Vol. 19 / No. 4 / April 2020

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR AND MOLECULAR BIOLOGY

‘‘ The magic isn’t the squid… The magic is the protein.’’ Don’t wait a lifetime for a decision.

C. elegans daf-2 mutants can live up to 40 days. JBC takes only 17 days on average to reach a fi rst decision about your paper.

Learn more about fast, rigorous review at jbc.org.

www.jbc.org NEWS FEATURES PERSPECTIVES 2 22 37 EDITOR’S NOTE ‘THE MAGIC ISN’T THE SQUID ... USE THE MIC! Caution: Tchotchkes at work The magic is the protein.’ 38 3 28 WHAT CAN YOUR OMBUDS OFFICE MEMBER UPDATE ‘START SIMPLE. IT ALWAYS GETS DO FOR YOU? MORE COMPLICATED.’ 6 A conversation with Paul Dawson IN MEMORIAM

10 ANNUAL MEETING RETROSPECTIVE Marilyn Farquhar (1928 – 2019) 32 MOLECULAR & CELLULAR PROTEOMICS SESSION 13 LIPID NEWS 32 A deeper insight into phospholipid MCP TO HOST PROTEOMICS SESSION biosynthesis in Gram-positive bacteria 33 GINGRAS STUDIES PROTEOMICS’ IMPLICATIONS FOR RESEARCH 14 34 JOURNAL NEWS SELBACH SEEKS THE SCIENCE BEHIND THE MAGIC 14 Scrutinizing pigs’ biggest threat 35 15 Progesterone from an unexpected source GARCIA USES MASS SPECTRONOMY TO UNRAVEL THE HUMAN EPIGENOME may affect miscarriage risk 16 Finding neoantigens faster — advances in the study of the immunopeptidome Don’t wait a lifetime for a decision. 18 From the journals

C. elegans daf-2 mutants can live up to 40 days. JBC takes only 17 days on average to reach a fi rst decision about your paper.

Learn more about fast, rigorous review at jbc.org.

52 www.jbc.org 28 22 MARCH 2020 ASBMB TODAY 1 EDITOR’S NOTE

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Caution: Tchotchkes at work OFFICERS COUNCIL MEMBERS

Gerald Hart Suzanne Barbour By Comfort Dorn

President Joan Broderick

e e _ Matt Gentry tchotchke (noun) \'chäch-k , -ke; 'tsäts-k \: knickknack, trinket Toni M. Antalis Blake Hill President-elect Audrey Lamb Origin: Yiddish tshatshke trinket, from obsolete Polish czaczko Wei Yang James M. Ntambi First Known Use: 1971 —Merriam Webster Unabridged Secretary Takita Felder Sumter Kelly Ten–Hagen Joan Conaway JoAnn Trejo Treasurer n my office windowsill I have a plastic margarita glass full of paper umbrel- ASBMB TODAY EDITORIAL las, a small pot of succulents, a pottery jar wearing a scarf and hat, a plastic EX-OFFICIO MEMBERS ADVISORY BOARD Obutterfly ring, a fidget spinner and a sign that reads “Crazy cat lady.” Robert S. Haltiwanger Rajini Rao These are my office tchotchkes. They’re usually more spread out, but I Carla Koehler Chair Co-chairs, 2020 Annual Ana Maria Barral wanted to pose them: Meeting Program Committee Natasha Brooks Kelly Chacón Cheryl Bailey Chair, Education and Beronda Montgomery Professional Development Bill Sullivan Committee Melissa Vaught Binks Wattenberg Daniel Raben Chair, Meetings Committee ASBMB TODAY Sonia Flores Angela Hopp Chair, Minority Affairs Executive Editor Committee [email protected] Nicole Woitowich Comfort Dorn Chair, Science Outreach and Managing Editor Communication Committee [email protected] Terri Goss Kinzy Lisa Schnabel Chair, Public Affairs Graphic Designer Advisory Committee [email protected] Ed Eisenstein John Arnst We all have these things, right? The random objects that accumulate in Chair, Membership Committee Science Writer our workspaces and make them our own. Look around your desk/office/lab. Susan Baserga [email protected] What do you see? You can probably tell a story about where each of these Chair, Women in Biochemistry Laurel Oldach and Molecular Biology Science Writter non–work-related things came from — and that’s what I want you to do. Committee [email protected] Regular readers might recall that we devote our August issue to the topic Sandra Weller Ed Marklin Chair, Publications Web Editor of careers. We invite you to submit essays and articles related to your career Committee [email protected] path, sharing what you’ve learned. We want to know what works (and what Lila M. Gierasch Allison Frick Editor-in-chief, JBC Multimedia and Social Media doesn’t) as ASBMB members seek and find the jobs that fit. A. L. Burlingame Content Manager We still want those serious, useful articles and essays (deadline: June 15), [email protected] Editor, MCP but we also want your tchotchkes. Barbara Gordon Nicholas O. Davidson Executive Director Take a picture of the knickknacks in your workspace (bonus points if Editor-in-chief, JLR [email protected] you’re in the photo too) and tell us their story: Where did you get them—and Kerry-Anne Rye Editor-in-chief, JLR when? What do you think about/feel when you look at them? You don’t need to write a lot. Keep it under 100 words. Then send your For information on advertising, contact Pharmaceutical Media Inc. at 212-904-0374 or [email protected]. picture (as a jpg file) and words to [email protected] by June 15. We’ll share them in our August 2020 issue.

Comfort Dorn Correction ([email protected]) is the The data sources for infographics in the story www.asbmb.org/asbmbtoday managing editor of ASBMB “A Matter of Degree” in the February issue were Today. Follow her on Twitter incorrect. Please refer to the web version of the PRINT ISSN 2372-0409 @cdorn56. story at asbmb.org/asbmbtoday for correct data citations. In the same article, Zerick Dunbar’s Articles published in ASBMB Today reflect solely the authors’ views and not school was misidentified; he attends Meharry the official positions of the American Society for Biochemistry and Molecular Medical College in Nashville. Also, Taylor Biology or the institutions with which the authors are affiliated. Mentions of Carmon’s compensation from Alabama A&M products or services are not endorsements. University was misstated; he is paid a stipend.

2 ASBMB TODAY MARCH 2020 MEMBER UPDATE

Young researchers present science The Emerging Researchers National Conference Molecular Biology, along with three faculty members. in STEM, hosted by the American Association for (See the full list of presenters at our website.) the Advancement of Science and the National Science Stephen Gonzalez, a student at California State Foundation, is an opportunity for underrepresented University, Fullerton, pictured above, said, “One of the undergraduate and graduate students to present their conversations that really stuck with me was with one research to peers and professors. of my poster judges … We got into a great talk about Among this year’s presenters were nine student my research. I cherished his time there, since he really members of the American Society for Biochemistry and made me grow more scientifically and as a presenter.”

Doudna, Charpentier share The 2020 Wolf Prize in medicine Biology’s inaugural Mildred Cohn will be awarded jointly to Jennifer Award in Biological . Doudna and Emmanuelle Char- Charpentier is a biochemist, pentier, whose work led to the microbiologist and geneticist rec- discovery of the gene-editing tool ognized as an expert in regulatory clustered regularly interspaced short mechanisms underlying processes of Doudna Charpentier palindromic repeats–CRISPR-associ- infection and immunity in bacte- ated protein 9, or CRISPR–Cas9. rial pathogens. She is scientific and Doudna is the Li Ka Shing managing director of the Max Planck Foundation will award the Wolf chancellor’s chair in biomedical Unit for the Science of Pathogens in Prize “to outstanding scientists and and health sciences and a professor Berlin, an institute that she founded artists from around the world … for of molecular and and with the Max Planck Society. achievements in the interest of man- professor of chemistry at the Uni- Doudna and Charpentier deter- kind and friendly relations among versity of California, Berkeley, and mined the mechanism of RNA-guid- peoples,” according to the founda- a Howard Hughes Medical Institute ed bacterial adaptive immunity by tion’s website. Wolf Prizes are given investigator. She studies how RNA the CRISPR-Cas9 system, enabling in art, agriculture, physics, medicine molecules control the expression them to harness the system for effi- and mathematics. A New York Times of genetic information. In 2013, cient genome engineering in animals article noted that the Wolf Prize is Doudna won the American Society and plants. thought of as one of the predictors of for Biochemistry and Molecular This is the 42nd year the Wolf a future Nobel Prize.

MARCH 2020 ASBMB TODAY 3 MEMBER UPDATE

National Academy of Inventors Society for Glycobiology presents awards names fellows Gerald Hart, Robert J. Linhardt and Manfred Wuhrer were among the researchers recently honored by the Society for Three ASBMB ­Glycobiology. members joined the Hart is president of the American Society for Biochemistry and ranks of the National Molecular Biology and a Georgia Research Alliance eminent scholar Academy of Inven- at the University of Georgia. He received the President’s Innovator tors in December as Award, given each year since 2015, which honors the contributions of Brown part of a class of 168 one scientist who has had a significant impact. new fellows. For Hart, that impact was not only creating a new field in glycobi- The academy was ology, the dynamic and inducible modification of nuclear and cytosolic launched in 2010 proteins via O-GlcNAc, but also shepherding its growth and providing to promote entre- “exemplary service to the glycobiology and life science community,” preneurship within the society’s website states. academia. According Linhardt, a professor at Rensselaer Polytechnic Institute, was Goldstein to the NAI website, honored with the Karl Meyer Lectureship Award. Established in 1990, its fellows program the award is given to well-established scientists who have made widely recognizes professors who have made recognized major contributions to the field of glycobiology. or contributed to “outstanding inven- Linhardt has contributed to the understanding of glycosaminogly- tions that have made a tangible impact cans and heparins. He was a co-discoverer of polyanhydrides for drug on quality of life, economic develop- delivery, which resulted in a wafer to treat brain cancer, and he also ment and the welfare of society.” helped introduce low-molecular-weight heparins into the market. These ASBMB members are Wuhrer, head of the Center for Proteomics and Metabolomics among the 2019 NAI fellows: at Leiden University Medical Center in the Netherlands, received Michael Brown and Joseph the Molecular & Cellular Proteomics/ASBMB Lectureship Award. Goldstein of the University of Texas Established in 2013, the award honors scientists who have been at the Southwestern, longtime colleagues forefront of the emerging field of glycomics and glycoproteomics. and collaborators, are known for dis- Wuhrer’s recent research has focused on analyzing the glycans of covering the low density lipoprotein, human proteins, with particular attention to immunoglobulins. His or LDL, receptor and the SREBP work on technology centers on higher throughput mass spectrometry transcription factor family, among glycomics workflows, which his lab applies to unravel protein glyco- other important contributions to the sylation signatures of various human diseases including autoimmune field of lipid . The two, diseases, infectious diseases, metabolic disorders and cancer. who shared a Nobel Prize in 1985, Also honored were Nancy Dahms, who received the Rosalind hold 29 patents jointly. Kornfeld Award for Lifetime Achievement in Glycobiology (reported Victor Hruby last month in ASBMB Today), and Jochen Zimmer, who received the of the University Press Glycobiology Significant Achievement Award. Arizona studies the These awards were presented at the Society for Glycobiology’s design and synthe- annual meeting, held in Phoenix in November. sis of biologically active peptides and Hruby peptide mimics with biological activity. He holds 27 patents for peptide hormone mimetics. The NAI has more than 4,000 members and fellows at more than Hart Linhardt Wuhrer 250 institutions worldwide.

4 ASBMB TODAY MARCH 2020 MEMBER UPDATE

Belfort wins honorary degree Honors for Hall and research partner The University of Biochemist Michael Hall has won two awards Cape Town has con- with David Sabatini for their roles in the discovery ferred an honorary of mTOR, the mammalian target of rapamycin: the doctorate of science BBVA Foundation Frontiers of Knowledge Award in on Marlene Belfort, biology and biomedicine and the Royal Swedish Acad- a distinguished pro- emy of Sciences’ Sjöberg Prize. Belfort fessor in the depart- Hall Hall, a professor of biochemistry in the Biozen- ments of biological trum Center for Molecular Life Sciences at the University of Basel, sciences and biomedical sciences at Switzerland, discovered the target of rapamycin in yeast in 1991. the State University of New York at Several years later, Sabatini, then a graduate student, discovered its Albany. mammalian homolog. Belfort received a bachelor’s de- Before Hall’s lab demonstrated that yeast’s TOR complexes link gree from UCT in 1965 followed by nutrient availability to protein translation and the growth phase of the doctoral and postdoctoral work at the cell cycle, researchers did not know that growth was actively regulated. University of California, Irvine, and Later work from the lab linked mTOR activity to nucleotide synthesis the Hebrew University of Jerusalem. and cytoskeletal organization. Her lab at SUNY Albany ex- This stronger understanding of mTOR signaling has had clinical plores the dynamics of elements that implications. The kinase is overactivated in many cancers and has been interrupt genes, introns and inteins, linked to diseases such as diabetes. Rapamycin, the original mTOR studying their structure, function inhibitor, is used as an anti-cancer agent, an immunosuppressant for and regulation and their applications organ transplantation and a coating for coronary stents to block new in biotechnology and infectious growth. Researchers believe reduced mTOR signaling is involved in disease. Her achievements include the the longer lifespans of mice fed restricted diets, leading to hopes that self-splicing of introns in bacterio- mTOR inhibitors might limit the effects of aging-related diseases. phage T4 and a detailed analysis of the Hall and Sabatini received the Frontiers of Knowledge award in splicing mechanism. Her recent work January; it includes a commemorative sculpture and a €400,000 cash has led to development of a model for prize split among the winners in each category. The Sjöberg Prize, the mechanism of intron evolution awarded in early February, consists of $1 million, divided between the that is applicable to prokaryotes and awardees. Hall also received a Lasker Award in 2017. may shed light on vertebrate genes. Belfort has mentored younger sci- entists, technicians, undergraduates, students to receive a 2020 Marshall ing and research presentation. In postgraduates and even high school Scholarship. March, undergraduates from across students. Within the global scientific Evensen is set to graduate this the region are expected to attend the community, she is known for her spring with a bachelor’s degree in bio- Molecules in the Midwest conference support of women in science. chemistry and mathematics. For three at UW–Madison. Belfort received her honorary years, she has researched the biophysics Established in 1953 to honor the doctorate in December. of transcription initiation with Thomas ideals of the Marshall Plan, the Mar- Record, the John D. Ferry professor of shall Scholarship Program gives Evensen wins Marshall biochemistry. She earned several cam- high-achieving young Americans the Claire Evensen, pus research grants to support her work opportunity to study at the graduate president of the and presented her research at national level at any university in the United American Society for conferences. She is a Goldwater scholar, Kingdom. Up to 50 scholarships are Biochemistry and an Astronaut scholar and a finalist for a awarded each year. Molecular Biology Rhodes scholarship. Evensen plans to join a master’s Student Chapter at As president of her ASBMB Stu- degree program in mathematical Evensen the University of dent Chapter, Evensen has organized modeling and scientific computing at Wisconsin–Madison, is one of 46 a regional conference on network- the University of Oxford.

