Trouble with testosterone test

Annual Meeting Special Section

CONTENTS

NEWS FEATURES PERSPECTIVES

2 14 36 EDITOR’S NOTE THE TROUBLE WITH PUBLIC AFFAIRS It’s time THE TESTOSTERONE TEST Are postdocs still invisible? 3 18 38 PRESIDENT’S MESSAGE MASTERS OF PHYSIOLOGY MINORITY AFFAIRS Celebrating serendipity 38 Exemplifying Sewer’s commitment to diversity 22 40 Diversifying the scienti c 4 THE 2017 ANNUAL MEETING NEWS FROM THE HILL workforce with IMAGE 23 Expand your scienti c horizons A lot at stake 42 Cultivating a focus on diversity 29 e spotlight is on you as a community 30 Promoting lifelong learning 5 34 Advance your careers, grad students MEMBER UPDATE 44 and postdocs! TRANSITIONS 35 Reminders for the 2017 ASBMB 7 Undergraduate Poster Competition Wrestling with life RETROSPECTIVE 7 Roscoe Owen Brady (1923–2016) 14 48 9 Roger Tsien (1952–2016) Experts are OPEN CHANNELS grappling with what constitutes 10 high testosterone 42 blood levels in elite NEWS track and eld Blind wins Tabor award women athletes. for work on nuclear lipids 11 JOURNAL NEWS 11 Blocking potato blight’s ability 22 to set up shop 12 Infant gut microbes’ thirst for milk proteins 13 How a single-cell marine organism makes fatty acids

12 44 TRANSITION STATES

NOVEMBER 2016 ASBMB TODAY 1 EDITOR’S NOTE

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY It’s time By Angela Hopp OFFICERS COUNCIL MEMBERS Natalie Ahn Squire J. Booker President Victoria J. DeRose Wayne Fairbrother. recently saw a documen- Ben Corb, in his “News Steven McKnight Karen G. Fleming tary on Net ix about from the Hill” column, Past President Rachel Green uncontacted tribes in writes about the count- Jennifer DuBois Susan Marqusee I Jared Rutter down to a new American Secretary the rainforest on the border Celia A. Shier of Brazil and Peru. Several presidency. I know that my Toni M. Antalis Michael Summers Treasurer factors — including hunger, blood pressure rises every ASBMB TODAY EDITORIAL drug tracking and log- time I think about how EX-OFFICIO MEMBERS ADVISORY BOARD ging — are forcing some close Election Day is. Tick Natalie Ahn Charles Brenner tock. Tick tock. Steven McKnight Chair tribespeople out of their Co-chairs, 2017 Annual Michael Bradley sanctuary. Leaving the for- e “Retrospective” Meeting Program Floyd “Ski” Chilton est is fraught with danger, articles we publish almost Committee Cristy Gelling as each new contact could every month are always a Cheryl Bailey Peter J. Kennelly Chair, Education and Rajini Rao result in illness or deadly good reminder that our Professional Development Yolanda Sanchez misunderstanding. time here is limited. We Committee Shiladitya Sengupta have one about Roscoe Brady and one Carol Shoulders e lm shows how those tribes- Daniel Raben about Roger Tsien in this issue. Chair, Meetings Committee people who requested assistance (by ASBMB TODAY e cover story is about the test Takita Felder Sumter law, they must make the rst contact) Chair, Minority Aairs Angela Hopp are adapting to their new circum- used to measure testosterone in Committee Executive Editor, [email protected] stances. ough they still live in the women athletes. How much testoster- omas Baldwin Rajendrani Mukhopadhyay forest, they get resources and care one does a sprinter need to trim a few Chair, Public Outreach Managing Editor, seconds o her race? e answer, as Committee from a protective agency. e men [email protected] said they are glad to have clothes and the story explains, isn’t simple. Wesley Sundquist John Arnst Chair, Public Aairs Science Writer, medicine. Pots and pans, the women You’ll also see a lot of information Advisory Committee [email protected] agree, are handy. about the ASBMB annual meeting. Amnon Kohen Valery Masterson But what I’ve been thinking about, ough the meeting is months away, Chair, Publications Designer, Committee [email protected] possibly because I’m just not com- the abstract-submission deadline is Lila M. Gierasch Ciarán Finn pletely buying it, was the suggestion close: Nov. 17. On top of that, unlike Editor-in-chief, JBC Web Editor, in past years, there will be no exten- c [email protected] by an anthropologist that the tribes- A. L. Burlingame sions. Do not be late! Allison Frick people are terrible at keeping time. Editor, MCP Media Specialist, ey use the sun, he said, but don’t Meanwhile, time plays a big role Edward A. Dennis [email protected] know their ages. I won’t quibble with in an essay by Zachary A. Kemmerer, Editor-in-chief, JLR Barbara Gordon a graduate student who is competing William L. Smith Executive Director, any of that here. I’m no expert. Editor-in-chief, JLR [email protected] However, this idea — of not living on NBC’s “American Ninja Warrior.” by the clock — is on my mind. Per- He wrote: “A clash of wills played out haps that is why, as I ipped through in those 1,800 seconds as we tried to break each other down.” For information on advertising, contact Pharmaceutical this issue of ASBMB Today, I saw the Media Inc. at 212-904-0374 or [email protected]. signicance of time everywhere. I hope that you will be blessed with In her column, Natalie Ahn, the a bit of uninterrupted peace to read president of the American Society for the issue. (But do not put o submit- Biochemistry and Molecular Biology, ting your meeting abstract!) www.asbmb.org/asbmbtoday writes about serendipity. If something PRINT ISSN 2372-0409 happens at the right time, it’s seren- Angela Hopp ([email protected]) Articles published in ASBMB Today reect solely dipitous. If it happens at the wrong is the communications director the authors’ views and not the ocial positions of for the ASBMB and executive the American Society for Biochemistry and Molecular time, it’s usually a real bummer. (Cue: Biology or the institutions with which the authors editor of ASBMB Today. Follow are aliated. Mentions of products or services are Alanis Morissette.) her on Twitter at twitter.com/ not endorsements. ASBMB Public Aairs Director angelahopp. ©2016 ASBMB

2 ASBMB TODAY NOVEMBER 2016 PRESIDENT’S MESSAGE Celebrating serendipity By Natalie Ahn

n September, the Lasker Founda- major roles of every breakthrough. peutics for HCV. Diverse individuals tion awarded the 2016 Albert For example, Semenza’s detection from many countries and of many I Lasker Basic Medical Research of a faint hypoxia-induced band on races and ethnicities, in both academic Award to Gregg L. Semenza, Peter J. an EMSA autoradiograph enabled and private settings, made key contri- Ratclie and William G. Kaelin Jr. for the biochemical purication of butions in each scientic team. the discovery of the HIF1 transcrip- HIF1, which launched the molecular Recognition for Alberts especially tion factor and the mechanistic steps mechanism for hypoxia signaling. is appreciated by the ASBMB, given in the universal pathway explaining Rice’s chance discovery of a 3’ segment the special regard that our society has the cellular response to hypoxia. e missing in the HCV genome and the for science education. roughout his 2016 Lasker–DeBakey Clinical Medi- invention of HCV minigenome rep- career, Alberts has led the way as an advocate for teaching critical-thinking cal Research Award went to Charles licons by Bartenschalger were critical skills to students, from his landmark M. Rice, Ralf F.W. Bartenschlager and to the development of a cellular model textbook “Molecular Biology of the Michael J. Soa for research charac- of HCV infection. And it was Alberts’ Cell” to his achievements as president terizing the molecular biology of the accidental discovery that DNA binds of the National Academy of Sciences hepatitis C virus, the development of tightly to cellulose that enabled him to in promoting curiosity and inquiry- in vitro systems for HCV replication, purify and reconstitute DNA replica- based methods for STEM undergrad- and the development of therapeutics tion proteins and realize that the repli- uate and K–12 education. to treat and in some cases cure chronic some is a macromolecular machine is advocacy impacts everyone, HCV infection and liver disease. And capable of simultaneous leading and at all levels — here in Colorado, my the 2016 Lasker–Koshland Special lagging strand synthesis. colleague Amy Palmer has overhauled Achievement Award in Medical Sci- e perspicacity to pursue initial freshman chemistry to emphasize ence went to Bruce Alberts for his leads, often murky and obscure, and concepts-based learning with transfor- fundamental discoveries of the protein the tenacity to follow the science to mative results. components and mechanism of DNA discover their full meaning are key to No matter what we do as scientists, replication and for his leadership in creating new knowledge. part of our mandate certainly must science education and international Also essential to their success were include instilling students with the collaborations in science teaching and the investigators’ interdisciplinary curiosity, self-condence and passion learning. e American Society for strategies, with chemistry, biochem- for scientic inquiry that will prepare Biochemistry and Molecular Biology, istry and molecular biology at their them for their own serendipitous which proudly counts four of the win- core. Essential as well were collabora- moments to come. ners as members, heartily congratu- tion and information sharing between lates all recipients. many labs, including the knowledge Natalie Ahn (natalie.ahn@ Importantly, serendipity and the ow in both directions between basic colorado.edu) of the University of Colorado, Boulder, is president of ability to glean deep insights from research and private sector R&D labs the ASBMB. hints and unexpected ndings played that was critical for successful thera-

Learn more about the 2017 meeting on page 22.

www.asbmb.org/meeting2017

NOVEMBER 2016 ASBMB TODAY 3 NEWS FROM THE HILL A lot at stake By Benjamin Corb

ith Election Day just a few famously has said, “Don’t tell me what However, the gridlock isn’t likely to be days away, here are my sug- you value. Show me your budget, unraveled. anks to senatorial rules W gestions for what to watch for and I’ll tell you what you value.” It’s and our hyperpartisan politics these in the outcomes and their possible the U.S. Congress that controls the days, a simple majority in the Senate impact on the scientic community. purse strings. e political makeup of isn’t likely to in uence policy all that Obviously, the big headline grabber the 115th Congress really will in u- much. In order to move from debate is going to be who will be the 45th ence research budgets. A Republican to voting on legislation, in most cases, president of the United States. In majority in the House following the a supermajority of 60 senators must previous columns and in numerous election, for sure, will keep the House vote to end debate. It is not likely that postings on our science policy blog focused on cuts in spending. However, we will see a supermajority for any (policy.asbmb.org), we have shared the previous Congress was supportive party after the election. what a Donald Trump or Hillary Clin- to the research community (particu- With research agency budgets on ton presidency might look like. e larly the NIH) and made important the line and mandatory spending caps president will help to shape some of attempts to support biomedical set to drop again, thanks to the 2011 the scientic priorities of the country. research. Unfortunately, proposed Budget Control Act, there is a lot of Will the next president take as warmly increases to the NIH budget remained work to do. ere is a lot at stake for to science as President Barack Obama tangled in conservative scal policies, the research community. e elec- has, or will science, and advisers like making increases possible but dicult. tion night results will give us our rst those in the Oce of Science and A Democratic majority in the House glimpse into how some key policy Technology Policy, nd a diminished likely would lead to drastic changes in debates may play out in Washington role in the next administration? scal policy, which could benet the in the next two years until the mid- Key cabinet-level and agency-head research community. A Democratic term elections. appointments to watch will be the majority in the House is also not nominees for directing the National particularly likely. Institutes of Health, the National Sci- Should Democrats take back Benjamin Corb (bcorb@asbmb. org) is the director of public ence Foundation and the OSTP. control of the Senate, which they affairs at the ASBMB. Follow him e president can set the country’s lost in 2015, it’s likely that we’ll see on Twitter at twitter.com/bcorb. agenda. Vice President Joe Biden more support for research budgets.

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

4 ASBMB TODAY NOVEMBER 2016 MEMBER UPDATE

ASBMB members Farber Cancer Institute and Harvard tribute groundbreaking research. e Medical School and Peter J. Ratclie award, presented annually on an alter- win Lasker awards from the University of Oxford and nating basis within the areas of natural In September, Francis Crick Institute. e three sciences, engineering, life sciences and the Albert and physician-scientists received the award the humanities, carries a prize of about Mary Lasker for their role in discovering the path- $840,000 to support future research. Foundation way that eukaryotic cells use to adapt announced the to and sense changes in oxygen avail- Harrison wins Vallee recipients of the ability. Kaelin is organizing a scientic RICE 2016 Lasker symposium about the pathway at Foundation award Awards. is the annual meeting in April at which Melissa Har- year’s awards Ratclie will speak. rison, an assistant recognize six ASBMB member Bruce M. Alberts professor in the researchers who at the University of California, San department of made outstand- Francisco, received the Lasker–Kosh- biomolecular ing contributions land Special Achievement Award chemistry at the to physiology in Medical Science. In addition to HARRISON University of BARTENSCHLAGER and virology, as devising tools for understanding the Wisconsin–Mad- well as one scien- mechanisms cells use to copy DNA, ison, is one of the recipients of the tist who helped Alberts has used his clout as a scientist 2016 Young Investigator Awards from pioneer the and a president of the U.S. National the Vallee Foundation. elds of DNA Academy of Sciences to improve sci- Harrison’s research explores the fac- replication and ence education. tors that drive transcriptional activa- science educa- Written by John Arnst tion of the zygotic genome. Her work SEMENZA tion. Among the focuses on exploring the fundamental recipients for the Bassler wins molecular mechanisms by which the awards were four embryonic genome is remodeled rap- members of the research award idly to create the pluripotent state. American Society e Alexander Awarded by the Vallee Founda- for Biochemistry von Humboldt tion, the Young Investigator Awards and Molecular Foundation and recognize independent investiga- Biology. the Max Planck tors who have conducted signicant ALBERTS ASBMB Society have research early in their scientic careers. members Charles named Bonnie e award provides recipients with M. Rice of Rockefeller University and BASSLER Bassler, a Howard $250,000 in discretionary funding to Ralf F. W. Bartenschlager of Heidel- Hughes Medi- be used for biomedical research. berg University received with e cal Institute investigator at Princeton Written by Erik Chaulk Lasker–DeBakey Clinical Medical University, one of two recipients of the Research Award for growing the hepa- Max Planck Research Award. Schepartz is new chief titis C virus in cultured cells. Michael Bassler is being honored for her K. Soa of Arbutus Biopharma shared role in discovering that bacteria com- editor of Biochemistry the prize with Rice and Bartenschlager municate with one another through Alanna for utilizing this system to test and chemical signaling molecules, a Schepartz, a pro- invent candidate drugs, which cul- process known as quorum sensing. fessor of chemis- minated in the development of the Her discovery shows the potential for try and molecu- hepatitis-C drug Sovaldi. application to a wide variety of elds lar, cellular and Gregg L. Semenza of the Johns including medicine, agriculture and developmental Hopkins University School of industry. SCHEPARTZ biology at Yale Medicine, an ASBMB member, was Since 2004, the Max Planck University, is the one of the recipients of the Albert Research Award has recognized two new editor-in-chief of Biochemistry, Lasker Basic Medical Research Award. internationally renowned scientists, a peer-reviewed journal published by Semenza won the award along with one who works in Germany and the American Chemical Society. She William G. Kaelin Jr. of the Dana– another who works abroad, who con- CONTINUED ON PAGE 6

