Vol. 18 / No. 10 / November 2019
THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY
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NEWS FEATURES PERSPECTIVES
2 24 50 GIANT GENE THIEVES SERVICE BEYOND SCIENCE EDITOR’S NOTE ese viruses are changing what we know Weaving social innovation and scienti c It’s about time about structural and evolutionary biology methods for a bright future 3 32 MEMBER UPDATE MEET SEAN DAVIDSON 7 e JLR associate editor rethinks cholesterol NEW MEMBERS 9 24 YEAR OF (BIO)CHEMICAL ELEMENTS For November, it’s that smell of sulfur 10 NEWS Bacterial invasion may explain recurrent urinary tract infections 11 13 JOURNAL NEWS 11 Snug as a bug in the mud 50 13 Researchers clock DNA’s recovery time 14 Lack of sleep a ects fat metabolism 15 is protein makes antibody drugs work 16 From the journals 22 LIPID NEWS Phospholipids and innate immunity 32
2020 Award Winners … page 37 Ruth Kirschstein Diversity in Science Award: ASBMB Award for Exemplary Contributions to Lizabeth Allison Education: Paul Black Herbert Tabor Research Award: Kevin Campbell Bert and Natalie Vallee Award: Edward Dennis ASBMB–Merck Award: Manajit Hayer–Hartl Alice and C. C. Wang Award in Molecular Parasitology: Patricia Johnson Avanti Award in Lipids: Jean Schaff er Earl and Thressa Stadtman Young Scholar Award: William C. Rose Award: Celia Schiff er David Pagliarini DeLano Award for Computational Biosciences: Mildred Cohn Award in Biological Chemistry: ANNUAL MEETING Yang Zhang Carol Fierke Walter Shaw Young Investigator Award in Lipids: Jeremy Baskin
NOVEMBER 2019 ASBMB TODAY 1 EDITOR’S NOTE
THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY It’s about time OFFICERS COUNCIL MEMBERS Gerald Hart Suzanne Barbour By Comfort Dorn President Joan Broderick Matt Gentry Toni M. Antalis Blake Hill President-elect Audrey Lamb Wei Yang James M. Ntambi Secretary Takita Felder Sumter Kelly Ten–Hagen ur concept of time is dictated, As managing editor of this mag- Joan Conaway JoAnn Trejo Treasurer at least in part, by how we azine, I have gone back to looking ASBMB TODAY EDITORIAL Ospend our days. many months into the future. We EX-OFFICIO MEMBERS ADVISORY BOARD For those who work in aca- spend a fair bit of time planning our Robert S. Haltiwanger Rajini Rao demia, the year is shaped by the feature stories and special issues, and Carla Koehler Chair Co-chairs, 2020 Annual Ana Maria Barral cycle of semesters and vacations we also need to keep in mind the Meeting Program Committee Natasha Brooks that make up a school calendar, calendar of the American Society for Kelly Chaćon Cheryl Bailey and days might include set hours Biochemistry and Molecular Biology Chair, Education and Beronda Montgomery Professional Development Bill Sullivan for teaching, study, writing and — the hub of which is the annual Committee Melissa Vaught Binks Wattenberg research. meeting. Daniel Raben When I was home taking care Here at ASBMB central, we Chair, Meetings Committee ASBMB TODAY Sonia Flores of infant children, I lived very constantly think and talk about Angela Hopp Chair, Minority A airs Executive Editor much in the moment, and many the society’s biggest event; the next Committee [email protected] moments dragged interminably. My annual meeting is forever looming, Nicole Woiowich Comfort Dorn sleep-deprived brain seldom could even the day after the last one ends. Chair, Science Outreach and Managing Editor Communication Committee [email protected] look beyond the next feeding or We aim to include annual meeting Terri Goss Kinzy Lisa Schnabel diaper change. Toilet training and information in almost every issue of Chair, Public A airs Graphic Designer Advisory Committee teething were processes that took ASBMB Today — because it’s that [email protected] Ed Eisenstein John Arnst months but seemed to go on for important. Chair, Membership Committee Science Writer years. Yet when my children went is month, we pro le the 12 Susan Baserga [email protected] o to elementary school, it had all fascinating people who have been Chair, Women in Biochemistry Laurel Oldach and Molecular Biology Science Writter passed in a ash. named recipients of the ASBMB’s Committee [email protected] For a couple of years, I had a annual awards and will speak at the Sandra Weller Ed Marklin Chair, Publications Web Editor job as an administrator in an Epis- 2020 annual meeting in San Diego. Committee [email protected] copal church. Many of my tasks, In the past, we’ve pro led award Lila M. Gierasch Allison Frick Editor-in-chief, JBC Media Specialist such as newsletters and bulletins, winners right before the meeting; A. L. Burlingame [email protected] had weekly or monthly deadlines, here, we’re trying something new. Editor, MCP Barbara Gordon but hovering overhead was the great e 2020 meeting may be ve Executive Director Nicholas O. Davidson [email protected] cycle of the liturgical year with its months away, but once you’ve read Editor-in-chief, JLR ancient rituals. e feast of Pente- about these researchers — their lives Kerry-Anne Rye Editor-in-chief, JLR cost might fall in May, but January and their science — I think you’ll wasn’t too early to start planning. want to register right away. For information on advertising, contact Pharmaceutical Media Inc. at 212-904-0374 or [email protected]. When I worked at a daily news- Depending on the pace of your paper, we had a 24-hour cycle that life right now, those ve months reset every night as soon as the next could just y by. day’s issue landed in the press room.
We all liked working on long-term Comfort Dorn www.asbmb.org/asbmbtoday projects, but every day we had to ([email protected]) is the PRINT ISSN 2372-0409 managing editor of ASBMB feed the beast — and that was the Today. Follow her on Twitter @cdorn56. Articles published in ASBMB Today re ect solely the authors’ views and not schedule that drove us. e advent the ocial positions of the American Society for Biochemistry and Molecular of 24-hour online news only made Biology or the institutions with which the authors are aliated. Mentions of products or services are not endorsements. the pace more frantic.
2 ASBMB TODAY NOVEMBER 2019 MEMBER UPDATE
Member Update By ASBMB Today sta
Gingras, Ueffing win HUPO awards transfer, DNA cleavage by anti-cancer drugs, enzymatic Anne-Claude Gingras and Marius formation of polyesters and purine biosynthesis,” accord- Ue ng were among those presented with ing to the ACS. awards at the Human Proteome Orga- A member of the National Academy of Sciences nization’s annual meeting in Adelaide, since 1992, Stubbe has received numerous accolades for Australia, in September. her work, including the Humboldt Research Award, the
Gingras Gingras, a principal investigator at the Welch Award and the National Medal of Science. Lunenfeld–Tanenbaum Research Institute at Mount Sinai Hospital in Toronto, a Trejo named assistant vice chancellor professor at the University of Toronto and Joann Trejo, a professor of pharma- a deputy editor of the journal Molecular cology at the University of California, San & Cellular Proteomics, was one of two Diego, School of Medicine, was appointed scientists recognized with the HUPO Dis- assistant vice chancellor for health sciences Uef ng covery in Proteomics Award. e award faculty a airs in June. highlights single discoveries in the eld of proteomics Trejo Trejo, who has been on the faculty at and honored Gingras’ development of tools and methods UCSD since 2008, studies the role of G for interactomics. Gingras is known for systems biology protein–coupled receptor signaling in vascular in amma- research focused on signal transduction networks, with tion and cancer. applications in diseases from cancer to diabetes. She has served on the council of the American Society Ueng, a professor at the University of Tuebingen in for Biochemistry and Molecular Biology and the Board Germany, received the HUPO Clinical and Translational of Scienti c Advisors for the National Cancer Institute. Proteomics Award. His research has demonstrated that Her work on equity and inclusion was recognized in 2016 Parkinson’s disease risk factor LRRK2 contributes to the with a UC San Diego Inclusive Excellence Award. disease by perturbing vesicular tracking in neurons. His As vice chancellor, Trejo is responsible for developing team also has studied retinal degeneration and genetic strategies for enhancing success, recruitment and reten- ciliopathies, contributing to new diagnostic approaches tion of an engaged diverse faculty and for comprehensive for these diseases. faculty development at UCSD. Stubbe honored with Priestly Medal Justement elected FASEB president JoAnne Stubbe, Novartis professor Louis Justement, a professor of mi- emerita of chemistry and biology at the crobiology at the University of Alabama at Massachusetts Institute of Technology, has Birmingham, has been elected president been named the 2020 Priestly Medal win- of the Federation of American Societies ner by the American Chemical Society. for Experimental Biology. Stubbe e award, the society’s highest honor, Justement Justement served as chair of the recognizes lifetime achievement. It is FASEB Science Policy Committee’s Train- named for Joseph Priestly, the chemist who discovered ing and Career Opportunities Subcommittee from 2008 oxygen and several other gases. to 2018 and FASEB vice president for science policy from Stubbe has spent her career investigating the mecha- 2018 to 2019. nisms of ribonucleotide reductases — enzymes that play At UAB, Justement’s research involves analyzing the an essential role in DNA replication and repair. She is molecular and functional roles of the adaptor protein being recognized for “pioneering studies of enzymatic HSH2 and the transmembrane receptor TLT2 as well as radical chemistry, long-range proton-coupled electron the virulence factors produced by Mycobacterium tuber-
NOVEMBER 2019 ASBMB TODAY 3 MEMBER UPDATE
culosis. He is also the director of the university’s Graduate Benning named distinguished professor Biomedical Sciences Immunology Graduate eme and Christoph Benning, director of the the Undergraduate Immunology Program. Michigan State University Department He will become president in July 2020 after serving of Energy Plant Research Laboratory, was for a year as president-elect. promoted in July to university distin- guished professor, MSU’s highest honor Maquat joins Expansion Therapeutics board Benning for its professors. Lynne Maquat, J. Lowell Orbison Benning studies the biosynthesis and endowed chair and professor in the dynamics of lipids in plants, particularly in the chloro- biochemistry and biophysics department plast. His group uses biochemical and synthetic biology at the University of Rochester School of approaches to understand how the thylakoid, a subsection Medicine, joined the scienti c advisory of the chloroplast, maintains a specialized lipid membrane Maquat board of the biotech startup company in which the proteins responsible for photosynthesis are Expansion erapeutics in June. embedded. e group also studies lipid-derived plant Maquat, who directs Rochester’s Center for RNA Bi- metabolites, such as terpenoids. ology, is best known for her research on nonsense-mediat- Born and raised in Germany, Benning earned his ed mRNA decay. She is a fellow of the National Academy Ph.D. at MSU in 1991 and returned there as a professor of Sciences, the National Academy of Medicine, and the after a stint as an independent young investigator at a American Academy of Arts and Sciences as well as a past German research institute. He became the director of the recipient of both the American Society for Biochemistry MSU–DOE plant research lab in 2015. and Molecular Biology’s William C. Rose Award and the Federation of American Societies for Experimental Biolo- Beggs wins Lasker essay prize gy’s Excellence in Science Award. Grace Beggs, a graduate student in Expansion erapeutics develops small molecules that the biochemistry department at Duke bind RNA based on its tertiary structure. e company’s University, was one of three winners of the goal is to use such molecules to treat genetic disorders Lasker Essay Contest this year. caused by nucleotide repeat expansions, such as the mus- In her essay titled “Game on: Smart-
cle-wasting disease myotonic dystrophy. Beggs phone technology for science education,” Beggs argues in favor of an augmented-re- Showalter promoted to full professor ality smartphone app to promote molecular biology edu- Scott Showalter, a structural biologist cation through play. You can read her essay at the Lasker at Pennsylvania State University, has been Foundation’s website. promoted from associate to full professor. In the Brennan lab at Duke, Beggs, a fth-year Ph.D. Showalter has been at Penn State since candidate, works on multidrug binding proteins involved 2008. Prior to starting as an assistant in antibiotic resistance in strains of public-health impor- Showalter professor, he was a postdoctoral fellow at tance, such as Neisseria gonorrheae and E. coli. Florida State University and the National High Magnetic Field Laboratory. University of Alberta honors Kay Showalter’s group uses biophysical techniques such as Cyril M. Kay, professor emeritus of calorimetry and nuclear magnetic resonance spectroscopy biochemistry at the University of Alberta, to investigate protein structures and interactions, with received an honorary doctorate of science particular emphasis on RNA polymerase and RNA-bind- at the university’s June convocation. ing proteins. Kay, who has served on the faculty of In his 11 years as a junior professor at Penn State, Kay the University of Alberta since 1958 and Showalter has received numerous awards and grants, has belonged to the American Society for including Agilent’s new investigator award in NMR spec- Biochemistry and Molecular Biology since 1961, is best troscopy and a National Science Foundation CAREER known for his studies of protein structure and function. award. He as an editorial board member for the Journal of ose investigations, 28 of which Kay published in the Biological Chemistry. Journal of Biological Chemistry over the years, covered
4 ASBMB TODAY NOVEMBER 2019 a wide biochemical range, including conformational IN MEMORIAM changes in myosin proteins; functional changes induced by post-translational modi cations; calcium-regulated in- Raymond W. Ruddon Jr. teraction in the endoplasmic reticulum; and proteins with antifreeze, antimicrobial and lipid-binding characteristics. Kay was the founding co-director of the Medical Research Council of Canada Group in Protein Structure and Function, which became internationally respected in the protein world. For 10 years he was the vice president for research of the Alberta Cancer Board. He is a fellow of the Royal Society of Canada and an ocer of the Order of Canada.
Hunter delivers IUBMB Jubilee lecture Raymond W. Ruddon Jr., a professor emeritus Tony Hunter was the International of pharmacology at the University of Michigan, Union of Biochemistry and Molecular died April 26. He was 82. Biology’s Jubilee lecturer at the IUBMB Ruddon’s research helped determine a September meeting on inhibitors of pro- mechanism of cancer-cell resistance for the tein kinases in Warsaw, Poland. anticancer drug nitrogen mustard and character- Hunter IUBMB Jubilee awards support travel ize the biosynthesis and secretion of the cancer to small symposia by prominent scientists diagnostic marker human chorionic gonadotropin, to deliver plenary lectures. or hCG. His lab was the rst to determine the Hunter, a professor at the Salk Institute and the Uni- intracellular folding pathways of hCG. versity of California, San Diego, studies cellular growth Born in Detroit in 1936, Ruddon earned a control. He is known best for the discovery in the late bachelor’s degree from the University of Detroit in 1970s of tyrosine kinases, which started the study of those 1958 and then a Ph.D. in 1964 and M.D. in 1967 proteins. His work, which uncovered a new type of pro- from the University of Michigan. He joined the tein regulation and enabled development of a new class of University of Michigan faculty as an instructor in cancer drugs, has been recognized widely with prizes and 1964 and was named a professor in 1974. awards, most recently the 2018 Tang Prize, for which he’ll Ruddon interrupted his academic career give an award lecture at the Experimental Biology meeting twice, rst to work at the National Institutes of in April in San Diego. Health’s National Cancer Institute for ve years and later to serve for seven years as a corporate Barbour moves to UNC Chapel Hill vice president at Johnson & Johnson. He was also Suzanne Barbour, who until recently a professor at the University of Nebraska for seven was a professor of biochemistry and bio- years. At Michigan, he chaired the pharmacology physics and the dean of the graduate school department, was associate director of the cancer at the University of Georgia, moved to the center and served as senior associate dean at the University of North Carolina at Chapel Hill medical school. He authored more than 100 sci- Barbour in September to become the dean of that enti c papers and ve books, including the widely university’s graduate school. used oncology text, Cancer Biology. Barbour, whose research background is in phospholi- For many years, Ruddon kept a foot manne- pase signaling, had overseen UGA’s hundreds of graduate quin wearing a white sock on his desk, a reminder programs since 2015. She has been an active member of the of advice he received and shared in response to American Society for Biochemistry and Molecular Biology’s researchers asking what experiments they should Education and Professional Development Committee for do next. The answer: “Whatever snaps your more than a decade and recently was elected to the society’s socks.” governing council. She also serves as a coach for the Acade- my for Future Science Faculty.
NOVEMBER 2019 ASBMB TODAY 5 MEMBER UPDATE
IN MEMORIAM
Edward J. Massaro Seymour S. Cohen
Edward J. Massaro, a toxicologist, died June 1, The American Society for Biochemistry and a few days before his 85th birthday, in Cary, North Molecular Biology recently learned that Seymour Carolina. S. Cohen of Woods Hole, Massachusetts, died in Massaro, a native of Passaic, New Jersey, December. He was 101. studied mercury poisoning in sh, wrote textbooks Cohen, a New York native, earned his Ph.D. on biochemistry and toxicology, and according to in biochemistry from Columbia University in his family was “the coolest biochemistry professor 1941 and studied virology both for the U.S. Army at the University of Buffalo” when he taught there during World War II, when he helped to develop from 1968 to 1978 at what is now the Jacobs a new vaccine for typhus, and later when he re- School of Medicine and Biomedical Sciences. turned to academia. He held faculty positions at The Buffalo News reports that during that time, a number of institutions, including the University he spoke out against industrial ash and mercury of Pennsylvania, the University of Colorado Med- pollution and participated in the rst observation ical School in Denver and the State University of of Earth Day. New York at Stony Brook. Later in his career, Massaro worked at Mason Cohen won the Eli Lilly Prize in 1951 for his Research Institute in Worcester, Massachussetts; work on bacteriophage biochemistry and for the department of veterinary sciences at Penn- describing how radiolabeled viruses spread be- sylvania State University, where he studied the tween cells. He was involved in the development effects of micronutrient de ciencies and lead ex- of early chemotherapeutic compounds, including posure; and the Environmental Protection Agen- 5- uorouracil, which is still in use to prevent cy’s National Health and Environmental Effects DNA replication in skin cancer; for that develop- Research Lab in North Carolina, where as a senior ment, Cohen was named a lifetime professor of scientist he researched teratogenic compounds. the American Cancer Society. Among his many He continued to conduct and publish on toxicolo- other honors were membership in the American gy research until he retired in 2015. Academy of Arts and Sciences and the National Massaro was elected a fellow of the American Academy of Sciences. He is said to have been Association for the Advancement of Science in nominated for the Nobel Prize several times. 1986. In 1992, he received the EPA’s Scienti c At age 98, he was elected to serve as a and Technological Achievement Award. member of a National Academies panel that put He is survived by his wife of 41 years, Arlene together a national strategy for the elimination of Massaro, M.D., and their four children, 11 grand- hepatitis B and C. That report was published in children and four great-grandchildren. 2017. Cohen is survived by his two children and their spouses, ve grandchildren, and ve great-grandchildren.