MARCH 2020 ASBMB TODAY 5 IN MEMORIAM

Kenneth Standing Judith Saffran

Kenneth G. Judith Saffran, a cancer Standing, a pioneer researcher and a quiet pioneer in in time-of-flight women’s postgraduate education, mass spectrometry died Jan. 14 in Queens, New York. and its applications She was 96. to study biological Born Judith Cohen in Montreal macromolecules, in 1923, she attended McGill Uni- died March 21, versity, earning a bachelor’s degree 2019. He was 93. in chemistry in 1944 and a Ph.D. in Born and raised biochemistry in 1948. She married in Winnipeg, Can- Murray Saffran, a fellow McGill stu- ada, Standing earned an undergraduate degree at dent, in 1947 and did postdoctoral research at Montreal’s Jewish the University of Manitoba and completed his M.A. General Hospital. She taught an advanced biochemistry lab class and Ph.D. in nuclear physics under Rubby Sherr at McGill for several years. at Princeton University. He joined the University of The Saffrans moved to the U.S. in 1969 and settled in Ohio, Manitoba faculty in 1953; there he designed, built where Judith worked as a researcher first at Toledo Hospital and and commissioned a cyclotron particle accelerator. later at what was then the Medical College of Ohio (now the Uni- In the late 1970s, Standing changed the focus versity of Toledo College of Medicine and Life Sciences). Murray of his research to TOFMS, an essential component founded the department of biochemistry at the college and was a of the proteomics field. He collaborated with biolo- pioneer in the research of stress hormones. He died in 2004. gists to solve a range of problems; during the SARS Judith Saffran and her colleagues examined the binding and outbreak in 2002 and 2003, his group provided metabolic activity of the hormone progesterone, which is crucial sequence information for much of the virus’ protein to a wide array of biological activity such as neuronal develop- structure before the genome was sequenced. He ment, steroid production and breast development. In its synthetic retired as a professor in 1995 but continued his research as an emeritus professor well into his 80s. Standing’s many awards and accolades includ- ed the American Chemical Society Field and Frank- Harold W. Gardner lin Award for outstanding achievement in mass spectrometry and the Encana Principal Award from Harold W. Gardner, a biochemical researcher and environ- the Ernest C. Manning Foundation, known as Cana- mental activist who lived most recently in Carlisle, Pennsylvania, da’s Nobel Prize. He was elected as a fellow of the died Nov 6. He was 84. American Physical Society and of the Royal Society After service as a U.S. Navy courier, Gardner earned a Ph.D. of Canada. In 2009, the University of Manitoba in biochemistry at Pennsylvania State University. He worked as a awarded him its highest honor, the honorary degree researcher at the Pineapple Research Institute in Honolulu, at the of doctor of science. University of California, Los Angeles, and at the Agricultural Re- Standing is survived by his children and their search Service (an agency of the U.S. Department of Agriculture) spouses: Mike and Brenda Janz; Tim; Liz and in Peoria, Illinois. His focuses included lipid chemistry, enzymolo- Clarence Jackson; and Jon and Andrea Jackson. gy, free radical chemistry, fungal products and plant ecology. He He also is survived by his grandchildren, Willem, published more than 120 papers and was an associate editor for Tannin, Rachel, Luke and Corin. the journal Lipids. Gardner worked with the Sierra Club on projects to preserve water quality in the Illinois and Mississippi rivers. After his retire-

6 ASBMB TODAY MARCH 2020 IN MEMORIAM

Albert S. Mildvan forms, progesterone is prescribed in therapies including meno- Albert Samuel pausal hormonal therapy and gender-affirming therapy. It also is Mildvan, an emer- involved in the pathophysiology of breast cancer. To help elucidate itus professor of this function, Saffran investigated the hormone’s activity in cul- biological chemistry tures of uterine cells derived from rats and guinea pigs. She also and chemistry at explored the regulatory effect of hormone on the production of the Johns Hopkins other endogenous steroids. She retired from the Medical College University School of of Ohio in 1997. Medicine, died Oct. Saffran, who was descended from a Russian Jewish family, 24 in Baltimore after volunteered in the 1990s with the Toledo chapter of ORT, an in- a prolonged illness. ternational charity founded in 19th century Russia that describes He was 87. itself as a “global educational network driven by Jewish values.” Born in Philadelphia, Mildvan earned a bach- She moved to New York in 2014 to be closer to her daughter, who elor’s degree in chemistry and mathematics from was a professor of biochemistry at Queens College. the University of Pennsylvania in 1953 and an M.D. Few women of Saffran’s generation had doctoral degrees. from Hopkins in 1957. After postdocs at the Nation- “She was a pioneer in women’s higher education and in women’s al Institutes of Health and Cambridge University, work as scientists,” her son David Saffran told the Toledo Blade. he did an advanced postdoctoral fellowship with “She was also humble. She never thought she was special, and Mildred Cohn at the University of Pennsylvania, she never bragged about her education and her status as a scien- where he developed expertise in nuclear magnetic tist.” resonance and electron paramagnetic resonance, Saffran is survived by her daughter, Wilma Saffran; sons, spectroscopic techniques that became the back- David, Arthur and Richard Saffran; nine grandchildren; and five bone of his research career. He was on the faculty great-grandchildren. of the University of Pennsylvania before returning to Baltimore in 1981 to join the Hopkins faculty. The author of more than 270 publications covering a range of protein biochemistry and enzy- mology, Mildvan studied the mechanism of enzyme action and its relevance to neoplastic, cardiovascu- lar and metabolic disease. He discovered the first ment, he focused on tallgrass Mn2+ metalloenzyme, pyruvate carboxylase, and prairie restoration in Illinois, made key contributions to the interpretation of the writing a book and numerous effects of site-directed mutagenesis. papers on native plants. He later Mildvan served on the editorial board of the owned a 70-acre preserve Journal of Biological Chemistry from 1979 to 1991, in Pennsylvania and advised the and in 1988 he received the American Society Penn State Arboretum on their for Biochemistry and Molecular Biology’s Herbert prairie project. Sober Prize recognizing outstanding biochemical He is survived by his wife, and molecular biological research. Cheryl Pauli; two daughters, Kelly He is survived by his wife, Patricia June Tarr Gardner and Denali Brooke; three Mildvan; children Heather Mildvan Pytel, Pamela sons, Scott Gardner, Michael Gardner and Bryce Gardner; and five Mildvan Cummins and Margo Susan Mildvan; sons- grandchildren. in-law Theodore R. Cummins and Eric T. Arnold; sister Donna Mildvan; and grandchildren Hannah and Benjamin Cummins and Clement Pytel.

MARCH 2020 ASBMB TODAY 7 IN MEMORIAM

Robert L. Herrmann Ervin Erdös

Biochemist Ervin G. Erdös, who survived Robert L. Herrmann a German concentration camp to died Dec. 12 at the become a distinguished professor age of 91. and medical researcher in the U.S., Herrmann was died Nov. 17 at the age of 97. born in 1928 in New Erdös was born into a Jewish York City and grew family in 1922 in Budapest, where up in Queens. His his father worked as an engineer pursuit of an under- until Hungary joined the Axis na- graduate degree in tions after Hitler’s rise to power. He chemistry at Purdue was conscripted to a forced labor University was interrupted by two years of service in brigade, and after invaded Hungary in 1944, he and his the Navy on the U.S.S. Shenandoah, after which he father were sent to the Sachsenhausen concentration camp in married his childhood sweetheart, Betty Ann Cook. Germany, where they witnessed many atrocities. He then returned to Purdue, finished his degree After the camp was liberated, Erdös returned to Budapest and enrolled as a graduate student at Michigan and enrolled in medical school. In 1950, he fled the Communist State University. In 1956, he accepted a Damon regime and completed his medical degree in Munich. He then Runyon fellowship at the Institute of worked in a German laboratory, where he began studying how Technology. In 1957, Herrmann joined the American Scientific Affiliation, or ASA, a Christian religious or- Hans Kornberg ganization of scientists, and remained active in the group for many decades. There, he met the investor and philanthropist Sir John Templeton, with whom University biochemist Sir Hans Kornberg died Dec. 16. he collaborated in writing several books, including He was 91. Templeton’s biography. Herrmann was a founding Born in 1928 to a Jewish family in Germany, Kornberg fled to member of the John Templeton Foundation, which the United Kingdom in 1939, staying with an uncle in Yorkshire. supports research at the intersection of science After finishing grammar school, he gravitated toward chemistry and religion. and became a junior laboratory technician for , who After completing his postdoctoral fellowship, discovered the eponymous metabolic cycle, at the University of Herrmann took a faculty position at Boston Uni- Sheffield. Kornberg worked in Krebs’ lab through his time at the versity, where he taught biochemistry for 17 years. university, where he earned a bachelor’s degree in chemistry in Following a stint teaching biochemistry at Oral Rob- 1949 and a Ph.D. in biochemistry in 1953. erts University in Tulsa, Herrmann moved back to After postdoctoral stints in the U.S. and U.K. and lecturing at New England in 1981 to serve as executive director the University of Oxford at Krebs’ behest, Kornberg was appointed of the ASA, a position he held until his retirement in as the first chair in biochemistry at the in 1994. 1960. In 1975, he moved to the , where Herrmann is survived by his wife, Elizabeth he was appointed the Sir William Dunn chair of biochemistry. He Herrmann; sister, Carol; children, Stephen, Karen, also served as the master of Christ’s College and then deputy vice Holly and Anders; and eight grandchildren. chancellor until his mandatory retirement in 1995. He then took a job at , where he continued his research and taught upper-level biochemistry. Kornberg’s seven-decade research career focused on the reg- ulation of carbohydrate transport in microorganisms. He authored

8 ASBMB TODAY MARCH 2020 IN MEMORIAM

Irwin Fridovich enzymes and peptides aid in the control of blood pressure. Irwin Fridovich, Erdös moved to the U.S. in 1954. He worked first at Carnegie a professor emeritus Mellon University and then moved to Oklahoma City, where he at Duke University served as head of pharmacology at the University of Oklahoma and past president Medical School from 1963 to 1973. From there, he moved to the of the American University of Texas Southwest Medical Center in Dallas, where he Society for Biochem- became a professor of pharmacology and ran a research labora- istry and Molecular tory. In 1985, he moved to Chicago and served as a distinguished Biology who also professor at the University of Illinois at Chicago. served on the Erdös was recognized for his work on angiotensin I converting Journal of Biological enzyme, or ACE. He discovered that ACE exerted a dual effect on Chemistry editorial blood pressure by controlling two oppositely acting peptides. board and on the ASBMB Today editorial advisory He is survived by his wife, Sara Rabito; sons Peter and Philip board, died Nov. 2. He was 90 years old. and their wives; and four granddaughters. He was preceded in Born in 1929 in Brooklyn, New York, Fridovich death by his son Martin Erdös. attended the Bronx High School of Science and Read “An exploration of bioactive peptides: My collaboration the City College of New York before earning a Ph.D. with Ervin G. Erdös” by Rajko Igic at jbc.org. in biochemistry at the Duke University Medical Center. Duke invited him to become a faculty member, and he remained at the university for more than 60 years. In his long and distinguished career, he published more than 500 scientific articles and discovered superoxide dismutase, or SOD, es- more than 250 papers and sentially founding the field of free radical biology. notably elucidated the glyoxylate A November 1969 paper about SOD, written by cycle, which is used by plants Fridovich and then–grad student Joe M. McCord and other nonanimals to enable and published in the Journal of Biological Chemis- the biosynthesis of biomass from try, has been cited more than 9,300 times. 2-carbon compounds, as well Fridovich served as president of several profes- as the concept of anaplerosis, sional societies, including the ASBMB in 1982, and an important mechanism for earned several lifetime achievement awards. He ensuring carbon oxidation by the was a member of the National Academy of Sciences Krebs cycle. and the American Academy of Arts and Sciences. In He was made a fellow of the 1997, he shared the Elliott Cresson Medal from the Royal Society in 1965 and knighted in 1978. He was a fellow of Franklin Institute with McCord. He was appointed the the American Academy of Microbiology and a foreign associate James B. Duke professor of biochemistry in 1976. member of the National Academy of Sciences and the American He continued to go to Duke every weekday until Academy of Arts and Sciences. about four months before his death to read the lat- Kornberg met Monica King at Oxford; they married in 1956 est scientific journals and to enjoy weekly lunches and had four children. King died in 1989, and Kornberg remar- with friends and colleagues. ried in 1991; his wedding with Donna Haber was the first Jewish Fridovich was married for 59 years to the for- wedding to take place on the Cambridge campus. He is survived mer Mollie Finkel. He is survived by his daughters, by Haber; his daughters, Julia and Rachel; his twin sons, Jonathan Sharon F. Freedman and Judith L. Fridovich-Keil; and Simon; and grandchildren and great-grandchildren. brother, David Fridovich; two grandchildren and

MARCH 2020 ASBMB TODAY 9 RETROSPECTIVE

Marilyn Farquhar (1928 – 2019) By John Bergeron & J. David Castle

he passing of Marilyn Farquhar on Nov. 23 brought to a close a T long and inspiring career in cell biology. She rightly ranks among the pioneers in her field and especially as a role model for women in science.