NOVEMBER 2016 ASBMB TODAY 5 CONTINUED FROM PAGE 5 more online material in this third in Ireland, Ines Mandl became inter- edition. ested in science, studying chemistry at took the helm in August. Schepartz’s Books on bioinformatics tradition- the University of Cork. research covers biochemistry, cell ally deal with topics such as gene After the war, Mandl and her biology and chemical biology with discovery and database searching. husband moved to America, where a focus on macromolecular interac- In “Evolutionary Bioinformatics,” she obtained her master’s degree in tions. “With her broad knowledge Forsdyke explores “new bioinformat- 1947 and her Ph.D. in chemistry in of biochemical research, extensive ics,” considering genomes as informa- 1949 from the Polytechnic Institute of relationships in the community, and tion channels through which multiple Brooklyn. Mandl subsequently joined outstanding editorial experience, I am forms of information have passed Columbia University as a chemist and condent that the journal will excel through the generations. research associate before becoming a under her leadership and remain one Forsdyke is professor emeritus of full professor. of the most-cited titles in the eld,” biochemistry at Queen’s University in In 1972, she founded the journal said James Milne, senior vice president Canada. He has published more than Connective Tissue Research, for which of ACS Journals Publishing Group in 200 papers as well as several books. she served as editor-in-chief until her a press release that announced Schepa- retirement in 1986. rtz’s appointment. In memoriam: Ines Mandl Regarded as a leading expert in the Written by Kamalika Saha Ines Mandl, study of enzymes and elastic tissue, professor of Mandl received numerous honors Forsdyke releases biochemistry at throughout her career, including the third edition of textbook Columbia Uni- Carl Neuberg Medal and the Garvan versity, passed Medal. e third edi- away Aug 5. She In 2000, Mandl helped establish tion of Donald MANDL was 99. the Ines Mandl Research Foundation Forsdyke’s book Born Ines as a means of supporting students “Evolutionary Hochmuth in Vienna on April 19, studying chemical engineering or Bioinformat- 1917, she married Hans Mandl at the biomedical or biological sciences. ics” is available. age of 19. When Germany invaded e foundation serves as a legacy FORSDYKE Originally pub- Austria in 1938, the two ed and of Mandl’s profound impact on the lished in 2006, eventually settled in Cork, Ireland, for scientic industry. the book has been supplemented with the duration of World War II. While Written by Erik Chaulk

6 ASBMB TODAY NOVEMBER 2016 RETROSPECTIVE Roscoe Owen Brady (1923–2016) By Sarah Spiegel & Richard L. Proia

t is with sadness, honor and deep istry. For more than 50 years, he respect that we note the passing remained at the intramural program Iof Roscoe Owen Brady, a pioneer of the National Institutes of Health, in biomedical research, on June 13. rising to the rank of chief of the devel- He was a world-renowned scientist opmental and metabolic neurology whose eorts have beneted many branch. It was here that he developed patients suering from inherited a team of scientists and clinicians to disorders of lipid metabolism. Brady’s investigate the causes and treatment of early scientic work helped form the the sphingolipidoses, most of which basis of the biochemistry of fatty acid, have profound neurological manifesta- lipid and sphingolipid metabolism. tions. As a quintessential physician-scientist, At that time, these disorders, he expanded this research into the aecting primarily children, were not biomedical arena and developed diag- well studied, and their causes were nostic tools for patients and carriers unknown. After initiating studies to as well as treatments for a devastating increase the basic understanding of class of lysosomal storage diseases sphingolipid metabolism, Brady and known as the sphingolipidoses. ese Roscoe Brady his team set out to nd the underlying are severe, often fatal, disorders at the University of Pennsylvania defects in several sphingolipidoses, a caused by genetic defects in lysosomal School of Medicine, he was a fellow line of research that ultimately led to sphingolipid catabolism. His pioneer- in the department of medicine and a the development of targeted therapies. ing therapy still is being used clinically postdoctoral fellow in the department eir pioneering research elucidated today, and the approach now has been of physiological chemistry, where he the biochemistry, the enzymatic basis extended for the treatment of several collaborated with Samuel Gurin to for the metabolic defects of sphin- other lysosomal storage diseases. study the metabolism of long-chain golipidoses such as Gaucher disease, Brady’s more than six decades of fatty acids, lipids and sterols using Niemann–Pick disease, Fabry disease work was admired widely throughout radiolabeled precursors. In addition and Tay–Sachs disease. the world as evidenced by the numer- to helping elucidate various metabolic In their most well-known work, ous honors he received, including the pathways, precursors and enzymes Brady and his team discovered that Lasker Award, the National Medal involved, these studies formed the Gaucher disease, the most common of Technology and Innovation from foundation for Brady’s later seminal LSD, is caused by the accumulation President George W. Bush, and mem- work in uncovering the metabolic of the sphingolipid glucosylceramide. bership in both the U.S. National defects and the enzymes involved in Brady’s team developed in vitro assays Academy of Sciences and the National sphingolipidoses. that they used to demonstrate that Academy of Medicine. In 1953, Brady was called to active patients with Gaucher disease have a Born in Philadelphia in 1923, duty and served in the U.S. Navy deciency in glucocerebrosidase, the Brady received his bachelor’s degree Medical Corps. He then was recruited enzyme that breaks down glucosylce- from Pennsylvania State University to the U.S. National Institute of ramide. ey found a similar motif and his M.D. from Harvard Medical Neurological Disorders and Blindness underlying the other sphingolipidoses, School in 1947. He then returned (later renamed the National Institute an inherited deciency in a lysosomal to Philadelphia, where he interned of Neurological Disorders and Stroke) enzyme that, when absent, results at the University of Pennsylvania in Bethesda, Maryland, as a section in the accumulation of its sphingo- Hospital. Over the next four years chief in the laboratory of neurochem- CONTINUED ON PAGE 8

NOVEMBER 2016 ASBMB TODAY 7 CONTINUED FROM PAGE 7 tating, and often lethal, consequences tenacious eorts, which culminated in of these incurable diseases. the development of the rst eec- lipid substrate. ese included Fabry After determining the enzymatic tive treatment for a lysosomal storage disease, an alpha-galactosidase A deciency in Gaucher disease, in disease, have improved markedly the deciency leading to the accumulation 1966, Brady recognized and then lives of thousands of Gaucher disease of the sphingolipid Gb3, and Nie- began pursuing a novel treatment patients and paved the way for similar mann–Pick type A and B, caused by option: enzyme replacement therapy. treatment designs for a growing list acid sphingomyelinase deciency and In 1973, he and his team isolated a of other lysosomal storage diseases, the accumulation of sphingomyelin. few milligrams of glucocerebrosidase beneting even more patients and giv- is work inspired numerous scien- from human placenta and showed that ing hope to families aected by these tists throughout the world to unravel administration of the puried enzyme formerly untreatable disorders. the biochemical causes of other related into two Gaucher patients reduced Brady was a groundbreaking lipid disorders. the level of glucosylceramide stor- biochemist as well as a committed In the late 1960s, Brady’s group clinician working to improve the lives developed additional diagnostic tests age in liver and plasma. Although it took decades with many experimental of patients with lysosomal storage to determine whether individuals were diseases. ough his shining example asymptomatic carriers of the autoso- twists and turns to develop, in 1991 they received approval from the U.S. lives on, his presence will be missed mal recessive sphingolipidosis genes sorely by his friends and colleagues. as well as for prenatal testing. ese Food and Drug Administration for breakthroughs helped introduce the the use of their puried glucocerebro- modern era of genetic counseling, in sidase as a Gaucher disease treat- Sarah Spiegel ([email protected]) at ment. With the advent of molecular the Virginia Commonwealth University School of which Brady actively and insightfully Medicine and Richard L. Proia ([email protected]) at participated. ese issues were all the cloning technology, the therapeutic the National Institute of Diabetes and Digestive more important in the case of the enzyme subsequently was produced and Kidney Diseases wrote this retrospective. It sphingolipidoses because of the devas- by recombinant methods. Brady’s first appeared in the Journal of Lipid Research. The Do-Over If you could erase a part of your life and do it over again, which part of your life would that be? What would you do differently?

For an essay series in 2017, ASBMB Today is asking its readers to send in essays about do-overs. Maybe you regretted your choice of college. Maybe you trusted someone who let you down. Perhaps you wonder what would have happened if you had picked that other research project. Whatever it is, be honest and true.

Essays must be unpublished and between 500 to 1,000 words. Submissions can be sent to http://asbmbtoday.submittable.com/. Submit under “e Do-Over.” Deadline: Dec. 1. Please include in your essay a title, complete contact information and an author bio of no more than 50 words.

8 ASBMB TODAY NOVEMBER 2016 RETROSPECTIVE Roger Tsien (1952–2016) By Scott LaFee & Heather Buschman

oger Tsien, co-winner of adventurer, the pathnder, the the 2008 Nobel Prize in free and soaring spirit. Courage, R chemistry and professor determination, creativity and of pharmacology, chemistry and resourcefulness were hallmarks of biochemistry at University of his character. He accomplished California, San Diego, School of much. He will not be forgotten.” Medicine for 27 years, died Aug Roger Yonchien Tsien was born 24 in Eugene, Oregon. He was Feb 1, 1952 in New York City, 64. the third son of immigrant par- Tsien’s work literally illumi- ents. He was a scientist from early nated science. With Osamu Shi- childhood, sketching out chemis- momura, an emeritus professor at try experiments as an 8-year-old the Marine Biological Laboratory in a notebook now kept in the in Woods Hole, Massachusetts, Nobel Museum in Stockholm, and Martin Chale, a professor of Sweden. His rst Boy Scout merit biological sciences at Columbia badge was in chemistry. PHOTO COURTESY OF UC, SAN DIEGO In 1968, at the age of 16, he University, Tsien helped scientists Roger Tsien peer within living cells and organ- took rst prize in the prestigious isms as never before, earning not just GFPs have become a fundamental Westinghouse Science Talent xture in life-sciences labs around the the 2008 Nobel Prize but scores of Search for high school seniors. He world, allowing researchers to look subsequent awards and accolades. attended Harvard College, graduating into cells or whole animals, to watch Tsien, Shimomura and Chale summa cum laude in chemistry and molecules interact in real-time and ask collaborated to discover and develop physics in 1972, and then earned his questions once thought impossible. green uorescent protein, derived doctorate in physiology in 1977 at the Tsien was never content to rest from the jellysh Aequorea victoria, as University of Cambridge in England. upon his Nobel laurels. He wanted his a new and soon-indispensable tool. Before going to UC San Diego in research to be clinically relevant. As a 1989, he worked as a research assistant Shimomura identied the crucial distinguished Howard Hughes Medi- in Cambridge and then as a junior jellysh protein and revealed that it cal Institute investigator, Tsien sought professor at UC Berkeley. glowed bright green under ultraviolet better to visualize cancer in other Tsien was a member of the light. Chale showed how it could be ways — or maybe treat it. He and Institute of Medicine, the American used as a biological marker. Combin- colleagues have designed U-shaped Academy of Arts and Sciences, the ing his deep skills in chemistry and peptides able to carry either imaging U.S. National Academy of Sciences, biology, Tsien found ways to make molecules or chemotherapy drugs to and the Royal Society of London. GFP glow more brightly and consis- targeted cancer cells. Among his awards were the Gairdner tently; then he created a full palette His lab created a new generation Foundation International Award, the of uorescent proteins that scientists of fast-acting uorescent dyes that American Chemical Society Award could use to track dierent cellular optically highlight electrical activity for Creative Invention, the Heineken processes at the same time. in neuronal membranes, deciphering Prize for Biochemistry and Biophysics, “I’ve always been attracted to how brain cells function and interact. the Max Delbruck Medal in Molecu- colors,” Tsien told the San Diego And using a modied plant protein, lar Medicine, the Wolf Prize, and the Union–Tribune in 2008. “Color helps he and colleagues created a new type Keio Medical Science Prize. make the work more interesting and of genetic tag visible under an electron endurable. It helps when things aren’t microscope, allowing researchers to see going well. If I had been born color- life in unprecedented detail. Scott LaFee is the director of media relations and blind, I probably never would have “He was ahead of us all,” said Heather Buschman is a senior public information gone into this.” Tsien’s wife, Wendy. “He was ever the officer at UC San Diego Health.

NOVEMBER 2016 ASBMB TODAY 9 NEWS Blind wins Tabor award for work on nuclear lipids By Mariana Figuera Losada

In August, Raymond Blind of Vanderbilt Uni- versity won the Journal of Biological Chemistry/Herb Tabor Young Investigator Award at the 2016 Phospho- lipid Signaling in Cancer, Neurodegeneration and Car- diovascular Disease Confer- ence in Steamboat, Colorado. Blind, who has demonstrated that lipid-signaling enzymes can activate genes, received the award from JBC Associ- ate Editor George M. Car- man from Rutgers University. In addition to being part of cell membranes, lipids, in particular a pool of nonmembrane associ- ated nuclear lipids, also can act as signaling molecules. Researchers have shown that lipid-signaling enzymes are involved in several cancers and in the progression of diabetes. Using genomics, biochemistry and structural biology, Blind and colleagues showed that the phospho- lipid-binding domains found on lipid-signaling enzymes PHOTO COURTESY OF RAYMOND BLIND may sense the presence of Raymond Blind nuclear phosphoinositides Holly Ingraham at the University of can Cancer Society. Besides doing and induce gene activation. ese California, San Francisco, where he research, Blind is also an educator discoveries, when coupled to work developed the work recognized by the who works to support young under- published by others, suggest that Tabor award. In 2015, Blind became represented scientists as evidenced by nuclear phosphoinositides may act an assistant professor at Vanderbilt his postdoctoral experience teaching similarly to chromatin histone modi- University School of Medicine in the biochemistry at Muhimbili School of cations by reversibly regulating gene division of endocrinology, metabolism Medicine in Dar es Salaam, Tanzania, transcription. and diabetes, with appointments in to help improve East African health Blind, a native of Bualo, New the departments of pharmacology and care in collaboration with UCSF York, completed his Ph.D. on nuclear biochemistry. Global Health Sciences. receptor transcriptional activation Blind’s research is funded by the Mariana Figuera Losada in Michael Garabedian’s labora- National Cancer Institute, the Vander- ([email protected]) is an tory at New York University. For bilt Diabetes Research and Training associate scientist at Albert his postdoctoral training, he joined Center, and the Vanderbilt–Ingram Einstein College of Medicine. the laboratories of Tom Scanlan and Cancer Center through the Ameri-

