appreciated and amazement as he framed the begin- ity to inspire enthusiasm. His dedica- valued for the work and realized that I ning of the chapter in a larger context tion was contagious; I couldn’t stop had to be more involved with Future and detailed recommendations from working on it either. At that moment, of Research, because it had become a several National Academies’ reports. it was clear that I had developed a large part of who I was as a person. And there was something symbolic passion for this topic. So in a sense, I committed for about two former postdocs writing At around 3 a.m. on Friday, we more than one night. I committed to this chapter late at night on why post- were still going, and neither of us something life-changing in terms of docs should be treated better. planned to sleep until it was done. I discovering my professional direction. While writing, I was relaxed; I quickly wrote a conclusion. To date, That late night working on the chap- knew that I had found what I was it’s still one of the best things I’ve ever ter solidified my passion for postdoc looking for, and I was soaking it in. written, because by then I could see advocacy, and I was satisfied to have At the same time, I felt random bursts both the broad vision of the chapter completed something so large. of excitement because I couldn’t and the details, and I knew exactly I wondered later whether it’s believe I’d been given the opportunity what I wanted people to take away unusual to be so engrossed in work. to work on this topic. from it. I was surprised that Gary Why did writing a book chapter until I realized how well we worked trusted me to write this section and 5 a.m. seem normal and make me so together. We were collaborating on a made only a few small edits. I remem- happy? When I knew I’d found my pretty significant write-up in addition ber thinking what a great privilege it passion and was working toward a to a previous publication. Gary was was to work with someone who gave larger goal, that kept me motivated, very good with the vision and the big me intellectual freedom and trusted even when I could barely stay awake. picture, while I filled in the details my judgement. And after you’ve had a night like and pointed out holes in the argu- We proofread the entire document that, you commit for more than one ment. It was a pretty good combina- and made more edits. At about 4:30 night. tion of talents, and it was fun. a.m., Gary told me he was going As I felt myself almost falling to take care of the references and I Adriana Bankston (abankston81@ asleep, I wondered how Gary just should go to sleep. I said, “No, I will gmail.com) is a former bench sci- entist with a passion for improv- couldn’t and wouldn’t stop this not sleep until this is done.” ing training and policies for junior advocacy work, no matter what time We finished about 5 a.m., and scientists. She is a policy activist of night. That motivated me to keep Gary submitted the chapter. with the Future of Research.

The 10 commandments of grantsmanship

Peter Kennelly, a professor of biochemistry at Virginia Tech, recently gave a seminar on grantsmanship. He put together his top-10 takeaways in a biblical format. Aspiring grant writers might want to cut this out and post it prominently.

JANUARY 2019 ASBMB TODAY 55 56 ASBMB TODAY JANUARY 2019