We met Marilyn more than 50 PRESS years ago at the Rockefeller Univer- sity when she was a visiting professor in George Palade’s lab. Marilyn had worked previously with Palade, and their early and classic insights into the organization of epithelial junc- tions, published in the period 1963- 65, remain a staple in medical and cell biology textbooks to this day. Here were characterized, in detailed resolution, tight junctions, intermediate junctions, and des- mosomes, along with basement membranes that Marilyn was later to study in detail, especially in the kidney glomerulus. These are the defining feature of all epithelia in our bodies. At Rockefeller in 1969, Marilyn Marilyn Farquhar was an electron microscopy pioneer and a treasured mentor to generations was part of an amazing group of of cell biologists. colleagues that included David Sabatini, Günter Blobel, Phil partment of experimental of numerous students and colleagues Siekevitz, Jim Jamieson and David at the University of California, San and a host of collaborators. Luck. Marilyn and George had close Francisco. Shortly after she arrived, She married George Palade in interactions with a paper from her work at UCSF was 1970, and her sabbatical at Rockefel- and his group, located in the same published that conceptually unified ler turned into an extended trans- building at Rockefeller. Collectively, and showed in intricate detail the continental migration. Together, they the pioneers’ focus was on decipher- structures that captivated the Palade moved to in ing mechanistically the workings and De Duve labs. 1973, where she became the Sterling of the cell, especially its mem- She was clearly among the stan- professor of cell biology. At Yale, she brane-bounded organelles, which dard setters in a department and in- was a major force in shaping the new often were being seen and studied stitution loaded with scientific talent. section of cell biology that ultimate- for the first time. Furthermore, because she was both ly became the department of cell Marilyn came for her sabbatical friendly and easily approachable, she biology. As she continued to make at Rockefeller from her lab in the de- enriched the scientific environment contributions in discovery research,

10 ASBMB TODAY MARCH 2020 RETROSPECTIVE ROCKEFELLER UNIVERSITY PRESS ROCKEFELLER UNIVERSITY PRESS

This image from a 1965 paper in the Journal of Cell Biology by Marilyn Farquhar and George Palade shows a desmosome linking the plasma membranes of cells located in the granular (SG) and cornified layers of amphibian skin. Magnification x 135,000.

This image from a 1970 paper in the Journal of Cell Biology by Dorothy Bainton and Marilyn Farquhar shows concentration of myelocyte peroxidase within the secretory pathway of a rabbit eosinophil beginning in the endoplasmic reticulum (labeled er) and progressing through the Golgi (Gc) and maturing secretory granules (ig). Parallel observations for acid phosphatase and arylsulfatase pointed to the -like nature of these granules. Magnification x 43,000.

she also developed a modern cell She earned her undergraduate and recycling. Her discoveries on the bio- biology course that became a valued graduate degrees at the University of genesis of glomerular basement mem- component of the medical school California, Berkeley, and then moved branes included the classic definition curriculum. to the Rockefeller University in New of the role of associated proteoglycans At Rockefeller and at Yale, Mari- York City for postdoctoral training in regulating glomerular filtration. lyn and George were close friends and with George Palade before joining She and her colleagues clarified the colleagues of visiting Romanian sci- the faculty at UCSF. In 1990, she re- organization, trafficking, signaling entists Nicolae and Maya Simionescu, turned to California as the founding and pathological roles of podocalyxin and they strongly encouraged Nicolae chair of the department of cellular and megalin in renal and and Maya, who were pioneers in and molecular medicine of the proximal tubule cells. bringing modern cell biology to University of California, San Diego, As time progressed, Marilyn Romania. Marilyn and George were Medical School. became a major force in exploring the honored guests at the inauguration We continue to appreciate Mar- roles of G protein-coupled receptors, of the Institute of Cell Biology and ilyn’s early contributions to under- growth factor receptors and associated Pathology in Bucharest, celebrated in standing the developmental regula- regulatory complexes in intracellular 1979 with an international sympo- tion of leukocyte granulogenesis and membrane trafficking. As with sium featuring giants in the field, all granule turnover in endocrine cells by the work of all great scientists, the of whom were Marilyn’s close friends lysosomal degradation. She made nu- approaches employed by Marilyn’s and colleagues. merous contributions to unraveling laboratory evolved with the times. Marilyn was always proud that the intricacies of the Golgi apparatus, She maintained her creative use of she was California born and raised. including biogenesis, sorting and electron microscopy as a signature

MARCH 2020 ASBMB TODAY 11 RETROSPECTIVE COURTESY OF MAYA SIMIONESCU COURTESY OF MAYA

This photo taken in 1979 at the inaugural symposium of ICBP Bucharest shows, in the front row, from left to right, Werner Franke, Maya Simionescu, Gunter Blobel, Marilyn Farquhar, George Palade, Christian De Duve, Nicolae Simionescu and David Sabatini.

experimental tool throughout her colleagues, including us, with eager career. interest and always with encourage- John Bergeron ([email protected]) Marilyn’s achievements were ment. We remember her ready smile is emeritus Robert Reford recognized with many awards and and cheerful disposition. Her mem- professor and a professor of medicine at McGill honors including election to both the ory provides enduring inspiration to University. National Academy of Sciences and all of us who had the good fortune to the American Academy of Arts and follow the beauty and impact of her Sciences. She received the American discoveries.

Society for Cell Biology’s E.B. Wil- The authors thank Maya David Castle son Medal and the American Society Simionescu (ICBP, Bucharest); ([email protected]) is a professor emeritus of cell of Nephrology’s Homer W. Smith Susan Ferro-Novick (University biology at the University of Award. She was particularly grati- of California, San Diego); Stuart Virginia School of Medicine. fied by the Federation of American Kornfeld (Washington University, Societies for Experimental Biology St. Louis); Colin Hopkins (Imperial Award for Excellence in Science that College, London); Bill Brown (Cornell she received in 2006 at the American University); Pietro De Camilli (Yale Society for Biochemistry and Molec- University); David Sabatini (New ular Biology Annual Meeting in San York University) and Kathleen Dickson Francisco. (McGill University) for their comments Marilyn followed the accom- and suggestions. plishments of her trainees and

12 ASBMB TODAY MARCH 2020 LIPID NEWS

A deeper insight into phospholipid biosynthesis in Gram-positive bacteria By Diego E. Sastre & Marcelo E. Guerin

ram-positive bacteria can cause Journal of Biological Chemistry, serious and sometimes fatal in- we propose a model in which Gflammatory diseases including membrane fluidity governs the DIEGO SASTRE pharyngitis, pneumonia, myocardi- membrane insertion of PlsX, which tis, meningitis, and septicemia. These is required for the proper acyl- bacteria synthesize phosphatidic acid, phosphate delivery to PlsY. the central precursor of membrane Our model breaks a paradigm in phospholipids, using an unusual membrane biology: The membrane acyl-phosphate intermediate in a fluidity and unsaturated fatty acids, three-step pathway mediated by or UFAs, do not seem to hold hands. three phospholipid synthesis en- At higher membrane fluidity, PlsX zymes: PlsX, PlsY and PlsC. inserts deeper into the membrane, This schematic representation shows binding/ PlsX is a peripheral membrane but increased UFA content reduces insertion of PlsX to lipid bilayers. transacylase that catalyzes the con- PlsX binding and insertion. version of acyl-acyl carrier protein to How can PlsX sense the UFAs, channeling as well as the protein acyl-phosphate and helps coordinate and why do UFAs repel PlsX bind- crowding, regulating the phospholip- fatty acid and phospholipid biosyn- ing and insertion? We suspect the id biosynthesis. thesis. PlsX binds and inserts directly repulsion effect might be part of a These results highlight the to lipid bilayers, a process mediated mechanism to downregulate the total relevance of spatial organization for by an amphipathic four alpha-helical phospholipid synthesis observed at metabolic pathway functioning and bundle subdomain that protrudes low growth temperature. tell us more about how membrane from the main core of the enzyme. In membrane insertion, periph- composition and protein mobility In disentangling this binding eral proteins can cluster as transient can modulate this biosynthesis route. and insertion of PlsX, our lab has oligomers when interacting with PlsX and PlsY are present in patho- found that PlsX membrane binding lipid bilayers. This crowding would genic bacteria and absent in eukary- is mediated by phospholipid charge, be intensified with increased protein otes, so the results offer exciting whereas unsaturation of fatty acids radius and depth of penetration possibilities for inhibitor design to and membrane fluidity influence into the hydrophobic region of the fight antibiotic-resistant bacteria. membrane insertion. Superficial membrane. PlsX mostly is distrib- DOI: 10.1074/jbc.RA119.011122. access to the membrane is not suffi- uted homogenously at the bacterial Diego E. Sastre was cient to ensure efficient delivery of cell membrane, but PlsX foci also are recently hired as an the acyl-phosphate from PlsX to the transiently and randomly observed, assistant research scientist in the Sundberg acyltransferase partner PlsY, which which could represent physiological lab in the department depends on proper and stable inser- oligomeric states related to the regu- of biochemistry at the Emory University School tion of PlsX in the membrane. Such lation of PlsX activity. of Medicine. substrate channeling can make this We propose that PlsX inserts Marcelo E. Guerin (mrcguerin metabolic pathway more efficient deeper into more fluid membranes @cicbiogune.es) is an and prevents the release of unstable (containing little or no unsaturated Ikerbasque full research professor and head of the intermediates, protecting them from fatty acid content), causing oligo- structural glycobiology decomposition and/or diffusion mers, in the form of foci at the mem- laboratory at the Structural Biology Unit of the Center through the aqueous cytoplasm. brane. Thus, modulating membrane for Cooperative Research in In a recent paper in the insertion could regulate the substrate Biosciences in Derio, Spain.

MARCH 2020 ASBMB TODAY 13 JOURNAL NEWS

Scrutinizing pigs’ greatest threat

By John Arnst

frican swine fever virus is harm- author Rebecca Dillard’s lab at the less to humans, but the virus — University of Leiden in the Nether- Aendemic to warthogs, bushpigs lands to collect images of a thousand and soft ticks in sub-Saharan Africa viral particles with a Titan/Krios — causes a hemorrhagic fever in transmission electron microscope. domestic swine and has devastated The virus’ size also causes its capsids pig population across China and to span more than one focal plane, southeast Asia. ABRESCIA ANDRÉS, N.G. CHARRO, G. D. contributing to image blur, so Abres- The virus’ unique multi-layered cia and Andrés biochemically decon- architecture may be blocking vaccine structed the virus in solution, and development. Nicola G. A. Abrescia, then purified and resolved the fold of German Andrés and their colleagues the individual protein composing the recently peered between those outer capsid. membranes to capture the structure Abrescia’s team isn’t alone in of ASFV’s virion. They described pursuing the structure of ASFV. Just its architecture in the Journal of African swine fever, which ravaged domestic before their JBC paper appeared Biological Chemistry. and feral pig populations in Spain and Portugal online, a group at the Chinese Acad- “What was striking is that in the 1980s, was eliminated from the Iberian emy of Sciences in Beijing described actually you have four layers: two Peninsula by 1995. Today, the Georgia 2007 the pathogen’s structure at greater envelopes and two protein capsids strain, which originated in sub-Saharan Africa resolution in the journal Science, and for this virus,” said Abrescia, a but emerged in the Republic of Georgia in later a third group at the University structural biologist at the Center for 2007, poses a monumental threat to the pork of Science and Technology of China Cooperative Research in Biosciences industries of Central and East Asia. published another cryo-EM analysis near Bilbao, Spain. “So you have this in the journal Cell Host & Microbe. outer envelope which is acquired A fourth group earlier described the when the virus goes out of a cell, but vaccine design. structure of ASFV’s major capsid below this envelope you have anoth- One challenge: ASFV is big — a protein p72 in the journal Cell er set of icosahedral capsids and in giant virus, in fact, almost twice the Research. between a membrane bilayer, all of size of influenza virions and thicker Despite these successes, the inner them enclosing the genome-contain- than the typical layer of ice in which capsid remains a challenge. “Even ing nucleoid.” particles are suspended for cryo-elec- the high-resolution structures that In previous studies, Andrés — a tron microscopy. This complicates our Chinese colleagues have ob- senior researcher at the Centro de sample preparation. Most micro- tained do not fully explain the inner Biología Molecular Severo Ochoa’s scopes’ field of view can capture only capsid,” Abrescia said. “Indeed, it has Electron Microscopy Unit in Madrid a few virus particles, challenging remained something that requires — found that both the extracellular efficient data collection. And despite more exploration.” and intracellular forms of ASFV are its size, ASFV’s outer membrane isn’t infectious. This suggested that the resilient outside of a host. outer membrane might not be neces- “The outer lipid envelope is rela- John Arnst (jarnst@ sary for infectivity, as the virus sheds tively fragile,” Abrescia said, “so you asbmb.org) is an ASBMB Today science writer. its coat while entering into a host have to set up a very good purifica- Follow him on Twitter @ cell. The researchers hope a better tion protocol which doesn’t destroy understanding of ASFV’s structure so much of the virus’s envelope.” might contribute to more efficient The researchers went to co-