10 ASBMB TODAY NOVEMBER 2016 JOURNAL NEWS Blocking potato blight’s ability to set up shop By John Arnst

True to its name, Phy- and interfering with its tophthora infestans is a ability to perform its normal destroyer of plants. (In cellular function. Greek, “phyto” means For this JBC paper, the “plant”; “phthora” means investigators wanted to “ruin.”) Most notorious explore further the interac- for the Irish potato fam- tion. e researchers rst ine, the pathogen also can determined the crystal struc- target other members of the ture of PexRD54. ey then Solanaceae family of plants, focused on the protein’s dis- which includes tomatoes, ordered C-terminus, a region spices, weeds, herbs and of around 10 to12 amino vines. While a global, potato- acids that the researchers based famine isn’t imminent, knew bound directly to the the pathogen still causes ATG8 molecule, and used about $6 billion of dam- X-ray crystallography to age to crops of the versatile show the complex. tubers each year, according With the components to the American Phytopatho- of the linked region well logical Society. dened, they then turned to In a Paper of the Week a low-resolution technique recently published in the A potato showing the characteristic signs of blight. known as small-angle X-ray scattering to get an image Journal of Biological for their own benet,” he says. “But of the surface of the entire bound Chemistry, researchers in the U.K. the plants have also evolved ways of protein complex. ey were then able report detailed crystallographic infor- recognizing the presence of these mol- to dock the separately dened features, mation about the interaction between ecules as foreign objects inside cells including the individual proteins and one of the pathogen’s eector proteins and then are able to mount a response the interacting region, into the protein and one of the potato’s proteins. ey to those molecules directly.” surface, forming a complete image of ultimately hope to exploit this result Baneld and his colleagues at the the interaction. to engineer plants that are resistant to Sainsbury Laboratory Norwich and With this interaction now well the pathogen. the Imperial College London, with characterized, Baneld and his col- “If you can understand interactions whom he collaborated on the cur- leagues hope to engineer the ATG8 and then modify the host–cell target rent paper, previously had character- protein to ignore the presence of the in such a way that it retains its original ized the PexRD54 eector protein of PexRD54 eector from the pathogen. function in the plant, but is no longer Phytophthora infestans and veried “If we can engineer that molecule able to be acted on by the eector, its interaction with the host cells’ in the plant cell to no longer be per- that might push the balance of the ATG8 proteins. eir characterization turbed by the presence of the eector, disease progression in the favor of the appeared in the journal eLife earlier clearly the pathogen has then lost plant,” says Mark Baneld at the John this year. the benet of delivering that eector Innes Centre, the senior author on the ATG8 is a protein located in the to host cells,” Baneld said. “It goes paper. membranes of eukaryotes’ autopha- all the way to delivering it, but it no According to Baneld, the eec- gosomes, which are double-layered longer has the activity that it’s evolved tors, which tend to be small proteins membrane organelles involved in to have.” that bind to specic host proteins and delivering damaged cellular structures modify their activity, often possess to the lysosomes for degradation, John Arnst ([email protected]) dual activities for host and pathogen. among other functions. PexRD54 is ASBMB Today’s science writer. Follow him on Twitter at “One of them is to work on behalf of works on behalf of the pathogen by twitter.com/arnstjohn. the pathogen to manipulate host cells binding to this protein in host cells

NOVEMBER 2016 ASBMB TODAY 11 JOURNAL NEWS

Infant gut microbes’ thirst for milk proteins By John Arnst

Milk is a complicated liquid. pairs enrolled in the uni- Among its ingredients, which include versity’s Foods for Health lactose, lipids, free oligosaccharides Institute Lactation Study. and proteins, the free oligosaccharides ey then isolated and perform the essential prebiotic roles cultured the dominant of stimulating the growth of benecial bacterial subspecies of Bi- bacteria and preventing harmful bac- dobacteria longum from the teria from binding to epithelial cells in stool samples. B. longum, the gut. In a paper recently published in aggregate, accounts for in Molecular & Cellular Proteomics, up to 90 percent of the researchers at the University of Cali- gut microbiota in milk-fed fornia, Davis, report that the bacteria infants. in infants’ guts are also capable of e investigators fed the digesting glycoproteins. bacteria the milk glycopro- e researchers previously had teins extracted from the thought of glycoproteins as a source of breast milk. After demon- carbohydrate-bound amino acids that strating that the bacteria were only consumed by the infant, were breaking down the gly- “but it turns out that parts of it, par- coproteins, Lebrilla’s group ticularly the oligosaccharide, may also obtained a detailed prole be feeding the microbiota,” explains of the oligosaccharides that Carlito Lebrilla, the paper’s senior had been released from the author. “It has a dual use here — to glycoproteins by subjecting give nutrition to the host, but also to the fecal samples to tandem glycoprotein-cleaving endoglycosi- enhance the microbiota.” mass spectrometry. e researchers dase. e researchers also noted that e new paper is a unication of were surprised to nd the presence an exogalactosidase, BLNG_00015, sorts for the researchers, who have of degraded N-glycans in the fecal was present in another dominant B. focused on the oligosaccharide com- samples. N-glycans had been hypoth- longum subspecies and capable of ponents of human milk for a number esized as digestive targets because they degrading glycoproteins with a termi- of years and had an interest in the were present in breast milk, but until nal monosaccharide galactose residue. interactions between the microbiota now, they had not been observed post- is, Lebrilla explains, is evidence and oligosaccharides. digestion. e nding by Lebrilla and of the specicity of the microbial While there was a good deal of colleagues indicates that the bacterial enzymes for the glycoproteins. research involving the milk oligosac- species act upon the oligosaccharide Future work for Lebrilla and his charides, Lebrilla explains, he and his components of the compound, which colleagues will include examining the colleagues hadn’t scrutinized what suggests the sugar moieties on breast milk proteins that are being deglyco- happens after the milk oligosaccha- milk glycoproteins can fuel the gut solated, exploring why certain milk rides interact with the microbiota. microbiome. protein concentrations seem to confer “is is one of the rst times we’ve A collaborating group led by greater protection against stunting in looked … in deep structural detail at David Mills at the university’s Foods infants than others, and investigating what happens to the actual com- for Health Institute then sequenced how the microbiota change in humans pounds as they go through” the gut, the bacteria to get a comprehensive from a milk-oriented micobiota to a he says. look at which enzymes were respon- plant-based microbiota as we age. To determine the eects of diges- sible for breaking down the milk tion on the oligosaccharide portions oligosaccharides and when they were John Arnst ([email protected]) of glycoproteins in breast milk, the expressed, as well as their specicity. is ASBMB Today’s science writer. Follow him on Twitter at researchers collected breast milk and ey found that one of the subspecies twitter.com/arnstjohn. stool samples from mother–infant of B. longum contained genes for a

12 ASBMB TODAY NOVEMBER 2016 JOURNAL NEWS How a single-cell marine organism makes fatty acids By Courtney Chandler

Omega-3 fatty acids have uses enzymes to build the been heralded as crucial to VLCPUFAs sequentially our health and well-being. from a small base molecule Humans and other mam- instead of making modica- mals cannot synthesize tions to existing PUFAs. these fatty acids on their What about the aerobic own. Organisms capable of synthesis pathway that also synthesizing these impor- was shown to be present in tant molecules, such as a the same species? “Although single-celled marine organ- both aerobic and anaerobic ism called raustochytrium, pathways for biosynthesis are of interest for their use coexist in the raustochy- as dietary supplements. In a trium, the aerobic pathway recent paper published in the is not complete,” explains Journal of Lipid Research, Qiu. is pathway has Dauenpen Meesapyodsuk several enzymes that are and Xiao Qiu of the Uni- specic enzymes to build VLCPUFAs ineective. is makes it versity of Saskatchewan in Canada directly from small precursor mol- incapable of generating VLCPUFAs. report the pathway that is responsible ecules, such as acetate. ere is a simple explanation for for the synthesis of these fatty acids in Qiu’s laboratory previously had why both pathways may exist in a spe- raustochytrium. demonstrated the presence of an cies — evolution. “It is believed that Omega-3 fatty acids, which can enzyme involved in the aerobic path- the aerobic pathway is a progenitor be categorized as very long chain way in a species of raustochytrium system, while the anaerobic pathway is polyunsaturated fatty acids, known as called raustochytrium sp. 26185. later acquired by the species,” explains VLCPUFAs, are important com- ey also recently had observed the Qiu. e anaerobic pathway is more ponents of cell membranes. ey coexistence of the anaerobic pathway ecient at producing VLCPUFAs. As time went on, components of the less also form products that are involved in the same organism. “is prompted eective aerobic pathway could have in blood circulation, metabolism, us to investigate the function and become unnecessary and been lost. neurotransmission and in ammation. importance of the two pathways for VLCPUFAs are important for our Mammals can obtain omega-3 fatty the biosynthesis of VLCPUFAs in the health, so it is important to under- acids from foods such as salmon and species,” explains Qiu. stand how they are produced in the walnuts or from dietary supplements. Qiu and Meesapyodsuk investi- organisms we rely on to supplement raustochytrium has been used as gated the pathways by analyzing the our diets. is knowledge could in a commercial source for these healthy important genes of each in E. coli turn help engineer similar systems fatty acids. Scientists knew that these or yeast, which essentially served as that produce VLCPUFAs. Qiu says, organisms produced large quanti- a blank slate to isolate the raus- “Metabolic engineering of VLCPU- tochytrium genes and examine their ties of VLCPUFAs but didn’t know FAs in heterologous systems (could) function. ey used gas chromatogra- exactly how they did it. provide an alternative source of these phy coupled to mass spectrometry to Organisms are thought to synthe- fatty acids for human and animal analyze fatty acid structure; they used size VLCPUFAs through two possible consumption.” pathways. e rst is the aerobic path- feeding experiments to track VLCP- way. It requires oxygen and involves UFA formation. lengthening and adding double bonds e data “show that the anaerobic Courtney Chandler (cochandl@ umaryland.edu) is a biochemistry to existing fatty acid intermediates. pathway is responsible for the VLCP- Ph.D. candidate at the University e second is the anaerobic pathway. UFA biosynthesis in the raustochy- of Maryland, Baltimore. It does not require oxygen and uses trium,” states Qiu. raustochytrium

NOVEMBER 2016 ASBMB TODAY 13 FEATURE

The trouble with the testosterone test While the test does what it should, using a ‘baseline’ level of testosterone becomes problematic when women compete in track and eld events By John Arnst

14 ASBMB TODAY NOVEMBER 2016 lite athletes tend to be a self- endogenously produce 10 times more selecting group for physical testosterone than women. E outliers. Someone naturally has “We know that testosterone is of a better shot at rising to the top if he importance for physical performance or she has an uncommon advanta- due to several eects,” says Angelica geous trait, whether it’s massive feet Hirschberg at the Karolinska Institu- or a higher percentage of fast-twitch tet and Karolinska University Hospital muscle bers. But when it comes in Sweden. Hirschberg served as the to testosterone, a steroid hormone ocial gynecologist for the Swedish that controls the development and Olympic committee for 15 years. maintenance of male characteristics, “Testosterone has some direct the issue of how the molecule aects anabolic eect on muscle tissue. It women athletes has dogged profes- stimulates increase in protein synthesis sional sports. and the increase of muscle growth,” While men and women tend to she says. produce dierent amounts of testos- Hirschberg adds that testoster- terone, the dierences aren’t black one also increases the production of and white. “ere are very distinct oxygen-binding red blood cells by dierences between males and females upregulating the hormone erythro- in terms of how much androgen is poietin. Erythropoietin stimulates present within a body, but, yes, there proliferation and dierentiation of red are variations within that spectrum,” blood cell precursors, which lead to says Fred Schaufele at the University increased athletic performance. Men of California, San Francisco, School also tend to produce more red blood of Medicine. “Everybody is on all cells and have larger hearts and lungs. dierent parts of that spectrum, e connection between the including females with high levels of performance gap and testosterone androgens.” levels is the reason testosterone can be So how does a governing body exploited as a performance-enhancing overseeing elite athletes establish substance in sports. It’s also why who can compete as men and who the use of exogenous testosterone is can compete as women? e answer banned in sports. isn’t clear. In July 2015, the Court of But the androgens produced natu- Arbitration for Sport in Lausanne, rally in the body can be a headache in Switzerland, ruled that the Interna- sports circles, because their levels can tional Association of Athletics Federa- vary over a range between individuals tions, which oversees track and eld, (see “e passport and the prostate”). had to suspend use of its controversial For the T-test that the IAAF intro- “T-test” for two years. e test, which duced in 2011, which set the upper is based on the measurement of testos- boundary for female testosterone terone levels in blood, was introduced levels in blood at 10 nanomoles per in 2011 as the most recent method in liter, the goal was to gure out which a convoluted history of determining athletes could compete against one which athletes could compete against another as women. other women. But the test quickly ran into prob- lems; while 10 nanomoles per liter is many times greater than the aver- Testosterone age concentration of testosterone in and performance women, there are a variety of condi- tions that cause the excess production It’s long been argued that the of androgens. Women athletes with 10- to 15-percent performance gap some of these conditions unexpectedly between men and women in sports is due to the fact that men, on average, CONTINUED ON PAGE 16

NOVEMBER 2016 ASBMB TODAY 15 CONTINUED FROM PAGE 15 the excess hormone to build muscle mass and produce red blood cells due nd themselves being pulled out from to insensitive receptors, the athlete competition. is eligible to compete according to the IAAF’s 2011 rules, says Hirsch- Too much testosterone berg. If women can suppress the high testosterone level by some means, they In 2009, an 18-year-old South also can compete. But other than that, African runner won the 800-meter women with a blood level of 10 nano- sprint at the World Track and Field moles per liter of testosterone were Championships in Berlin. banned from competing in track and “Caster Semenya won with a eld events. (Women who have higher very great margin, and there were than normal levels of testosterone but some accusations that she was not a don’t hit the 10 nanomoles-per-liter woman,” says Hirschberg. “is was level, such as those with polycystic the starting point to develop guide- ovary syndrome, were not aected by lines for severe hyperandrogenism.” the guidelines.) Semenya was subjected to testing, Before the T-test came into play the results of which have not been in 2011 to measure testosterone made public. in blood, athletes with androgen In 2011, the IAAF issued guide- insensitivity typically were agged by lines on female hyperandrogenism, chromosome testing, which looks for which prevent women the presence of the SRY gene on the Y who naturally produce chromosome. at test was introduced more than 10 nano- by the International Olympic Com- moles of testosterone mittee at the 1968 games in Mexico per liter from compet- City and was used to prevent women ing. with Y chromosomes from competing Hyperandrogenisms for nearly three decades. occur when the body In 1992, the IAAF ceased routinely produces excess levels using the chromosome test on all ath- of androgens, such as letes but kept the option to employ it testosterone. Andro- if any suspicions about an athlete’s sex gen insensitivity, the arose. e IOC voted to discontinue most extreme version the practice in June 1999. of hyperandrogenism, is a rare condition that occurs when a person Looking ahead has internal testes and e T-test’s suspension in 2015 XY chromosomes but came as the ruling in Dutee Chand’s is unable to utilize appeal to the Court of Arbitration in the testosterone the Sport. Chand, an Indian sprinter with body produces, which hyperandrogenism, had been banned usually causes them from competing in track and eld to grow and develop events in 2014 by the IAAF’s Indian female characteristics. aliate, the Athletics Federation of ere are excep- India. tions made to the e court determined that there’s 10-nanomoles-per- not enough evidence that athletes with liter rule. In the case hyperandrogenism necessarily have an of complete androgen unfair advantage over their competi- insensitivity, in which tors. According to the court’s ruling, women are unable “we have two years, as more scientic to take advantage of evidence is required to show the

16 ASBMB TODAY NOVEMBER 2016 degree of the advantage if a women liter to 1 nanomole per liter.” has testosterone levels in the male e issue of testosterone levels range,” says Hirschberg. in women track and eld athletes is For some ocials in the global complicated, as proved by the 2016 athletic community, the test’s rein- Olympic Games in Rio. Chand statement, or the establishment of a nished 50th in the 100-meter dash; benchmark of some sort, appears to be Semenya won the gold medal in the an inevitability. 800-meter dash. “I believe some kind of regulation Women athletes will have to wait is necessary, otherwise I don’t think until July for the Court of Arbitra- other athletes will like to compete tion in Sport’s response after the IAAF when you know in advance who will presents the scientic evidence it’s win,” says Hirschberg. been gathering and after experts in Were the T-test to be reinstated in testosterone and performance evaluate two years, Hirschberg notes, testos- the evidence. terone levels can be brought down Until then, the IAAF said in a 2015 to a manageable level in advance of press release, “e IAAF will make no competition. further comments on this subject until “It’s easy to suppress the testoster- those discussions are concluded.” one levels. You can do it by taking oral contraceptives, for instance,” she John Arnst ([email protected]) is ASBMB Today’s science writer. says. “It could be gradual, but within Follow him on Twitter at a couple of weeks you could suppress twitter.com/arnstjohn. from more than 20 nanomoles per