6 ASBMB TODAY NOVEMBER 2019 NEW MEMBERS
Paulina Alatriste, Lorencia Chigweshe, Ko Khamit-Kush, Sophia Pirinea, University of Kentucky Wesleyan University Clark Atlanta University Providence College Scott Aoki, Indiana University Ekram Ahmed Chowdhury, Moon Kim, Inha University Nava Poudyal, School of Medicine Texas Tech University Kobie Kirven, Clemson University Jessie Arneson, Health Sciences Center Presbyterian College Tanadje’ Price, Washington State University Scott Clark, Crystal Kotan, University of Presbyterian College Zerubabbel Asfaw, Franklin Western Texas College Nevada, Las Vegas Jonathan Pruneda, Oregon and Marshall College Evan Collins, Yale University Neetij Krishnan, Health & Science University Stephan Azatian, Mae Covacevich, St. Olaf College Pablo Ranea Robles, Texas Tech University Texas Wesleyan University Andrew Kyzer, Icahn School of Medicine Arun Balasubramaniam, Jaclyn Daigle, Presbyterian College at Mount Sinai National Central University Thermo sher Scienti c Jamila Labee, Hernandez Ricardo, Katherine Bearden, Elizabeth Duchow, Univeristy Presbyterian College Presbyterian College University of Florida of Wisconsin–Madison Madison Ladines, Prateeksha Rout, Rutgers Ian Belger, Amanda Dwikarina, Presbyterian College University–New Brunswick Wayne State University University of Missouri Andrew Lane, Kristian Ruiz, Alana Belkevich, Christabel Ebuzoeme, University of Kentucky Houston Baptist University State University of New York Texas Southern University Miranda Leek, Nolan Ryan, University of Upstate Medical University Inayah Entzminger, Oregon State University Wisconsin–Parkside Sandrine Belouzard, City University of New York Javier Leo, Chase Sanders, Centre national de la Graduate Center University of New Mexico University of Kentucky recherche scienti que Maria A Feliz Norberto, Jonathan Licht, Russell Sapio, Graduate Elayne Benson, Lehman College University of Florida School of Biomedical Presbyterian College Sciences, Rowan University Mona Fendereski, University Mlana Lore, Eckerd College Gifty Blankson, of Southern Mississippi Sarah Seeherman, Martin Martin, University Maryville University Daniel Ginsburg, Lake Erie College of California, Los Angeles of Osteopathic Medicine Rider Bodkin, Immaculata University School of Medicine Presbyterian College Victoria Godieva, Florida Theophilus Tandoh, Bryan Mata, Mississippi College Kayla Bramlett, International University Texas Tech University Presbyterian College Xuemei Tong, Shanghai Jiao Stephen Gonzalez, California Timothy Meredith, Brandon Buck, State University, Fullerton Tong University School of Pennsylvania State Medicine Florida State University Christian Goossen, Rochester University Amber Buhagiar, Institute of Technology Tina Tootle, Robin Mockett, University of Iowa Yale University Alla Grishok, University of South Alabama Amatullah Burhani, Boston University Gea-Ny Tseng, Virginia Efehi Nehikhare, Commonwealth University Wayne State University School of Medicine Lanzhou University Tannor Byrd, Vaibhavi Gujar, of Technology, China Jennifer Tuokkola, Ohio State University Presbyterian College Southern Illinois Angelo Nicolaci, Albert Campbell, University Carbondale H. Lee Mof tt Cancer Center Tomas Vaisar, Kennesaw State University Chandan Gurung, University & Research Institute University of Washington Elizabeth Cervantes, of Southern Mississippi Holiness Olasore, Zhiyong Wang, Carnegie Texas Wesleyan University Nesma Hassan, University of Lagos Institution for Science Aaron Chamberlain, Cairo University Jesus Olmos, Blake West, Object Pharma, Inc. Tyler Higginbotham, Texas Wesleyan University Presbyterian College Edmond Chan, Virginia Tech Gabriela Ortiz-Soto, Shay Wigginton, GENEWIZ Queens University Richard Holz, Universidad Central del Hong Wu, St Jude Children’s Guanqun Gavin Chen, Colorado School of Mines Caribe School of Medicine Research Hospital University of Alberta Liliana Jaraczewski, Joseph Osinubi, Martin Wühr, Rong Chen, Wake Forest Presbyterian College University of Delaware Princeton University School of Medicine Kayla Karnes, Jason Pajski, Shouling Xu, Carnegie Jennifer Chesko, Genesis Texas Wesleyan University University of Mount Olive Institution at Stanford Biotechnology Group: Andy Karplus, Sophia Pantazelos, Valentin Yakubenko, East Medical Diagnostic Oregon State University Providence College Tennessee State University, Laboratories Anahita Keer, John Pascal, Quillen College of Medicine Eva Chi, University Texas Wesleyan University Université de Montréal of New Mexico
NOVEMBER 2019 ASBMB TODAY 7 NEW MEMBERS
Diabetes, obesity and the metabolic syndrome A JBC virtual issue at jbc.org
Diabetes, obesity and the metabolic syndrome
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8 ASBMB TODAY NOVEMBER 2019 A YEAR OF (BIO)CHEMICAL ELEMENTS
For November, it’s that smell of sulfur
By Quira Zeidan SULFUR e mark the 150th anniversary of Dimitri Mendeleev’s periodic Wtable of chemical elements this year by highlighting elements with MIKEJL921/WIKIMEDIA COMMON fundamental roles in biochemistry and molecular biology. So far, we’ve covered hydrogen, iron, sodium, potassium, chlorine, copper, calcium, phosphorus, Depiction of the intermolecular disulfi de bridge between cysteine residues 48 A and 139 B on carbon, nitrogen, oxygen, manganese opposite chains of the human phenylethanolamine N-methyltransferase dimer. and magnesium. In November, families all over present even in many types of mete- atulence in humans. the U.S. celebrate anksgiving orites — and the fth most com- In stark contrast, some micro- by eating roasted turkey. During mon element in the Earth. Natural organisms, such as green and purple digestion, the proteins in that turkey events such as volcanic eruptions, sulfur bacteria, can use reduced sul- (and other foods) break down into hot spring vents and tidal ats emit fur compounds, and even elemental smaller amino acids that are used by abundant sulfur that later accumu- sulfur, as an energy source to pro- the body’s cells to synthesize its own lates either as pure elemental crystals duce sugars by chemosynthesis, using proteins. or as sulfate and sul de minerals and oxygen as the nal electron acceptor. Methionine and cysteine — two rocks. Giant tube worms that live on the of the 20 amino acids normally In most ecosystems, the weath- Paci c Ocean oor rely on these present in the proteins we consume ering of ore minerals releases stored bacteria to feed on seawater sul de. — are our major dietary source sulfur that reacts with the oxygen Plants and bacteria use environ- of the element sulfur. e organic in the air to produce sulfate parti- mental sulfate for the synthesis of compound methysulfonylmethane, cles. Sulfate is assimilated by plants the nonessential amino acid cysteine. or MSM, present in vegetables, le- and microorganisms and converted Mammals also can synthesize cyste- gumes, herbs and animal products, is into essential biomolecules such as ine from the glycolytic intermediate another important natural precursor vitamins and proteins, subsequently 3-phosphoglycerate, but they use of sulfur. moving up the food chain. Sulfur is methionine — an essential amino With chemical symbol S and released back onto the land either by acid that must be ingested — as the atomic number 16, sulfur is a decomposition of organic matter or supplier of the sulfur atom. Neigh- reactive nonmetallic element with in rainfall. Terrestrial sulfur drains boring cysteine residues in peptide oxidation states ranging from -2 to into water systems, where it cycles chains can form covalent disul de +6. Depending on the environment, through marine communities or bonds that contribute to protein ex- sulfur compounds may accept or deposits in deep ocean sediments. ibility and control protein structure donate electrons. Sulfur reacts with Some anaerobic bacteria in and assembly. almost all other elements — except human gut ora can oxidize organic for noble gases — and commonly compounds or molecular hydrogen forms polycationic compounds. as an energy source and use sul- Quira Zeidan Sulfur is created inside massive fate instead of oxygen as the nal ([email protected]) is stars as the product of the nuclear electron acceptor during respiration. the ASBMB’s education and public outreach coordinator. fusion between silicon and helium. ese sulfate-reducing prokaryotes Follow her on Twitter By mass, sulfur is the 10th most often produce hydrogen sul de, @quirazeidan. common element in the universe — which causes intestinal gases and
NOVEMBER 2019 ASBMB TODAY 9 NEWS
Bacterial invasion may explain recurrent urinary tract infections
By Courtney Chandler
rinary tract infections, better associated with all of the patients,” cal care, and the pain and discomfort known as UTIs, are the most Orth said. “Instead, we found a associated with the infection can Ucommon bacterial infection in number of di erent types of bacteria lead to reduced quality of life. Anti- women of all ages, and an estimated that correlated with diseased tissue.” biotics are the standard prescribed 50% of women will experience a When they examined and ana- treatment, but doctors are seeing a UTI at least once during their lives. lyzed the tissue further, the research rise in antibiotic-resistant RUTIs, Postmenopausal women are team found both swelling and an which are especially dicult to treat. especially susceptible and many suf- increased presence of antibody- Yet research on the underlying cause fer from repeated infections. Recent secreting B-cell lymphocytes, a key can be challenging. Most studies are research suggests that this recurrence component of the adaptive immune done on mice, which have limited may partially be explained by where response; normally, in the absence lifespans and don’t accurately repre- the infecting bacteria go — namely, of infection, antibody-secreting sent postmenopausal women. Orth, into the walls of the bladder. DeNisco and Zimmern’s study of Kim Orth, a professor at the postmenopausal patient samples is, University of Texas Southwestern therefore, important. Medical Center, and Nicole De- “Solid data about what causes Nisco, an assistant professor at the the disease from patients that have University of Texas, Dallas, along RUTI, rather than making assump- with colleagues at UT Southwestern tions, is in itself a major break- found bacteria in bladder-wall biopsy through,” Orth said. samples of postmenopausal women. Future research can build on e presence of these bacteria within Orth, DeNisco and Zimmern’s the tissue seemed to initiate local ndings to learn how di erent treat- adaptive immune responses, which ments a ect RUTIs both for patient may contribute to the pathology of outcome and at the molecular level recurrent UTIs, or RUTIs. at the site of infection itself. ey Orth and DeNisco partnered have planned future studies on how with urologist Philippe Zimmern to to remove the invading bacteria from study the host-pathogen interactions the bladder and target the local im- involved in RUTI using urine from mune response e ectively. e results postmenopausal women as well could help guide medical treatment as the bladder-wall samples. ey plans to reduce the recurrence of expected to nd bacterial species UTIs in postmenopausal women. associated with bladder and urinary B-cell lymphocytes are at low levels. tract infections, such as Escherichia Scientists long have thought that this coli. Instead, they saw that more response may contribute to RUTI; Courtney Chandler diverse species of bacteria were able these ndings support that theory ([email protected]) is a postdoctoral researcher to invade the bladder’s surface, which and provide better insight into the at Johns Hopkins University is called the urothelium. disease mechanism. and a careers columnist for “ ese results were very sur- Women with RUTIs spend the ASBMB. Follow her on Twitter @CourtneyEChan. prising as we expected to see E. coli billions of dollars annually on medi-
10 ASBMB TODAY NOVEMBER 2019 JOURNAL NEWS
Snug as a bug in the mud
How anaerobic bacteria make unsaturated fatty acids
By Martin J. Spiering
ipids are ubiquitous molecules, they couldn’t use molecular oxygen.” with Bloch, because he was a man of serving as structural building To answer this, Bloch studied really great depth and understand- Lblocks for membranes, messen- fatty acid biosynthesis in two species ing,” Gold ne said. “It was a turning gers in cell signaling or compounds of the anaerobic bacteria clostridia. point in my career.” for energy storage. eir versatility “Clostridia are present anywhere Gold ne’s expertise soon was relies in part on the presence of where there’s no oxygen,” Gold ne tested: Removing all oxygen from one or more double bonds in the said. “If you look in mud several the experimental system to study long lipid carbon chains. e more inches below the surface, you’ll unsaturated fatty acids in anaerobic double bonds a lipid has, the more nd clostridia, and they’re happily organisms posed a challenge. He unsaturated it is; and the more growing.” rst tried to grow the clostridia in a unsaturated lipids there are in a In 1961, Bloch, Gold ne and helium atmosphere in a vacuum des- membrane, the more exible the colleagues published two papers in iccator, “but that didn’t completely membrane tends to be. the Journal of Biological Chemis- remove oxygen, because there could To make unsaturated fatty acids, try on unsaturated fatty acid biosyn- be a trace of oxygen in the helium,” cells growing in the presence of thesis in clostridia. e papers, now he said. molecular oxygen have an advantage; recognized as JBC Classics, reported So Gold ne resorted to a chem- they can use this powerful oxidant that the clostridia species produce ical trick and skillful lab acrobatics. to insert a double bond into a fatty unsaturated fatty acids via a route He poured a 5% potassium carbon- acid chain via a dehydrogenation distinct from that in aerobic cells. ate solution into the desiccator base, reaction. But what about organisms Gold ne’s association with Bloch above which he placed the asks that cannot grow in the presence of began through their shared interest holding the bacteria along with a molecular oxygen? in anaerobic metabolism. Gold ne beaker containing pyrogallic acid. is question piqued the curi- was working on anaerobic bacteria in After sealing the desiccator, Gold ne osity of Harvard professor Konrad Earl Stadtman’s lab at the National gingerly tilted it to tip the pyrogal- Bloch, who had a long-standing Heart Institute of the National Insti- lol into the potassium carbonate interest in oxygen as a biosynthetic tutes of Health. solution. e resulting mixture reagent and knew that molecular “(Bloch) was coming down to removed any traces of oxygen from oxygen is toxic to some microorgan- NIH for a study section, and he the helium- lled desiccator. isms. During a summer course in the asked if we could have lunch togeth- e researchers relied on Bloch’s 1950s taught by the eminent micro- er, and then he asked, would I be expertise in radiocarbon labeling and biologist Cornelius van Niel, Bloch interested in coming to visit his lab?” detection. After feeding 14C-labeled became acquainted with obligately Gold ne said. lipid precursor acetate to the bacte- anaerobic bacteria that thrive only in Gold ne knew Bloch’s work on rial cultures, Bloch and Gold ne ex- the absence of oxygen. cholesterol and fatty acids, for which tracted the lipids from the cells, used Howard Gold ne, an emeritus Bloch was to win the Nobel Prize in gas chromatography to separate fatty professor of microbiology at the Uni- physiology or medicine with Feodor acids, identi ed them with standards versity of Pennsylvania, worked with Lynen in 1964. Gold ne jumped at and assessed them for 14C labeling Bloch on bacterial fatty acid bio- the opportunity and stayed for three in a scintillation counter. synthesis. He said Van Niel’s course years in the Bloch lab. In the rst study, Gold ne and caused Bloch “to wonder what goes “I was really very, very fortunate Bloch reported incorporation of two- on in anaerobes, because obviously, to have had the opportunity to work thirds of the 14C-labeled acetate into
NOVEMBER 2019 ASBMB TODAY 11 JOURNAL NEWS
CENTERS FOR DISEASE CONTROL AND PREVENTION Konrad Bloch
Anaerobic bacteria such as clostridia (Clostridium di cile is shown here) can produce Howard Goldfi ne unsaturated long-chain fatty acids in the absence of molecular oxygen.
saturated lipids and one-third into ing in di erent fatty acid isomers. eir experiments clearly showed monounsaturated lipids, showing To nd out how these isomers that the individual isomers don’t that bacteria can produce unsatu- were made, as described in the sec- arise from interconversions among rated fatty acids in the absence of ond JBC paper, Bloch, Gold ne and them and established which short- molecular oxygen. another member of the lab, Günter chain fatty acids are the precursors But how could the anaerobic Scheuerbrandt, fed 14C-labeled to the various long-chain fatty acid clostridia create double bonds in octanoic and decanoic acids to a isomers. fatty acids? clostridium and again measured 14C us, innovative rejiggering To answer this question, Gold- incorporation into fatty acids. ey of lab equipment, foundational ne and Bloch fed a series of 14C-la- tweaked their procedure to include biochemistry methods and several beled saturated fatty acids ranging in exposure to a strong oxidant that incisive blackboard sketches helped length from 8 to 18 carbons to the breaks lipid double bonds, enabling uncover how anaerobes make unsat- cells. ey found that the clostrid- them to home in on the mechanism urated fatty acids. ia do not make unsaturated fatty that creates the di erent fatty acid e results of Bloch’s lab stood acids by desaturating bonds in their isomers. the test of time. “ e pathway that saturated counterparts. Instead, the “I distinctly remember Paul is in the second JBC (Classics) paper clostridia produce a single double Baronowsky — he was a graduate has held up for 60 years,” Gold ne bond during elongation of the short student at the time — standing at said. “It’s pretty astonishing.” (8–10 carbons long) saturated fatty the blackboard at the end of the
acids, resulting in long-chain mono- lab writing that pathway,” Gold- Martin J. Spiering unsaturated fatty acids. ne said. “‘ is is how you get the ([email protected]) is the technical editor at Bloch and colleagues then no- double bond here. And if you do it the Journal of Biological ticed that the unsaturated fatty acids with another precursor, you get the Chemistry. Follow him di ered in where the double bond double bond there.’ He drew it all on Twitter @spieringmj. was located in the lipid chain, result- out beautifully.”