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Progesterone from an unexpected source may affect miscarriage risk By Laurel Oldach

bout 20% of confirmed preg- nancies end in miscarriage, Amost often in the first trimester, for reasons ranging from infection to chromosomal abnormality. But some

women have recurrent miscarriages, ZEPHYRIS/WIKIMEDIA COMMONS a painful process that points to un- derlying issues. Clinical studies have been uneven, but some evidence shows that for women with a history These illustrations show the fingerlike projections called villi that attach the surface of the nascent of recurrent miscarriage, taking pro- placenta to the uterine lining during early pregnancy. gesterone early in a pregnancy might moderately improve these women’s chances of carrying a pregnancy face tissue organized into fingerlike to term. projections that integrate into the from the placenta than it is among A recent study in the Journal endometrium and absorb nutrients. women with healthy pregnancies. In of Lipid Research sheds light on a Some cells leave those projections contrast, levels of the enzyme don’t new facet of progesterone signaling and migrate into the endometrium, differ between healthy and miscar- between maternal and embryonic where they help to direct the reorga- ried pregnancies in cells from the tissue. The work hints at a prelimi- nization of arteries. surface of the placenta. nary link between disruptions to this Using cells from terminated The team’s findings suggest that signaling and recurrent miscarriage. pregnancies, Austrian researchers production of progesterone by the Progesterone plays an important led by Sigrid Vondra and supervised migratory cells may have a specific role in embedding the placenta into by Jürgen Pollheimer and Clemens and necessary role in early pregnancy the endometrium, the lining of the Röhrl compared the cells that stay on and that disruption to that process uterus. The hormone is key for thick- the placenta’s surface with those that could be linked to miscarriage. ening the endometrium, reorganiz- migrate into the endometrium. They “If we can identify the exact ing blood flow to supply the uterus discovered that the enzymes respon- mechanisms and cells that are affect- with oxygen and nutrients, and sible for progesterone production ed,” Vondra said, “that would lead us suppressing the maternal immune differ between those two cell types one step closer to understanding the system. early in pregnancy. big picture of what causes recurrent Progesterone is made in the ova- As a steroid hormone, proges- miscarriages and possibly to being able ry as a normal part of the menstrual terone is derived from cholesterol. to intervene and allow these women to cycle, and at first, this continues Although the overall production of have successful pregnancies.” after fertilization. About six weeks progesterone appears to be about the DOI: 10.1194/jlr.P093427 into pregnancy, the placenta takes same in migratory and surface cells, over making progesterone, a critical migratory cells accumulate more Laurel Oldach (loldach@ handoff. (The placenta also makes cholesterol and express more of a key asbmb.org) is a science writer for the ASBMB. other hormones, including human enzyme for converting cholesterol to Follow her on Twitter chorionic gonadotropin, which is de- progesterone. Among women who @LaurelOld. tected in a pregnancy test.) Placental have had recurrent miscarriages, that progesterone comes mostly from sur- enzyme is lower in migratory cells

MARCH 2020 ASBMB TODAY 15 JOURNAL NEWS

Finding neoantigens faster — advances in the study of the immunopeptidome By Laurel Oldach

he immune system may seem new mutant antigens — diseases like pool data on the peptides presented quiescent until an infection autoimmunity and cancer can result. by HLA proteins in various tissues T prods it to leap into action. In Two papers in Molecular & and disease states, among them the fact, it maintains active surveillance Cellular Proteomics highlight recent Immune Epitope Database and the to distinguish what belongs in the advances in the study of the immuno- Human Immuno-Peptidome Project. body from what does not. As part peptidome. Based on this hard-won knowledge of this surveillance, T cells prowl about the binding preferences of through tissues, seeking signs of Excitement over HLA proteins, researchers have gen- something amiss. Special constitutive- immunopeptidomics erated algorithms to predict which ly active mechanisms report to T cells The first tumor-specific peptides HLA proteins may display, on cell contents that otherwise would HLA-binding peptide was identified enabling computational study of be hidden. in 1997. But immunopeptidom- the immunopeptidome. But these David Gfeller leads the compu- ics really took off in 2014, when algorithms still fall short in predict- tational cancer biology group at the researchers discovered that cancer ing display of post-translationally University of Lausanne in Switzer- treatments to boost T cell activity, modified peptides. land, where his lab works to charac- overcoming immunosuppression terize immune infiltrations at the cell induced by tumors, depend on T Phosphorylated immunopeptides level. “In order to detect cells that cell recognition of tumor-specific In addition to genetic changes, are infected or malignant, something antigens. Predicting the composition many cancers undergo major changes intracellular has to be presented at the of the immunopeptidome and how it to signaling pathways — for ex- cell surface,” Gfeller said. differs between healthy and cancerous ample, 46% of cancer samples in a That presentation is the job of tissue became part of a medical fron- recent study carried alterations in the human leukocyte antigens, or HLAs, tier with enormous potential: cancer MAP kinase pathway. Quantifying a subset of which display peptides immunotherapy. how those signaling changes might pulled from chopped-up intracellular Such is the history reviewed by be reflected at the cell surface is a proteins. The repertoire of peptides Juan Antonio Vizcaíno, a proteomics matter of conjecture. they present, which varies according team leader at the European Bioin- Michal Bassani–Sternberg, an in- to HLA alleles, protein expression formatics Institute, and colleagues in vestigator at the Ludwig Institute for patterns across tissues and other fac- a perspective in MCP. The authors Cancer Research in Lausanne, studies tors, is called the immunopeptidome; summarize technical advances in im- cancer-specific HLA ligands. “We it determines what antigens T cells mmunopeptidomics and findings that cannot yet extract or purify phos- can recognize and respond to. have linked HLA alleles with human phorylated HLA-binding peptides Understanding how peptides are diseases. They also look ahead to a to a really good depth of coverage as selected to become part of the im- time when immunopeptidome-wide opposed to the depth of unmodified munopeptidome is key to harnessing association studies may make it possi- peptides,” she said. adaptive immunity. For example, an ble to predict an individual’s suscep- Until recently, this technical effective vaccine must use a peptide tibility to autoimmunity, infection or limitation hampered efforts to under- that HLA proteins will take up and cancer — and they discuss the possible stand whether unusual phosphopep- display. When antigen presentation challenges in the way. tides might be unique tumor markers goes amiss — if T cells mistakenly Immunopeptidomics experiments in some cases of cancer. recognize ordinary components of the remain technically challenging. Now, doctoral student Marthe cell as dangerous invaders or overlook Several fieldwide initiatives aim to Solleder and collaborators in

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An HLA protein (orange) is shown presenting a T cell receptor (violet) with a peptide antigen (green). Researchers are working to find out more about how peptides are selected for presentation.

Bassani–Sternberg’s and Gfeller’s labs ly had been overlooked. This let them the proteins are likely to be presented have come up with a new bioinfor- make inferences about HLA proteins’ as HLA ligands.” matics tool for predicting phosphor- phosphopeptide binding preferences. The researchers have shared all ylated HLA ligand peptides. They “For example, of the three types their data and computational tools. report the work in MCP. of HLA class I molecules, one called They hope the extra information “We collected a huge data set HLA-C is especially apt to bind to about phosphorylated peptides may of peptides displayed at the cell phosphorylated peptides,” Solleder said. help others find novel antigens. In surface that were measured by mass The algorithm may be useful for the long term, such insights may help spectrometry,” Bassani–Sternberg expanding the known range of targets guide tumor-targeting treatments. said, “and we searched the spectra displayed on cancer cells. Bassani– DOI: 10.1074/mcp.R119.001743 for modified peptides that contain a Sternberg said, “If we know where DOI: 10.1074/mcp.TIR119.001641 phosphate group.” the mutations are in the genome of a Working mostly with previously patient, we can apply these prediction Laurel Oldach (loldach@ collected spectra from immuno- algorithms to predict which of the asbmb.org) is a science writer for the ASBMB. peptidomics experiments, the team mutations is likely to be presented as Follow her on Twitter reanalyzed immunopeptidome a ligand on the HLAs of the patient. @LaurelOld. data, uncovering phosphorylated Similarly, we can now predict which HLA-binding peptides that previous- of the known phosphorylated sites

MARCH 2020 ASBMB TODAY 17 JOURNAL NEWS

From the journals

By Jack Lee & Anand Rao

Stress-free pathways Norris Cotton Cancer Center and protein interaction networks and to pathological TDP-43 researchers in the U.S. and Belgium discuss important considerations in Amyotrophic lateral sclerosis, or identified a new pathway for lipid designing co-elution studies, such as ALS, and frontotemporal dementia, uptake. Experiments in multiple the choice of separation method and or FTD, are devastating neurological breast cancer cell lines showed that how to analyze co-elution profiling conditions characterized by progres- very low-density lipoprotein, or studies. The researchers also discuss sive degeneration of nerve cells. There VLDL, is taken up via receptor-me- the benefits of co-elution versus is growing evidence that the two diated endocytosis through interac- other mapping methods, including diseases are closely related — with tions with surface-bound lipopro- the time and resources required to overlapping genetic, neuropathologi- tein lipase, or LPL, and the VLDL perform the protein mapping and the cal and clinical presentations. Among receptor. The researchers propose that number of protein interactions that the similarities is hyperubiquitylated LPL may be binding free VLDL and can be explored. TAR DNA-binding protein of 43 concentrating it at the cell surface, DOI: 10.1074/mcp.R119.001743 kDa, or TDP-43, which is insoluble thereby promoting VLDL uptake by and aggregates in ALS and subtypes the VLDL receptor. These findings What are bacterial cell walls of FTD. While the origin of patho- have therapeutic implications and made of? logical TDP-43 aggregation remains add to an increasing body of evidence Gram-negative bacteria exist in unknown, some research has suggest- that targeting fatty acid synthesis nearly all life-supporting environ- ed that stress granules play a key role. alone may not be effective in certain ments on Earth. Many Gram-nega- In a study published in the tumor types. tive bacteria, such as Pseudomonas Journal of Biological Chemistry, DOI: 10.1194/jlr.RA119000327 aeruginosa, Neiseseria gonorrhoeae Friederike Hans and colleagues at the and Chlamydia trachomatis, cause University of Tübingen used time- Using co-elution to study disease in plants and animals, course experiments conducted in protein interactions including humans. Understanding cells to show that TDP-43 ubiquityl- Studying how the vast network the composition of the bacterial cell ation occurs even when stress granule of proteins and molecules in a cell wall helps scientists to design more formation has been inhibited. Their interact, a discipline known as effective antibiotics. findings demonstrate a novel path- interactomics, is crucial to research- Peptidoglycans, or PGs, are way by which TDP-43 is modified ers’ fundamental understanding polymers composed of sugars and and becomes insoluble, expanding of biological processes and for the amino acids that form a critical our knowledge of the pathological development of new medicines and component of bacterial cell walls. manifestations of this protein. biotechnology. Among the technical In Gram-negative bacteria, PGs are DOI: 10.1074/jbc.RA119.010617 strategies for mapping the interac- assembled in the cytoplasm and tome, co-elution is a global protein exported to the periplasm, where Breast cancer cells acquire interaction mapping method. How- they undergo important functional lipids by endocytosis ever, strategies vary across studies modifications and are thought to be Researchers long have thought that utilize co-elution, depending on relatively consistent in composition that breast cancer tumor cells syn- experimental considerations. across species. In a paper published in thesize lipids as they multiply; more In a review in the journal Molec- the Journal of Biological Chemis- recent studies show that cancer cells ular & Cellular Proteomics, Daniela try, Erin Anderson and colleagues at also can take up lipids. In a recent Salas and colleagues at the University the University of Guelph in Ontario paper published in the Journal of of British Columbia delineate co-elu- present an optimized mass spectrom- Lipid Research, Leslie Lupien of the tion methods used to map protein– continued on p. 20

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Chemical activator of GPR120 affects fat taste detection

In addition to sweet, sour, salty, bitter and umami, the researchers found that adding TUG891 or linoleic there might be a sixth taste: fat. Researchers have iden- acid, a fatty acid, could promote calcium signaling through tified two receptor proteins, CD36 and GPR120, that are GPR120. They also tested whether TUG891 could activate involved in detecting fat taste in both humans and mice. the tongue–brain–gut loop by applying TUG891 or linoleic Mice that don’t express any GPR120 protein, for example, acid directly to the tongues of sedated animals. In both have less preference for fatty acids than normal mice. cases, pancreatic and bile duct secretions increased, as did Studies also have shown an association between fat blood circulation of the gut hormone cholecystokinin. The taste sensitivity and obesity. In both mice and humans, treatment also had an anti-inflammatory effect: The con- GPR120 deficiency led to increased obesity. Thus, obesity centration of adiponectin, an anti-inflammatory cytokine might be modulated by tricking the body into thinking it secreted by fat tissue, in the blood increased, while levels of is consuming fat when it’s taking in a small molecule that inflammatory cytokines decreased. binds a fat taste receptor. In behavioral tests, the researchers found that mice In a recent paper in the Journal of Lipid Research, typically preferred drinking a solution of water, linoleic acid Babar Murtaza from the University of Burgundy in Dijon and a stabilizer over a solution of water and the stabilizer and colleagues report that they tested whether a small alone. Adding TUG891 to the linoleic acid solution removed molecule that binds GPR120 could be used for such a any preference. These findings suggest that TUG891 may treatment. TUG891 previously had been shown to reduce be helpful in human treatments to decrease consumption of obesity in mice. fats and reduce obesity. In studies using mouse and human taste bud cells, DOI: jlr.RA119000142 —Jack Lee BABAR MURTAZA BABAR

In the researchers’ model of how TUG891 might be working, after the chemical is detected on a mouse’s tongue, resulting activation of a fat-sensing area in the brain leads to the release of gut hormones.