The passport and the prostate Because women don’t have a prostate gland, it was widely believed that they didn’t produce prostate-specic Whether someone’s high testosterone level is caused antigen, says Eleftherios Diamandis at the University of by doping or natural causes can be hard to determine. Toronto and Mount Sinai Hospital in Canada. But, he “One reason that testosterone is more popular among says, “20 years ago, we found that women actually make doped individuals is that they believe that it’s more di- PSA, and this PSA in women is usually made in the cult to discern the exogenous testosterone” in urine tests breast tissue.” for doping, says Anders Rane at the Karolinska Univer- He adds that because the PSA gene is regulated by sity Hospital in Sweden. androgens, “we speculate that women who have hyperan- One of the methods for ensuring that an athlete’s drogenic syndrome will have elevated PSA.” androgens aren’t a byproduct of doping is the World In the past, Diamandis says, it was very dicult to Anti-Doping Agency’s Athlete Biological Passport. e measure PSA levels in women, but recently developed program, which was implemented in 2009, monitors assays have made it possible to detect the protein at athletes’ endocrine and steroid levels year-round. It pro- minute concentrations. In a recent study, he and his vides a record of what an athlete’s normal baseline signals colleagues found that normal women make about 1,000 are for various molecules, including testosterone. femtograms per milliliter of PSA, which is about one “e system tells you, ‘OK, if you’ve naturally got one-thousandth of men’s production. a high testosterone, this is your baseline,’” says Olivier “We were surprised to see that the (women) athletes Rabin, the science director at the World Anti-Doping have lower PSA than normal women who do not exer- Agency. “e anti-doping monitoring takes this into cise,” says Diamandis. “We don’t know the mechanism.” account.” In another study involving women undergoing Another potential method for discerning between hormonal transition therapy, the researchers noticed that exogenous and endogenous sources of elevated testos- testosterone consumption tended to increase PSA levels. terone could be testing for the levels of prostate-specic With this knowledge about PSA levels, Diamandis antigen, a protein produced by the prostate. Elevated lev- says, “this may be a good test for doping, because, if a els in men commonly are used as an indicator of prostate woman takes a steroid, an androgenic steroid, the PSA cancer. levels will go up, in both serum and urine.”

NOVEMBER 2016 ASBMB TODAY 17 FEATURE Masters of physiology By Christie Wilcox

is is an excerpt from Wilcox’s book from animals. Chemists had nearly “Venomous: How deadliest creatures mastered the art of separating vastly mastered biochemistry,” which was dierent types of compounds, such as published earlier this year by Scienti c lipids and proteins, but such methods American/Farrar, Straus and Giroux. didn’t nely separate venom com- e chapter “Masters of physiology” ponents. It was like sorting laundry: opens with a description of the pecu- ey could pull shirts from socks but liarities of the platypus, one of the 12 couldn’t separate based on fabric color venomous mammals, and then delves or distinguish long sleeves from short into the characteristics of venoms and ones. Some venoms have hundreds of why venomous animals invest the eort dierent peptides (small proteins), all into making them. e excerpt below, of which might be soluble in water, which has been edited for length and for example. at means that an style, is the latter half of the chapter and “aqueous fraction,” or subsection of a describes how the analyses of venoms venom separated using water, might have changed over time. contain hundreds of dierent venom compounds, making it impossible to ne of the problems with study- determine if one or many are respon- ing venoms until very recently sible for any activity seen when that O was that we didn’t have very fraction is injected into a mouse. good ways of teasing apart what was Luckily, back in the early 20th present in the crude substances milked century, the Russian scientist Mikhail Tsvet invented a method to separate pigments from plants that came to be known as chromatography, which, with many later variations and rene- ments, has helped current scientists to isolate and identify venom compo- nents. In chromatography, mixtures are dissolved in a uid (referred to as the mobile phase), which is then passed through a structure (the sta- tionary phase) with certain properties. is structure can be simply a column of material through which the solu- tion passes, drawn by gravity, or it can have specic chemical properties that make it “sticky” to particular types of molecules. When the mixture is run through the stationary phase, even small variations in the compounds’ IMAGE COURTESY OF ART RESOURCE “Fight of the Mongoose and the Serpent Armies”, a watercolor depiction of the age-old battle between snake- size, 3-D structure or chemical eaters and their prey. properties cause molecules to travel

18 ASBMB TODAY NOVEMBER 2016 at dierent speeds, allowing scientists to separate venom components on a much ner scale. roughout the 1940s and 1950s, new kinds of chromatography were invented, and what is now known as high performance liquid chroma- tography entered the scene. HPLC, which uses high air pressure instead of gravity to move the solution through a ner-textured column, is now one of the most important techniques in the study of venoms, as it allows scientists to separate venom samples into indi- vidual components. And conveniently, during the mid- 20th century, scien- tists also invented gel electrophoresis for separating molecules of protein, PHOTO BY CHIP COCHRAN DNA or RNA. Gel electrophoresis The speckled rattlesnake has impressive camouflage. uses an electric eld to pull com- lated (from the venom of a Brazilian pounds through a gel by attracting pit viper, Bothrops jararaca) during negatively charged molecules to one this time, as were many other venom end, while the gel’s properties aect compounds. which things will move through it As a part of his Ph.D. thesis pub- more easily, traveling farther in a given lished in 1973, Peter Temple-Smith amount of time. You can imagine how took advantage of the new battery of much faster a needle can be pushed techniques to determine the contents into molasses than a nger can, for and activities in platypus venom. He example, if they were both pressed found at least 10 dierent proteins with the same amount of force. When through electrophoresis and chroma- it comes to proteins, electrophoresis is tography, and isolated the components mostly used to separate based on size, that were lethal in mice from ones giving scientists a rough idea of the that caused convulsions. However, the number of dierent proteins pres- scope of his research was limited, as ent in a venom. It also has become the separation methods and bioassays an invaluable method for determin- still required relatively large amounts ing whether genetic extractions or of venom (Temple-Smith couldn’t amplications were successful, and is complete lethality tests, for example, an absolute requirement in just about because he didn’t have enough venom every lab that studies venom today. to work with). Snakes are easy, as they e modern era of venom research can be milked repeatedly and produce followed on the heels of these two milliliters, and even liters, of venom major advances in separation technol- fairly readily, but many of the other ogy. By the 1970s, labs worldwide groups of venomous animals provide could examine dierent components only 1/1000th or less of the volume of a venom and their individual activi- required to run such tests. ough ties rather than the crude venom as the platypus is capable of delivering a whole, and they began separating upwards of 4 milliliters of venom with out the ones responsible for the most each spur, actually getting that much noticeable venom actions. Capto- raw material is exceptionally dicult. pril—one of the best-selling drugs On average, Temple-Smith and others of all time, used to treat high blood found they could extract only 100 pressure and heart failure—was iso- CONTINUED ON PAGE 20

NOVEMBER 2016 ASBMB TODAY 19 CONTINUED FROM PAGE 19 entists taking a closer look at platypus venom isolated active peptides, two microliters at a time—too little, in dierent proteases and a hyaluronidase those days, for detailed analyses. (enzymes also referred to as venom But soon enough, tests miniatur- “spreading factors” because they cut ized, and better technologies emerged hyaluronic acid, a major component to determine the shape and structure of skin and the connective “goo” of dierent molecules, removing the between cells). ey could even obtain large-volume requirements that had short sequences from some of these hindered progress. Scientists who components, and determine that they made advances in mass spectrometry are similar to snake venom and nuclear magnetic resonance won constituents. Nobel Prizes in chemistry, and for en a new technology completely the rst time, these advances allowed changed the way in which scientists them to deduce the chemical compo- study venomous animals and their sition of larger, more complex com- toxins: genomics. (James) Watson, pounds like those found in venoms. (Francis) Crick, and (Rosalind) Frank- Even small volumes of crude venom lin had deduced the structure of DNA could be evaluated to nd compounds in 1953. e rst sequencing technol- that are responsible for key activities ogy, Sanger sequencing, came about such as reducing blood pressure, shut- in the 1970s followed by a method for ting down nerve impulses, or destroy- amplifying fragments of DNA based ing red blood cells. on their sequence. e rst full gene In the 1990s, several studies picked was sequenced in 1989, and the rst up where Temple-Smith left o. Sci- full non-viral genome (a bacterium) in 1995. In the 20 or so years since, genetics and genomics have proved to be among the most rapidly changing elds in science. High-through- put technolo- gies can now sequence entire genomes in a matter of hours, and new meth- ods are regularly introduced that produce more information in less time for a lower price. It took years and cost millions to sequence the rst human PHOTO BY CHRISTIE WILCOX Komodo dragons are a species of venomous lizards. genome, which

20 ASBMB TODAY NOVEMBER 2016 FIGURE BY BRYAN GRIEG FRY The diversity of hemotoxic venom compounds which disrupt the coagulation cascade. was nished in 2003—and it’s possible single drop of it. Drug companies can that within the next ve to 10 years, build libraries of venom toxins and sequencing an entire human genome search them for ones that might act will cost less than $1,000. as enzymes, or have the potential to When it came to studying venoms, interact with a “target” such as an ion the genetics revolution opened up channel. By combining venom separa- avenues that had never been imagined. tion and component isolation with Scientists could use genes to look genomics, researchers have shifted at evolutionary relationships, and from the study of venoms to venom- determine which species were closely ics. rough such integrated research, related. ey could compare the we have come to know venomous sequences of toxins to other proteins, animals far more intimately than at and begin to understand how venoms any point in history, and we have evolve. And it wasn’t just DNA—sci- learned that their biochemical prowess entists have developed methods of is far more impressive than we ever sequencing ribonucleic acid, the step imagined. in between DNA and proteins, and can determine which genes are being Christie Wilcox is a scientist and expressed. Genomics meant that they an award-winning science writer. could sequence every protein expressed Follow her on Twitter at twitter. in a venom gland to look at the com- com/NerdyChristie. Copyright 2016 Christie Wilcox, reprinted position of a venom even without a with permission of Farrar, Straus and Giroux.

NOVEMBER 2016 ASBMB TODAY 21 ANNUAL MEETING

23 Expand your scientific horizons 29 The spotlight is on you 30 Promoting lifelong learning 34 Advance your careers, grad students and postdocs! 35 Undergraduate Poster Competition

22 ASBMB TODAY NOVEMBER 2016 Expand your scientific horizons

“To succeed in science, you have to learn new strate- that lie within the realm of biochemistry and molecular gies, form new collaborations and see your work from a biology. To those 17 leading scientic researchers, Ahn and fresh angle. At the ASBMB annual meeting, you can meet McKnight have given the freedom to put together their new people in other areas, fertilize your mind with their dream scientic symposia. knowledge and use this to spark new avenues in your own And they have. On the following ve pages are descrip- endeavors.” tions of the 17 scientic symposia that have been brought e quote above comes from Natalie Ahn, president together by these leaders. (e 17th event, devoted to of the American Society for Biochemistry and Molecular antibiotics and antibiotic resistance, is sponsored by the Biology, who wrote it in the President’s Message for the ASBMB Minority Aairs Committee.) October issue of ASBMB Today. Ahn, who also is serv- What this setup means for attendees is that they will ing as a co-organizer of the 2017 annual meeting with the have a veritable smorgasbord of science. From lipid bio- ASBMB’s past president, Steven McKnight of the Univer- chemistry to metabolomics, these symposia showcase the sity of Texas Southwestern Medical Center, is putting those best and the most exciting research endeavors happening words into action. right now in the life sciences. Cutting-edge science from At the next ASBMB annual meeting in Chicago, four all over biochemistry and molecular biology will be made scientic events will run concurrently for two hours available at this one, must-attend conference. Submit your between April 23 and April 26. Ahn and McKnight have abstract for this meeting by Nov. 17. recruited 17 leaders from a wide variety of research areas CONTINUED ON PAGE 24

NOVEMBER 2016 ASBMB TODAY 23 Life at higher resolution: single-molecule and single-cell technologies e biological questions we can answer are determined by the precision of the measurements done by the tools at our disposal. In this symposium, speakers will present the latest in single-molecule and single-cell technologies, which can probe DNA and chromatin processes at higher resolution than ever possible and use DNA as a precision self-assembled material to probe cellular and molecular mechanics. You will get a glimpse of the future of single- molecule biology, which lies in the convergence of emerg- ing technologies, such as protein and genome engineering, DNA origami, genomics, micro uidics and plasmonics, to enable capabilities that are currently unthinkable. — Taekjip Ha, Johns Hopkins School of Medicine and Howard Hughes Medical Institute

Pharmacological manipulation of the HIF pathway CONTINUED FROM PAGE 23 e HIF transcription factor is a master regulator of genes that promote adaptation to hypoxia. Mounting evidence suggests that increasing HIF would be benecial SUNDAY, APRIL 23 in diseases such as renal anemia and regional ischemia, and Biochemistry, physiology and decreasing HIF would be benecial in diseases such as spe- pathophysiology of sphingolipids cic cancers and pulmonary hypertension. First-generation drugs that stabilize HIF have entered the clinic. Recent Lipid biochemistry is experiencing a Renaissance. structural insights have opened the door for the develop- Unprecedented developments in tools and insights are ment of the rst inhibitors that work directly on HIF. is coming to bear on this eld of study and its relevance to symposium will feature talks related to HIF biology and biology and human disease. I am organizing a special group structure and to drugs designed to modulate HIF activity. of international leaders in lipid biochemistry and biology — William Kaelin, Dana–Farber Cancer Institute, Har- who will present the status of their respective domains and vard Medical School and Howard Hughes Medical Institute cutting-edge developments within this eld. Howard Riez- man of Weill Cornell Medical College will discuss links Dynamics of cytoskeletal assembly between amino acid and sphingolipid metabolism and their is symposium will feature research that brings eects on sphingolipid functions in health and resistance to together insights from biochemical analysis of reconsti- anoxia. Timothy Hla of Weill Cornell Medical College will tuted systems, quantitative measurements in live cells and describe studies that support the notion that sphingosine- mathematical modeling to understand cellular mechano- 1-phosphate-binding chaperones modulate sphingosine chemistry. Melissa Gardener at the University of Min- 1-phosphate’s signaling in vascular function in pathophysi- nesota analyzes how microtubule dynamics contribute to the movements of chromosomes during mitosis. Margaret ology. Antonella De Matteis of Telethon Institute of Genet- Gardel at the University of Chicago uses measurements on ics and Medicine will discuss new insights on membrane reconstituted networks of actin laments and myosin to contact sites and advances in approaches to study them. understand the physics of their assembly and force genera- Gregory Fairn of St. Michael’s Hospital, who is receiving tion. Ohio State University’s Marco Sotomayor studies how the Walter A. Shaw Young Investigator Award, will discuss cadherins contribute to mechanotransduction in the ear. subcellular localization and dynamics of lipids. I will pres- My laboratory combines measurements on live cells and ent the structure of neutral sphingomyelinase and discuss mathematical modeling to explain how the contractile ring its roles in the DNA damage response. divides cells during cytokinesis. — Yusuf Hannun, Stony Brook University — omas Pollard, Yale University