12 ASBMB TODAY NOVEMBER 2019 JOURNAL NEWS
Researchers clock DNA’s recovery time
By Jonathan Grin
n the time it takes for an Ama- zon Prime delivery to arrive, cells Idamaged by chemotherapy can x their most important DNA almost completely. at’s true in mouse livers mice at least, according to a new study. Researchers found that DNA damaged by the chemotherapy drug cisplatin is mostly good as new in
noncancerous tissue within two HUMAN GENOME RESEARCH INSTITUTE NATIONAL circadian cycles, or two days. e results, published in the Journal of Biological Chemistry, could inform strategies for administering chemo- therapy at times that maximize tumor Circadian rhythmicity of metabolic processes has a significant impact on physiology and behavior. damage while minimizing side e ects. Side e ects of cisplatin include kidney, liver and peripheral nerve in- expressed, repair was less ecient but circadian cycles, Sancar said. Most jury. Cisplatin kills cells, cancerous or also clock-controlled, and maximum repair in the rst 48 hours was to not, by damaging their DNA, so No- repair occurred between 4 p.m. and these genes. bel laureate Aziz Sancar and his team 6 p.m., Sancar said. e remaining damage in non- aimed to uncover the pattern of DNA In this previous experiment, transcribed DNA is not harmful in repair in healthy cells. In normal cells, they examined DNA two hours after normal cells that aren’t replicating, the circadian clock drives the rhythm injecting cisplatin, but in their new Sancar said. But for cancer cells, of DNA repair, but not in tumors. work in JBC, Sancar’s team wanted which divide uncontrollably, this “Most cancers do not have a func- to study recovery on a more clinically damage could lead to cell death. tional clock and so, basically any time relevant time scale. Before this information is consid- that it’s good for the normal tissue, Patients get cisplatin intrave- ered in the clinic, further experiments you can hit the cancer,” said Sancar, a nously at weekly, 10-day or two week are needed, Sancar said. professor at the University of North intervals, allowing recovery time be- Sancar is working with on- Carolina School of Medicine. tween doses, Sancar explained. “And cologists, evaluating new cisplatin In an earlier study, Sancar’s team so we wanted to know what happens regimens in mice implanted with looked at DNA repair across a mouse over those long periods.” human tumors to nd a treatment genome, uncovering two mechanisms Using a technique developed in that reduces toxicity in normal tissue of circadian-controlled DNA repair. their lab, the team captured and se- while hitting cancer hard. ey found that for some genes, quenced fragments of damaged DNA DOI: 10.1074/jbc.RA119.009579 transcription — during which dam- from mice injected with cisplatin.
aged DNA is recognized and patched Over 70 days, they produced maps Jonathan Grif n up — was controlled by the circadian displaying where and when DNA (jonmgrif n93@gmail. clock. e pattern was speci c to each was xed at the resolution of a single com) is a freelance science writer. gene, with repair peaking at di er- nucleotide. Follow him on Twitter ent times of day. For the remaining e DNA of transcribed genes @spelledjon. DNA that is not transcribed or was just about fully mended in two
NOVEMBER 2019 ASBMB TODAY 13 JOURNAL NEWS
Lack of sleep affects fat metabolism
By Laurel Oldach
e all tend to be a little short on sleep during the work W week. A new study adds to the mounting evidence of how harm- ful insucient sleep can be. In the Journal of Lipid Research, research- ers at Pennsylvania State University report that just a few days of sleep deprivation can make people feel less full after eating and cause them to metabolize the fat in food di erently. Researchers have known for to keep them awake and engaged of fat from food was slightly better some time that sleep disruption has and positive.” after a night of recovery sleep, they harmful e ects on metabolism. Or- To nd out how this schedule didn’t recover to the baseline healthy feu Buxton, a professor at Penn State a ected metabolism, the researchers level. and a senior author of the new study, gave the participants a standardized is study was highly controlled, contributed to much of the earlier high-fat dinner, a bowl of chili mac, which makes it an imperfect model research demonstrating that long- once early in the study and again for the real world, Ness said. It term sleep restriction puts people at after four nights of sleep restriction. focused on healthy young people, a higher risk of obesity and diabetes. “It was very palatable — none who are usually at a lower risk of However, Buxton said, most of those of our subjects had trouble nishing cardiovascular disease, and all the studies focused on glucose metabo- it — but very calorically dense,” participants were men. e research- lism, which is important for diabetes, Ness said. ers wondered whether giving more while relatively few assessed digestion Most participants felt less satis- recovery time would change the of lipids from food. ed after eating the rich meal while magnitude of recovery they observed. Kelly Ness, now a postdoctoral sleep deprived than when they had Nonetheless, Buxton said, the fellow at the University of Wash- eaten it well rested. study gives worthwhile insight into ington, ran the study when she was en researchers compared blood how we handle fat digestion. a graduate student in Buxton’s lab. samples from the participants. ey “ is study’s importance relies After spending a week getting plenty found that sleep restriction a ected on its translational relevance. A of sleep at home, 15 healthy men in the postprandial lipid response, lead- high-fat meal in the evening, at their 20s checked into the sleep lab ing to faster clearance of lipids from dinnertime — and real food, not for 10 nights, she said. After three the blood after a meal. at could something infused into the vein? nights spent establishing a baseline, predispose people to put on weight. at’s a typical exposure. at’s very the participants spent no more than “ e lipids weren’t evaporating — American.” ve hours in bed for the next ve they were being stored,” Buxton said. DOI: 10.1194/jlr.P094375 nights. e researchers designed the e simulated work week ended
schedule to resemble a work week. with a simulated Friday and Saturday Laurel Oldach During the study, Ness said, she night when participants could spend ([email protected]) is a science writer for the and other researchers collected data, 10 hours in bed catching up on ASBMB. Follow her on but they also spent time “interacting missed shut-eye. After the rst night, Twitter @LaurelOld. with the subjects, playing games with they ate one last bowl of chili mac. them, talking with them — helping Although their metabolic handling
14 ASBMB TODAY NOVEMBER 2019 JOURNAL NEWS
This protein makes antibody drugs work
By Laurel Oldach
undreds of therapeutic antibody drugs target cell-surface mole- Hcules in cancers and other dis- eases. But di erent patients respond di erently to antibody therapy, and doctors struggle to predict who will bene t most. Except for a few used to ferry drugs or toxins to a speci c cell population, most antibodies work by recruiting the immune system. When natural killer cells, the body’s tiny assassins, recognize antibodies coating a target cell, the NK cells latch onto the target and kill it. An artist’s rendering shows CD16 receptors on a natural killer cell (blue) binding to the constant Kashyap Patel, a gradstudent at region of an antibody (orange) that also is bound to a target molecule. Iowa State University, studies the receptor CD16a, receptor protein It isn’t clear whether that polymor- what to make of the glycan variabili- on natural killer cells that recognizes phism a ects glycans directly or ty, because the donor pool was small and binds to antibodies. Patel and whether genetic changes that do and few studies of this type have his advisor, Adam Barb, now a pro- a ect glycans a ect CD16a-antibody been done. However, now that the fessor at the University of Georgia, binding. Studying the variations protocol for studying glycan compo- were interested in changes to CD16a in glycan structure at each site is sition from a single person is worked that might underlie binding changes. dicult, because isolating enough out, Barb’s lab hopes to determine “CD16a in our bodies is di er- CD16a from a single person to ana- whether changes to that composition ent than the CD16a that’s used to lyze poses a technical challenge. a ect the immune system’s response test monoclonal antibodies,” Patel In a recent article in the journal to antibody therapy. said. Whereas the recombinant ver- Molecular & Cellular Proteomics, When Patel started this project, sion used in laboratories has limited Patel, Barb and colleagues report that he didn’t know much about protein posttranslational modi cations, the they studied post-translational mod- glycosylation, but he said he intends human version is glycosylated at ve i cations to CD16a in glycopeptide to keep studying it as a postdoctoral di erent sites. Glycosylation, which samples harvested from the natural fellow. happens in the endoplasmic retic- killer cells of individual plasma “Once you see a protein with ulum, can add complex branched donors. en they used glycomics N-glycans on it, you cannot unsee it. structures to a protein; those modi- tools to determine the structures of You can’t ignore it.” cations can alter proteins’ binding the glycans. DOI: 10.1074/mcp.RA119.001607 characteristics and could in principle “We weren’t expecting the
make CD16a more or less likely to variability we saw,” Patel said. At Laurel Oldach bind to antibodies. ve sites in CD16a, the team found ([email protected]) is a science writer for the Scientists know that a genetic substantial variability in the structure ASBMB. Follow her on polymorphism near one N-glyco- of glycans — both among the donors Twitter @LaurelOld. sylation site in CD16a can in uence and within each individual. how well antibody treatment works. e researchers don’t know yet
NOVEMBER 2019 ASBMB TODAY 15 JOURNAL NEWS
From the journals
By John Arnst, Isha Dey, Jonathan Grin & Dawn Hayward
A link between stress the immune system by triggering the livers exhibited upregulated serine, and depression release of cell proliferation factors. glycine and one-carbon metabolism Chronic stress a ects the elec- us, researchers need comprehen- and increased in ammation. ese trophysiology of neurons in various sive understanding of the diversity of results, recently published in the regions of the brain including the BMMSCs in dog breeds to speculate Journal of Biological Chemistry, medial prefrontal cortex, or mPFC, on their biological function. suggest that adult and juvenile livers increasing risk for depression. e In a collaborative study pub- employ di erent strategies to main- mechanisms underpinning these lished in the journal Molecular & tain homeostasis. alterations are not understood fully, Cellular Proteomics, Filip Hu- DOI: 10.1074/jbc.RA119.009864 however. In a recent paper in the menik and a team of researchers Journal of Biological Chemistry, from France and Slovakia used a A new enemy for drug- Chenghui Song and colleagues at multi-omics approach to character- resistant cancer cells Scripps Research write that they ize BMMSCs from adult dogs of Two drugs constitute medicine’s studied chronically stressed mice to six breeds and assessed their ability rst line of defense against acute my- uncover the downstream e ectors to di erentiate into bone, cartilage elogenous leukemia: daunorubicin of GPR158 — a receptor enriched and fat cells. Conditioned medium and cytarabine, or Dnr and Ara-C. in the mPFC. ey found that a derived from these cells showed an AML cancer cells quickly grow complex between GPR158 and angiogenic response in a chicken resistant to these drugs, however, and RGS7, which is a negative regulator embryo model, meaning it promoted often require further treatment. Past of GPCR signaling, limited potassi- the formation of new blood vessels research has shown that Dnr raises um current from mPFC neurons in from existing blood vessels, which is the levels of ceramides, lipids that stressed mice, leading to suppressed bene cial for regenerating tissue, but contribute to apoptosis, in treated neuronal excitability. e authors critical for cancer development. is cancer cells. Researchers at the East suggest this freshly uncovered work reinforces the need for more Carolina Diabetes and Obesity mechanism could support the devel- clinical studies before considering Institute recently generated Dnr- and opment of new therapies for stress- MSCs for veterinary treatment. Ara-C-resistant AML cell lines to induced depression. DOI: 10.1074/mcp.RA119.001507 further investigate ceramide’s role. DOI: 10.1074/jbc.RA119.00753 eir work was published in the How liver response Journal of Lipid Research. Using stem cells changes with age Ceramide is broken down to in veterinary therapy e glutamine- and asparag- sphingosine, another lipid that can Stem cells can regenerate them- ine-depleting enzyme asparaginase be catabolized further. Li-Pin Kao selves and di erentiate into various is used as a treatment for blood and researchers in the Cabot lab cell types. In recent years, adult stem cancers, but its clinical success is found that in drug-resistant cell cells have become important can- hindered by side e ects including lines, ceramide levels were low and didates for therapy both in human hepatotoxicity. To uncover how age breakdown products were high, in- diseases and in veterinary science, could a ect the liver’s response to dicating cancer cells rewired normal exempli ed by the use of bone mar- asparaginase, Inna Nikonorova of cells’ pathway to evade apoptosis. row-derived mesenchymal stem cells, Rutgers University and colleagues e enzymes involved in ceramide or BMMSCs, to repair locomotor examined livers from mice of varying breakdown had higher activity in disorders in hard tissues such as ages treated with the enzyme. While resistant cell lines, and ceramide ad- bone and cartilage in dogs and cats. juvenile mouse livers experienced ste- dition no longer a ected cancer cells. However, BMMSCs also can a ect atosis and iron accumulation, adult Treatment with inhibitors that
16 ASBMB TODAY NOVEMBER 2019 Demystifying mitochondrial morphology in fatty livers
For an ailment nonchalantly dubbed “the unnamed In a paper published in the Journal of Biological disease” in 1980, nonalcoholic fatty liver disease has Chemistry, Lingzi Li and colleagues found that knocking out become disconcertingly prevalent. NAFLD is now the most Phb2, which normally forms large ring-shaped complexes common cause of chronic liver disease, affecting between with its sibling molecule Phb1, caused the mitochondria 80 and 100 million people in the United States and close to fragment and stop producing glucose. The absence of to one billion people worldwide. True to its name, the dis- Phb2 also led to excessive cleavage of OPA1, a protein ease is characterized by a buildup of lipids in the liver; over essential to mitochondrial dynamics. time, the excess fat can cause in ammation, scarring and, When the researchers then used adenovirus to express ultimately, organ failure. a cleavage-resistant long version of OPA1, L-OPA1 delta, Over the past four decades, researchers have been they found that hepatic mitochondria returned to a normal unable to clarify the role of mitochondria in NAFLD — the shape due to a stabilization in dynamics but did not regain organelles have been found both to overproduce glucose their previous function of glucose production. When they and to shut down in different patients, changing shape all then expressed L-OPA1 delta in mice that didn’t have Phb2 the while. knocked out, they found it caused excessive mitochondrial To understand whether a change in mitochondrial respiration and glucose production. Together, their results morphology causes dysfunction or vice versa, researchers suggest that cycles of mitochondrial fusion and ssion, at the University of Geneva engineered a mouse lacking regulated by prohibitin, play a role in controlling glucose in prohibitin-2, a protein in the organelle’s inner mem- production. brane that plays a role in cell proliferation, apoptosis and DOI: 10.1074/jbc.RA119.007601 mitochondrial dynamics, or coordinated cycles of ssion — John Arnst and fusion.
Mitochondria often lose their normal rodlike or spherical shapes in the livers of people with nonalcoholic fatty liver
DAVID FURNESS/WELLCOME COLLECTION DAVID disease.