MARCH 2020 ASBMB TODAY 19 JOURNAL NEWS

continued from p. 18 plaque progression but also reversed it attention to citrullination because etry–based strategy for assessing PG and improved plaque composition. of its role in inducing anti-citrulli- composition and making inferences The researchers fed mice a nated proteins/peptide antibodies, about enzymatic activity. Using this high-cholesterol, high-fat diet and which results in an autoimmune approach, the researchers identified treated them with atorvastatin in com- reaction where the host’s immune 160 unique muropeptides in P. bination with monoclonal antibodies system attacks its healthy tissue. The aeruginosa, demonstrating that its alirocumab and/or evinacumab. The bacteria Porphyromonas gingivalis PG composition is more diverse than mice treated with the statin and one generates citrullinated epitopes in the previously thought. Their findings, antibody had lower cholesterol and periodontium, which contributes to which provide an important contri- slower plaque progression compared chronic periodontitis and recently has bution to our understanding of this to mice that received no treatment. been linked to rheumatoid arthritis. bacterium, will benefit development Mice treated with a combination of Using a new two-dimensional of more effective antibiotics. all three drugs had plaques that were heptafluorobutyric acid–based sepa- DOI: 10.1074/mcp.RA119.001700 not only smaller but had less macro- ration system combined with liquid phage content and were less likely to chromatography–mass spectrometry, Triple therapy to treat rupture. These findings indicate that Daniel Larsen and colleagues at the atherosclerosis high-intensity treatment with multiple University of Southern Denmark Atherosclerosis is the leading cause drugs could be a promising approach analyzed the outer membrane vesicles of cardiovascular disease. Statins can in humans as well. and other related elements of P. help lower the low-density lipoprotein DOI: 10.1194/jlr.RA119000419 gingivalis to identify 79 citrullinated cholesterol that causes plaque, but proteins with 161 citrullination sites. treatment typically leads to only a Confident identification of These results were reported in a paper modest reduction in plaque volume. citrullinated peptides published in the journal Molecular In a recent paper in the Journal of Citrulline is an amino acid not & Cellular Proteomics. This work Lipid Research, Marianne Pouwer encoded in the genome. It is gener- establishes a method for identifying of the Netherlands Organization of ated by a post-translational modifi- citrullinated proteins that will ad- Applied Scientific Research in Leiden cation to the amino acid arginine, a vance development of treatments for and a team of researchers in the U.S. process known as citrullination. In human autoimmune and inflamma- and the Netherlands identified a com- recent years, scientists concerned with tory diseases. bination of drugs that not only slowed the immune system have been paying DOI: 10.1074/mcp.RA119.001700

VIRTUAL ISSUE Coronaviruses Anand Rao ([email protected]) is a science communicator for the ASBMB. Follow www.jbc.org/site/vi/ him on Twitter @ AnandRaoPhD. coronaviruses

Jack Lee (jackjleescience@ gmail.com) is a graduate student in the Science Communication Program at the University of California, Santa Cruz. Read more of his work at jackjleescience.com/ writing and follow him on Twitter @jackjlee.

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Plant protein parodies Ludwig-Maximilians-Universität signaling cascades, which may suggest and human immunity researcher Dzmitry Sinitski and col- new ways plant proteins affect human When certain ligands bind laborators recognized that MIF has biological processes. chemokine receptors, such as significant sequence homology with DOI: 10.1074/jbc.RA119.009716 CXCR4, a response is triggered that a family of plant proteins known regulates host immunity and stimu- as MIF/d-dopachrome tautomer- lates immune cell migration. Human ase–like proteins, also known as Jack Lee (jackjleescience@ macrophage migration inhibitory fac- MDL proteins. Using spectroscopy, gmail.com) is a graduate tor, or MIF, is a structurally unique the researchers characterized MDL student in the Science protein capable of binding its cognate proteins in the plant Arabidopsis Communication Program at the University of California, receptor CD74 and chemokine re- thaliana and found similar pro- Santa Cruz. Read more of his ceptors. MIF has been implicated in tein structure to human MIF. Cell work at jackjleescience.com/ writing and follow him on autoimmunity, cancer and inflam- migration experiments showed that Twitter @jackjlee. matory diseases, and researchers have plant MDL proteins were able to found it to be essentially unchanged stimulate CXCR4 signaling and act Anand Rao throughout evolution in organisms as a chemoattractant for primary ([email protected]) is a ranging from mammals to unicellular human monocytes and T cells. These science communicator for the ASBMB. Follow parasites. findings demonstrate that proteins in him on Twitter @ In a paper published in the plants that are homologous to human AnandRaoPhD. Journal of Biological Chemistry, proteins and cytokines can stimulate

The curious case of Benja-mouse Button: SIRT6 and aging

aging process. Sangeeta Maity and colleagues at the In this digital age, we see no shortage of product Indian Institute of Science in Bengaluru sought to close advertisements that promise to make us feel young again. this gap in knowledge, and the results of their study According to a recent Statista report, the global anti-ag- were published in the Journal of Biology Chemistry. ing market was estimated to be worth approximately $50 Using Western blot analyses and luciferase activity billion in 2018 and is projected to grow in coming years. assays, the researchers demonstrated that signaling by While it’s no surprise that many manufacturers make TGF-beta, a well-known driver of fibrosis, was activated exaggerated claims of their products’ efficacy, one method in SIRT6-deficient cardiac cells. Subsequent experi- is scientifically supported: calorie restriction. ments showed age-dependent multiorgan fibrosis in Calorie restriction has been suggested as a strategy mice engineered to be SIRT6-deficient, confirming the to increase life span and reduce aging-related disorders findings in cells. Their results suggest that under normal including heart failure and inflammatory disease. Stud- circumstances, SIRT6 represses the transcriptional ies have demonstrated that limiting calories can lessen activity that hyperactivates TGF-beta. However, SIRT6 fibrosis, the formation of scarlike tissue on organs such as activity decreases with age, resulting in increased the heart and lungs, in a variety of cardiovascular disease TGF-beta activity, leading to fibrosis. These results models. improve our understanding of the molecular players SIRT6, an enzyme linked to aging, is activated during involved in aging and identify potential therapeutic calorie restriction, but researchers lack a complete mech- targets to treat aging-related disease and illness anistic understanding of how SIRT6 may be involved in the DOI: 10.1074/jbc.RA119.009432

MARCH 2020 ASBMB TODAY 21 FEATURE

The magic isn’t the squid… ‘‘ The magic is the protein. THE BIOPHOTONIC SECRETS OF A BRILLIANT ANIMAL ’’ By Laurel Oldach

ust offshore from Redondo Beach in Los Angeles, connecting, checking each other out.” there’s an underwater canyon. According to local At those moments, watching the squid’s rapidly chang- scuba enthusiasts, once a year it becomes a highway ing color displays, a diver may glimpse something unique Jto an invertebrate orgy in the shallows. to the California market squid and a few of its cousins: Underwater photographer–videographer Brent Du- their tunable iridescence. The phenomenon is a remarkable rand and others in the Los Angeles scuba diving commu- feat of optics not known to happen in other biological con- nity keep an eye out each December for signs of the squid texts. New research in the Journal of Biological Chemistry run, when the footlong animals emerge en masse from the sheds some light onto the biochemistry that makes it work. canyon into the shallow water near shore to mate. “The squid are just filling the entire water column,” How is iridescence generated? Durand said. In some places near the bottom, divers find Most cephalopods can change color swiftly through a themselves “surrounded by a wall of squid so dense that small palette of pigmentary yellows, reds and browns — if you reach to grab one of your gauges, you might have a an ability that makes them stars of many “now you see squid between your hand and the gauge. me, now you don’t” camouflage videos. This is controlled “You have to be OK with squid being pressed against by chromatophores, cells with a sac of pigment that your face.” expand or contract with muscle activity. In a small family Squids are intensely visual animals, and the swarm of shallow-water squid species that includes the California is attracted by the divers’ lights. According to Durand, market squid, the Caribbean reef squid, and a few other it is easy to tell whether another dive group has passed flashy cousins, the palette is nearly unlimited. through recently by how many are already amassed when On these squids’ mantles, when the chromatophores he descends to the bottom. For him, while the throngs are are retracted, they reveal splashes of color arranged in impressive, the moments when he’s near fewer animals can a pattern that looks a bit like leopard skin. Each bright be even more compelling. splotch is made up of a few dozen to a few hundred cells “On the outside of the mating aggregation, you can called iridocytes. Unlike chromatophores, iridocytes use really quiet down,” Durand said. Sometimes a single squid structural color. Pigment produces a color by absorbing “will hover in front of you, and you feel like you’re almost certain wavelengths and reflecting others that eventually

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THE BIOPHOTONIC SECRETS OF A BRILLIANT ANIMAL ’’

Caribbean reef squids, like this colorful specimen, are members of the loliginid family.

reach the observer’s eye. But structural color depends on a different optical phenomenon, which occurs when light reflects from a regular, repeated structure. It’s a phenomenon called Bragg BRENT DURAND reflection. Dan Morse, a distinguished professor at the University of Califor- nia, Santa Barbara, explained: “An ex- ample is the rainbow of reflection that you can see from the surface of a CD disk. The distance between the grooves Dan Morse determines the color, the wavelength, at which constructive reflection occurs.” Squid iridocytes have just such a structure. “The iridophore cells contain a stack of membrane-enclosed sandwiches of protein that are very thin, something like A male market squid (left) clasps a female (right) during the squid run off a stack of Frisbees within the cell,” Morse said. “The light of Redondo Beach. The camera’s illumination lights up multicolored irido- scattering is coming from the interfaces between the phores on the female’s mantle. Underwater photography “turns the regular membrane and the external space.” scuba divers into citizen scientists,” Brent Durand said. “As a photographer Whether light is passing through layers of plastic and and videographer, you start paying more attention to the details, and trying air, as in the CD, or of cell contents and extracellular flu- to capture footage of them.” id, as in the squid, whenever a large number of alternating layers with different refractive indices are repeated at the

MARCH 2020 ASBMB TODAY 23 FEATURE

same distance apart, some light can be reflected off each book — and they’re sure not by the vertebrate books.” layer. For light whose wavelength is about four times the So he considered it possible that, like a starfish’s tube distance between layers, those reflections will be in phase, feet, iridophores might be responding to acetylcholine allowing constructive interference between rays. Other that diffused in from another tissue. But there were wavelengths will not get this brightness boost. problems with that hypothesis, too — mostly the speed at In most animals with structural coloration, such as ir- which iridophores change compared with sluggish starfish. idescent beetles, bright butterflies or even certain types of As the squids get visual information, Hanlon said, cuttlefish and octopus, the reflectors’ dimensions are fixed, “The animal has to integrate that information ‘upstairs’ keeping the reflection at one wavelength — or, in the case and it has to make all the motor output — that being the of iridescence, a few wavelengths that differ according to millions chromatophores and iridophores — they have to the observer’s angle. But squids in the loliginid family can be turned on, and it all happens in about one to one and alter the structure of the tiny features inside iridophores, a half seconds.” changing the color that results — or even whether irides- It was a puzzle until, in 2012, Hanlon’s lab reported cent patches appear on their milky skin at all. that the delivery of acetylcholine to control color was, indeed, neuronal. In a follow-up paper, they worked out Dynamic iridescence depends on the brain the unusual neuroanatomy that had so confused their For a long time, researchers were stumped about how previous investigations. squids could turn their iridescence on and off. A colleague and friendly collab- Protein phase separation drives color change orator/competitor of Morse, Roger In the meantime, the researchers had made some Hanlon of the Marine Biological progress on how acetylcholine could alter the spacing Laboratory in Woods Hole, Mas- of light reflectors within iridophores. The accordionlike sachusetts (now an affiliate of the ruffled-membrane stacks are packed with a protein called University of Chicago), was part of a reflectin. A 2009 collaboration between Morse and Han- team that reported in the late 1980s lon’s labs had found that reflectin is phosphorylated upon Roger Hanlon and early 1990s that iridophores’ acetylcholine stimulation. Morse’s recent research shows change from colorless to iridescent exactly how that phosphorylation drives color change. came with a change in thickness of the protein-dense “This very complex, multistep process is largely con- plates within iridocytes and could be stimulated by apply- tained in (reflectin),” Morse said. ing the neurotransmitter acetylcholine. Morse’s lab showed in 2013 that the distance between Among neuroscientists who study vertebrates, acetyl- the stacks was determined by water efflux. At rest, an intact choline is most familiar for its role in the neuromuscular iridocyte’s membrane-folded plates are swollen with water. junction (though cholinergic cells also are found through- Using deuterated water, the researchers showed that the out the brain). It is responsible for the signaling between cell will expel that water after treatment with acetylcholine. neurons in the peripheral nervous system and the muscle “Dehydration shrinks the thickness and spacing of cells that do those neurons’ bidding. the membrane-enclosed layers, changing the wavelength The same light-scattering properties that make that’s reflected,” Morse said. The more water is expelled, iridophores so bright also made them difficult to study the shorter the distance between stacks and the shorter the using light microscopy. Scientists could not see whether wavelength that will be reflected best. neurons were forming synapses at iridophores; stimulating Since 2013, research from Morse’s lab, chronicled in various nerves did not seem to cause the iridescence to a series of papers in the Journal of Biological Chemistry, change. And as cephalopod researchers had learned in one gradually has elaborated a biochemical mechanism linking physiological system after another, to expect squid systems water expulsion with acetylcholine signaling. The color to behave just like human systems was to be disappointed change is driven by inducible phase separation that hap- by eons of divergent evolution. pens after reflectin is phosphorylated. “These goofy animals are built so differently (from Reflectin proteins are conserved among many ceph- us),” Hanlon said. “They’re doing things that aren’t by the alopod species. There are four isoforms in the California