24 ASBMB TODAY NOVEMBER 2016 MONDAY, APRIL 24 Partridge from the Max Planck Institute will discuss the New insights into nuclear pathways that can slow the aging process and promote structure and function longevity. Andrew Dillin from the University of Califor- nia, Berkeley, will present how dierent cells and systems Recent developments in our understanding of nuclear communicate to modulate aging. Matt Kaeberlein from organization and gene expression have helped us bet- the University of Washington will discuss how companion ter comprehend the inner workings of the cell nucleus. dogs can help us discover aging therapeutics. I will present Four leaders in this eld will provide critical insights into our work developing the African killish as a new model transcriptional regulation using single-molecule imaging for aging and longevity. approaches, genetic and biochemical approaches to study- — Anne Brunet, Stanford University ing pre-mRNA splicing, the role of the nuclear lamina in nuclear organization and disease, and the role of nuclear retained long noncoding RNAs in cancer biology. Attend- Discovery and development ees will become immersed in the exciting world of nuclear of new enzyme chemistry biology and learn how recent advances in technology have With their ability to catalyze complex reactions at high helped to move this eld ahead at a remarkable pace. rates and with absolute regio- and stereospecicity outside — David Spector, Cold Spring Harbor Laboratory the repertoire of today’s synthetic chemists, enzymes hold unfullled promise to transform the way we make drugs Supramolecular complexes and other high-value chemicals. Eorts to map the path- Proteins associate with one another to form complexes ways by which natural products are constructed continue and perform their activities. Edward Marcotte from the to reveal unmatched enzymatic transformations. ese University of Texas at Austin and I will describe comple- discoveries, coupled with our ability to evolve enzymes in a mentary approaches to the identication of protein- directed fashion, will enable entirely new synthetic routes. complex components, through extensive biochemical Leaders in this area will highlight recent progress toward fractionation of cellular lysate or through in vivo biotinyl- the discovery and evolution of new enzymatic reactions ation coupled to mass spectrometry. ese presentations with potential utility in synthetic chemistry. will highlight the requirement for computational strategies — J. Martin Bollinger Jr., Penn State University to derive the composition of the complexes and dene changes in these complexes after perturbations. e other CONTINUED ON PAGE 26 two presentations will emphasize the complementary nature of mass spectrometry and cryoelectron microscopy to reveal the structural organization of supramolecular complexes. Albert Heck of Utrecht University will discuss advances in mass spectrometry to assist in the structural determination of protein complexes. John Rubinstein from e Hospital for Sick Children will discuss the develop- ment of cryoelectron microscopy and its application to bridge the resolution gaps between more conventional microscopy and the types of high-resolution analyses mostly done by NMR spectroscopy and X-ray crystallog- raphy. — Anne-Claude Gingras, Lunenfeld–Tanenbaum Research Institute at Mount Sinai Hospital

Basis of longevity and age-related diseases Aging is one of the most fascinating mysteries in biology. Old age is associated with a plethora of diseases, including neurodegenerative diseases, metabolic diseases and cancer. is symposium will cover the most excit- ing questions at the forefront of the aging eld. Linda

NOVEMBER 2016 ASBMB TODAY 25 is linked to numerous human diseases. e virulence of pathogens depends on a complex interplay between metal acquisition by the pathogen and immune response by the human host. Understanding molecular mechanisms of metal homeostasis is critical to developing new therapeu- tics, combating microbial infections and even mitigating heavy-metal pollution in the environment. is sympo- sium will highlight recent research at the front lines of this eld. — Amy Rosenzweig, Northwestern University

Biochemical basis of cellular processes Biochemistry continues to be a major tool in our quest to understand the fundamental processes of living organ- isms. Four leading biochemists will demonstrate how classical biochemical approaches, coupled with modern molecular biological and chemical methods, can reveal the molecular mechanisms of several fundamental biologi- cal processes. e processes include cell death, epigenetic CONTINUED FROM PAGE 25 regulation and ghting microbial infections. — Xiaodong Wang, National Institute of Biological Sciences, Beijing TUESDAY, APRIL 25 Organelle trafficking and signaling Glycobiology, glycan receptors is symposium will focus on how various cells ensure and functional glycomics the integrity of organelles. Neurons are highly dier- is symposium will cover the exciting roles of gly- entiated, long-lived cells that depend on autophagy to cans in antibody functionality, infectious diseases, innate maintain homeostasis in response to proteotoxic stress or immunity and organelle biogenesis. Galit Alter from organelle dysfunction. Erika Holzbaur from the University Ragon Institute of Massachusetts General Hospital will describe her work on innate-immunity proling tools and of Pennsylvania will discuss the mechanisms regulating high-throughput antibody glycosylation proling that autophagy in neurons. Navdeep Chandel at Northwestern highlight the immunologic programs driving antibody University will describe how his work has elucidated that glycosylation and function. Her work is paving the way for mitochondria function as signaling organelles for various the rational design of highly eective vaccine strategies and biological processes. Martin Hetzer from the Salk Insti- monoclonal antibodies to prevent infectious diseases, such tute will describe the mechanisms underlying the repeated as HIV/AIDS. Using modern glycomics and microarray rounds of nuclear envelope rupture and repair that have approaches, Richard Cummings from Beth Israel Deacon- been observed in laminopathy and cancer cells. Finally, my ess Medical Center has discovered a wide variety of mam- group studies membrane contact sites between the endo- malian glycans that are required for infections by dierent plasmic reticulum and other organelles. I will discuss pathogens. ese glycans are recognized by both glycan- mechanisms that allow membrane contact sites at the binding proteins as well as pathogen-stimulated anti-glycan endoplasmic reticulum to drive constriction and division of antibodies. Laura Kiessling from the University of Wiscon- other organelles. sin, Madison will describe how glycan-binding proteins — Gia Voeltz, University of Colorado, Boulder function as microbial detectors in innate immunity. I will discuss my group’s structural studies on the glycan-binding Metal homeostasis receptors that are essential for the generation of lysosomes Acquisition, management and delivery of metal ions and are targeted in the treatment of lysosomal storage is a signicant part of metabolism for all domains of life. diseases. Aberrant handling of copper, zinc, iron and manganese — Nancy Dahms, Medical College of Wisconsin

26 ASBMB TODAY NOVEMBER 2016 WEDNESDAY, APRIL 26 low-complexity proteins form protein assemblies that bind New insights in regulated lipid metabolism RNAs and control the formation of germ cells in ies and is symposium will highlight some of the most exciting worms. More recent work has shown that proteins with recent discoveries in the area of lipid metabolism. Russell such characteristics are instrumental in germ-cell formation Debose–Boyd at the University of Texas Southwestern in most, perhaps all, organisms. Low-complexity domain Medical Center will present his recent work regarding proteins with RNA-binding properties control meiosis, the an understudied area in the regulation of cholesterol cell division that produces germ cells, and are critical for metabolism: e regulated degradation of the key enzyme the development of germ-cell characteristics. Talks sched- involved in cholesterol biosynthesis, hydroxymethylgutaryl- uled in this session will address the mechanistic basis for coenzyme A reductase. Lina Obeid from Stony Brook how this class of proteins mediates these essential germ cell University will present some of her work on the impact of functions and a discussion of why this form of regulation is regulated sphingolipid metabolism in cancers. Stephen G. so critical in germ-cell development. Young at the University of California, Los Angeles, will — Angelika Amon, Massachusetts Institute of Technology outline exciting discoveries that expand our understand- and Howard Hughes Medical Institute ing of the triglyceride-rich lipoprotein metabolism and laminopathies. Finally, my laboratory has identied a new Redox signaling and the metabolome lipase critical for regulating lipid metabolism, the adipocyte Oxidation-reduction reactions are the ultimate drivers of triglyceride lipase. I will present recent research on the all life processes. Redox-active metabolites are the products role of this enzyme in physiological and pathophysiological of energy metabolism, the drivers of biosynthetic reactions processes. and purveyors of cellular signaling. is symposium will — Rudolf Zechner, Institute of Molecular Biosciences, capture important aspects of the eld by featuring talks Karl Franzens Universität Graz about biocatalysts by Joan Broderick from Montana State Molecular quality control University and David Sherman from the University of Michigan, redox regulation by Vadim Gladyshev from Har- Molecular quality control is the process by which the vard Medical School and Brigham & Women’s Hospital, capabilities of macromolecules are judged. ose found and signaling by me. wanting are destroyed, and their components are recycled. — Ruma Banerjee, University of Michigan is cellular process is central to the tness of biologi- Medical School cal systems. We shall explore the subject from dierent perspectives. Adam Frost from the University of Califor- nia, San Francisco, will tell us about quality control at the CONTINUED ON PAGE 28 level of the ribosome. Bernd Bukau from the Zentrum für Molekulare Biologie der Universität Heidelberg will tell us how chaperones are implicated in post-production protein quality control. Chris Lima from the Memorial Sloan–Kettering Cancer Center will provide structural insight into the workings of the machinery that turns over defunct macromolecules. Susan Ackerman from University of California, San Diego, and Howard Hughes Medical Institute will provide a physiological perspective on the role Annual meeting of quality control in the context of mouse models of neuro- degenerative disease. I will examine the question of quality abstract submission control in the high- ux environment of the early secretory deadline: Nov. 17 pathway of complex eukaryotic cells. — David Ron, University of Cambridge

Low-complexity domain proteins and the making of germ cells is symposium will address exciting new develop- ments in germ-cell formation. It has long been known that

NOVEMBER 2016 ASBMB TODAY 27 CONTINUED FROM PAGE 27 Issues in depth Issues in Depth is a series of symposia focused this year on antibiotics and antibiotic resistance. e series is sponsored by the ASBMB Minority Aairs Committee.

Antibiotics, the drugs that kill pathogenic bacteria, are the most successful medicines ever found by humans. How- ever, due to Darwinian selection, bacteria can develop resistance to the antibiotics. ere is a constant race between our ability to nd new inhibitors of bacterial growth and the ability of pathogens to nd ways to become tolerant to the new drugs. is multi-day series of symposia on antibiotics and resistance will bring together top researchers to discuss new approaches for drug discovery, new insights into the molecular mechanisms of antibiotic action, and new understanding of the principles of appearance and spread of antibiotic resistance. — Alexander Mankin, University of Illinois at Chicago

Sunday, April 23: New approaches for antibiotic discovery

Monday, April 24: New insights into mechanisms of antibiotic action

Tuesday, April 25: Antibiotic resistance

28 ASBMB TODAY NOVEMBER 2016 ANNUAL MEETING

The spotlight is on you By Yan Jessie Zhang & Jessica M. Ellis

You have put your heart into your experi- the status quo of scientic areas. ments. You have skipped parties and even Allow us to celebrate your new and occasional free meals because your curiosity exciting discoveries by putting them in the will not allow you to tear yourself away from limelight. Please submit your abstract for that bench! You are driven by the desire to consideration for the Spotlight Sessions at answer the biological question that is your www.asbmb.org/meeting2017/abstracts/sub- obsession. Finally, you have gured it out! missions/ by Nov. 17. Your hard work has paid o, and you have e submitted abstracts will be evaluated shed light on the scientic question that by a committee of Spotlight Sessions chairs haunted your dreams. who are dedicated to the promotion of your Now, let us shine a light on you! Share breakthrough science. e selected abstracts your euphoric moment of scientic discovery will be grouped by scientic area and at the upcoming ASBMB annual meeting, presented in concurrent Spotlight Sessions April 22–26, in the big, lake-front city of between April 23 and April 25. Chicago. e meeting features new Spotlight We are waiting for your glowing Sessions to highlight your brilliant, illuminat- scientic news. ing work. e Spotlight Sessions will empha- size the most recent and exciting ndings that make our scientic passion glow bright. Yan Jessie Zhang ([email protected]) In the format of short talks, the newest is an associate professor in the department scientic discoveries will be placed at the of molecular biosciences at the University of center of discussion. e presentations for Texas at Austin. Jessica M. Ellis (jmellis@ purdue.edu) is an assistant professor in the the Spotlight Sessions will be chosen from department of nutrition science at Purdue your submitted abstracts with simple criteria University, West Lafayette. Zhang and Ellis for selection: We want to hightlight innova- are part of the ASBMB Meetings Committee tion, novel technological approaches and and are overseeing the Spotlight Sessions paradigm-shifting discoveries that challenge for the ASBMB 2017 annual meeting.

NOVEMBER 2016 ASBMB TODAY 29 ANNUAL MEETING

Promoting lifelong learning

Science involves a dedication to learning new things Beyond DNA methylation about the world and ourselves. e American Society for and histone modifications Biochemistry and Molecular Biology will be hosting a vari- Epigenetic mechanisms, such as DNA methylation ety of workshops that promote learning about cutting-edge and histone modications, can change gene expression techniques and improving professional skills at the 2017 and cause diseases without changing the underlying DNA annual meeting. sequence. Next-generation sequencing has been transform- ing the eld of epigenetics, generating large datasets of BS- LEARNING LABS seq, ChIP-seq and RNA-seq information. is poses great Academic drug discovery: challenges for data analysis, requiring knowledge of best ways to distill high-dimensional information into compre- charting a roadmap for moving hensible conclusions. In this workshop, Wei Li from Baylor basic ideas into the clinic College of Medicine and Kai Tan from the University of So you have identied a biological target or a path- Pennsylvania will present several cutting-edge analytical way. Now what? is workshop is designed to teach frameworks for epigenomic data analysis and demonstrate academic investigators how to navigate the challenging but how to integrate multidimensional epigenomic datasets highly rewarding process of small-molecule drug discovery. to construct condition-specic transcriptional regulatory e workshop will cover major techniques and steps in networks. drug discovery and present specic examples of moving tar- gets and molecules through the drug-discovery process. e CRISPR-based versatile tools and workshop leaders, Zhong-Yin Zhang from Purdue Univer- their major application areas sity and Shaomeng Wang from the University of Michigan, is workshop, led by Mazhar Adli at the University also will share their best practices and lessons learned. Virginia School of Medicine and Jacob Corn at the Uni- versity of California, Berkeley, will present leading-edge CRISPR/Cas9-based technologies and their applications. e wide range of versatile CRISPR-based tools will be covered, with focus given to the design of experiments, downstream analysis and major pitfalls. Specic applica- tions of CRISPR to genome-scale knockout screening and locus-specic epigenetic editing approaches will also be presented.