NOVEMBER 2019 ASBMB TODAY 17 JOURNAL NEWS
prevent ceramide breakdown proved astrocytomas, oligodendrogliomas elucidate how moonlighting WRS is bene cial; the researchers saw higher and glioblastomas, are the most regulated in the extracellular milieu, ceramide levels and higher cancer cell common brain tumors. Based on Parker Jobin of the University of apoptosis rates. Higher mitochon- histology and genomic and transcrip- British Columbia and colleagues drial respiration rates in resistant cell tomic data such as DNA and RNA performed secretion and cleavage lines were reversed as well. Resistant copy number and DNA methyla- assays and proteomic studies of WRS cancer cells tend to rely on oxidative tion, gliomas broadly are classi ed from macrophages. ey write in the phosphorylation, which produces as isocitrate dehydrogenase-mutant Journal of Biological Chemistry more ATP than glycolysis. is dual or IDH–wild-type. Patients with that they found that WRS increases inhibitor e ect on ceramide levels IDH mutations typically live longer, the activity of matrix metalloprotein- and mitochondrial respiration could but the mutations are not yet used ases, some of which were shown to help patients with chemoresistant as therapeutic biomarkers. Ugljesa cleave WRS at several sites, curbing AML. Djuric and a team in Toronto recent- the proin ammatory signaling initi- DOI: 10.1194/jlr.RA119000251 ly did a proteomic analysis of di use ated by the moonlighting enzyme. gliomas to improve understanding of DOI: 10.1074/jbc.RA119.009584 Disrupting pathogens’ the downstream pathways involved protective biofilms in their malignancies. eir nd- An isolation strategy e fungal pathogen Aspergillus ings were published in the journal for cytokines fumigatus causes invasive infections Molecular & Cellular Proteomics. Cytokines initiate biological in immunocompromised patients e authors used mass spectrom- activities by binding to and dimeriz- and evades host immune responses etry and protein cluster analysis to ing receptors. ese ligands have by encapsulating itself in a bio lm. study more than 5,000 unique pro- garnered interest for use in immuno- A cluster of genes in A. fumigatus teins in tissue samples from a variety therapies, but their short half-lives recently was linked to the production of gliomas. Overall, IDH-mutant and pleiotropic binding have raised and modi cation of key components gliomas had an increased abundance concerns. To improve the stability of the fungal bio lms, galactosami- of proteins involved in mRNA splic- of cytokine-receptor interactions, nogalactans, or GAGs. Natalie ing, whereas IDH–wild-type gliomas Jamie Spangler, Ignacio Moraga and Bamford of the Hospital for Sick were enriched in proteins involved in colleagues at Stanford University de- Children in Toronto and colleagues invasiveness and epithelial-to-mes- vised an evolutionary strategy for the expressed a gene from this cluster in enchymal transition, an important isolation of monovalent antibodies yeast, producing the protein Ega3 driver of the disease progression. is that lock receptors into a dimerized from the glycoside hydrolase family study sheds light on the changes at state. ey developed a stapler that 114, or GH114. Functional assays the protein level caused by genetic al- could stabilize the interleukin-4 revealed that Ega3 disrupts GAG-de- terations in glioma subtypes, de ned receptor dimer and another that pendent bio lms, and structural by their IDH status, and identi es could stabilize the bond between in- analysis revealed substrate binding distinct targetable proteins and path- terleukin-2 and its receptor subunit. sites on the enzyme. ese ndings, ways, which might aid in developing ese new methods potentially o er recently published in the Journal speci c and personalized treatments. a means to modulate the activity of Biological Chemistry, provide DOI:10.1074/mcp.RA119.001521 of other ligands for a wide scope of valuable mechanistic insights into therapeutic applications. is study the GH114 family, which contains Inactivating a moonlighting was published in the Journal of hundreds of members found in enzyme Biological Chemistry. plants and human pathogens. Tryptophanyl-tRNA synthe- DOI: 10.1074/jbc.RA119.009213 DOI: 10.1074/jbc.RA119.009910 tase, or WRS, plays key roles in protein synthesis within cells, but The lipid buildup problem Analyzing diffuse gliomas the enzyme also performs nonclas- Our intestinal cells store lipids for personalized medicine sical extracellular functions such as through carefully regulated path- Di use gliomas, including the regulation of in ammation. To ways. When there are problems,
18 ASBMB TODAY NOVEMBER 2019 A deep dive into mesenchymal stem cell differentiation
Human mesenchymal stem cells, or MSCs, are part of published in the journal Molecular & Cellular Proteomics, our bodies’ connective tissue. They can differentiate into identi ed cellular pathways and key factors involved in bone, muscle, cartilage and fat cells and are thus bene - ESC-to-MSC differentiation. cial for treating conditions like type 1 diabetes and spinal Using RNA sequencing and performing RNA-to-protein cord injury and for organ transplantation. However, quite correlation, the authors identi ed speci c subsets of genes a few challenges are associated with using these cells for coding for transcription factors, kinases and phosphatases therapy. For example, tissue-derived MSCs can trigger an as well as noncoding RNAs, all of which are differentially unnecessary immune response, leading to uncontrolled expressed in ESCs and MSCs. Using phosphoproteomic cell proliferation, or can undergo unwanted differentiation. analysis, the authors deduced that the proteins that most To better control such off-target effects of tissue-derived were most expressed during differentiation also underwent MSCs, these cells can be differentiated from human the most extensive phosphorylation, hinting at the bio- embryonic stem cells, or hESCs, in the lab in a more con- logical function of such proteins in this process. Overall, trolled manner. But researchers need to know more about proteins involved in cell-to-cell adhesion, cytoskeleton the changes that occur during this differentiation. organization and extracellular matrix formation were the To address this, an international team of researchers most prominent players driving this differentiation. This came together for a multidisciplinary study of hESC-to- study enriches our understanding of the biology of ESC– MSC differentiation. Led by Anja M. Billing of Weill Cornell MSC differentiation, paving the way for better use of MSCs Medicine – Qatar, the team combined transcriptomics, in stem cell–based therapy. proteomics and phosphoproteome analysis for an in-depth DOI:10.1074/mcp.RA119.001356 understanding of the process. Their ndings, recently — Isha Dey WIKIMEDIA COMMONS
These two images show human embryonic stem cells on mouse fibroblast cell feeder layer (left) and a more highly magnified electron micrograph of a mesenchymal stem cell (right).
NOVEMBER 2019 ASBMB TODAY 19 JOURNAL NEWS
Even more reasons to take your DHA
The fatty acids DHA and EPA are popular dietary sup- treated with saturated and unsaturated fatty acids. Unsat- plements and are known to slow tumor growth, but how do urated fatty acids such as DHA and EPA lowered melanin they do it? Researchers at Iwate Biotechnology content in the tumor cells. To determine further Research Center in Japan investigated the the role of fatty acids, the researchers looked at effects of docosahexaenoic acid and eicos- melanin synthesis, which involves several steps. apentaenoic acid on melanoma cells, uncov- They found that EPA reduced the protein levels ering a pathway that fatty acids take to reduce of an enzyme involved in making melanin in melanin content in tumor cells. If cancer cells cancer cells, which could contribute to EPA’s no longer can make melanin, the pigment in anti-tumor effects. skin cells, they can undergo apoptosis. The researchers also found that unsaturat- DHA and EPA are considered omega-3 ed fatty acids prevented synthesized melanin fatty acids because of their structure. Like from getting to its destination. Actin, a protein saturated fatty acids, omega-3 or unsaturat- that other molecules can ride on as they move ed fatty acids have a hydrophilic head and throughout the cell, was reduced in cells DAWN HAYWARD DAWN a long hydrophobic tail, like a snake, but an treated with EPA. DHA decreased a speci c omega-3’s tail has double bonds, or “kinks,” signaling pathway in cancer cells and disrupted in certain places. These kinks make it dif cult DHA, a supplement many their cell cycle. for unsaturated fatty acids to stack on top of one already take, could play These ndings, which were published in another. Saturated fatty acids, with no kinks, a role in suppressing the Journal of Lipid Research, strengthen the easily can stack and potentially clog arteries. melanoma growth. argument that increased unsaturated fatty acid Hidetoshi Yamada and the research team intake is bene cial against certain cancers. analyzed melanin content in melanoma cells DOI:10.1194/jlr.M090712 — Dawn Hayward
Lipid control of chromatin, epigenetics and gene expression
www.jlr.org/site/collections/ chromatin/
20 ASBMB TODAY NOVEMBER 2019 lipids can accumulate, causing cells with GTPase knockout, indi- after. e GH74 family of enzymes in ammation and oxidative stress. To cating a disruption in homeostasis. has demonstrated a speci city for investigate the enzymes that may play GTPase function is therefore critical XyG, but there have been con icting a role in this regulation, researchers to preventing lipid accumulation reports of their structures and modes at the Université de Montréal used and in ammation that can occur in of action. In a paper in the Journal genetically modi ed intestinal cell chylomicron retention disease. of Biological Chemistry, Gregory lines to nd out what happens when DOI: 10.1194/jlr.RA119000119 Arnal of the University of British Co- an important GTPase (an enzyme lumbia and colleagues write that they involved in breaking down GTP) Solving structure of performed an in-depth biochemical called Sar1b is knocked out. Sar1b is useful enzymes characterization of several proteins, involved with transporting fat-car- Xyloglucans, or XyGs, are glycans solving the crystal structures of four rying molecules called chylomicrons contained in the cell walls of most GH74 enzymes. e study unveiled and associated with certain intestinal land plants. Because of their poten- critical structure-function relation- lipid diseases. eir ndings were tial applications in various industrial ships that help re ne our under- published in the Journal of Lipid sectors, enzymes that can alter or standing of GH74 catalysis. Research. degrade these glycans are sought DOI: 10.1074/jbc.RA119.009861 Alain Sane and the research team looked at oxidative stress, in am- mation and fatty acid oxidation to John Arnst Isha Dey ([email protected]) is an ([email protected]) is a determine the e ects of losing the ASBMB Today science scientist at Thermo Fisher GTPase protein. ey found a re- writer. Follow him on Scienti c in India. Twitter @arnstjohn. duction in antioxidant protection by measuring levels of glutathione along with a decrease in redox homeostasis regulation. In ammation markers Jonathan Grif n Dawn Hayward also were increased in response to (jonmgrif n93@gmail. ([email protected]) com) is a freelance science is a recent graduate of the GTPase knockout. e researchers writer. Follow him on Twitter Johns Hopkins University then looked at fatty acid synthesis @spelledjon. School of Medicine and a and breakdown. Breakdown was science news writer. decreased but synthesis increased in
STIMULATING ANALYSES DEFINING NEW DIRECTIONS IN SCIENCE Save yourself from a landslide of literature. Read JBC Reviews to get expert insights into recent ndings, ongoing controversies and unsolved questions in biological chemistry. Use JBC Reviews in the classroom and at journal club.
NOVEMBER 2019 ASBMB TODAY 21 LIPID NEWS
Phospholipids and innate immunity
By Valerie O’Donnell
he innate immune system is an ancient evolutionary arm of Tdefense that responds to acute trauma by generating a barrier that prevents pathogen invasion and ar- rests bleeding. It also patrols healthy epithelial tissues, monitoring and responding to foreign antigens and supporting development of adaptive immunity. Healthy functioning of the innate immune system relies on communication among diverse cell types, both from the bloodstream This representation of a phospholipid bilayer shows integral membrane proteins protruding and based in stromal tissues such as throughout. epithelia and broblasts. Here, phos- pholipid signaling takes center stage expressed in a cell-speci c manner. lipase D: Families of enzymes called in diverse ways, many of which we Prostaglandins signal by activating PLCs cleave PLs to form diacyl- are only beginning to understand. well-characterized G protein-coupled glycerol and release the phosphor- Phospholipids, or PLs, provide receptors, or GPCRs, after they are ylated headgroup. Diacylglycerols the membranes that hold our cells secreted from immune and stromal are potent activators of the protein together. Researchers increasingly cells during in ammation. kinase C pathway, while the PL appreciate how these unique and di- Phosphoinositides: e phos- headgroup mobilizes calcium. PLD verse lipids also play essential roles in phorylation of inositol headgroups of metabolizes phosphatidylcholine to communicating within the immune phosphatidylinositol at up to three form phosphatidic acid, an intracel- system and how this is required for sites leads to a multitude of PL prod- lular molecule that regulates proteins human health and disease. Indeed, ucts that are potently bioactive and involved in Ras and Rac1 signaling. PLs and their metabolic products are highly transient. ese lipids form Enzymatically oxidized PL: central players in vascular in amma- short-lived membrane anchors for ki- Researchers long have known that tion, hemostasis, immunity, cancer, nases that regulate GPCRs, apoptosis PLs oxidize in atherosclerosis and infection and cardiovascular disease. and endocytosis. in ammation via nonenzymatic Here is some of what we know Platelet activating factor: is processes. Now, they are nding that about PL biology in mammals so far: structurally unusual and extreme- a cell-speci c group of related lipids, Prostaglandin and eicosanoid ly transient phosphatidylcholine generated by enzymatic oxidation, precursors: Researchers long have PL has a plasmalogen fatty acyl (a is formed in innate immune cells known that PL hydrolysis provides specialized bond) at sn1 and an in the bloodstream. ese lipids polyunsaturated fatty acid substrates acetyl group at sn2. It signals via the allow the interaction of coagulation for generation of eicosanoids and PAF receptor (a GPCR) to stimulate factors with cell membranes, an prostaglandins by cyclooxygenases innate immune cell functions in the event required for blood clotting. A and lipoxygenases. is involves vasculature. de ciency of enzymatically oxidized large families of phospholipases Phospholipase C and phospho- PLs, or eoxPLs, leads to too much
22 ASBMB TODAY NOVEMBER 2019 bleeding, and studies suggest eoxPLs as natural killer T cells then recog- are involved in vascular in amma- nize the lipid-CD1 complexes. is Valerie O’Donnell (O-DonnellVB@cardiff. tory diseases such as aneurysms. In type of antigen recognition shows ac.uk) is co-director of some situations, eoxPLs and their signi cant molecular diversity in the Systems Immunity nonenzymatically generated analogs terms of PL species implicated, and Research Institute at Cardiff University, U.K. may be regulators of ferroptosis, an a role is emerging for CD1-lipid iron-dependent cell-death process presentation in human allergies, relevant for cancer and organ failure. including to dust mites, pollen and Phospholipid innate immune bee sting. recognition: Both self- and patho- Our lab recently published a gen-derived PLs can act as ligands review covering these aspects of PL for a family of MHC class I-like signaling in the innate immune antigen-presenting molecules called system in the Journal of Clinical CD1. Lipid reactive T cells such Investigation.
Exploring the nuances and complexity of lipoprotein clearance A JLR virtual issue at jlr.org
NOVEMBER 2019 ASBMB TODAY 23 FEATURE Giant gene thieves
From Siberian ice cores f the words “giant viruses” strike fear — or nihilistic delight — you need not worry. e vast majority of the pseudo-lifeforms want nothing to do to Australian lakebeds, with humans, preferring to prey instead on cyanobacteria, phytoplank- massive viruses are ton, and protists and prokaryotes writ large. e corpulent cocci-catchers are of interest, however, to a close-knit community of virus hunters, changing what we know geneticists and structural biologists. One of those structural biologists, Chuan Xiao, who goes by River among about evolutionary colleagues and in correspondence, is an associate professor at the University of ITexas at El Paso, where he co-directs the university’s cryo- biology and viral electron microscopy facility. Xiao recently received a $1.75 million grant structure from the National Institutes of Health to continue characterizing the processes by which a giant virus, cafeteria roenbergensis virus, or CroV, assembles its protein shell. Xiao’s analysis of CroV is made possible by a 14-foot-tall electron micro- scope housed in an interference-minimizing room — a dedicated piece of equipment that, while not rare, carried a $1.8 million price tag for the depart- ment and demands intense computing power to render images of viruses that are more than three times larger than HIV or in uenza virions. “It took me almost two years about — 3 million CPU hours at the su- percomputer center — to get the reconstruction (of CroV’s membrane) to 14 Angstrom de nition,” Xiao said. “You almost can see the 14 atoms lined up together — that’s how accurately we can put all these pieces together.” While some of these viruses have potential medical applications — the methods CroV uses to assemble its protein shell, or capsid, are similar to those used by in uenza viruses — many more play a quiet role in bringing balance to aquatic ecosystems.
24 ASBMB TODAY NOVEMBER 2019 Giant gene thievesBy John Arnst
Massive missives When Bradfordcoccus rst was isolated from the amoebae that had caused a pneumonia outbreak in Bradford, England, in 1992, it refused to replicate in the lab. is response confounded the researchers at the Université de la Méditerranée in Marseille, France — Bradfordcoccus was the size of a small bacterium, and it responded to Gram staining but not to ampli cation of 16S ribosomal RNA, a slowly evolving sequence used to reconstruct prokaryotic evolutionary trees. It took several years for the French microbiologists Didier Raoult and Bernard La Scola to recognize that Bradfordococcus was, in fact, a virus nearly as large as the amoeba Acanthamoeba polyphaga that it was hunting. In a paper PIERRE AGUIRRE/UTEP COMMUNICATIONS IVAN published in the journal Science in 2003, La Scola, Raoult and their colleagues renamed the pathogen Acanthamoeba polyphaga mimivirus, and “mimivirus” — short for “mimicking microbe” — stuck. Some of Raoult’s samples made their way to the lab of the late Michael Ross- mann, a structural biologist and X-ray crystallography pioneer who led the rst team to map the common cold on an atomic level, at Purdue University. At the time, Xiao was a graduate student in Rossmann’s lab working with picornaviruses, a viral family that includes Rhinovirus, Poliovirus and Hepatovi- rus. He immediately was drawn to the challenge presented by the new, massive quarry. “Cryo-EM was just beginning to become a powerful tool,” Xiao said. “Mostly we were working on smaller viruses (because) we still couldn’t get high resolution.” In cryo-EM, researchers ash-freeze molecules and microorganisms in an aqueous environment and then re electrons at them with a transmission electron microscope, gathering data about a sample from the electrons that pass through it. is gets around the diculty of crystallizing samples but results in a At the University of Texas at El Paso, Chuan Xiao, who also lower-resolution image. goes by River, makes use of a 10-foot transmission electron microscope to puzzle out how Cafeteria roenbergensis virus assembles its protein shell.