24 ASBMB TODAY MARCH 2020 FEATURE DEMARTINI ET AL. JBC 2015 DEMARTINI ET AL.

In a figure from a JBC paper, Morse and his colleagues zoomed in on the iridescent patches of a female California market squid’s mantle, illustrating the cells’ anatomy with both light microscopy and transmission electron microscopy. market squid. The relectin that fills and determines the Morse said that the phosphatase seems to be constitu- distance between alternating layers in the iridocyte has an tively active. “The result is that the signal that activates alternating structure of its own. Between conserved do- iridescence is ephemeral. From moment to moment, mains, it has linker regions rich in arginine and aromatic there’s a pulse of neuronal signal in response to whatever amino residues. These domains have a strong net positive the animal sees. The brain fires this neuron; acetylcholine charge and do not lend themselves to secondary structure. is released and diffuses to these cells, activating the color According to Morse, reflectin’s two types of domains change; but then the phosphates quickly are removed. have opposing activities. “The cationic linkers are like That means the system produces a color in response to a compression-resisting shock absorbers. Because of elec- neuronal signal and then can be reset very quickly. trostatic repulsion, they want to stretch out and keep the “You can see the tissue return to colorless if you protein in an extended, unstructured form. The alter- provide no further stimulus. But if stimulus is continuing nating domains are like the spring on our screen doors: and changing, then the color can continuously change.” They want to compress, but they’re held in check by the Morse’s work has garnered attention for his meticu- repulsion of the linkers.” lous attention to the biophysics of reflectin’s response to When acetylcholine is released, it activates a tyrosine signaling. Hanlon said, “I think Dan’s avenue of inquiry, kinase — the enzyme’s exact identity is not yet known — that phosphorylates the linker regions. Adding negatively charged phosphates neutralizes the positive charge of those domains, reducing their repulsion and letting reflec- tin assemblies begin to form. With more phosphorylation, the positive charge eventually is neutralized, allowing formation of larger complexes. COURTESY OF DANIEL MORSE “As the reflectin particles become fewer and bigger, osmotic pressure within the stacks drives more and more liquid out,” Morse said. “Now, the contents are very dense by this time … which means that the opacity increases. But the color of that reflectance is set by the dimensions separating the membrane layers.” A schematic cartoon illustrates the change in iridophores’ reflective While acetylcholine activates the kinase in question, platelets after acetylcholine treatment.

MARCH 2020 ASBMB TODAY 25 FEATURE STEVE ZYLIUS/UCI

looking more and more carefully at very specific mecha- nisms of subtle changes in nanostructure and in how the reflectin protein changes its conformation is really going to be important to understand the system.”

Engineering materials based on reflectin As reflectin has come into focus, researchers have begun considering ways to use the protein, which Morse often calls a “marvelous molecular machine,” to inspire Alon Gorodetsky, a professor at UCI, and graduate student Erica Leung bioengineering efforts. made composite material inspired by squid skin. It combines layers “Because of its domains’ opposing physical activities, transparent to infrared light with adjustable layers that reflect infrared the protein works as a sensor that can measure signals and light, and it is responsive to stretching. produce a proportional calibrated output,” Morse said. “Can we transport this very precisely calibrated trans- Back in the world of basic science, Morse is also duction … into other signal-dependent, proportionally curious about whether the reversible assembly of reflec- switching reconfigurable materials? If so, we could design tin could shed light someday on other types of protein reconfigurable materials that might be used for many assembly — such as the formation of amyloid plaques in applications.” the brain that occurs early in Alzheimer’s disease. “Both For example, he said, the ability to control the viscos- classes of proteins, the amyloids and the reflectins, have ity of bulk quantities of protein might be used to solve extended domains of positively charged amino acids that problems in protein manufacturing for pharmaceutical or appear to form liquid–liquid phase separated droplet industrial purposes. intermediates,” Morse said. “It raises the question: Why Meanwhile, researchers led by materials scientist Alon is this process reversible, harmless and even advantageous Gorodetsky at the University of California, Irvine, are in the case of reflectin, but irreversible and pathological in working on developing stimulus-responsive biomaterials the case of Alzheimer’s?” inspired by reflectin. Plenty also remains to be learned about reflectin’s “The first day I was starting my independent position, function in the squid. Gorodetsky said that one of the I walked into a room where Roger Hanlon was giving a most interesting questions is how different reflectin iso- talk about cephalopods’ camouflage ability,” Gorodetsky forms, which have high sequence identity, create different said. “It was just mindblowing. I said, ‘OK, I’m dropping optical effects in different cells. half the research that I was planning on doing and switch- Ask Morse about his favorite aspects of his work, and ing to reflectin.’” the answer is the same. “Its elucidation of this complex According to Gorodetsky, reflectin’s combination of molecular machine embodied in the reflectin protein. The properties is unique. “I can’t think of another protein that magic isn’t the squid. The magic isn’t the photonics. The has this high refractive index and excellent electrical prop- magic is the protein machine and its mechanism erties, can be processed so easily, and is also very stable.” of action.” It’s stable enough, in fact, that his lab developed a tape coated in a thin film of reflectin that changes infrared reflectivity after being stretched. On the other hand, it Laurel Oldach ([email protected]) is a science is so responsive to many stimuli — pH, ionic strength, writer for the ASBMB. Follow her on Twitter humidity, charge — that it is not an ideal material for @LaurelOld. reusable technologies. Instead, Gorodetsky said, his lab now uses the protein as inspiration to derive materials that improve upon its qualities.

26 ASBMB TODAY MARCH 2020 FEATURE

Colorful, yet colorblind

Researchers don’t know exactly why squid use tun- a very dim green. If an iridophore reflects green, that’ll able iridescence. According to Lydia Mäthger, a scientist be a really bright green at the depths at which they at the Marine Biological Laboratory in Woods Hole, occur.” Massachusetts, “There isn’t anything that really proves Another feature of marine light is that nearly all of it that any of this is used for communication between the comes straight down. That enabled Mäthger to predict squid.” exactly how an activated iridescent patch would appear But, Mäthger added, it is difficult to study ocean to an observer above, below or alongside the animal. animals’ behavior and very difficult to prove a hypothesis Her results suggested that the iridescence may help about intraspecific signaling. “Say you did film some- both with camouflage and schooling. To an observer thing that was definitely a signal. Then the question still looking straight down from above, the squid will be is, did the neighboring squid that looked at it perceive it scarcely visible. To an observer at the same depth, as a signal? And what does it mean?” it will appear about four times as bright as the back- In her first paper as a graduate student, published in ground. 2001, Mäthger investigated how iridescence might look Subsequent research has suggested other poten- underwater. She recalls her adviser telling her to imag- tial explanations for tunable iridescence. Among male ine the squid 30 meters below the surface and think loliginid squid, a flash of iridescence is part of aggres- about how their skin might appear at that depth. sive displays. Among females, some researchers have Using data collected by divers, Mäthger did just that. argued that when two stripes of iridescence flanking a At the depths the squid frequent, sunlight is filtered to white stripe show up, that may be a signal that they are blue-green by the water above, so it is unlikely that the not receptive to mating. However, no one has proved animals enjoy the color displays they are famous for. the function of any visual signal conclusively. That’s doubly certain since cephalopods express just Still, Mäthger said, given the small size of the field one photoreceptor, well suited to blue-green light, and and the squids’ reliance on light, “It would be kind cannot differentiate between wavelengths as humans do. of silly to assume, only because it’s not been proved “When one of these iridophores reflects red under scientifically, that they don’t use it.” white light,” Mäthger explained, “for the squid, red is just — Laurel Oldach

Lydia Mäthger

Deep water filters white light from the sun to blue-green. Here, a Caribbean reef squid swims in the brighter shallows.

MARCH 2020 ASBMB TODAY 27 FEATURE COURTESY OF PAUL DAWSON COURTESY OF PAUL Start simple. It always gets more ‘‘complicated. A conversation with Paul Dawson By Laurel Oldach

ellow bile, one of the four hu-’’ inhibitors can block the development of fatty mors of ancient and medieval liver disease in mice. physiology, once was believed to Dawson, a professor at Emory University cause irritability. Scientists since School of Medicine and an associate editor have determined that its biological of the Journal of Lipid Research, talked function is solubilizing fat from to ASBMB Today about his work. The Yfood so it can be absorbed into the intestinal conversation has been condensed and Be fearless. Find epithelia. Bile acids, amphipathic molecules edited. a good question, produced in the liver, are the key to this and think through process. In the gut, they form micelles with I understand that you run your lab jointly with a colleague who is a physician? what you would fats, sterols and fat-soluble vitamins that then are absorbed. I’ve been camped in a clinical department need to answer that Paul Dawson knows more about bile than for most of my faculty career. It’s been a question. And start the average person. Dawson has studied how very good experience: My clinical colleagues simple, because it bile acids are absorbed and recycled — or left like to hear about the basic science, and I’ve always gets more in the gut to be eliminated — for most of his certainly learned from their experience with career. His lab identified transporter proteins patients. complicated as you at the far end of the small intestine that are I’ve known Saul Karpen for many years. move forward. responsible for picking up bile acids after When I came to Emory, we realized that they’ve shed their lipid payload and returning there would be benefits to working together. them to the hepatic portal vein. We focus on our own research interests, but ’’ These days, Dawson’s work focuses on there are other areas where the synergy is inhibitors of bile acid transport, especially really powerful. Since Saul is a practicing pe- of the protein apical sodium-dependent diatric hepatologist and investigator, we work bile acid transporter, or ASBT. Because on basic science questions about observations bile acids are made from cholesterol in the that he makes in the clinic. Our offices are liver, researchers hypothesize that drugs that right next to one another, and people in our block their reabsorption might help to clear labs all work together as one larger group to excessive cholesterol in fatty liver disease. answer scientific questions. I think that’s not Dawson’s lab has shown that bile acid uptake uncommon now in academia.

28 ASBMB TODAY MARCH 2020 FEATURE

Start simple. It always gets more complicated.

Tell me about your training. cholesterol homeostasis. Paul Dawson is shown in his I went to Stony Brook University think- I had a chance to meet with Brown office at Emory University, ing I was going to work with someone who when I was getting ready to graduate, which where he and a colleague was doing nerve regeneration. As graduate emboldened me to apply to their lab for a who is a practicing physician students, we often think we know what we’re postdoc. It was a nerve-wracking period, be- work together to address interested in, but we’re pretty undifferenti- cause I didn’t hear anything for a while, and research questions. ated. My first rotation was with an amazing then they won the Nobel Prize. I thought, mentor named David Williams, who was “Well, I don’t know if I’m going to make it applying cutting-edge molecular biology into their lab or not.” I was amazed when techniques to study cholesterol metabolism literally two weeks after they won the prize, I and apolipoproteins. I was so excited by that got an acceptance letter. I still have it. It was work I abandoned my idea of working in the a real turning point in my career. other lab and threw myself into learning all I I took over a project from Thomas Süd- could about cholesterol metabolism. hof, who was leaving the lab to do his Nobel In the summer, Michael Brown would Prize–winning work on synaptic transmis- visit Long Island with his wife, Alice, and sion. Helen Hobbs was in the lab, and Tim children. (Note: Brown and Joe Goldstein Osborne — really great scientists, early in are longtime collaborators at the University their careers. I learned so much vicariously of Texas Southwestern.) I remember Mike by talking to others around me. Brown and Brown visiting my advisor to talk about what Goldstein were wonderful mentors — de- was going on in cholesterol metabolism. This manding, but appropriately so. It was an is just prior to Brown and Goldstein winning amazing time in their lab. their Nobel Prize; they were doing amazing When I was finishing, Larry Rudel work on the LDL receptor and control of recruited me to Wake Forest School of Medi-

MARCH 2020 ASBMB TODAY 29 FEATURE

work that out. Looking back now, it wasn’t exactly as charted, but we were able to do the things I wanted. We identified a sodium cotransporter called ASBT that’s responsible for absorbing bile acids from the intestine, and a binding protein that helps move bile acids within the cell. We also discovered that

MARATHONFOTO, COURTESY OF PAUL DAWSON COURTESY OF PAUL MARATHONFOTO, mutations in ASBT cause primary bile acid malabsorption and congenital diarrhea. Then the question was, “If a bile acid gets in on one side of the (epithelial) cell, how does it get out the other side?” That took longer to figure out, but we were ultimate- ly able to show that another transporter, organic solute transporter alpha-beta, moves the bile acid across the basolateral side into blood. If it’s mutated in patients, this trans- porter also causes congenital diarrhea. It was very satisfying establishing that this is the basic permeation pathway for how Paul Dawson in motion cine. Larry built a vibrant ecosystem for lipid bile acids traverse the intestinal epithelial during the Toronto half- investigators. He was in a sense a Johnny cell. marathon in May 2019. Appleseed, training investigators and then He and his wife, Anu Rao, sending them out around the country. There’s You moved to Emory a few years ago. often plan their travels a whole generation of lipid researchers that Has your research focus stayed the same? around races. passed through the Section on Lipid Sciences I’m interested in how preventing the he put together. return of bile acids to the liver can poten- tially produce benefit there. The transporter What research questions did you work on on the apical membrane turned out to be an at Wake Forest? interesting drug target for small-molecule When I was getting ready to leave my inhibitors. We’ve worked with industry over postdoctoral lab, in discussions with col- the years, and they ultimately developed leagues, I recognized an interesting niche: nonabsorbable inhibitors that can block bile The transporters responsible for moving acid uptake. Now there’s a whole group of I came up in that bile acids hadn’t been identified. These are these therapeutics in clinical development. generation when important control points that establish the I was interested in helping to evaluate them ‘‘ it was possible to fate of bile acids, either enterohepatic cycling critically and, if they’re promising, to move start out focusing or elimination from the body, and could po- them forward into patients. Coming here tentially contribute to the pathophysiology of was an opportunity for me to work with Saul on something a variety of diseases. When I moved to Wake Karpen and other clinical investigators on very basic with Forest and started my lab, the question was, that. translational “How do bile acids — which are charged You mentioned working with implications and molecules and prevented from just passively diffusing across a membrane — get from the pharmaceutical researchers. spend much of your lumen of the gut into the portal circulation?” What was that like? career trying to I came up in that generation when it was Early on in the development of the in- work that out. possible to start out focusing on something hibitors for ASBT, Wake Forest patented the very basic with translational implications use of cells for screening and then licensed and spend much of your career trying to them to various companies. I helped them