High-performance mass spectrometry for proteomics e improvements in performance metrics of mass spectrometers, coupled with the development of new MS/ MS methods and new strategies for quantitation, have signicantly accelerated the eld of proteomics, to the point where nearly every protein in a human cell can be quantied. is workshop, led by Jenny Brodbelt from the University of Texas at Austin, and Josh Coon from the University of Wisconsin–Madison, will showcase some of the latest mass spectrometry technologies for identifying proteins and their post-translational modications, as well as forefront applications of bottom-up and top-down pro-

30 ASBMB TODAY NOVEMBER 2016 teomic approaches to untangling the multifaceted networks Principles and applications that regulate complex organisms and their diseases. of modern kinetic and equilibrium analysis is workshop will teach attendees how to answer Lipidic cubic phase crystallography important questions about enzyme mechanisms by Lipidic cubic phase crystallography and related methods designing the right experiments and interpreting them have transformed membrane-protein structural biology. quantitatively. e workshop will be taught by Kenneth ey have led us to most of the known structures of G-pro- Johnson at the University of Texas at Austin and founder of tein–coupled receptors, as well as structures of many other KinTek Corporation, a leader in precision stepped- ow and membrane proteins, enzymes and transporters. is work- quench- ow instruments for rapid transient reaction kinet- shop, led by Andrew Kruse of Harvard Medical School and ics. It will present basic foundations and applications of Aashish Manglik of Stanford University, will focus on how kinetic analysis and then cover topics ranging from chemi- to crystallize membrane proteins by the lipidic cubic phase cal kinetics and enzymology to pharmacokinetics and cell biology. It will demonstrate the use of KinTek computer method and will include a live hands-on demonstration of the technique. CONTINUED ON PAGE 32

NOVEMBER 2016 ASBMB TODAY 31 CONTINUED FROM PAGE 31 sive knowledge of all aspects of the process for National Institutes of Health and National Science Foundation simulation software to t multiple data sets simultaneously, submissions, and will focus on practical methods that have including kinetic and equilibrium measurements. Attendees been used with great success in the more extensive two-day will learn how to perform a wide range of experiments and program for Interactive Mentoring Activities for Grants- interpret them rigorously, without simplifying approxi- mations and making errors inherent to tting data using manship Enhancement. equations. How to get a life in the life sciences Every scientist can benet from helpful and entertaining SUCCESS IN SCIENCE Grant success demystified tips on how to navigate graduate school, postdoctoral posi- tions, job hunts and steady funding while nding personal e ASBMB grantwriting workshop hosted by the fulllment. Two self-proclaimed “chronologically gifted” ASBMB Minority Aairs Committee will provide par- biochemists, William Wickner of Dartmouth University ticipants with an eective set of tools to enhance their and Nobel laureate Randy Schekman at the University of grantsmanship and demystify the grant submission and review process. e workshop presenters are Sonia Flores at California, Berkeley, will share how lifelong friendships the University of Colorado, Boulder and Suzanne Barbour grown in the lab and bold and feasible directions for your from the University of Georgia, Athens. ey have exten- science can lead to long, fullling scientic careers.

32 ASBMB TODAY NOVEMBER 2016 Publishing in the JBC 101: Networking 101 advice from the experts Whether you are an early-career scientist or an estab- Interested in publishing your research in the Journal of lished member of your scientic community, developing Biological Chemistry? Make sure you are presenting your and maintaining a network of professional contacts will research rigorously, clearly and compellingly! e JBC edi- help grow your career. Graduate students and postdoctoral tors will discuss important aspects authors need to consider fellows interested in learning how to cultivate professional when preparing their manuscripts for submission. Topics relationships will develop a personal action plan during this to be covered include clarity of the text, including title workshop, which will be led by the ASBMB Education and and abstract, data presentation, database compliance and Professional Development Committee.is workshop will transparency. be part of the Graduate and Postdoc Career-Development Event (page 34). PROFESSIONAL DEVELOPMENT WORKSHOPS Why do science outreach? Advocacy town hall Participating in science outreach usually is not seen as essential for a successful scientic career. However, a grow- You’ve got questions about policy? Join the ASBMB’s ing body of research has begun to point to several benets public aairs sta and leaders from the ASBMB Public of getting involved with outreach. During this workshop, Aairs Advisory Committee, who will be hosting a town- representatives from the ASBMB Public Outreach Com- hall style meeting. You will have your questions answered mittee and Northwestern University’s Science in Society about almost anything happening in the policy world. Your research center will discuss how taking part in science questions can range from funding levels to the in uence of outreach activities can have both short- and long-term the 2016 elections on science. We’ll help you connect how positive impacts on scientists, focusing in particular on skill policy decisions in Washington, D.C., aect your science. development, professional advancement and establishment of strong community relationships. is workshop will be Constructing your elevator pitch part of the Graduate and Postdoc Career-Development Being able to describe your research eciently is a skill Event (page 34). that all scientists should have. In this interactive workshop led by members of the ASBMB Public Outreach Com- mittee, you will learn how to construct an elevator pitch, which is a brief, engaging description of your research. We will discuss tips and real-life examples of approaches to communication that work (and don’t work) and provide plenty of opportunities for practice and feedback. is workshop will be part of the Graduate and Postdoc Career- Development Event (page 34).

Identifying transferable skills Scientists build many dierent skills — from techniques Annual meeting to communication to personnel management — through- abstract submission out their careers. However, communicating these skills outside the academic research environment can be challeng- deadline: Nov. 17 ing. Zach Marks, co-founder and chief operating ocer of Oystir, an online jobs marketplace that matches candidates and employers based on skills, will lead graduate student and postdoctoral fellows in learning how best to present their skills to potential employers. is workshop will be part of the Graduate and Postdoc Career-Development Event (page 34).

NOVEMBER 2016 ASBMB TODAY 33 ANNUAL MEETING

Advance your careers, grad students and postdocs! By Erica Siebrasse

For the past 10 years, the American Society for Bio- chemistry and Molecular Biology has provided robust career-development programming for graduate students and postdoctoral fellows at its annual meeting. Next year’s annual meeting again will have career-development programming for grad students and postdocs, but this time there will be some exciting changes to the Saturday agship event. Please help us spread the news about these exciting changes to your trainees, colleagues and friends so that they can submit abstracts for the meeting and join us for our events! In the past, only travel awardees were invited to attend 2017 PRELIMINARY PROGRAM the entire career-development event. While ASBMB travel e full program, including conrmed speakers, awardees will continue to be required to attend, up to 100 is available at www.asbmb.org/meeting2017/gradstu- additional seats will be available for non-travel awardee dentpostdoc/ participants, who may register for the event when they complete their Experimental Biology registration. Remem- April 21 ber, though, that the ASBMB oers 200 travel awards of • Networking reception with participants and up to $1,000 to graduate students and postdocs (deadline speakers Dec. 1). More information can be found at www.asbmb. org/meeting2017/. April 22 e 2017 Graduate and Postdoc Career-Development • Career options: the bench, the boardroom or in Event will be organized by Christopher D. Heinen from between? the University of Connecticut Health Center and Timothy Speakers will share their stories of nding ful lling industry, academic and nonresearch careers. D. O’Connell from the University of Minnesota, along • Panel discussions with me. Speakers will host Q&A panel discussions on industry, To strengthen the skill-development oerings, the academic and nonresearch careers. organizers added workshops on Saturday afternoon where • Networking luncheon with participants and participants can develop an elevator pitch, improve their speakers networking skills, identify their transferrable skills and • Career-development workshops learn how to build their skill sets through outreach activi- Participants will choose among several skills-building ties. (More information on each workshop is available on workshops. pages 30–33 of this issue.) e 2017 Graduate and Postdoc Career-Development Event is an opportunity to learn about dierent careers in science and develop or improve skills before the main Erica Siebrasse ([email protected]) is the education and professional development manager for the ASBMB. Follow her scientic programming starts on April 22. on Twitter at twitter.com/ericasieb. We look forward to seeing you at the 2017 ASBMB annual meeting!

34 ASBMB TODAY NOVEMBER 2016 ANNUAL MEETING

Reminders for the 2017 ASBMB Undergraduate Poster Competition

e Undergraduate Poster Competition at the ASBMB annual meeting is an opportunity for undergraduate students to present their research at an international gathering and compete for awards. Students can network with leaders in the elds of biochemistry and molecular biology and their peers. Each winner of the competition receives a $500 cash prize.

ELIGIBILITY Each undergraduate who submits an abstract as the rst author to an ASBMB topic category (#2000–2324) is eligible to apply for the competition. e abstract submission deadline is Nov. 17.

HOW TO APPLY FOR THE COMPETITION • In early February, eligible students will receive an emailed invitation to apply for the competition. • Students should apply early! Spots for the competition are limited. • After submitting an application, each student will receive an email receipt. e email receipt is not a registration conr- mation. • In late February, approved applicants will receive registra- tion conrmations.

TRAVEL AWARDS Visit the ASBMB website to learn about our undergradu- ate student travel awards and to apply. All undergraduate travel awardees are required to present at the ASBMB Under- graduate Poster Competition as well as at a regular poster session that is part of the main ASBMB meeting.

Learn more about the 2017 meeting: www.asbmb.org/meeting2017

NOVEMBER 2016 ASBMB TODAY 35 PUBLIC AFFAIRS Are postdocs still invisible? By Mike Schaller & Gary McDowell

n 1969, the National employee,” “postdoctoral fellow” Research Council published a and “postdoctoral fellow paid I report entitled “e Invisible direct.” All three titles would be University.” It was referring to the allotted the same career-develop- status of postdoctoral researchers, ment opportunities and would or “postdocs,” as a rarely appre- participate in the same post- ciated part of academe despite doctoral benets program. e being essential to producing the rst classication, “postdoctoral future leaders of the research employee,” would be paid from enterprise. is status prevented a grant. “Postdoctoral fellow” equitable compensation and would refer to those paid by the opportunities for career develop- institutional allowance attached ment. Postdoctoral fellows had to a fellowship. “Postdoctoral fellow paid direct” would mean no voice to express their needs. those paid with funds made avail- While progress has been made that the range of postdoctoral benets able for benets paid directly to the and some institutions have devel- and salaries is vast, and individuals postdoc. In collaboration with institu- oped exemplary postdoctoral training remain in postdoctoral positions for tions and human resources groups, experiences, this type of training is not unknown periods of time. It is not we are preparing a detailed plan to universal, and one factor contributing unheard of for postdoctoral research- ers to be on salaries of around $25,000 provide guidance for implementation, to the disparity of postdoc experiences comparing best practices and common after more than a decade of experi- is the diverse titles used to classify challenges to establish the plan. ence. ese incidents illustrate the dif- postdocs. is proposed change comes at culty in tracking the career develop- We already have too many names an important time, given the new ment of postdoctoral researchers. We for “postdoc” to count. Even though regulations regarding salary exemp- the postdoctoral position is a crucial do not know who they are, how long tions for overtime pay through the step on the academic career path and they hold postdoctoral positions or Fair Labor Standards Act. Institutions research productivity is highly depen- where they go afterward. is means will need to track postdoctoral trainees dent on their experience, postdoctoral that a group recognized federally as to demonstrate compliance with these researchers have been slotted into vari- both trainees and employees and and other federal regulations. What ous designations across departments mostly federally funded is largely an we propose will lessen the administra- and institutions in a piecemeal and unknown entity both in demographics tive and, potentially, legal burden for unregulated fashion. eir positions and training. is is a very real barrier institutions in addition to providing often depend on the hiring depart- to eorts to establish how postdoctoral equitable training opportunities and ments, international tax codes and researchers are contributing to the aiding in the analysis of this critical grant requirements. society that invests in them beyond population in academe. Academe is unable to count them research output. It is also a hurdle to (most often, individual institutions creating a diverse and highly trained Mike Schaller (mschaller@hsc. cannot even give an accurate gure for professoriate. wvu.edu) is a member of the their own postdoctoral researcher pop- We are proposing a reform of post- American Society for Biochemistry doctoral categorization. Institutions and Molecular Biology Public ulation). Consequently, an unknown Affairs Advisory Committee and fraction of postdoctoral researchers are should collect all postdoctoral hires chairman of the Department of missing institutional training oppor- into one grouping labeled “postdoc” Biochemistry at West Virginia Uni- tunities designed to enhance career that can then be broken down into versity School of Medicine. Gary as many subtitles as the institution McDowell (garymcdow@gmail. development beyond the laboratory, com) is the executive director of the nonprofit such as grant writing, mentoring and wishes. For example, an institution organization Future of Research and a resident at leadership. is invisibility also means may choose three titles: “postdoctoral Manylabs.

36 ASBMB TODAY NOVEMBER 2016 Upcoming ASBMB events and deadlines Nov. 9–12: Annual Biomedical Research Conference for Minority Students, booth #701, Tampa, Fla.

NOVDEC Nov. 17: Abstract submission deadline for ASBMB 2017 Annual Meeting, Chicago

Dec. 1: Travel award deadline for the ASBMB 2017 Annual Meeting, Chicago Dec. 1: Deadlie for 2018 Special Symposia proposals Dec. 3–7: American Society for Cell Biology annual meeting, booth #835, San Francisco

NOVEMBER 2016 ASBMB TODAY 37 MINORITY AFFAIRS Exemplifying Sewer’s commitment to diversity Minority Aairs Committee announces scholarship winners By Andrew Macintyre

his year’s recipients of the have conquered while pursuing their high-school diploma or a GED. Marion B. Sewer Distinguished education. In addition to working with T Scholarship for Undergraduates Applications for the 2016 scholar- inmates, Brown established a partner- exemplify the late Sewer’s unwavering ship were evaluated by members of the ship between Yale students and A commitment to biomedical research MAC and Student Chapters Steering Better Chance House, a residential and workforce diversity and inclusion. Committee. ere were a number program for academically talented e highly accomplished Sewer was a of exceptional applications from young people of color. ABC House professor of pharmacology at the Uni- which it was evident that many of the brings ABC scholars together to versity of California, San Diego, and society’s undergraduate members are attend high school and helps them to former deputy chair of the American both actively engaged with their local prepare for leading four-year colleges Society for Biochemistry and Molecu- communities and enthusiastic about and universities. rough the partner- lar Biology Minority Aairs Commit- building an inclusive scientic envi- ship, Yale tutors help the scholars with tee. Sewer died in January. ronment. After extensive discussion, homework, exam preparation, and Sewer believed in doing com- the reviewers identied ve students other academic and personal munity service for the biomedical whose scientic and service accom- challenges. research enterprise and played a key plishments best align with the goals of Besides her community service, role in organizing the ASBMB’s grant- the scholarship. Brown has undertaken two neurosci- writing workshop. is workshop ence research internships at the phar- is now a central component of the e following are the 2016 recipi- maceutical company Pzer. For the MAC’s Interactive Mentoring Activi- ents of the Marion B. Sewer Distin- past year, she has been working in a ties for Grantsmanship Enhancement, guished Scholarship for research lab at Yale to understand bet- or IMAGE, mentorship program for Undergraduates. ter the neuroscience of nicotine addic- senior postdoctoral scholars and junior tion. Once she graduates, Brown aims faculty. Samantha Brown to continue to explore the molecular In recognition of Sewer’s untir- mechanisms of brain disorders by ing commitment to the support (Yale University) obtaining an M.D.–Ph.D. degree. of underserved populations in the For the past biomedical research community, the three years, Matthew Cheung ASBMB established the Marion B. Samantha Brown Sewer Distinguished Scholarship for has acted as a (Saint Louis University) Undergraduates in March. tutor and men- Matthew e scholarship provides tuition tor for juvenile Cheung previ- support for ASBMB undergraduate inmates at correctional facilities ously received an members who excel academically and throughout the state of Connecticut ASBMB distin- are committed to enhancing diversity via the Yale Undergraduate Prison guished under- in science. To apply, students have Project. Brown works one-on-one graduate scholar- to explain how they foster diversity with inmates to build their writing ship when he was a rising junior at on their campus or in the scientic and math skills. In addition, she coor- Saint Louis University. After receiving community, outline how a scholar- dinates the project’s post-GED pro- the scholarship, he spent a summer ship will help them reach their career gram, a weekly roundtable discussion performing research at Washing- goals, and describe the challenges they for inmates who already have either a ton University through the Amgen