NOVEMBER 2019 ASBMB TODAY 25 FEATURE
When the mimivirus samples arrived, sity of Texas at El Paso’s emerging structural Xiao was one of the only students capable biology program. Within two years, a grant of both operating the electron microscope from the National Science Foundation would and writing programs to compensate for the fund the towering modern microscope Xiao limitations of the computer’s encoded mem- and his colleagues use today. ory running up against the sheer size of the micrographs. Xiao, who had almost nished A lost domain? Thomas Klose his thesis, quickly wrapped up his work on While mimivirus was the rst identi ed picornaviruses and stayed on as a postdoctoral nucleocytoplasmic large DNA virus, or NCL- fellow in the lab. DV, it wasn’t alone for long. Giant viruses In autumn 2005, just months after he began cropping up anywhere wet — o the received his Ph.D., Xiao’s cryo-EM descrip- coast of Chile, in a 30,000-year-old Siberian tion of mimivirus at the level of 70 angstroms ice core, inside an amoeba in the contact appeared in the Journal of Molecular Biology. lens of a woman with keratitis — all of them For Xiao, the paper marked the beginning bulked up with almost enough transcriptional of a nearly three-year struggle to reconstruct machinery to exist outside of a host. Matthias Fischer the virus’ membrane, which is dotted with Because these massive genomic caches asymmetrical, rodlike bers. had previously been seen only in eukaryotic “It’s very hard to work with, because those cells, their presence left microbiologists and bers don’t follow any symmetry. ey just geneticists unsure whether the viruses had add noise to your images,” he said. “I spent evolved from smaller viruses that had scooped close to two and a half years trying to break up genes from hosts or from cellular ancestors through it, because at that time, we didn’t trading lives of full-time protein synthesis have an electron detector.” and ribosomal activity to live o the ATP e recent explosion of cryo-EM facilities of others. CHUAN XIAO/UTEP has been largely thanks to the development According to Matthias Fischer, an envi- of direct electron detectors, which allow for ronmental microbiologist at the Max Planck digital renderings of cryogenic samples. Institute for Medical Research in Heidelberg, “Now, we have cameras that can essen- Germany, who specializes in gigantic viruses tially detect electrons and count electrons,” and provides samples for structural biologists said omas Klose, the technical director at like Xiao, the latter hypothesis, suggesting a the Purdue Cryo-EM Facility and a frequent lost fourth domain of life outside of Archaea, collaborator with Xiao. “So we can recover Bacteria and Eukarya, was tantalizing for much, much more of the theoretical signal a time. that one would expect in an image. And that “ ere were two opposite hypotheses,” makes it easier to see things, and the contrast Fischer said. “One was that they reduced from of your image improves greatly.” a cellular ancestor and became viral, and that’s But when Xiao was a postdoc, images why they’re so large, because they retained a created by the scattering of electrons o a lot of the genes they had previously.” sample’s surface were recorded on lm that Comparative genomics, however, appears needed to be developed in a darkroom. His to have provided an answer in the form of a portfolio ran into the thousands. small number of genes, including those used “I collected almost 3,000 lms. So just to make viral capsids and the DNA poly- think about developing 3,000 lms in a dark- merase essential for viral replication, that are Mimivirus, here pictured with E. coli, room,” he said. “Every session of cryo-EM, we conserved across all known giant viruses. were initially mistaken for bacteria when could only take about 128 lms maximum … “It’s sometimes tricky to infer a common they were isolated in 1992. we did a reconstruction, but never were able ancestry based on less than a percent of your to improve resolution.” genome,” Fischer said. “But these genes are In 2008, Xiao took a job in the Univer- so-called core genes, and they are present in
26 ASBMB TODAY NOVEMBER 2019 so many di erent viruses, because they’re very important.” Even viruses have predators. Over eons of acquiring e remaining 99% of giant virus and shedding genes, a number of giant viruses picked genomes, which sometimes can include up smaller viruses known as virophages, whose DNA virophages, could be accounted for by the has in ltrated their own and springs to pseudo-life when mechanisms the viruses use to cycle through the host virus begins its own transcriptional hijacking of genes, something Fischer likens to a “genomic bacteria. accordion.” “Complexity comes at a cost, right?” said Matthias “ ere’s a hypothesis called the genom- Fischer, a microbiologist at the University of Heidelberg. ic accordion, where these giant viruses can “These giant viruses have acquired so many genes, and duplicate genes very rapidly to select for the they can do so many things that other viruses rely on best adapted version after mutations happen, the host cell for, that now they’re paying the price for and then they get rid of all the other copies that by attracting this other type of parasite. they don’t need. And then it collapses again,” “One was isolated from a patient with keratitis — he said. there was an amoeba causing an eye infection, the “In the long term, you nd these ex- amoeba was infected with a giant virus, and that giant
tremes. You nd a norovirus, for example, virus was infected with a virus.” Viruses viruses of which has apparently had tremendous genome expansion, and it’s 2.5 megabases, CHANTAL ABERGEL/CNRS CHANTAL
Megavirus chilensis, colloquially referred to as “megavirus,” was discovered o the coast of Chile in 2010. It was the largest identified nucleocytoplasmic large DNA virus until pandoraviruses — so named because the scientific team that discovered them, led by French virologist Chantal Abergel, were primarily women — were found in 2013.
NOVEMBER 2019 ASBMB TODAY 27 FEATURE
It doesn’t matter all with genes that we don’t really recognize think about these virus host relationships like “whether you go out because they are mostly only found in that that,” Wilhelm said. “ e viruses are trying in the open ocean, lineage of viruses. So, for example, by gene to evolve constantly to a ect all the hosts, whether you go to duplication and diversi cation, you don’t rec- and hosts are being pushed away from the ognize the genes anymore or where they came viruses by selection and evolving. And the the bottom of the from. And this is speci c for each subgroup of two of them keep moving forward to just stay ocean, whether you giant viruses.” in one place.” go to freshwater Genomic arsenals Viral bloom ponds, soil samples Why these viruses need such massive By numbers alone, viruses rule the oceans. — they’ll pretty genomes, however, remains unclear. ey also outnumber every other microorgan- much always have “Maybe that enables them to quickly ism in lakes, rivers and rivulets. viruses as the most switch hosts and adapt to many di erent “In every environment, you nd some- abundant biological intracellular environments if they’re already where around 10 million virus particles per bringing a large set of genes,” Fischer said. milliliter (of water),” Fischer said. “It doesn’t entities. “Combine that with the genomic exibility matter whether you go out in the open ocean, – Matthias” Fischer — that they can lose genes and take o genes whether you go to the bottom of the ocean, from the hosts — that makes them very versa- whether you go to freshwater ponds, soil sam- tile and adaptable organisms, right?” ples — they pretty much always have viruses Whether those viruses are able to utilize as the most abundant biological entities.” their genome fully is another question — one “ e big ecological question is, What Steven Wilhelm, an environmental microbiol- is the e ect of these viruses, right? Now, do ogist at the University of Tennessee, Knox- they all kill the hosts and are bad for them?” ville, recently set out to answer. In research Fischer said. “No, that doesn’t seem to be the published in Frontiers in Microbiology, he case. Instead, it looks like they’re fueling the and his colleagues performed a transcriptomic ecosystem by providing nutrients.” analysis of the infection of the bloom-causing Giant marine viruses such as Wilhelm’s algae Aureococcus anophage erens with its quarry AaV accomplish this by breaking giant predator virus, AaV. up blooms of phytoplankton, whose bodies “One obvious question is, Do the viruses then rain down to the sea oor to sequester actually use these genes? Are they just tagging carbon. By doing so, AaVs return valuable along like spare baggage? Or are the viruses phosphorus, iron and nitrogen that had been actually transcribing them?” Wilhelm said. hoarded by a handful of highly competitive “We detected all but, I believe, three of the bacteria in the food web. genes in the entire virus genome, which was “Without viruses, all this would stagnate, kind of surprising to me. I thought there basically. And you would get a few winning would be genes that weren’t being used, but microbes that just do the same thing,” Fischer that wasn’t the case.” said. “And also, the diversity would be much And AaVs constantly are refreshing their lower, because viruses a ect the most abun- genetic arsenal to keep up with mutations, dant hosts.” born out of natural selection, that allow Last year, two Tupanviruses, named after surviving Aureococcus anophoge erens to Tupã, the indigenous South American Gua- subvert them. Wilhelm likens this genomic rani god of thunder, that had been isolated arms race to the Red Queen in Lewis Carroll’s from water samples o the coast of Brazil and “ rough the Looking-Glass.” at the bottom of an alkaline lake bed in the “She stopped at one point and quipped, same country, were described by a team of ‘Sometimes it takes all the running you can Brazilian and French scientists in a paper in do just to stay in the same place.’ And we Nature Communications. e viruses, mem-
28 ASBMB TODAY NOVEMBER 2019 bers of the viral family Mimiviridae, possess ized — its membrane, its genome, its relatives the long tails, or bers, that confounded Xiao ancient and extant — is not insigni cant, in his days at Purdue as well as extraordinarily especially for a eld with fewer than a dozen complex translational apparatuses. senior researchers. While dozens of giant viruses are discov- La Scola, the virus hunter in Marseille ered each year, far fewer are characterized who was the rst author on the 2003 paper and added to the tree of terrestrial ancestry. that identi ed Mimivirus as a virus and the Last year, researchers at the U.S. Department senior author on the paper identifying Tupan- Steven Wilhelm of Energy’s Joint Genome Institute brought virus, has a backlog that could take him more mini-metagenomics tools to bear on soil than two decades to work through, collabora- samples from Harvard Forest, a 4,000-acre tion and technology notwithstanding. ecological research area in Petersham, Massa- “In my freezer, I have 24, 25 completely chusetts, discovering 16 novel giant viruses. new giant viruses, but I have no time to pub- Wilhelm chalks the boom up to techno- lish about them,” La Scola said. “Each time logical growth. you nd a virus, to describe it is probably one “ at, in part, is due to the democratiza- year of work, between microscopy and all the tion of tools for high-throughput molecular genome analysis.” Bernard La Scola biology and bioinformatics and our ability to understand how to use these tools better,” Continuing resolution he said. At UTEP, Xiao continues to examine the Unfortunately, the time it takes for each mechanisms CroV uses to assemble its capsid. newly identi ed giant virus to be character- ough he has ample access to cryo-EM
Giant viruses have recently been found in marine arrow worms. In 2018, scientists at Truman State University in Missouri discovered a giant virus, which they named Meelsvirus, in the epidermal cells of the arrow worm Adhesisagitta hispida. Inspired by this discovery, researchers at Aix Marseille University scrutinized electron micrographs taken in 1967 and 2003 of dissections of the arrow worms Spadella cephaloptera and Paraspadella gotoi, reasoning that structures previously described as bristles and bacteria bore were, in fact, giant viruses. They named the viruses (above) Megaklothovirus horridgei and Klothovirus casanovai
CREDIT: ROXANE-MARIE BARTHÉLÉMY/AIX MARSEILLE UNIVERSITY ROXANE-MARIE BARTHÉLÉMY/AIX CREDIT: after both the Greek spindle-spinning goddess of fate Klotho and the names of the professors who had micrographed each, George Adrian Horridge and Jean-Paul Casanova. While twice as long as a typical Escherichia coli bacterium and significantly longer than an average Pithovirus sibericum, M. horridgei’s total volume falls short of the largest observed pithoviruses.
NOVEMBER 2019 ASBMB TODAY 29 FEATURE
are carrying the torch from the lab of Xiao’s former PI, Michael Rossman, and continu- ing to bring the cryo-EM facility’s modern, fully digital electron microscopes to bear on pathogenic viruses, including Zika, West Nile and hepatitis C. But their work puzzling out understudied CHUAN XIAO/UTEP viruses still is informed by and dependent on the discoveries of their colleagues. “It’s kind of challenging for a lot of these projects to establish the right foundation, be- cause we do structural biology so we don’t do any of the proteomics or genomics part, and we rely on our collaborators,” Klose said. “But if they’ve moved on to the next giant virus, it can be sometimes very dicult for us to get the information that we need.” Basic research can be a hard sell when it comes to pulling in grants from the National Institutes of Health and National Science In 2017, Chuan Xiao and colleagues found that Cafeteria Foundation, something Klose predicts may roenbergensis virus assembles its protein shell by spiraling become more dicult without Rossmann. together capsomers, colored here by their orientation, on While interrogating the capsids of giant a five-fold axis. viruses sometimes provides insight into struc- tures with relevance to pathogenic viruses facilities, he worries about running up against — as with CroV and in uenza viruses, or his computer’s memory restrictions while with African swine fever and faustovirus, an reconstructing the virus’ capsid. NCLDV that Klose and Rossmann recon- “I don’t know how long it would take us structed a few years ago — those connections to nish the reconstruction, because we im- can’t be predicted. mediately hit a memory issue,” he said. “One “In the last few years, we have made a lot terabyte of memory, which is the biggest they of progress in understanding what actually can put on the current supercomputer, isn’t holds these (giant viruses) together and how enough. If we just look at the protein shell, if they assemble,” Klose said. “But we also still we count all of the hydrogens, it’s about 120 have a long way to go to fully understand million atoms. A couple of years ago, when I what’s going on and understand what these tried to load and visualize 120 million atoms, viruses do in the environment, which was my computer crashed.” always a question that Michael had. About two years ago, Xiao and his “ ere are so many of them. ey’re so colleagues discovered that CroV assembles diverse, they’re so big. ey’ve been ig- its protein shell in a spiral pattern made nored for so many years. But what do they up of ve interlocking vertices. ey hope actually do?” eventually to develop therapeutic viruslike
nanoparticles by re ning their resolution of John Arnst CroV’s capsids. ([email protected]) is an ASBMB Today science writer. Follow him on “ at’s what my new project is really Twitter @arnstjohn. focused on,” Xiao said. “We need to push the resolution higher.” At Purdue, Klose and Richard J. Kuhn
30 ASBMB TODAY NOVEMBER 2019 MEET THE JLR JR ASSOCIATE EDITORS
As a way to oer early career researchers an opportunity to learn the ropes of the peer-review process, the Journal of Lipid Research launched its junior associate editor program in 2019. Throughout the year, each of the four new junior associate editors will curate a virtual collection that focuses on their research area and highlights standout researchers who are pushing each field forward.
Raymond Blind Gissette Reyes−Soer Brandon Davies Rotonya Carr Vanderbilt University Columbia University University of Iowa University of Penn- School of Medicine Irving Medical Center Carver College of sylvania Perelman Research area: Research area: Medicine School of Medicine Nuclear lipid signaling Regulation and Research area: Research area: and structure metabolism of Lipid metabolism in Metabolism and Mentor: Lipoprotein(a) endothelial cells lipid droplets in liver George Carman Mentor: Mentor: disease Henry Ginsberg Stephen Young Mentor: Nick Davidson
Read more about the JLR Jr. AEs in the December issue of ASBMB Today.
NOVEMBER 2019 ASBMB TODAY 31 FEATURE COURTESY OF SEAN DAVIDSON COURTESY SeanMEET Davidson The JLR associate editor rethinks cholesterol
By Laurel Oldach
ean Davidson is a con rmed particles within the family of HDL,” he said, Midwesterner. “we can impact biology that a ects a lot of “My entire career has been di erent disease states.” pretty much on the I-70 corridor,” ASBMB Today writer Laurel Oldach said Davidson, a professor at the talked to Davidson, an associate editor of the University of Cincinnati. “I’ve been Journal of Lipid Research, about his research Sacross the highway but not more than an into the composition of HDL particles and hour north or south of it.” their roles in disease. e interview has been Davidson grew up and went to college in edited for length and clarity. Indiana. After doctoral studies at Drexel Uni- versity in Philadelphia and a postdoc at the What draws you to studying high-density University of Illinois Urbana–Champaign, lipoproteins? he started as an assistant professor at the HDL has been a controversial area in the University of Cincinnati in 1998. Today, he past couple of years. Epidemiological evidence leads the university’s division of experimental suggests that HDL cholesterol levels in blood pathology, has won numerous excellence in are a negative risk factor for cardiovascular teaching awards, and runs a research lab with disease. People thought for a long time that physician-scientist Amy Shah. it promotes cholesterol eux and removes e lab focuses on high-density lipo- cholesterol from the coronary arteries around protein particles, which to many people are the heart, helping to prevent cardiovascular synonymous with “good cholesterol.” But disease. But there’s been a lot of evidence re- Davidson cringes at that term. To him, HDL cently that drugs that can raise HDL choles- is much more than a vessel for cholesterol terol really high — which makes your doctors transport; it’s a complex mixture of dozens of very happy — don’t translate to the protec- proteins and hundreds of lipids. tion you’d expect from the epidemiology. “If we can understand the di erent sub- From that perspective, HDL is not popular
32 ASBMB TODAY NOVEMBER 2019 Sean Davidson expresses his appreciation for high-density lipoprotein with a vanity plate on his 1966 Mustang convertible.