30 ASBMB TODAY ’’ MARCH 2020 FEATURE

set up the screens used to identify some of When did you first become involved the high-affinity small-molecule inhibitors with the Journal of Lipid Research? that were developed. What have you most enjoyed It took more than a decade from the about joining its leadership team? identification of the transporter to the The JLR had always been one of my development of the inhibitors and their use go-to journals to follow what’s going on in in patients. When we were first cloning it in the lipid field. I joined the editorial board When we were first the lab, if someone had said to me, “Years in 2011. Then in 2019, Nick Davidson and cloning [ASBT] in down the road, these cloned transporters Kerry-Anne Rye (the JLR’s editors-in-chief) the lab, if someone will be used in screens that will lead to a invited me to be an associate editor. I have ‘‘ had said to me, drug that will end up in a patient,” I’m not enjoyed working with the editors, other AEs sure I would have believed them. But that’s and staff as the group works to chart the ‘Years down the ultimately what happened. future for the JLR. road, these cloned transporters will be What’s it like getting a glimpse Is there advice for research that you find into pharmaceutical research? yourself giving again and again? used in screens that It’s refreshing. You learn so much from That idea of being fearless; in Brown will lead to a drug the way these colleagues think about how to and Goldstein’s lab, they really instilled that that will end up in address questions. In the lab, we sometimes concept. Find a good question, and think a patient,’ I’m not take a meandering approach, which can be through what you would need to answer that sure I would have valuable; but sometimes we’ve meandered question. And start simple, because it always off a little too far in one direction or the gets more complicated as you move forward. believed them. But other before we came back to the center and Also, talk a lot with other people in the that’s ultimately figured out where we were going. lab and other students and postdocs and what happened. There are times when the efficiency that faculty. A lot of science is tacit; you read I’ve seen from people in industry would be the methods section of a paper, and a lot of useful, especially for students. At the end nuances aren’t there. But if you have a chance ’’ of the day, they need to produce a body of to talk to somebody in the next lab, you can work that will be publishable and provide all learn so much from them. the research skills that they need to move on with their training and careers. What are you most interested in outside the lab? So how do you balance following My wife, Anu Rao, and I — she’s a sci- your curiosity with productivity? entist too — are both runners. We’ll get up Typically, students start out with a couple early in the morning and go for a run with of potential projects. After a certain period of friends; it’s a really good way to start the day time, we say, “Okay, set that one on the back and helps clear our heads. burner and shift your attention to this one. If we’re at a meeting, we’ll look to see if You’re making good progress here, and this there’s a race nearby. If we go on a trip, we is a project that can carry you to the finish try to plan it along with a race — typically line.” something not so long, like a half-marathon, We looked for the basolateral bile acid so that it’s manageable. We’d always wanted transporter, which gets the bile acid out to visit Iceland, so we went there in August of the enterocyte, for about eight years. when there was a half-marathon in Students would work on that project, trying Reykjavik. various strategies, and then, if it looked like Running is something you can do on Laurel Oldach it wasn’t going to work, they moved on to most mornings. You can just go out the door, ([email protected]) is a science writer for something safer so they could move forward run and come back and feel pretty good as the ASBMB. Follow her in their careers. you get started on your day. on Twitter @LaurelOld.

MARCH 2020 ASBMB TODAY 31 ANNUAL MEETING

Dear ASBMB Today reader,

As you probably know by now, the be presenting at the meeting this year, we American Society for Biochemistry thought you would enjoy reading about these and Molecular Biology and the other three scientists and their work. We hope you host societies have canceled the 2020 will have an opportunity to hear their talks in Experimental Biology meeting due to the future. concerns about spread of COVID-19. Sincerely, We learned of this decision just as we Comfort Dorn, managing editor were sending the March issue of ASBMB Today to the printer. Although they will not

MCP to host proteomics session By Saddiq Zahari

he editorial leadership team of the journal Molecular & Cellular Proteomics has chosen three investigators T to present their current research during a symposium at the 2020 American Society for Biochemistry and Mo- lecular Biology Annual Meeting in San Diego. “These are mid-career scientists leading and gaining penetrating discoveries of the workings of biological sys- Anne-Claude Gingras Matthias Selbech Benjamin Garcia tems through the tools of molecular proteomics,” said Al Burlingame, MCP editor-in-chief and chair of the session. uses mass spectrometry–based quantitative proteomics to The session, titled “Exciting Biological Insights investigate proteome dynamics and cellular signaling on a Revealed by Proteomics,” will be held at 3:15 p.m. on global scale. Monday, April 6. Read more about the speakers and their Benjamin Garcia is a presidential professor of bio- research in the following pages. chemistry and biophysics at the University of Pennsylva- nia. His group studies histone post-translational modifica- The speakers tions and systems epigenetics using novel methodologies in Anne-Claude Gingras is a senior investigator at the mass spectrometry. Lunenfeld–Tenenbaum Research Institute in Toronto. Her group employs mass spectrometry and a proximity-de- Saddiq Zahari ([email protected]) is the pendent biotinylation technique called BioID to study manager of compliance for Molecular & Cellular Proteomics. Follow him on Twitter @saddiqzahari. protein–protein interaction and spatial localization. Matthias Selbach is a professor at the Max Delbrück Center for Molecular Medicine in Germany. His group

32 ASBMB TODAY MARCH 2020 MOLECULAR & CELLULAR PROTEOMICS SESSION Gingras studies proteomics’ implications for research By Adriana Bankston

hen Anne-Claude Gingras was working on her Ph.D. Tools for studying proteomics W in Nahum Sonenberg’s lab changes in organelles at McGill University, she focused on the regulation of the protein To determine where proteins synthesis machinery by phosphoryla- are in a cell, Anne-Claude Gingras’ tion. Her thesis described the role of group uses mass spectrometry as the mechanistic target of rapamycin a high-resolution discovery-based complex in phosphorylating a trans- microscope. They employ a tech- lational inhibitor. nique known as BioID that reports on Curious about the unexplored the proximity of a protein to another Anne-Claude Gingras protein phosphatase components of used as bait. phosphoregulation, Gingras real- Her student Christopher Go created 200 stable cell lines that each ized that then-emerging proteomics express one organelle marker as a probe and performed proximity-depen- technologies would be key to solving dent biotinylation to identify the composition of each organelle. Research this puzzle. She moved to Seattle to associate James Knight then developed computational tools to analyze study mass spectrometry with Ruedi and visualize the data. This revealed new addresses for many unexplored Aebersold, and there she improved proteins and showed proteins that are at contact interfaces between methods for protein–protein interac- organelles. tion detection. She started her own Using this work as a reference map, the Gingras lab is creating sen- research group in late 2005. sors to report on proteomic changes in an organelle after perturbations Gingras now runs a signal such as drug treatment, various growth conditions and genetic modula- transduction, systems biology and tion with CRISPR. In profiling the surface of the lysosome, postdoctoral proteomics lab at the Lunenfeld– fellow Geoffrey Hesketh found a new pathway that activates the mecha- Tanenbaum Research Institute in nistic target of rapamycin complex by extracellular protein through the Toronto. Her team works to improve process of macropinocytosis. This work has implications for disease in experimental and computational ap- which macropinocytosis is activated, such as Ras-dependent cancers. proaches for interaction proteomics. Misregulation of protein phosphor- ylation is implicated in numerous new biological complexes and path- committed to sharing data, methods, diseases, including cancer and diabe- ways implicated in disease heavily reagents and protocols and to helping tes, so she applies these techniques relies on the contributions of tal- other scientists realize their objec- to identify and understand new ented students, fellows and research tives. Her motto, she said, is “Science components of signaling pathways assistants with diverse expertise in works much faster when you help related to these . More biochemistry, cell biology, mass spec- one another.” recently, she began systematically trometry and bioinformatics, as well Adriana Bankston applying the proximity-dependent as a large network of key scientific ([email protected]) biotinylation approach BioID to collaborators. is a principal legislative analyst at the University study the composition and organiza- Her Ph.D. and postdoc advisors of California’s Office of tion of membraneless organelles and, shaped not only her scientific direc- Federal Governmental Relations in Washington, ultimately, of human cells. tions but also how she interacts with D.C. Follow her on Twitter @ Her group’s success in defining other scientists, Gingras said. She is AdrianaBankston.

MARCH 2020 ASBMB TODAY 33 ANNUAL MEETING

MOLECULAR & CELLULAR PROTEOMICS SESSION Selbach seeks the science behind the magic By Kerri Beth Boggs

hen Matthias Selbach was a child, he loved science and Investigating the dynamic W magic tricks. His father gave proteome him a book of science experiments that he could do with household Proteins are the key actors in items. He spent many afternoons most biological processes, and testing tricks like the inverted water Matthias Selbach’s lab studies the glass. With just an index card, he dynamic proteome to interpret how magically could keep a glass of water genomic information yields specific from spilling when he turned it phenotypes. upside down. The results fascinated In his recent work, Selbach Matthias Selbach him, but he wanted to understand aimed to understand how bird flu what made the experiments work. affects the proteome of human cells. Although bird flu usually does not “For me, science was a bit like a spread efficiently from human to human, specific strains could trigger magic trick,” he said. “There is some pandemics. Scientists hypothesize that the 1918 H1N1 flu virus that truth behind it that may not be obvi- killed millions of people worldwide originated in birds. ous at first. Once you understand the Selbach’s team infected human lung cells with bird or human flu virus explanation, you can share it with and analyzed changes in the proteome using mass spectrometry. They others and excite them about it.” found that the viral matrix protein M1 was produced in higher quantities That curious instinct was the in the cells infected with human flu virus. The M1 protein is required for foundation for Selbach’s future exporting newly synthesized viral RNA from the nucleus and assembling career. He earned his Ph.D. in a infectious progeny for release. Their findings provide a molecular basis for cell biology lab at the Max Planck understanding the species barrier for flu virus. Institute for Infection Biology in The influenza virus study, recently published in the journal Nature Berlin. However, he felt constricted Communications, is just one example of how Selbach uses proteomics by the classical, hypothesis-driven to analyze the underlying causes of human disease. His lab also studies methods he used in his Ph.D. work. how disease-associated mutations and cell signaling events affect pro- He wanted a system for asking broad tein-protein interactions. They use high-throughput techniques to identify scientific questions that he could mechanisms linked to strong disease phenotypes. Selbach hopes these answer on a global scale. methods eventually will lead to earlier patient diagnosis and advances in During his postdoc with Matthi- personalized treatment. as Mann, Selbach immersed himself in the world of proteomics. In this field, he asked fundamental biolog- as protein–protein interactions. ical questions that he could address He is particularly interested in the Kerri Beth Boggs (kerri. [email protected]) is a with mass spectrometry technology interface between biology and mass graduate student in the to yield big-picture data sets. spectrometry technology. biochemistry department at the University of Selbach is now a professor at the “This technology is like a Swiss Kentucky. Follow her on Max Delbrück Center for Molecular Army knife for biomedical research,” Twitter @KB_Boggs. Medicine in Berlin, where he and he said. “It’s extremely versatile, and his team use proteomics to analyze you can always find new ways to protein synthesis and decay as well apply it to biological questions.”

34 ASBMB TODAY MARCH 2020 MOLECULAR & CELLULAR PROTEOMICS SESSION Garcia uses mass spectrometry to unravel the human epigenome By Nivedita Uday Hegdekar

hen Benjamin Garcia was introduced to mass spec- Advanced MS approaches elucidate W trometry as an undergrad in ‘diseased’ epigenome Carlito Lebrilla’s lab at the University of California, Davis, he thought it Benjamin Garcia’s research was an “interesting and useful analyt- group has developed novel method- ical technique,” he said. Little did he ologies for MS analysis of histones guess the central role it would play for application in post-translational throughout his research career. modifications and systems epi- “Lebrilla was an amazing men- genetics. Their most recent ap- tor,” Garcia said. “Despite my lim- proach shows promise in the analysis Benjamin Garcia ited knowledge in analytical chem- of isolated histones from human clin- istry, he treated me like a… regular ical samples. Advantages over standard proteomics experiments include member of the group. I enjoyed the its quicker sample run time and improved quantification. scientific discovery process and de- The group has used MS for high-throughput global profiling of histone cided to apply to graduate school.” post-translational modifications to better understand several cellular His timing could not have been mechanisms and diseases. For example, they recently unraveled how better. In the early 2000s, the human recurrent loss-of-function alterations in polycomb-repressive complex 2, genome just had been sequenced, a histone-modifying complex, drive the formation of cancer cells in malig- and Garcia became interested in nant peripheral nerve sheath tumors, an aggressive sarcoma. investigating the various proteins The group’s findings will help identify several epigenetic targets. The encoded by genes. long-term goal is to treat diseases with histone-modifying enzymes or “Proteomics research was in its targeted small-molecule inhibitors. infancy, and MS opened up a lot of opportunities to explore the area,” he said. His interest led him to pursue ic journals, including Molecular large and productive research group, doctoral research with Don Hunt at & Cellular Proteomics, and has he believes mentorship is a key aspect the University of Virginia. received numerous awards, including of scientific discovery. Under the guidance of Hunt, the Presidential Early Career Award “As a PI, the most enriching expe- whom he described as “brilliant and for Scientists and Engineers. rience has been training and mento- visionary,” Garcia studied tandem Excited by the progress being ring researchers from different walks mass spectrometry of complex made in large-scale omics, Garcia of life,” he said. biological mixtures. By the time he said he hopes scientists can apply earned his Ph.D. in chemistry in their knowledge to eventually “re- 2005, he was fully immersed in the program a diseased epigenome” in Nivedita Uday Hegdekar field of proteomics. various diseases. (nivedita.hegdekar@ umaryland.edu) is a “And after that, there was no Besides his regular responsibili- graduate student at the looking back,” he said with a laugh. ties as a professor at the University University of Maryland working toward a Ph.D. Garcia has established himself of Pennsylvania, Garcia develops in biochemistry and as a leader in mass spectrometry programs that support diversity and molecular biology and an M.S. in patent law. and proteomics. He serves on the underrepresented minority scientists Follow her on Twitter @ editorial boards of several scientif- at the university. As the leader of a NiveditaHegdek1.