38 ASBMB TODAY NOVEMBER 2016 Scholars program. Now a senior better with the students and made for young black men, Austin Maduka undergraduate, Cheung continues a bigger impact than if I only spoke pursued his interest in chemistry and to serve as a resident adviser for the English.” biology throughout high school. He Health Sciences Learning Community was accepted into the prestigious at Saint Louis and recently won the Sofia Gonzalez Meyerho Scholarship Program at the Excellence in Community Building University of Maryland, Baltimore Award from the department of hous- (Truman State University) County, and he now serves as a peer ing and resident life. Soa Gonzalez adviser to junior participants in the After graduating, Cheung intends has worked on program. “I can accredit much of my to undertake postbaccalaureate research projects success to the support I found within training at the National Institutes of at Purdue Uni- the Meyerho program,” wrote Mad- Health and become a physician-scien- versity, A.T. Still uka in his application. “It is important tist. After completing an M.D.–Ph.D. University and the for every student who faces barriers degree, he says, he intends to “run Scripps Research Institute. “Research to education to develop a network of my own disease-specic outpatient is more complex than a test” in class, support, academically, socially and clinic while simultaneously running wrote Gonzalez in her application. “I emotionally.” a laboratory that aims to elucidate nd that (it) favors how I look at sci- Maduka has helped found a the underlying mechanisms of that ence and the world.” number of programs to mentor and disease.” Currently in her nal year at Tru- support students interested in pursu- man State University in Missouri, ing careers in science and medicine. Gonzalez intends to obtain a Ph.D. Wesley Godfrey He is a founding member of the rst and pursue her passion for research. “I professional fraternity at the UMBC, (University of Texas at nd immense satisfaction in knowing the Phi Delta Epsilon Medical that I am contributing a small drop to Fraternity. He is also vice president Austin) the sea of knowledge that is required Wesley God- for improving science,” she said with and co-founder of Achievement frey is studying enthusiasm. and Inspiration through Mentor- biology at the For the past two years, Gonzalez ship, which is an initiative to provide University of has led United Speakers, an on-cam- long-term mentoring to underserved Texas at Austin, pus organization that works with the adolescents in the city of Baltimore. where he also is local immigrant community to break AIM has more than 30 mentors, many performing research on T-cell acute down barriers by providing ACT prep of whom are working with black and lymphoblastic leukemia. Once he and classes in English. Gonzalez her- Hispanic students interested in math graduates, he intends to combine self is an immigrant from Mexico, and and science. his research and clinical interests by she aims to continue her outreach and Alongside his outreach activities, obtaining an M.D.–Ph.D. degree. tutoring work when she goes to gradu- Maduka has worked in research labs at Godfrey was raised largely by his ate school. Indeed, in her scholarship the Johns Hopkins University School Mexican-American grandparents in application, Gonzalez noted that “it is of Medicine and the Massachusetts El Paso, Texas, a few miles from the a privilege to have the trust of people Institute of Technology. He presented U.S.–Mexico border. He speaks both who have experienced the world in his work from Johns Hopkins at the English and Spanish. Godfrey volun- such a dierent manner.” 2015 ASBMB annual meeting in Bos- teers with UTeach Outreach, a pro- ton. After graduating, Maduka said gram in which college students teach Austin Maduka he intends to earn an M.D.–Ph.D. weekly science lessons to students degree, practice cardiology, and “teach living in disadvantaged neighborhoods (University of Maryland, and inspire the next generation of around Austin. While the lessons are Baltimore County) leaders in health care.” taught in English, the students often come from Spanish-speaking homes. Despite “I would often explain concepts in growing up in Andrew Macintyre (am277@ Spanish to students who couldn’t an environment duke.edu) was an education where science was and professional development understand,” wrote Godfrey in his not emphasized manager at the ASBMB. He now application for a scholarship. “Because is a shared-resource laboratory as a career path I spoke Spanish, I was able to connect manager at the Duke Human Vaccine Institute.

NOVEMBER 2016 ASBMB TODAY 39 MINORITY AFFAIRS Diversifying the scientific workforce with IMAGE By Takita Felder Sumter

he American Society for Bio- Interactive Mentoring Activities for percent of the 2015 cohort success- chemistry and Molecular Biology Grantsmanship Enhancement pro- fully secured federal funding, with 45 T Minority Aairs Committee has a gram, known as IMAGE, with gener- percent of these grant recipients being longstanding commitment to diversi- ous support from the National Science URM faculty members or faculty from fying the workforce engaged in life-sci- Foundation. e program is designed minority-serving institutions. ese ence research. Federally funded eorts to increase the number of federally data provide further support for the to increase the number of underrepre- funded minority faculty members as importance of mentoring in STEM sented minority, or URM, undergrad- well as faculty members at minority- disciplines with culturally competent uates who pursue biomedical graduate serving institutions to build a more role models. Given that 50 percent of training have been very successful in inclusive scientic enterprise. the workshop mentors are URM fac- promoting the matriculation of these is long-term goal is being ulty members, our outcomes empha- students into doctoral programs. In addressed by providing assistant size the pivotal role that interactions fact, the National Institute of General professors and senior postdoctoral between junior and senior URM fac- Medical Sciences Postbaccaulaureate scientists with intensive mentoring ulty members can play in career devel- Research Education Program matricu- on grantsmanship skills and career- opment. ese positive outcomes have lates 65 percent of its participants into development strategies. Although provided the impetus for the 2016 Ph.D. programs; of these participants, the program is open to everyone, grant writing workshop component of 63 percent complete their Ph.D.s (1). we place particular focus on URM IMAGE that recently occurred in July. However, the growth in the num- faculty members and faculty members e workshop included the participa- ber of doctorates awarded to URM at minority-serving institutions. e tion of several members of the MAC, students has not led to a commensu- IMAGE program has a three-pronged including Suzanne Barbour at the rate number of URM individuals in approach: University of Georgia, Squire Booker tenure-track faculty positions or in At an annual workshop, mentors at the Pennsylvania State University, higher-level administrative positions who have a demonstrated track record Sonia Flores at the University of Colo- within academia. In fact, the number of securing federal funding share best rado School of Medicine, Christopher of URM STEM faculty members in practices on proposal preparation. Meyer at the California State Univer- tenure-track positions in the U.S. stag- ey provide real-time feedback on sity and me. Booker, Flores and I were gers below 10 percent. It is even lower potential specic aims. One-on-one the workshop co-organizers. at the rank of professor. We still need guidance assists with proposal prepara- is year’s applications were solic- innovative approaches to address criti- tion and submission. A web-based ited via advertisements on the ASBMB cal junctures in the biomedical career interactive forum allows for the dis- website and diversity mailing lists as path where minorities drop out of semination and exchange of career- well as through letters to department the academic pipeline. Recent studies development resources. chairs. Application materials included clearly have illustrated racial disparities Data from the rst three years of a summary of the candidate’s research in securing funding from the National the program (2013, 2014 and 2015) interests and a letter of support from Institutes of Health (2). indicate that 70 percent of par- the department chair; these were Based on an exploration into the ticipants felt that the feedback about reviewed with several goals in mind. barriers that URM investigators their research objectives was likely to First, we sought to identify projects encounter when competing for federal improve their grant-writing skills, and that were well rationalized and were funding, the MAC has been working 80 percent found the interaction with within the scope of the ASBMB’s on developing mentoring approaches the mentors valuable. Signicantly, interests. Second, we aimed to have 30 to address these needs. As part of 44 percent of the 2013 cohort, 53 to 50 percent of the mentees be URM this eort, the MAC developed the percent of the 2014 cohort and 39 senior postdoctoral fellows and assis-

40 ASBMB TODAY NOVEMBER 2016 The 2016 IMAGE workshop helped participants improve their grant-writing skills and provided career development opportunities. tant professors or non-URM senior experimental approaches, and future broader impacts (led by Jory Wein- postdoctoral fellows and assistant pro- directions in a low-risk and safe-space traub from Duke University), and fessors from minority-serving institu- peer-review setting. Presentations managing collaborations and navigat- tions. Finally, we aimed for gender and were clustered based on research topic ing departmental politics. e various geographical diversity. ese selection (e.g., molecular biology, enzymology). types of programmatic activities criteria resulted in a dynamic cohort. Mentors and other attendees provided helped mentees interact with mentors e workshop agenda included feedback and suggestions. Examples of and NIH and NSF funding ocials. presentations from program ocers mentors’ suggestions included provid- Mentees also got opportunities to from the NSF (Christopher Meyer ing more preliminary data, suggesting interact with each other. In the future, and Wilson Francisco) and the NIH collaborators, focusing the research mentees also will have an invaluable (Vernon Anderson from NIGMS). plan, and targeting another funding opportunity to receive guidance with We also conducted an NSF proposal agencies (such as the Department of proposal writing and revisions from review panel and held presentations on Defense or the Research Corporation). ASBMB members with expertise in the elements of a successful proposal, Additionally, the participants received the given area. Please contact us if you such as how to respond to reviewers guidance on how to integrate feedback have an interest in mentoring these in proposal resubmissions; how the from the workshop into proposal revi- bright young scientists. NSF and NIH dier with respect to sions during a presentation by a recent We conclude that the use of a funding; and general faculty-life issues, workshop attendee and CAREER multipronged approach to providing including managing productive collab- award winner, Rick Page at Miami opportunities for career development, orations. e most signicant portion University. networking and scientic exchange of the three-day workshop experience In addition to networking oppor- is critical to diversifying the STEM was dedicated to 15- to 20-minute tunities, a nal component of the workforce. e members of the MAC presentations from all mentees. e workshop was a panel discussion on and I use this article as a call to action workshop participants provided an balancing research, teaching and ser- for broadening the future of the life- overview of a potential research pro- vice, professional ethics, research ethics science enterprise. posal, which included a discussion of (led by William Trenkle from the U.S. the research area, the central hypoth- Department of Health and Human Takita Felder Sumter (sumtert@ esis to be addressed, preliminary data, Services Oce of Research Integrity), winthrop.edu) is a professor of chemistry at Winthrop University and the chairwoman of the Minor- REFERENCES ity Affairs Committee. The IMAGE 1. Hall, A. et al. Analysis of Scholar Outcomes for the NIGMS Postbaccalaureate Research grant honors the legacy of the late Marion Sewer Education Program (2015). and currently is being led by remaining members of the working group. 2. Ginther, D. Science 333, 1015–1019 (2011).

NOVEMBER 2016 ASBMB TODAY 41 MINORITY AFFAIRS Cultivating a focus on diversity as a community By Beronda L. Montgomery

is essay is in response to the call including the ASBMB, have responsi- in starting a chapter with faculty in the February 2016 issue of ASBMB bilities to support and advocate for all who are running established student Today for thoughts and opinions about society members in these endeavors. chapters. diversity in the scienti c enterprise. Frequently societies have a minority ese programs are just a sampling aairs or diversity committee. Indeed, of eorts spearheaded by entities such ecent national conversations the ASBMB has an active and eective as the ASBMB MAC. Such eorts regarding race relationships Minority Aairs Committee whose are still critical, as targeted attention R and interactions across diverse eorts are laudable. to the inclusion of individuals from demographic groups do not stop at e ASBMB MAC oversees a num- groups under-represented in particular the doors of our laboratories, institu- ber of eorts, including the Marion STEM elds can lead to short- and tions or disciplinary societies, because B. Sewer Distinguished Scholarship long-term change and opportunities. science, education and research do not for Undergraduates, which recently As we consider the roles and actions occur in vacuums. e national dis- changed its name to honor the prolic that societies, such as the ASBMB, cussions provide opportunities for us scholar and former MAC member currently are taking and those that to assess our eorts and commitment Marion Sewer. e award provides stand yet to be realized, there are in terms of promoting diversity and nancial support for recipients who many questions to contemplate. Have inclusion as an American Society for are committed to enhancing diversity our societies actively recruited and Biochemistry and Molecular Biology in science (see page 34). e Ruth engaged a membership that re ects community. Kirschstein Diversity in Science Award national demographics? If not, why? Indeed, in the context of these was established ve years ago. e e easy answer may be that the pool intense and needed discussions, there MAC also sponsors professional devel- of potential members from which the is a growing recognition in biochem- opment activities that are supportive society draws does not re ect national istry and many other areas of STEM of members from underrepresented diversity. If that is indeed the case, that eorts to increase access and groups and members at large. ese what eorts can the ASBMB make success of diverse individuals continue eorts include the Careers Beyond jointly as a society to contribute to to be an issue that requires targeted the Bench workshop, which high- changing that? An additional question attention and eort, as there are lights nonresearch-based careers and to re ect on is “Are the eorts of the perceptions in the ASBMB commu- the Interactive Mentoring Activities society actively supporting all of its nity itself that “although scientists say for Grantsmanship Enhancement, current members independent of the they want full equality, they don’t do or IMAGE, grant writing workshop demographic group of origin?” what’s necessary to achieve it” (1). e for early career scholars transitioning Why the targeted focus on the specic roles and responsibilities that to independence (see page 36). e role of societies such as the ASBMB? societies and professional associations careers of diverse ASBMB members In the “Summary of the broadening have to all of their members are criti- also are highlighted in the Research participation working group report on cal, and we continue to grapple with Spotlight forum. the NSF response to the Committee what discrete actions ow from those One collaborative eort between on Equal Opportunities in Science responsibilities. the MAC and the ASBMB Student and Engineering’s 2011–2012 recom- Disciplinary societies serve as Chapters Steering Committee is the mendation,” scientic societies speci- “an important organizational struc- Minority Serving Institutions student cally were highlighted as important ture through which scientists build chapters partnership program. is for their potential to “play a major communities of practices, reward program encourages the formation of role in deploying best practices to the achievements, and enable members new ASBMB student chapters at MSIs community and pursuing broadening to share information” (2). Societies, by partnering MSI faculty interested participation.”