to work on right now because the drugs that sure. But many are involved in the immune There’s been a target HDL haven’t been that successful. response; some are involved in blood clotting “lot of evidence But I tend to look at HDL from a di er- and protease inhibition; some are even recently that drugs ent viewpoint — as a platform that circulates involved in metal and vitamin transport. It’s that can raise HDL in the plasma that allows di erent proteins such a fascinating and complex platform for a to get together, dictating distinct functions. I lot of biology that we don’t fully understand. cholesterol really don’t think HDL evolved to protect us from high — which makes heart disease; I think it evolved as almost an Is HDL one thing? Or is it a lot of different your doctors very things that behave similarly? extracellular version of a plasma membrane. happy — don’t A plasma membrane has a barrier function, I don’t think there’s one type of HDL. but it also acts as a medium that allows I think there are probably upward of 50 translate to the proteins to nd each other more easily than di erent particles in a family that happen to protection you’d if they were di using randomly. HDL serves spin out at the same density in an ultracen- expect from the this function outside the cell — kind of a trifuge. If you put protein and lipid together, epidemiology. singles’ bar for circulating proteins. no matter what, they’re probably going to Some of the proteins it assembles are have about the density of HDL. In terms of ” involved in cardiovascular disease. at’s for its composition, there are about 100 di erent
NOVEMBER 2019 ASBMB TODAY 33 FEATURE
COURTESY OF SEAN DAVIDSON proteins that can be associated with HDL and be found in larger, spherical HDL particles. hundreds of di erent lipid species. e immunoreactivity is di erent in each of I think the initial studies may have done those states. us a disservice by thinking about HDL only And it’s so dynamic. I joke that apoA-I in terms of its cholesterol composition rather is like a piece of spaghetti that you take out than thinking of it as a constellation of di er- of the pot and throw on the wall. However it ent particles. We got onto cholesterol back in lands, that’s the shape it is. at’s the major the old days because it was easy to measure, challenge. and it has just carried over. Since di erent HDL particles have similar Are all these different types of HDL particles physical characteristics, it’s hard to tease them pretty highly regulated? Is the variety of apart and gure out what they do individually. compositions uniform, or is HDL more of a at’s what my lab is specializing in doing. random jumble? We’re trying to nd ways to separate HDL In the studies that we’ve done, di erent subspecies and gure out what they do and people have clearly di erent subspecies Sean Davidson (in red) outstrips how that functionality may di er from other patterns. I don’t think they’re randomly opponents in the 2018 Ohio state road particles. distributed. ere’s de nitely a method to racing championships. the distribution; it’s just we don’t fully Technically, how do you approach analyzing understand it. HDL particles? It sounds like they all look I really hope that we can understand similar in some ways. this heterogeneity and we can design drugs HDL is a good example of the observer or therapies that skew the HDL particle e ect problem in science. It’s kind of like populations toward the particles that are most counting butter ies in a box. You have to bene cial for certain disease states. open the box to count them, but opening the (With current therapies) we raise HDL box causes you to lose some before you can cholesterol in the general sense. Companies get an accurate count. Similarly, you have to have invested billions of dollars in a class of isolate HDL before you can study it, and how drugs that target cholesterol ester transfer you isolate it can a ect its composition and protein, which exchanges cholesterol and function. triglycerides between HDL and other lipo– We have taken the approach of using very proteins. If you shut that o , the HDL I joke that apoA-I gentle biochemical methods to get at these accumulates lots of cholesterol. And your “ is like a piece of particles without putting them under harsh doctor wants to see your HDL cholesterol spaghetti that you ionic strength conditions or high G-forces. levels as high as possible. So, from that take out of the pot We do a lot of chromatography to comple- standpoint, these drugs work great: ey ment analytical approaches, and we have been can raise HDL cholesterol levels upward and throw on the working to come up with antibodies that can of 100%. wall. However it label very speci c subspecies of HDL. e But these are very large, abnormal HDL lands, that’s the goal is to use those clinically to link certain particles that we think either are dysfunctional shape it is. subspecies to speci c functions and eventually themselves or have metabolically eliminated to di erent disease states. other HDL particles that are important. ” And unfortunately, these drugs haven’t been Are there special challenges to raising an terribly successful in preventing cardiac antibody against a lipoprotein? outcomes. So indiscriminately raising HDL ApoA-I, the major protein on HDL, cholesterol across the board is probably not exists in at least three di erent conformation the way to go. We think it will be better to states. It can be lipid-free; it can be bound in target certain subspecies that may be more nascent, immature HDL particles; and it can connected with disease.
34 ASBMB TODAY NOVEMBER 2019 Besides heart disease, what other disease riding my bike. I’ll usually go for a three- to states might HDL be involved in? ve-hour ride on Saturday and the same on Because a lot of these particles have Sunday. I do a lot of road racing, and I was di erent immune molecules, they could have fortunate enough to win the Ohio state cham- a role in many disease states. For example, pionship this year for road time trial among we’ve got a project now studying how di erent men in my age group. HDL subspecies might guard against sepsis in It’s hard to remain competitive in cycling When you do a series a mouse model. and still keep my lab running, but I think I’ve “of experiments, you e problem with sepsis is not necessarily struck a good balance. Physical exercise and learn something that the underlying infection. e clinical aspect doing something you love like that are import- nobody else knows that’s so damaging is the immune response ant to maintain a balance, because otherwise that follows. e immune system hyper-re- you’d go crazy. and nobody in the sponds, and that causes cytokine release and, And it’s important for creativity. Some- history of mankind eventually, organ damage. HDL is linked to times, I’ll be out for a long ride and I’ll zone has ever known. anti-in ammatory e ects, so we think that out, and I’ll come back and hang up my bike in That’s an amazing HDL is a natural target for calming the body’s the garage and have designed a whole experi- immune response in the face of sepsis. ment in my head without thinking about it. feeling. ” Stepping back a bit, how did you get How did you become associated with into science? What made you decide on the JLR? research? It’s always been one of my favorite jour- I’ve always been pretty analytical, a geek, nals. I have a le folder lled with papers from if you will. I was one of those annoying kids di erent people, but the JLR ones always seem that took things apart and wanted to gure to be the most ragged. e important papers out why things worked. Both my parents were that I go back to are usually in JLR. pharmacists, so I knew a bit about science I can’t remember when my rst JLR paper from them. In high school, I thought about was — it must have been not long after I being an architect. But as soon as I got to started my career. (JLR Associate Editor) Alan college and took my rst chemistry class, I Attie invited me to join the editorial board said, “ is is pretty cool stu !” and just locked soon after I became an assistant professor, and into it. after three or four cycles, they invited me to be When you do a series of experiments, you an associate editor. learn something that nobody else knows and nobody in the history of mankind has ever Do you have any advice for young scientists? known. at’s an amazing feeling. My advice is to stick with it. I see a lot I also enjoy training students in the of kids who see how tough grant writing is laboratory and helping them on their ca- and postdocs that last a lot longer than three reers. at’s been really ful lling, along with to four years, and a lot of them chose to do the science. something else. I hate to see that. is is a tough business. You put your best I hear you’re a cyclist in your spare time. work into a paper or a grant, and you send Is that a hobby where you get to take stuff it out to people whose job it is to criticize it. apart and put it back together again a lot? at can be hard. But the rewards outweigh Yes, unfortunately. e three important the setbacks, eventually. My advice is to get things in my life are my family, science, and as broad an experience as possible in di erent Laurel Oldach cycling — not necessarily in that order. I’ve laboratories, get with advisors who will help ([email protected]) is a science writer for the been racing a bicycle since I was in high you come up with a project that will be yours, ASBMB. Follow her on school, so pretty much all my spare time I’m and just keep working at it. Twitter @LaurelOld.
NOVEMBER 2019 ASBMB TODAY 35 ANNUAL MEETING SAN DIEGO | APRIL 4-7, 2020
Submit your abstract by Nov. 14 for the chance to present your work
SPOTLIGHT TALKS More than 200 brief research presentations will offer a scan of current findings and research trends.
FLASH TALKS More than 200 flash talk opportunities are available.
POSTER PRESENTATIONS Get noticed when you share your findings at this highly regarded research forum.
Submit your abstract today! asbmb.org/meeting2020/abstracts/ 2020 Award Winners ANNUAL MEETING ASBMB ANNUAL MEETING SAN DIEGO | APRIL 4-7, 2020 Among the unquestionable highlights of every American Society for Biochemistry and Molecular Biology annual meeting are lectures by the society’s award winners. These awards are given to outstanding professionals who have been recognized by their peers for contributions to their fields, education and diversity.
On the following pages, we introduce the dozen distinguished scientists who will be honored at the 2020 annual meeting, April 4 – 7 in San Diego. Our contributing and staff writers talked to them about their professional journeys and the research they plan to discuss in their lectures.
As you read these profiles, think about the outstanding scientists you know. We hope you’ll be inspired to nominate one of them (or yourself) for an award. Nominations for the 2021 awards will be accepted March 2 – May 11, 2020. Nominating instructions will be posted at asbmb.org/awards.
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Ruth Kirschstein Diversity in Science Award: Lizabeth Allison 38 Submit your abstract by Nov. 14 Herbert Tabor Research Award: Kevin Campbell 39 for the chance to present your work ASBMB–Merck Award: Manajit Hayer–Hartl 40 Avanti Award in Lipids: Jean Schaffer 41
SPOTLIGHT TALKS William C. Rose Award: Celia Schiffer 42 More than 200 brief research presentations will offer a DeLano Award for Computational Biosciences: Yang Zhang 43 scan of current findings and research trends. Walter Shaw Young Investigator Award in Lipids: Jeremy Baskin 44 FLASH TALKS More than 200 flash talk opportunities are available. ASBMB Award for Exemplary Contributions to Education: Paul Black 45 Bert and Natalie Vallee Award: Edward Dennis 46 POSTER PRESENTATIONS Get noticed when you share your findings at this highly Alice and C. C. Wang Award in Molecular Parasitology: Patricia Johnson 47 regarded research forum. Earl and Thressa Stadtman Young Scholar Award: David Pagliarini 48 Submit your abstract today! Mildred Cohn Award in Biological Chemistry: Carol Fierke 49 asbmb.org/meeting2020/abstracts/
NOVEMBER 2019 ASBMB TODAY 37 ANNUAL MEETING
2020 RUTH KIRSCHSTEIN DIVERSITY IN SCIENCE AWARD Allison focuses on thyroid hormone receptors and equity
By Nathalie Gerassimov
hen Lizabeth Ann Allison was the biology department Getting there: Thyroid hormone Wchair at William & Mary, she receptor intracellular trafficking recruited Shantá Hinton as the col- lege’s rst minority tenure-track-eli- The butter y-shaped thyroid gible scientist. Almost a decade later gland, located at the base of the and now a tenured professor, Hinton neck above the collarbones, uses remembers Allison’s words to her iodine derived from food together then: “You are scienti cally strong, with the amino acid tyrosine to make emotionally strong, and I know that the hormones thyroxine and triiodo- you are capable of handling this.” thyronine. These two hormones Lizabeth Ann Allison Allison, now a chancellor circulate in the blood and are taken professor of biology at W&M, will up by cells where they bind to thyroid hormone receptors, or TRs, which receive the American Society for Bio- then can act as transcription factors. chemistry and Molecular Biology’s TRs mainly are found in the nucleus but also can be shuttled to 2020 Ruth Kirschstein Diversity in the cytosol, and the Allison lab studies the post-translational regulation Science Award. Hinton nominated of the nucleocytoplasmic shuttling of TRs. In a recent paper the group her for the honor, writing, “She has showed that acetylation promotes cytosolic TR localization and affects the truly been a trailblazer in serving ligand-dependent transcriptional activity. and changing the dynamics of our Asked about her interest in this traf cking, Allison said that under- institution, and encouraging under- standing TR function “gets to be such a complicated story, which is, of represented minorities to continue to course, why I nd it all really exciting and fascinating.” pursue scienti c careers, by support- Molecular and cellular biologists sometimes can get lost in all the ing our passion for science.” details. “Although we want to know the nitty gritty of the molecular mech- Allison’s support for diversity anism,” she said, “we also have to keep a big picture in mind.” stems partially from her own experi- Allison’s lab at William & Mary continues to study how disruptions of ence in the 1980s when few women TR transport and interactions can lead to endocrine disorders. were high ranking academic scien- Allison will give a lecture tentatively titled “Getting there: thyroid tists. Without female role models, hormone receptor intracellular traf cking” at the ASBMB annual meeting. it was her male predoctoral research mentors who “saw a potential in me that I didn’t know I had,” she said. She explored many interests as an underrepresented minority students those are the students that most undergraduate at the University of graduating in biology and neurosci- bene t from my mentorship.” Alaska, but when those mentors told ence more than doubled. her she needed to earn a Ph.D. and Allison has a keen eye for un- become a faculty member, science tapped potential. “In my lab, there Nathalie Gerassimov won out over creative writing and are some students that would have (nathalie.gerassimov@ gmail.com) is a postdoctoral theater. succeeded in any lab,” she said, “and researcher at the Carnegie She was the rst woman to chair then there are those students that Institution of Washington the biology department at W&M; need just a little bit of extra encour- Department of Embryology. during her tenure, the percentage of agement to show their true potential;
38 ASBMB TODAY NOVEMBER 2019 HERBERT TABOR RESEARCH AWARD Campbell builds partnerships to study muscle biology
By Nathalie Gerassimov
evin Campbell always knew he wanted “a job with no tie,” he Elucidating mechanisms K said. His daily commute in a underlying dystrophies hot train to and from Wall Street for a summer college job reinforced that Kevin Campbell’s lab focused preference. on muscle excitation contraction More than four decades later coupling until a failed hypothesis and now a Howard Hughes Medical (that dystrophin associated with Ca2+ Institute investigator at the Uni- channel) opened a new research versity of Iowa, Campbell might be direction. His team puri ed and later tieless when he receives the Amer- cloned and characterized dystrogly- Kevin Campbell ican Society for Biochemistry and can. They elucidated the molecu- Molecular Biology’s 2020 Herbert lar pathway involved in dystroglycan maturation and how mutations in Tabor Research Award. In a joint dystroglycan processing enzymes therein cause muscular diseases. nomination letter, Gerald W. Hart The lab studied the functions of two molecules involved in dystro- and Lance Wells of the University glycan maturation and implicated in muscular dystrophies: LARGE and of Georgia called Campbell’s lab POMK. They showed that LARGE is a bifunctional glycosyltransferase that “the world leader in the study of the synthesizes a matriglycan, a polysaccharide containing a novel O-glycan. molecular mechanisms of muscular They found a mechanism where one disaccharide suf ces for high-af nity dystrophy.” binding of the extracellular matrix independent of the underlying protein. Campbell’s group has published POMK previously was thought to be a pseudokinase because its more than 450 papers, many on structure lacks several amino acids thought to be essential for a kinase. groundbreaking discoveries such as Campbell’s group in collaboration with Jack Dixon’s lab found that the the identi cation and characteri- ER-resident POMK adopts a kinase fold due to formation of disul de zation of dystroglycan as an extra- bonds, a nding that has reinvigorated the pseudokinase research eld. cellular matrix receptor involved in Jamey D. Marth wrote in support of the award nomination that such anchoring the muscle membrane discoveries make Campbell “the most innovative and accomplished and cytoskeleton to the basement biomedical researcher in the eld of muscular dystrophy.” membrane. He also is dedicated to maintaining the highest standards in training and mentorship for students discarded tissues for experiments that them rst to try odd jobs and learn and postdoctoral fellows in his lab. con rmed his hypothesis. to interact with all kinds of people; After starting his lab in the is began a decades-long his high school job at a cemetery and 1980s, Campbell realized he needed collaboration with physicians around his Wall Street job in college taught dystrophin mutant tissues to test a the world. It was also the conceptual him a lot about working with people. hypothesis. He met a physician who beginning of the Wellstone Muscular
routinely operated on patients with Dystrophy Cooperative Research Nathalie Gerassimov Duchenne muscular dystrophy, a ge- Center, dedicated to diagnosis and (nathalie.gerassimov@ gmail.com) is a postdoctoral netic disorder involving a dystrophin development of therapeutic ap- researcher at the Carnegie de ciency. During the operations, proaches. Campbell is its director. Institution of Washington tissues were removed and discarded. When high schoolers ask about Department of Embryology. Campbell started to collect these joining his lab, Campbell encourages
NOVEMBER 2019 ASBMB TODAY 39 ANNUAL MEETING
ASBMB–MERCK AWARD Winding path leads to plant enzyme breakthrough
By Elizabeth Stivison