MARCH 2020 ASBMB TODAY 35 ANNUAL MEETING SAN DIEGO | APRIL 4-7, 2020

Discover Common Bonds Congratulations to the 2020 ASBMB Leadership Award winners!

Anita Corbett Emory University ASBMB Mid-Career Leadership Award

Natalie Jura University of California, San Francisco Early-Career Leadership Award

Thank you for your dedication to advancing the careers of women in biochemistry and molecular biology!

Learn more about the ASBMB Leadership Awards in the career resources section at asbmb.org.

36 ASBMB TODAY MARCH 2020 PERSPECTIVES

Use the mic! By Rajini Rao

he glowing introduction is done. ing through the speakers, and enough to be seen at the back of There follows a smattering of adjust accordingly. the room, adds another layer of T anticipatory applause. You stride • When using a lapel mic, check comprehension. confidently to the podium and wave what side of the screen you’ll be • If you are a moderator or session away the microphone, saying, “I’ll standing on and wear the mic on chair, it’s your job to ensure that speak loudly; can everyone hear me?” the side you’ll turn toward when multiple people aren’t talking A few heads in the front row nod in you look at the screen; wear it at the same time and making assent, and you launch into your talk. high enough to accommodate it harder to tune in on any one Don’t be this person. Use the your turned head, and remove voice. microphone. chains or badge ribbons that may For more tips and firsthand You may be surprised to learn interfere. insights on how to give a hearing- that up to 20% of the population has • A hand-held mic must be kept friendly and inclusive talk, watch some degree of hearing loss, making at a steady distance from your “Like the mic,” a short video it the third most common physical mouth at all times. distributed by Rooted in Rights condition, after arthritis and heart disease, according to the Hearing Loss Association of America. Deaf- Hold the microphone in the middle of the handle to avoid audio deviations. ness gets progressively worse with age, RAJINI RAO affecting approximately one in three people between the ages of 65 and 74. More women, relative to men, find it hard to hear lower frequencies. When you decline to use the microphone, you are projecting your ableism, not your voice, by assuming that able-bodied people are the norm. If not, you reason, why wouldn’t they speak up? But people with disabilities often are exhausted from the con- stant need to self-advocate. Perhaps • A podium mic should be adjusted and the Hearing Loss Association of they don’t wish to bring attention to for your height. America. themselves. Investing just a few minutes to set The next time you come up When your audience cannot hear yourself up for an effective broadcast to the podium to give a talk, don’t you, they cannot fully participate. could make or break your success as say, “I don’t need the microphone.” Rather than engage with your data or a speaker. You may not, but someone in your your ideas, they struggle to make out Other practices that will ensure audience does. the words. When you use a micro- inclusion: phone, this cognitive burden is gone, • Additional microphones for ques- and now everyone can focus on your tions from the audience are good, Rajini Rao ([email protected]) splendid research! It’s a win-win for but if there aren’t any, be sure to is professor of physiology at the Johns Hopkins University all. repeat the questions using your School of Medicine and chair Here are some tips on using the microphone. of the ASBMB Today editorial advisory board. Follow her on microphone effectively. • The judicious use of labels and Twitter @madamscientist. • Listen to your own voice project- headings on your slides, large

MARCH 2020 ASBMB TODAY 37 PERSPECTIVES

What can your ombuds office do for you?

By Bill Sullivan

f you become embroiled in a ombuds often can identify campus time to speak with us. We are an conflict at an academic institution, resources for resolving or addressing a excellent and noncommittal point of I you should know you are not problematic issue. We also can serve first contact. If a visitor needs help alone. Whether the issue is between as mediators or engage in shuttle di- from another office, we gladly will students, between faculty members, plomacy between parties in conflict. refer them or help set up a meeting. or between a student and a faculty While our first function is to Nothing is hurt by reaching out to us member, if your campus has an om- assist the visitor, we also can bring first, as we are a confidential re- buds office, trained professionals are systemic problems to the attention of source. If someone is struggling with available to help. The primary func- administration and leadership. Exam- a perceived lapse in professionalism, tion of this office is to assist its visi- ples include widespread dissatisfac- mistreatment or unfairness, if they tors in determining how they might tion in a particular academic unit or need to talk and are not sure where best address their concerns about department, a flawed administrative to go, we are always happy to help conflict, allegations of mistreatment, process leading to simmering resent- however we can. If a person is unsure and/or a lack of professionalism in ment and/or dysfunction, or a gap in who to talk to, or whether they want an impartial, safe and confidential existing policies and procedures that to talk at all, we are completely confi- matter. needs attention. Often, these issues dential and available. After clarifying To learn more about ombuds, are brought to light only because of their issue and situation in a meeting I spoke to Marly Bradley and Joe the unique position and features of with us, many visitors decide to go DiMicco, who have been ombud- our office, most notably confidential- no further. In that case, no record spersons at the Indiana University ity. We meet regularly with the dean of that meeting exists. We keep School of Medicine for two years and and can reach out to other offices at no formal records with identifying three years, respectively. In that time, any time. However, we share infor- information, and we shred any notes more than 300 people have sought mation only if we have the visitor’s we take during a meeting at the close their help in dealing with a wide permission. of our interaction. array of concerns. Our conversation has been edited and condensed for Who does the ombuds office serve Are there things people should not ASBMB Today. on campus? expect from their ombuds office? Although originally formed A visitor should not expect a What does an ombuds office do? primarily to address the issue of personal advocate, although we can The first and most important medical student mistreatment, the and do advocate for fairness. A visitor thing we do is listen, listen, listen. office serves all teachers (faculty) and should not expect us to fix their The ombuds may serve as a sounding learners (medical students, residents, problems; our goal is to help visitors board. We try to help our visitors fellows, grad students and postdocs) help themselves. identify and choose potential actions on all nine campuses across the they might take to address their is- state. Our office is on the Indianap- What information do you consider sues. The concerns that bring visitors olis campus, but we visit the other confidential? Is there anything that to the office might include perceived campuses regularly. While we prefer is not kept confidential? unfairness in grading or evaluation, to meet face to face, we are open to Our most important operating a toxic or uncomfortable work envi- speaking by phone, Zoom, Skype or principle is confidentiality. Every- ronment, a difficult relationship with whatever else is mutually convenient. thing is confidential. We will not a particular individual — in fact, if disclose the details of our meeting, or it’s a conflict you can imagine, we’ve When should a person talk even the fact that we have met, unless probably heard some version of it to an ombudsperson? the visitor gives us explicit permis- in the confidence of our office. The Honestly, there is never a wrong sion to do so. We often discuss cases

38 ASBMB TODAY MARCH 2020 PERSPECTIVES

between ourselves (again, with the What inspired you to become Association website, visitor’s permission), as the confiden- an ombudsperson? ombudsassociation.org. tiality is held within our office. Marly Bradley: It There are a few exceptions to this was a natural fit. I’ve Bill Sullivan (wjsulliv @iu.edu) is a professor at absolute confidentiality. If we see clear always been inclined Indiana University School evidence that the visitor or someone to serve in areas of of Medicine and the else is in danger of physical harm, advocacy, and while author of several books. He is a member of the Indiana University requires that we ours is a neutral office, ASBMB Today editorial report this to an appropriate office or we do advocate for fairness. I chaired advisory board. Follow him on Twitter authority. Also, the university requires the university’s teacher–learner @wjsullivan. that we report clear evidence of sexual advocacy committee for almost 10 harassment or of discrimination on years, and this seemed like an ideal the basis of race, religion, nationality, opportunity to continue my service OMBUDSPERSON AT THE gender or sexual preference. in an expanded role. Our two-person ASBMB ANNUAL MEETING office was an added draw. I have a What is the history behind clinical background, and my partner The American Society for the ombuds office? ombuds has a research background. Biochemistry and Molecular The term ombuds derives from Our experiences over a combined 60 Biology and the other host the Swedish word for advocate, and years provide unique insight into the societies of the Experimental many people are familiar with om- issues that most of our visitors face. Biology conference have budspersons in settings where they Joe DiMicco: After I appointed an ombudsperson to would serve in this capacity (e.g., retired from my 30- serve as an independent, neutral student ombuds in an undergrad- plus years on the facul- off-the-record/confidential uate college or university setting or ty at the end of 2011, I resource for meeting attendees. patient ombuds in many hospitals). missed my connections EB prohibits all forms of However, ours is properly termed with students and my discrimination and harassment an organizational ombuds office, former colleagues. In 2016, the uni- and has enlisted the meaning that one of our operating versity approached me about the plan ombudsperson to support the principles is neutrality. That is, we to start an ombuds office at the school conference’s code of conduct remain neutral in conflicts between of medicine and invited me to apply. and anti-harassment policy. individuals while working to help our The administration thought that my The ombudsperson will visitors to resolve, defuse or mitigate many years of experience would afford assist individuals and, without these conflicts. (We can and do step valuable insight into the history and breaching confidentiality, out of this neutral stance to advocate culture of the institution and that inform the EB management for justice and fair treatment if the my position as an emeritus professor team of concerns raised at situation so dictates.) would afford me freedom and inde- the conference and insights or Our office was born out of the need pendence. I originally planned to stay observations about systemic for a confidential resource for conflict for five years, but the sense of purpose issues. The ombudsperson will resolution and support, and to encourage I achieve in working with visitors and be available by phone or email the reporting of mistreatment or breaches my terrific working relationship with April 2–8. of professionalism. From the beginning, Marly Bradley have me thinking that Questions? Email the dean tasked the office with being I’ll likely stick around a bit longer. management@ available and responsive to teachers and To learn more, check out experimentalbiology.org learners alike. the International Ombudsman

MARCH 2020 ASBMB TODAY 39 A new career center Browse jobs, post positions, have your resume critiqued and more.

asbmb.org/career-resources

40 ASBMB TODAY MARCH 2020 CLASSIFIEDS

Assistant Professor of Biochemistry Teaching Assistant Professor West Virginia University West Virginia University

The Division of Plant and Soil Sciences at West Virginia Univer- The Department of Biochemistry at West Virginia University, sity invites applications for a full-time, 9-month, tenure-track Morgantown, WV invites applications for a faculty position of position of Assistant Professor of Biochemistry (50% teaching, 50% Teaching Assistant Professor, Scientist Educator Track. This research). West Virginia University is the state’s flagship land grant fulltime, non–tenure track position will have a major commitment institution, currently enrolls nearly 32,000 students, and is an R1 to teaching medical, dental, and other health sciences students research university as defined by the Carnegie Foundation. The Davis College of Agriculture, Natural Resources, and Design has in the fields of biochemistry, molecular biology, and cell 110 faculty and 150 full-time staff, enrolls 1,700 undergraduate and biology. In addition, the candidate will contribute to course and 280 graduate students across a full spectrum of degree programs programmatic administration, educational innovation, and (28) housed in five academic divisions. The Division of Plant and scholarship in the Department. Soil Sciences is a diverse unit consisting of about 25 faculty and https://careers.asbmb.org/job/teaching-assistant- equivalent positions in agronomy, soil science, entomology, genet- ics, horticulture, environmental microbiology, and plant pathology. professor/53048278/ The Division houses four undergraduate academic majors and partners with other academic units to offer an intercollegiate major in Biochemistry. The Division also offers Masters and PhD degrees. The position is located on West Virginia University’s Evansdale campus in Morgantown, West Virginia. The successful applicant will be housed in a new, state-of-the-art facility and have access to a competitive start-up package. https://careers.asbmb.org/job/assistant-professor-of- biochemistry/53049193/

To see a full list of jobs, please visit asbmb.org/careers

Upcoming ASBMB events and deadlines

MARCH Endometriosis Awareness Month 13 Deadline for advance registration for 2020 ASBMB Annual Meeting 16 Deadline for ASBMB Networking Event Proposals

APRIL World Parkinson’s Awareness Month 4–7 2020 ASBMB Annual Meeting held in conjunction with Experimental Biology 25 World Malaria Day

MAY 1 Deadline for Promoting Research Opportunities for Latin American Biochemists (PROLAB) applications 12–18 National Women”s Health Week 20 World Autoimmune Inflammatory Arthritis Day Transcriptional Regulation: Chromatin and RNA Polymerase II Oct. 1–5, 2020 | Snowbird, Utah

Submit your abstract by July 15.