42 ASBMB TODAY NOVEMBER 2016 Professional societies also have impactful roles to play in assisting in quantifying progress toward improv- ing recruitment, retention and success of underrepresented groups, such as women of color (3). Society-driven initiatives can both motivate and serve members seeking specic and eec- tive avenues to engage in broadening participation and outreach activities. Such collaborative attention from soci- ety members has great potential for increasing the impact of societies in seeking and disseminating best prac- tices as well as promoting its members to serve a diverse pool of scientists eectively. Among many strategies that have proved eective for increasing access and success for individuals from diverse backgrounds, mentoring has emerged as a critical factor in pro- initiate internal discussions about the require the input and buy-in of many moting recruitment, retention and breadth and depth of our knowledge across the ASBMB and strategic col- persistence. Many societies, including and understanding of the ASBMB’s laboration to be eective. the ASBMB, have visible eorts in organizational culture and its potential ere is evidence emerging from mentoring, including the ASBMB’s for ensuring long-lasting change that the eorts of a range of societies aforementioned professional-develop- will broaden participation of current regarding eorts to increase represen- ment workshops. While professional and future members. Are the indi- tation of women and individuals from development interventions improve viduals that we attract to the ASBMB groups underrepresented in STEM in individual access to communities society activities and annual meetings. through outreach and intake eorts such as the ASBMB and success in Recent research indicates that ensuring and the work of the ASBMB MAC to individual careers, research also has that the programming committee is increase visibility of diverse members indicated that long-term transforma- aware of gender statistics results in tion of communities into ones that nding a welcoming environment in a signicant increase in the number serve a broad array of individuals from the ASBMB and at our annual meet- of female speakers at symposia and diverse backgrounds also includes ings once they arrive? Are they seeing conferences (8–10). Similar results are targeted attention to assessing com- diverse members recognized and cel- likely to emerge in regards to targeted munity or organizational climate and ebrated broadly — that is, outside of interventions for diversifying symposia culture (4–7). the recognized “diversity-sponsored” organizers across many demographic Here, an opportunity emerges to places and avenues? Such an eort will groups. It is time that we as members of REFERENCES the ASBMB and, indeed, the larger 1. Dockett, L. & Hopp, A. ASBMB Today 15, 2 (2016). society in which we belong, truly 2. Frehill, L. M. Disciplinary societies’ role in women’s status in chemical science, computer science, and ask what our specic roles may be in mathematics and statistics. In “Blueprint for the Future: Framining the Issues of Women in Science transforming our spaces into ones that in a Global Context” (Didion, C., Frehill, L. M., and Pearson, W. eds.), National Academies Press, fully embrace, engage and celebrate 101–104 (2012). everyone openly and in the most pub- 3. Frehill, L. M., & Ivie, R. New Directions for Higher Education 2013, 7–21 (2013). lic and accessible spaces and ways. 4. Whittaker, J. A., & Montgomery, B. L. JUNE 11, A44–A51 (2012). 5. Whittaker, J. A., & Montgomery, B. L. Innov High Educ 39, 263–275 (2014). Beronda L. Montgomery 6. Whittaker, J. A. et al. JUNE 13, A136–A145 (2015). ([email protected]) is a 7. Zambrana, R. E. et al. Am Educ Res J 52, 40–72 (2015). professor of biochemistry and 8. Sardelis, S. & Drew, J. A. PLoS ONE 11, e0160015 (2016). molecular biology at Michigan 9. Casadevall, A. & Handelsman, mBio 5, e00846–e00813 (2014). State University. You can follow her on Twitter at twitter.com/BerondaM. 10. Casadevall, A. mBio 6, e01146–e01115 (2015).

NOVEMBER 2016 ASBMB TODAY 43 TRANSITION STATES

Wrestling with life By Zachary A. Kemmerer

hen I was 5 rst practice of the years old, I day had just nished W stepped on at 7 a.m. My vision a wrestling mat and blurred as I kneeled began to dedicate my on the mat, replaying entire youth to the what just happened sport. As a product in my mind. After a of a violent, broken brief warm-up and 45 family, I held wrestling minutes of drilling, as my golden ticket to my wrestling partner the American Dream. and I had engaged in I wanted family a 30-minute nonstop dinners and bedtime grind match. irty hugs. Instead, division minutes to out-think, and foul rhetoric lled outmaneuver and out- the air. My parents perform my partner. separated when I was PHOTO BY LARRY SLATER A clash of wills played Kemmerer wrestled while in college. 7, and I spent most of out in those 1,800 my childhood with my No. 1 overall wrestler in the country. seconds as we tried to dad. Sadly, our relationship dynamic is sacrice landed me at the Univer- break each other down, both mentally mirrored the battles on the wrestling sity of Pennsylvania. and physically, with a constant bar- mat. If I won a match, life at home rage of shots, jarring head snaps and was peaceful; if I lost, my life was Embracing the grind counterattacks. unpleasant for weeks at a time. I was When my vision returned, I looked As a Division 1 wrestler at UPenn, scared in my own home more often down to see a puddle of sweat had my life was often chaotic. Juggling than I care to remember. At a young formed beneath me. Despite having academics and athletics, I constantly age, I reasoned that wrestling could reached a state of complete physical was competing both in the classroom rescue me from that life: I could be and mental exhaustion, I had barely to survive the grading curve and on the rst in my family to go to college, begun my day. I still had several more the mat to outlast my opponent. get a good job and start a family of my pounds to lose before my upcoming UPenn was the blacksmith of my own. e right way. Someday. dual meet with national powerhouse In my hometown of Lineld, character development as I continued Cornell University’s wrestling team, Pennsylvania, a small suburb one my wrestling career while doing a and I needed to prepare for my physi- hour northwest of Philadelphia, I put double major in chemistry and phi- cal chemistry exam the next day. I countless hours, blood, sweat and tears losophy as an undergraduate student. closed my eyes, took a deep breath into mastering this art. I sacriced my Although many college students call and slowly exhaled. I knew the real body and mind for a dream. In doing themselves student-athletes, the life challenge had yet to come. is chal- so, I became the winningest wrestler of a wrestler required a special kind of lenge was an internal one in which I of all time in high-school wrestling sacrice and discipline to be would wrestle with the uncomfortable history in the state of Pennsylvania successful. and daunting nature of my situa- and earned two state championships Just take a typical Wednesday tion. My path ahead was steep. But I along the way. I was recruited as the morning during my junior year. Our refused to quit and take the easy way

44 ASBMB TODAY NOVEMBER 2016 out. I continued to push forward. I learned not to resent or fear the tasks before me but rather to embrace the discomfort. Each day in college, I redened my notion of impossible on the wrestling mat and in the classroom until the concept of impossible didn’t exist in my mind. The rush of discovery In 2011, I earned All-American honors at the national wrestling tour- nament held in Philadelphia. I ended my wrestling career with 117 wins, which was good enough for fourth overall standing in UPenn wrestling history. PHOTO BY JOE ROBBINS/NBC When my wrestling career ended, Kemmerer’s stage name is “The Science Ninja” on the NBC reality show “American Ninja Warrior.” I was thrown into a period of self- discovery. How does my next chapter teaching responsibilities and mentor- DEAE or CM columns. And unfor- read? After declining an opportunity ing undergraduate researchers. tunately, Stuart Schreiber and Jennifer to work in industry, I started in the But I didn’t want the grind to Doudna were just ordinary names to master’s chemistry program at Vil- end! So I decided to pursue a Ph.D. me. I thought I had made a terrible lanova University. With a competitive resume in hand, I mistake. ere, I joined the laboratory of accepted an oer to join the biochem- I later realized that I was not alone Aimee Eggler, a chemistry professor. istry Ph.D. program at the University in my insecurity. My classmates were I was given the opportunity to delve of Wisconsin–Madison. all just as scared to embark on this into research on the cytoprotective e transition was not easy. I was journey, but we adapted. We placed response of phytochemicals via the leaving Pennsylvania for the rst time our faith in the investigative process Nrf2 transcription factor. I remember in my life to begin a journey quite and embraced the daily challenges the rush I got from reading new litera- dierent from what I was accustomed and endless questions in the world of ture, bouncing from one reference to to. Academia and wrestling are two science. another, immersing myself in the eld. professions rarely associated with one PubMed was a conduit to mechanisms another: I was climbing up the ivory Powered by mitochondria and models, catalytic residues and new tower after dedicating my life to a I joined Dave Pagliarini’s group to therapeutics. e Nrf2 eld was spill- blue-collar sport. I felt out of place. do my thesis work. I am now a third- ing over into metabolic regulation and Everyone seemed more qualied than year graduate student. e Pagliarini carcinogenesis, yet denitive identi- me. My peers had known for years group focuses on elucidating the bio- cation of the Nrf2 protein was still far that a Ph.D. was their next step. I had logical role of mitochondrial unchar- from trivial. not. My peers knew techniques and acterized proteins. For my thesis proj- I yearned for answers to the terms that I never had encountered as ect, I am using protein engineering number of gaps apparent even to an well as names and papers that I had and chemical biology to study Coq8p, untrained eye. I wanted to nd those not seen. I distinctly remember the a protein required for coenzyme answers. Once I picked up a pipette, I embarrassment I felt having never Q biosynthesis. Coenzyme Q is a knew science was my new passion. puried a recombinant protein. I had a basic understanding of bacte- requisite part of the electron transport rial overexpression, but I couldn’t chain that enables ATP production via Climbing into science explain the dierence between IPTG- oxidative phosphorylation. CoQ de- My two years at Villanova as a mas- inducible and auto-induction protein ciency is associated with a wide range ter’s student were countless 12-hour expression. Ion exchange chroma- of diseases, including cerebellar ataxia, days and weekends in the lab, many tography made sense in a textbook, nephrotic syndrome and various months of searching for funding, and but in a laboratory setting I couldn’t myopathies. It also is associated with drafting manuscripts. I also juggled distinguish between the HiTrap SP, Q, CONTINUED ON PAGE 46

NOVEMBER 2016 ASBMB TODAY 45 CONTINUED FROM PAGE 45

chronic disease states, such as diabetes, Parkinson’s disease and general aging. CoQ supplements are used by roughly 3.5 million Americans nationwide either as a therapeutic or for general health purposes. Unfortunately, the ecacy of CoQ supplementation is still clinically unclear. My current work is aimed at improving our understanding of CoQ biosynthesis to develop more eective therapeutics for raising endogenous CoQ levels. I love my work. Becoming ‘The Science Ninja’ PHOTO COURTESTY OF ZACHARY KEMMERER Success never is achieved alone. “Success never is achieved alone,” says Kemmerer who is shown here with his girlfriend. Friends, coaches and research mentors It was inspiration from both of crashed through my veins. In my all have contributed to my success. I these organizations and a passion for rookie season, I completed the India- am especially indebted to Tom Hontz competition that landed me on NBC’s napolis Qualier course, placing 15th (my high school wrestling coach), Jake hit reality TV show “American Ninja out of 120 competitors. Hunter (my best friend), Matt Valenti Warrior.” For those of you who don’t For the show, I adopted a stage (my college assistant wrestling coach), know, “American Ninja Warrior” name “e Science Ninja.” It seemed and Aimee Eggler (my research adviser selects interesting people to compete appropriate, as the past four years of in the master’s program). With their on the world’s most exciting and dif- my life had been dedicated to advanc- words and actions, they changed cult obstacle course. e show has ing basic science. As a mitochondria my life. ey each provided invalu- become immensely popular, as it pits enthusiast, I study the organelle and able guidance and unconditional men and women against seemingly the pathways that enable me to scale support, two essential intangibles I impossible obstacles. You cannot help a 14.5-foot wall. My diet is connected rarely received at home growing up. but root for each competitor who to energy production and metabolic Without their in uence, this essay steps up to the platform! homeostasis while I compete. An likely would read dierently. Because My rst appearances on the show intricate nexus of metabolism, nutri- of them, I believe that I should give were on April 27 and 28 in India- tion and tness is revealed within my back to society, so these days I engage napolis, just six days after passing my intellectual interests, athletic endeav- in science outreach and youth wellness preliminary exam that qualied me ors and extracurricular passions. programs. as a Ph.D. candidate. With ve of With my new ninja status, I have is past year, I volunteered with six obstacles completed, I stared up been granted a platform and a unique Adult Role Models in Science and at the infamous warped wall, the last opportunity to promote science, Beat the Streets. Sharing my passion obstacle. Nearly triple my height, this health and tness. Kids love ninjas, so for science and wrestling with the wall stood before me as a metaphor maybe they’ll like science ninjas just as Madison youth is beyond rewarding. for life — a seemingly impossible task much. And maybe, just maybe, I can When my students ask questions and that I had to face head on. impact their lives in a positive way just acknowledge the proper controls, I As thousands of fans chanted, “Beat as my mentors and friends have done know they are prepared for success. that wall! Beat that wall!” I steadied for me. When my athletes stay after practice myself. I darted toward the incline, to run sprints with me, I know they and, three big steps later, my ngers Zachary A. Kemmerer are chasing a newfound dream. I see latched onto the top of the tower- ([email protected]) is a third-year graduate student at outreach as a ripple eect: Impacting ing 14.5-foot wall. After an eort- University of Wisconsin–Madison. one child can change the lives of so less mount, I hit my rst buzzer and He also is training to become the many more. turned to the crowd as adrenaline next American Ninja Warrior.

46 ASBMB TODAY NOVEMBER 2016 NOVEMBER 2016 ASBMB TODAY 47 OPEN CHANNELS

Re: “A good little girl” as “all” or “never” — is the thin line is useless just because it does not lead between assignment of an undesirable to whatever direct personal gain one (October 2016) characteristic exclusively to a people might anticipate. October’s ASBMB Today fea- versus the assignment of an entire e third problem with the essay tured an essay by the pseudonymous people to a given characteristic. A is Dr. Phlox’s proposed solution to an “Sydney Phlox” on academic institu- parallel example from racist language overburden of institutional service. tional service. While the essay does would be the phrase “all good math Having built a case that males are per- raise valid concerns on the problem of students are Asian,” which is virtually haps better at saying no, her proposed balancing administrative workload in indistinguishable from “all Asians are solution is for females to get better at academia (a topic I also have writ- good at math.” Both phrases are oen- saying no. It does not take much logic ten about: www.psblab.org/?p=282), sive despite their very dierent mean- to realize the dire consequences of a its message is diluted by a somewhat ings. In her essay, Dr. Phlox claims all world in which everyone says no! sexist narrative, a cynical view on disobedience is male, without perhaps Clearly, there are areas of academic the importance of service for career realizing this may be interpreted as life where certain groups (males, if Dr. development and a proposed solution implying all males are disobedient. Phlox is to be believed) are not pull- that amounts to “screw the system.” e second part of the essay is a cri- ing their weight. When we see other It bears remembering that such a tique of the value of institutional ser- academics shirking their community complaint about the burden of being vice in general, in which we hear anec- responsibility, it may be tempting to involved in decision-making roles in dotes about committees Dr. Phlox has emulate them. But the result is a self- academia comes against a backdrop sat on being a “waste of time.” While ish race-to-the-bottom culture. In par- of decades of discussion regarding the most academics can relate to at least ticular, if women say no more often, lack of female representation in such some worthless administrative activity, what will that do for their already roles. there is a need for service to be looked poor representation in the decision- Dr. Phlox begins with a series of at in ways other than “what’s in it making processes of academia? Instead personal anecdotes about male versus for me?” ere are clearly numerous we should be thinking about how to female student behavior, but the indirect mechanisms by which service get everyone to contribute, incentiv- narrative quickly degenerates into can enhance one’s career: Serving on a ize service for those who do not see its sweeping statements in which vari- promotions committee can help with value and share administrative burdens ous undesirable character traits are preparing your own packet. Serving more fairly. If we all become refuse- assigned exclusively to males. Hiding on a National Institutes of Health niks, everyone loses. behind the universal disclaimer of “in study section undoubtedly improves — Paul S. Brookes, my experience,” Dr. Phlox tells us that your grant-writing skills. Exposure to University of Rochester Medical Center all obstinate students are male and the journal editing process results in that various atrocious study habits crafting better responses to reviewers. Re: A good little girl never are seen in females. Serving on an animal use commit- e problem with such statements tee may aord input on modifying (October 2016) regulations. Yes, committees are a time — particularly the use of words such OK, let’s follow this to logical suck, but it is naïve to claim service conclusions: We all quit reviewing. No reviews happen, and nothing gets published in a timely fashion. Administration does a further takeover of responsibilities, as faculty has abdicated them. No one is tending to admissions tasks, so you have no new students. Is that what functional academia looks like? Why not encourage men to step it up and do the service work that is required to make the profession go, to stand up to the man who called you a good little girl and say “at’s damned right, and you should be too?” —Ann Taylor, Wabash College

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