fter nishing high school in Singapore, where she grew up, Synthesizing plant RuBisCo in AManajit Hayer–Hartl trained E. coli for the first time as a teacher because, she said, “Most educated women in those days in RuBisCo is the most abun- Singapore ended up being teachers.” dant protein on Earth; all biomass She lasted about a year before depends on its function, because realizing that she didn’t want to read plants need it to incorporate carbon the science her 14-year-old students dioxide into glucose. But RuBisCo is read; she wanted new, exciting sci- inef cient. About 25% of the time, it ence. So she applied to a chemistry incorporates oxygen instead of CO2, Manajit Hayer–Hartl Ph.D. course in Scotland. It wasn’t effectively wasting the enzyme’s what her parents had in mind, but function, and this has a direct effect on crop yield. “my parents couldn’t really stop me Researchers have the skills to do mutagenesis and screen proteins since I wasn’t relying on (them) for for optimal function, but they could not do this with RuBisCo, because no funding,” she said. one was able to synthesize the enzyme from plants in the lab; its assem- “I can laugh about it now, but bly of eight large subunits and eight small subunits was too complicated. 40 years ago you really had to ght Manajit Hayer–Hartl and her lab team solved this problem when they against the system.” found the factors that help plant RuBisCo fold and assemble. In addition Her ght paid o with a distin- to the chaperone system that includes Cpn60/Cpn20, there are four other guished career and, most recently, required factors: Raf1 and 2, RbcX, and Bsd2. Each of these proteins the American Society for Biochem- acts at different stages: Some help with folding, some help stabilize the istry and Molecular Biology’s 2020 folded form and some assemble the whole hexadecameric complex. ASBMB–Merck Award for research When Hayer–Hartl’s lab expressed these factors in E. coli along with in biochemistry and molecular the components of RuBisCo, for the rst time scientists were able to syn- biology. thesize plant RuBisCo outside of chloroplasts, a huge step for optimizing After her Ph.D. and postdoc, its function. Hayer–Hartl met her future hus- band, Ulrich Hartl, at a meeting in Greece. He wanted to move to the U.S., and “I’m a nice wife so I went With the goal of studying how biochemistry but brings her daily joy. along,” she said. She worked in his the photosynthesis enzyme RuBisCo “Every day I learn something protein folding lab in New York, is synthesized in plant cells, in 2006 new,” she said. “ is is where I nd which led to some new experiences. Hayer–Hartl became the leader the greatest satisfaction.” “I’d never run a gel in my life,” of her own research group at Max she said. Others in the lab were Planck. She was the rst person to unfamiliar with her chemistry skills. synthesize plant RuBisCo in Esch- Elizabeth Stivison It was a great melding of knowledge. erichia coli and rmly established (elizabeth.stivison@gmail. com) is a Ph.D. student at When the couple moved to the Max herself as the leading expert on Ru- Columbia University studying Planck Institute of Biochemistry, BisCo biogenesis. is work not only mechanisms of DNA repair and a careers columnist for Hayer–Hartl worked independently earned her the respect of colleagues the ASBMB. in her husband’s lab. across elds from plant biology to
40 ASBMB TODAY NOVEMBER 2019 AVANTI AWARD IN LIPIDS Schaffer is motivated to pass on good mentoring
By Laurel Oldach
ean Scha er wasn’t expecting any more major news this summer Understanding — and preventing Jas she wrapped up a move from — lipotoxicity Missouri to Massachusetts. “I got the email from (ASBMB Inspired by cardiovascular President) Jerry Hart the day I was comorbidities in diabetic patients, closing on my house and getting on Jean Schaffer studies lipotoxicity, the a plane to come to Boston,” Scha er means by which metabolic stress said. “It was so unexpected.” can harm cells. Her award talk ten- at email advised Scha er, who tatively is titled “Death by lipids: The was moving to assume the role of role of noncoding RNAs in metabolic Jean Schaer senior investigator and associate re- stress.” search director at the Joslin Diabetes Using a genetic screen for variants that protect cells from death after Center at Harvard Medical School, excess lipid intake, Schaffer’s lab discovered a role in lipid-induced death that she had won the American Soci- for a class of noncoding RNAs known as small nucleolar RNAs. The ety for Biochemistry and Molecular snoRNAs in question are encoded in the introns of a protein-coding gene, Biology’s 2020 Avanti Award in so con rming the discovery involved some tricky genetic dissection and Lipids. rescue experiments; the unexpected result has become a core element of When she decided to move her Schaffer’s scienti c reputation. lab, Scha er’s main concern was for Projects involving other genes revealed in that screen are approaching her trainees. “ e most challenging a stage when they’ll be ready to present. It’s too soon to know whether part is to make sure that everybody they’ll be ready by the ASBMB annual meeting in April, Schaffer said, from my group who can’t come can “but you can rest assured that I will talk about how we’ve leveraged land on their feet and move ahead, genetics to uncover the molecular transducers of metabolic stress.” and that this won’t be a big bump in the road for them,” she said. Her commitment to mentoring comes from her own experiences. “I was incredibly fortunate to have id-induced metabolic stress and cell the Deuel and Kern conferences on worked with outstanding mentors death and was promoted to full pro- lipids for some years and service as who really helped shape my career,” fessor and director of the university’s an associate editor for the Journal she said. “So I’m highly motivated to Diabetes Research Center. Now she’s of Lipid Research and on two other pay that forward.” launching a new chapter in Boston. editorial boards. After graduating from Harvard “Colleagues who I’ve known for Medical School, Scha er pursued many years in the metabolism and further clinical training in cardiology diabetes elds are here in the Boston followed by a postdoc at the Mas- metro area,” Scha er said. “It’s won- Laurel Oldach sachusetts Institute of Technology derful to be closer to collaborators ([email protected]) is a science writer for the with cell biologist Harvey Lodish. and to really drink up some of this ASBMB. Follow her on She joined the faculty at Washing- exciting environment.” Twitter @LaurelOld. ton University in St. Louis in 1995. Scha er’s other service to the ere, she built a lab studying lip- eld includes helping to organize
NOVEMBER 2019 ASBMB TODAY 41 ANNUAL MEETING
WILLIAM C. ROSE AWARD Schiffer takes a multidisciplinary approach
By Mohor B. Sengupta
elia Schi er prefers to approach problems from a multidisci- Beating drug resistance C plinary viewpoint. She studied physics as an undergraduate at the Much of Celia Schiffer’s work University of Chicago and then is on elucidating how mutations in expanded to biophysics — combin- drug targets affect resistance to the ing biology, chemistry and physics drug. Schiffer is interested in the — for her Ph.D. at the University of speci city of molecular recognition. California, San Francisco. “Drug resistance occurs as a “Even when I did my Ph.D., … result of evolution,” she said, “when I worked at the interphase between drug pressure changes the balance Celia Schier doing experimental crystallogra- of molecular recognition events, phy and computational molecular selectively weakening inhibitor binding by mutation while maintaining dynamics,” she said, “and that the biological function of the therapeutic target.” These changes involve continues to this day when I apply alteration of both the structure and the dynamics of the target. biophysics, structural biology and In her award lecture at the 2020 ASBMB annual meeting, Schiffer will chemistry to elucidating the molecu- talk about strategies to avoid drug resistance in the drug-design process. lar mechanisms of drug resistance in One such strategy arose from her team’s recognition that many resis- quickly evolving diseases.” tance mutations occur where the inhibitor protrudes beyond the volume For her multidisciplinary work necessary for substrate recognition. on drug resistance, Schi er will By targeting an inhibitor to the substrate envelope, the probability of receive the American Society for resistance can be decreased, as a mutation impacting the inhibitor bind- Biochemistry and Molecular Biology ing will compromise substrate turnover. 2020 William C. Rose Award recog- “We discovered and validated this strategy through inhibitor design nizing contributions to biochemical and testing in several systems,” Schiffer said. These systems include viral and molecular biological research proteases in HIV and hepatitis C. The concept is broadly applicable to and commitment to the training of other quickly evolving diseases such as cancer. younger scientists. Schi er started the Institute for Drug Resistance in the University a successful lab where science can potential, she said. of Massachusetts Medical School, be pursued without stresses that “I try to encourage my students which she currently heads. Her lab often selectively a ect international so that they are able to see how their is known for a culture that enables students and those from underrepre- project ts into the bigger picture.” researchers from diverse backgrounds sented minority backgrounds. to pursue their work amicably within Schi er nds that some students the group. su er from imposter syndrome — Mohor B. Sengupta ([email protected]) “My lab has gained the reputa- believing they are not as good as has recently transitioned into tion for being a friendly, support- their peers — despite what their a science writing position from being a postdoctoral ive place to learn and do science,” professors or peers actually think. researcher at the National Schi er said. Exposure to broader scienti c plat- Institutes of Health. Read her blogs at mohorsengupta. She believes being respectful forms, such as attending conferences, com and sciencepolicyforall. to fellow researchers is the key to helps these students realize their wordpress.com.
42 ASBMB TODAY NOVEMBER 2019 DELANO AWARD FOR COMPUTATIONAL BIOSCIENCES Zhang takes the lead in protein modeling
By Courtney Chandler
he old adage “Function depends on structure” has been taught Enhancing protein structure Tin protein biology courses for prediction algorithms decades. Yet as some of the most complex and versatile biomolecules, Computation-based protein proteins can be challenging to structural modeling provides a fast structurally de ne. Bioinformatics and inexpensive way to investigate algorithms that predict 3D pro- protein-related scienti c queries tein structure based on amino acid across many disciplines. However, sequence are crucial for deducing the partially due to the complicated biological function of proteins that nature of proteins and their folding Yang Zhang have not been structurally character- patterns, the researchers behind ized by other methods. computational programs have struggled to make protein structure predic- Yang Zhang, a professor of tion methods more accurate. biological chemistry and computa- Using machine learning, Yang Zhang recently has leveraged big data tional medicine and bioinformatics from whole-genome sequencing studies to improve upon his existing at the University of Michigan, has computational models. This approach enables him to derive co-evolu- developed a repertoire of computa- tionary relationships among proteins, which helps improve prediction of tional methods for predicting protein protein structure. structure. For his work, Zhang is Zhang’s award lecture, “Toward the solution of the protein structure being awarded the American Society prediction problem,” will focus on the progress the eld has made in for Biochemistry and Molecular improving protein prediction models and what the future will look like. Biology’s 2020 DeLano Award for Computational Biosciences. After earning a Ph.D. in physics, “a worldwide leader in structural the increased power that comes with Zhang began applying his back- bioinformatics and protein structure machine learning, which enables ground to translational science, modeling” in his letter nominating computational systems to improve partially because biomolecules were Zhang for the award. their function based on experience more tangible than the theoretical For Zhang, the thrill of basic dis- without explicit programming. concepts of particle physics. covery goes hand-in-hand with trans- “Now you can tell a computer to “As a scientist and human being, lational impact. Both can be aided learn the principles of a system even I want to understand how and why a signi cantly by structural prediction if you don’t understand them, and protein that’s coded from DNA can and modeling algorithms. the computer will generate a model,” fold into a stable 3D structure,” he “If we can computationally mod- he said. “ is will represent a big said. “ at is the secret of life.” el protein shape, it will have a big change for the eld.” His methods, including pre- impact on drug design and discovery, diction algorithms I-TASSER and and on human health in general,” Courtney Chandler QUARK, have been listed consis- he said. “But … it is also important (courtneyec19@gmail. com) is a postdoctoral tently as top-tier based on eldwide for us to understand protein systems researcher at Johns assessments. William Smith, a and the life science systems they are Hopkins University and a careers columnist for the professor emeritus at the University involved in outside of disease.” ASBMB. Follow her on of Michigan, described Zhang as Zhang also has begun to harness Twitter @CourtneyEChan.
NOVEMBER 2019 ASBMB TODAY 43 ANNUAL MEETING
WALTER SHAW YOUNG INVESTIGATOR AWARD IN LIPIDS Labeling lipids and playing piano
By John Arnst
or Jeremy Baskin, learning a new arrangement on the piano isn’t Studying in a rich playground Fso di erent from tagging and tracking phospholipids. Jeremy Baskin’s lab at Cornell “When you play the piano, and University constantly is working on you want to learn a hard passage, new tools to interrogate phospholi- you have to do it slowly. And you pase D, an enzyme upregulated in a have to do it over and over again wide swath of cancers. to get the muscle memory correct,” “There’s a push in other said Baskin, a professor at Cornell academic laboratories to develop University’s Weill Institute for Cell selective inhibitors of phospholipase Jeremy Baskin and Molecular Biology and depart- D for the purpose of downregulating ment of chemistry and chemical the proliferation of cells, which is a hallmark of cancer,” Baskin said. “In biology. “ at’s a good preparation the phosphatidic acid area, we’ve really focused much of our energy on for laboratory research, where you the development of tools.” often have to repeat experiments and In his award lecture at the 2020 ASBMB annual meeting, Baskin will change variables in order to get it to speak about recently developed lipid imaging methods. work just right.” “These enzymes are, I think, a really rich playground for a chemical For about a decade of getting his biologist to operate in, because they have a relaxed speci city that it work right, Baskin has been select- allows us to come in with synthetic probes and trick the enzyme into ac- ed to receive the American Society cepting our synthetic probes instead of their natural substrates. And that for Biochemistry and Molecular is the key that allows us to develop our imaging tools,” Baskin said. Biology’s 2020 Walter Shaw Young “We’re currently using them to uncover how the phospholipase D Investigator Award in Lipids. enzymes and the phosphatidic acid lipids that they produce regulate He grew up in Montreal in a fundamental cell signaling and disease-associated signaling.” family with an artistic bent — both his parents are classical musicians, and his younger sister is now an actress. When he pursued chemistry as an undergraduate at the Massa- developing chemical tools for im- e lab recently has been focusing chusetts Institute of Technology, he aging cell-surface glycans. In 2009, on phospholipase D, a precursor to found relaxation and camaraderie he took a postdoctoral fellowship several cancer-associated phosphatid- among fellow musicians. in the lab of Pietro De Camilli at ic acids that often is upregulated “It being MIT, it wasn’t populat- Yale University, where he narrowed in cancer. ed with a bunch of future profession- his focus on membrane biology and al musicians,” he said. “ ere was a lipid metabolism.
lot of energy and focus on science Baskin’s lab primarily focuses John Arnst and engineering majors that were on two types of phospholipids that ([email protected]) is an ASBMB Today science doing music on the side.” represent extremes in terms of size: writer. Follow him on In 2004, Baskin joined Carolyn phosphatidic acids, which have tiny Twitter @arnstjohn. Bertozzi’s lab at the University of headgroups, and phosphoinositides, California, Berkeley, where he began which have massive headgroups.
44 ASBMB TODAY NOVEMBER 2019 ASBMB AWARD FOR EXEMPLARY CONTRIBUTIONS TO EDUCATION Black’s career balances teaching and research
By Mohor B. Sengupta
hen Paul Black was a postdoc at the University of California, Lipid metabolism WIrvine, two undergrads helped and its practical applications him with projects on long-chain fatty acid transport that succeeded Paul Black’s lab has done sem- due to their combined e orts. e inal studies addressing fatty acid research was published in the Journal uptake into the cell. His team puri- of Biological Chemistry, and that ed and characterized the bacterial one-on-one interaction with students fatty acid transport protein FadL became the foundation of Black’s and, working with a Harvard group, teaching philosophy. crystallized the protein and veri ed it Paul Black In honor of a career shaped by was a fatty acid-responsive chan- that philosophy, Black will receive nel. They discovered fatty acid transport protein 1, FAT1p, which plays a the American Society for Biochem- role in getting fatty acids into yeast. Recent work with the Wistar Institute istry and Molecular Biology’s 2020 shows increased expression of FATP2 (an ortholog of FAT1p) in certain ASBMB Award for Exemplary Con- cancers, where it appears to regulate arachidonic acid uptake. tributions to Education. Beginning with a $2.4 million Department of Energy grant, Black’s Black was teaching biochemis- team has addressed triglyceride synthesis in green algae for bioproducts try at the University of Tennessee and biofuels. By understanding the carbon–nitrogen balance during in 1992 when the dean of medical growth, they showed this system was also effective in removing nitrate education assigned him to develop a from groundwater. molecular cell biology program for The aim is to mitigate a broad spectrum of health issues caused by medical students. high nitrate levels in groundwater prior to use for municipal drinking water. “ is was in a time when there were more discipline-based classes being taught in the medical cur- riculum,” Black said. His course Black bucks tradition with a scienti c community.” used a multidisciplinary approach, specialized approach to designing As chair of the UNL biochemis- something new in those days, and biochemistry courses informed by try department, he is close to his goal the medical students and the bio- basic research. He introduced a sec- of a department with comparable chemistry department honored him ond-year course on scienti c writing numbers of male and female faculty. with the Golden Apple Award for and analysis of scienti c discourse He is proud that his lab is enriched excellence in teaching. and continues to receive positive by students from many demographic At the University of Nebras- feedback from students. and racial backgrounds. ka–Lincoln, Black developed a new Black is passionate about inclu- approach to biochemistry education sion in academia. “It is essential that Mohor B. Sengupta ([email protected]) using experiential learning and critical we have inclusive excellence,” he has recently transitioned into thinking skills. “His mission at UNL said, “and it is extremely important a science writing position from being a postdoctoral has been to develop a biochemistry that in the STEM disciplines there researcher at the National program of inclusive excellence,” is a balance between men, women, Institutes of Health. Read her blogs at mohorsengupta. Donald Becker wrote in his letter minorities and individuals from com and sciencepolicyforall. nominating Black for the award. communities marginalized by the wordpress.com.
NOVEMBER 2019 ASBMB TODAY 45 ANNUAL MEETING
BERT AND NATALIE VALLEE AWARD IN BIOMEDICAL SCIENCE A quest to understand plasma membranes and develop lipidomics
By Tori Zirul
hat began as a high school passion for science developed Paths to pain and inflammation Winto a fascination with ste- reochemistry when Edward Dennis In his lecture at the ASBMB took an organic chemistry class at annual meeting, Edward Dennis will Yale. Stereochemistry became a com- talk about how membranes inter- mon thread in his career, beginning act allosterically with enzymes to with his Ph.D. research with Frank regulate cell signaling and metabolic Westheimer at Harvard, where he pathways leading to in ammation. applied pseudorotation to explain Dennis has used substrate phosphate ester hydrolysis, and lipidomics coupled with molecular Edward Dennis continuing with lipid enzymes as a dynamics to reveal enzyme speci c- postdoc with Eugene Kennedy. ity linked to hydrophobic binding sites for membrane phospholipid sub- Now a professor at the University strates. He discovered unexpected headgroup and acyl chain speci city
of California, San Diego, Dennis will for each of the major human phospholipase A2 enzymes that explains the receive the American Society for Bio- observed speci city at a new structural level. chemistry and Molecular Biology’s Dennis’ lab discovered that a unique hydrophobic binding site — and 2020 Bert and Natalie Vallee Award not each enzyme’s catalytic residues or polar headgroup binding site —
for his accomplishments in biomedi- dominates each enzyme’s speci city. Each PLA2 shows unique speci city cal research. for its required fatty acid ranging from pro-in ammatory arachidonic acid As a new assistant professor at to membrane remodeling linolenic acid, antibacterial saturated fatty acids UCSD in the 1970s, Dennis was and oxidized fatty acids in low-density lipoproteins.
studying enzymes acting on phospho- PLA2 releases a speci c fatty acid after the enzyme associates lipid membranes when he obtained a allosterically with membranes and extracts the phospholipid substrate, vial of snake venom from India. Co- which can be blocked by stereospeci c inhibitors. After decades of work,
bra venom contains a small stable en- Dennis and his team now can correlate PLA2 speci city and inhibition potency with molecular structure and physiological function, using a novel zyme, phospholipase A2, or PLA2, that is easy to work with in the laboratory. lipidomics platform. e Dennis group took advantage of this, analyzing PLA2 from struc- ture to function. What they learned as the principal investigator of a $73 the opening and promotion of an en- from this research and the lab’s later million, multisite 10-year grant from tirely new eld of research, lipidom- work on human PLA2s advanced the the National Institutes of Health, ics, together with the creation of an understanding of enzymes acting on he conceived of and led the LIPID international consortium of scientists membranes and in ammation’s role MAPS initiative, which developed at the world scale.” in numerous illnesses. It also led to and applied techniques for charac- the development of stereo-speci c terization and classi cation of tens of Tori Zirul ([email protected]) studied molecular virology inhibitors as potential drugs for thousands of lipid molecular species. at Montclair State University conditions such as in ammation and In recommending Dennis for the and is passionate about neurological diseases. Vallee award, Jean-Pierre Changeux communication, advocacy and education of the Dennis also has been a pioneer in noted “his many basic discoveries sciences. the lipidomics movement. In 2002, on lipids and phospholipases and …
46 ASBMB TODAY NOVEMBER 2019 ALICE AND C.C. WANG AWARD IN MOLECULAR PARASITOLOGY Johnson innovates in the study of a neglected parasite
By Courtney Chandler
he parasite Trichomonas vag- inalis causes the world’s most Killing a parasite with trogocytosis T common nonviral sexually transmitted infection. In 2014, the Trichomonas vaginalis infects Centers for Disease Control and an estimated 3.7 million people Prevention named trichomoniasis annually in the U.S. Men typically one of the U.S.’s “Neglected Parasitic have no symptoms, but in women Infections.” Yet Patricia Johnson has the parasite causes pain, itching done anything but neglect this para- and, if they are pregnant, a risk of site — she’s made a career of it. premature delivery. For her work, Johnson, a distin- Patricia Johnson’s recent re- Patricia Johnson guished professor at the University of search focuses on the aspects of the California, Los Angeles, will receive host–parasite interaction that affect infection outcome. Her lab has found the American Society for Biochem- that neutrophils, white blood cells involved in the early immune response istry and Molecular Biology’s 2020 to infection, use a mechanism called trogocytosis to kill T. vaginalis. Alice and C.C. Wang Award recog- Trogocytosis is essentially immune cells nibbling away at the parasite until nizing seminal contributions to the a critical level of damage is reached, leading to the parasite’s death. This eld of molecular parasitology. work is the rst to describe trogocytosis as a mechanism of neutrophil Johnson began working on killing. Trichomonas 30 years ago. Research Johnson also has characterized extracellular vesicles called exosomes on this parasite was minimal at the that are secreted by T. vaginalis during infection. These vesicles then time, she said, describing the eld as are internalized by host cells and can modify the host cell response to a blank slate. She used her train- infection, essentially reprogramming these cells and the host response in ing in molecular biology to lay the a way that is bene cial to the parasite. Johnson’s research will continue to groundwork for what we know about expand the eld’s understanding of parasite–host interactions. Trichomonas today. She was the rst researcher to clone and analyze a gene in T. vaginalis, and she led T. vaginalis and has de ned criti- real-life worries, which is part of a team of researchers to sequence cal factors that in uence infection what keeps her motivated, along and annotate the rst T. vaginalis outcome, including parasitic surface with the challenge of answering genome. molecules that are involved with scienti c questions. “I realized that many systems adherence and lysis of host cells. “I like solving the puzzle,” she could be studied in parasites,” In her letter nominating Johnson said, “looking at new information Johnson said. “I’m fascinated by for the award, Sabeeha Merchant, and trying to make sense of it.” how many properties parasites have distinguished professor at the Uni- evolved to interact with the host versity of California, Berkeley, laud- and survive in such hostile environ- ed Johnson’s “distinguished career, Courtney Chandler ments.” de ned by innovation, creativity, and (courtneyec19@gmail. com) is a postdoctoral For the past decade, Johnson discovery” and called her a “leader researcher at Johns has focused on these interactions. and innovator” in the eld. Hopkins University and a careers columnist for the Her work has shed light on a novel Johnson said she nds comfort ASBMB. Follow her on mechanism of immune-cell killing of in her research as a refuge from Twitter @CourtneyEChan.
NOVEMBER 2019 ASBMB TODAY 47 ANNUAL MEETING
EARL AND THRESSA STADTMAN YOUNG SCHOLAR AWARD Pagliarini chanced into groundbreaking mitochondrial research
By Gelareh Abulwerdi
ave Pagliarini’s research career had a bumpy start. By his third MitoCarta: the key to unlock Dyear of graduate school, he had mitochondrial diseases followed his advisers to three labs across the Midwest and West Coast. As a postdoc, Dave Pagliarini He nished his Ph.D. in biomo- led the development of MitoCar- lecular sciences at the University of ta, a compendium providing an California, San Diego. Pagliarini extensive map of mitochondrial learned a lot from each adviser, he proteins. Since then, his lab has said, and “those challenges became become known for using systematic my accelerators.” lipidomics, proteomics and metab- Dave Pagliarini ose accelerators have propelled olomics screens to study the effects him through almost a decade of of the loss of individual mitochondrial proteins and then digging into those productive mitochondria research, proteins’ biochemical activities. One example is the team’s analysis of the for which Pagliarini will receive the biosynthetic pathway that generates coenzyme Q. American Society for Biochemistry Coenzyme Q, or CoQ, a lipid member of the mitochondrial electron and Molecular Biology’s 2020 Earl transport chain remarkable for its redox activity, was discovered in the and ressa Stadtman Young Scholar late 1950s just down the street from Pagliarini’s laboratory in Madison, Award. Wisconsin. Although this unusual lipid is involved in myriad mitochondrial Pagliarini got into mitochondria diseases, its biosynthesis and transport are not completely understood, research by chance when, as a grad which makes understanding the associated diseases dif cult. student, he identi ed a new mito- Mapping the CoQ synthesis pathway led Pagliarini’s lab to discover chondrial phosphatase that plays a the functions of multiple orphan proteins. One is CoQ9, a lipid chaper- critical role in biosynthesis of the one that binds to CoQ intermediates and is essential for its biosynthesis. essential cardiolipin required for Another is CoQ8A, an atypical kinase/ATPase essential for the assembly of optimal mitochondrial bioenergetics. the CoQ biosynthetic complex. Each of these proteins has been shown to is discovery led him to look for play a role in mitochondrial diseases. other mitochondrial proteins with unknown functions that could play a role in mitochondrial diseases. computational biology and biochem- tigator and Arthur C. Nielsen chair Mitochondrial diseases a ect istry. He called it MitoCarta and of metabolism at the Morgridge one in every 4,000 individuals; published his ndings in the journal Institute for Research. His lab works uncharacterized mitochondrial pro- Cell. Although this approach at rst to discover additional orphan mito- teins contribute to diseases such as provided only a descriptive dataset, chondrial proteins and characterize mitochondrial encephalomyopathy, a what set Pagliarini apart from others them from molecular to organ level. neurodegenerative disorder for which in his eld was “his ability … to gain there are no curative treatments. understanding of underlying cellular, Gelareh Abulwerdi During his postdoc in Vamsi biochemical, and physiological pro- ([email protected]) is a Ph.D. candidate at the Mootha’s laboratory at Harvard, cesses and mechanisms,” Christopher University of Maryland, Pagliarini established a compendium Newgard wrote in a letter supporting Baltimore. Follow her on Twitter @gelareh_science. of more than 1,000 mitochondrial the award nomination. proteins by combining in-depth Pagliarini is now the lead inves-
48 ASBMB TODAY NOVEMBER 2019 MILDRED COHN AWARD IN BIOLOGICAL CHEMISTRY Fierke works as a catalyst for change
By Kerri Beth Slaughter
hen she was a professor at the University of Michigan, Carol Analyzing protein W Fierke helped draft a proposal deacetylase mechanisms to increase diversity in the chemistry department. With funding from the Biological catalysts have unique National Science Foundation Michi- active sites that determine the spec- gan ADVANCE program, Fierke and i city and ef ciency of substrate her colleagues developed strategies to binding. Carol Fierke’s research has make the department more welcom- focused on understanding how met- ing for women and minorities. al ions in the enzyme active site can Building her knowledge of social regulate catalytic mechanisms. Her Carol Fierke science literature was crucial to award lecture during the ASBMB modifying the culture, Fierke said. 2020 annual meeting will highlight her work on a group of enzymes She worked with a universitywide known as protein deacetylases. committee to develop a workshop to Deacetylase enzymes are involved in removing speci c post-transla- teach faculty about the literature and tional modi cations from proteins. Fierke uses her expertise in catalysis to train search committees on best and metal homeostasis to answer questions about which metal ions are practices. e Michigan chemistry physiologically important for the function of the enzymes. Additionally, she department faculty went from a low has made strides in understanding how metal ion switching may regulate of 8% to now almost 30% women. biological function. Her lab is developing a toolbox of methods to identify “We completely changed the face the pathways and substrates utilized by these deacetylases. of the department,” she said. The Food and Drug Administration has approved several histone Now provost and executive vice deacetylase inhibitors as anticancer compounds, but the inhibitors often president of Texas A&M University, have serious side effects. Findings by Fierke and others may contribute to Fierke is a distinguished enzymol- the development of new histone deacetylase inhibitors with reduced side ogist who continues her work on effects and enhanced ef cacy as therapeutic agents. behalf of underrepresented groups. Scientists like Mildred Cohn, the rst woman to hold the presidency building con dence. pathways to get to a nal goal.” of the American Society for Bio- “I tell my students you don’t Fierke’s advocacy continues at chemistry and Molecular Biology, have to be con dent, just act con- Texas A&M, where she aims to opened doors for women in the sci- dently — eventually you become increase faculty diversity, enhance in- ences and inspired her to follow their con dent because people see you terdisciplinary research and increase example, Fierke said, so it is tting that way,” she said. student success. that she will receive the ASBMB’s She encourages her students to 2020 Mildred Cohn Award in Bio- learn skills beyond the bench and do logical Chemistry. some soul searching to nd careers in Kerri Beth Slaughter Fierke’s experience as an advocate which they can thrive. ([email protected]) is a graduate student for diversity in uences the way she “I know that when I was a in the biochemistry mentors her students, particular- doctoral student, I thought there department at the University of Kentucky. ly women and underrepresented was one career pathway, but that’s Follow her on Twitter minorities, who often struggle with not true,” she said. “ ere are lots of @KB_Slaughter.
NOVEMBER 2019 ASBMB TODAY 49 SERVICE BEYOND SCIENCE
Weaving social innovation and scientific methods for a bright future
By Pingdewinde Sam
hen I was growing up in a parents never gave up. ey encour- I was a young immigrant from a small district of Ouagadou- aged me to do well in school, and I developing country who spoke no W gou, the capital city of Burki- realized then that knowledge is so English. Fortunately, my wonderful na Faso, my parents made sacri ces powerful no one should be deprived and supportive uncle Beniwendé that showed me the importance of of it. George Kabré lived there and was an education, sharing knowledge and Over the years, seeds were plant- exceptional mentor to me. giving back to my community. ed in my heart to create learning Because I was studious and My native country is small, just opportunities for those who couldn’t worked hard, my chemistry teacher a little larger than Colorado, and un- a ord school and, above all, to men- in junior college, Ronald Drucker, derdeveloped. Although the United tor and help those in need. advised me to apply to the National Nations Development Programme Institutes of Health Bridges to the ranked us second to last in the world The land of opportunity Baccalaureate Research Training for education in 2009, I believe it rough a green card lottery, Program in 2011. I seized the oppor- is a country with a better future. I immigrated to the United States tunity and was accepted. Since then, For the past eight years, through a at the age of 19. My older broth- I have been guided and trained by foundation I call Teêbo, I have been er Barkwendé Bonaventur, who incredible mentors at the City Col- working from the U.S. to help make dreamed of coming to the U.S., lege of San Francisco; San Francisco that future. registered himself in the U.S. Diver- State University; the University of My parents never made it past sity Immigrant Visa Program and California, San Francisco; and Johns primary school. rough their faith, forcibly took my weekly allowance Hopkins University. I am now a they showed what it means to love of 500 CFA francs (the equivalent fth-year Ph.D. candidate in cellular and give with very limited resourc- of $1) to register me as well. e and molecular physiology at the es. We were poor, yet they joyfully registration was free, but my precious Johns Hopkins University School of practiced true hospitality. Sometimes dollar paid 60 cents for one hour Medicine. But I never forgot where I more than 14 people lived in our at a local internet café to complete came from. house; we didn’t have enough, but the online application and 40 cents my parents welcomed others who to scan in my pro le picture. e Making a difference needed help, o ering a place to stay average Burkinabé lives on less than On Christmas Day 2005, my or a meal. Continually exposed to $1 per day. dad taught me a lesson about the this spirit of giving, I wanted to help I was angry when my brother impact of a small action of gener- improve other people’s lives. took my money. He applied two osity. It was a dicult year for my My childhood in one of the years in a row before me but never family. My father didn’t make much poorest countries in the world was selected, and to this day, he still pro t from his jewelry shop, and my shaped my mind. My parents made applies. I wasn’t interested, but he mother was medically disabled. My sacri ces to send me and my three believed I had a chance. It turned parents always gave us new clothes siblings to school. I was sent home out to be a wonderful opportunity and shoes on Christmas, so I went to many times during primary school that changed my life and created my dad expecting these gifts. He said for not paying the full $70 tuition. nancial sustainability for my family that he didn’t make enough money Public schools were full, and my and many people in my community. to get us new clothes. I went to my grades were not excellent enough Without any of my immediate room crying. for a national scholarship, but my family, I moved to San Francisco. My dad called me back a few
50 ASBMB TODAY NOVEMBER 2019 Farmers in the Goennega village show samples of their corn harvest at an August 2015 meeting to measure the impact of Teêbo’s End Starving Season agricultural program. TEÊBO
ABOUT THE SERIES Scienti c research can be an all-consuming passion, inspired by a desire to build knowledge and make the world a better place. Some scientists nd time to go outside their labs and give time to help their communities in other ways. We are sharing their stories in this 2020 essay series, Service Beyond Science. To contribute an essay, go to asbmb.org/asbmbtoday and click the Submit button. Questions? Send an email to [email protected].
TEÊBO A sixth-grade student, age 12, in the Vipaolgo Village shows o school supplies she received in October 2017 through the Teêbo Exam Prep Program. The supplies were donated by the Science Education Partnership and Assessment Laboratory at San Francisco State University.
NOVEMBER 2019 ASBMB TODAY 51 SERVICE BEYOND SCIENCE
The Teêbo Exam Prep Program provided these sixth graders at Primary School A in Goumsin village with new required French reading books in October 2018 to help them prepare for the national exam to enter seventh grade.
minutes later and gave me two enve- to the U.S. What I saw saddened Starving Season program aims to in- lopes with less than $10 in each. He me, and I felt called to o er hope to crease crop yields that sustain thou- told me to take them to two neigh- Burkinabés who lack basic needs. sands of lives. We equip hardworking boring families from my childhood We named our organization farmers with animal-powered plows JAMES OSEI-OWUSU church. I was confused — he didn’t Teêbo, which is the word for hope and bags of fertilizer, and we teach make enough money to buy clothes in Mooré, the national language them new farming techniques. for us, but he had some to share? e in Burkina Faso. e organization In Burkina Faso, students must rst family was a widow with seven focuses on eliminating poverty and pass a national exam to enter the children. When I handed her the hunger, increasing the literacy rate, seventh grade, but many fail and small gift, the emotions in the house combating water-related diseases by drop out of school. Only 29% of changed; the family was overjoyed drilling wells, and improving health adults are literate, and just 2% of all and super excited. e second family in Burkina Faso. In 2012, it was in- Burkinabés have a secondary edu- responded in the same way, and this corporated as a 501(c) 3 U.S.-based cation. My team has developed an transformed my bitterness to joy. nonpro t organization. Exam Prep Program for sixth-grade From that lesson in sharing, I learned students in villages. e six-month that a small act of generosity could More crops, more education program provides private tutoring, make a big di erence. Teêbo is run by volunteers here school supplies, meals and mentors. I had my rst real job in 2008 and in Burkina Faso. Our U.S.-based At the end of the pilot program in after I moved to San Francisco. My board of directors helps us secure - 2014, the rst school more than people in Burkina Faso struggle nancial resources. In Burkina, a local tripled their success rate, from 30% with basic needs such as education, team runs day-to-day activities, while to 98%. Since then, we continue to food, clean water and sanitation. To in each village we choose four or ve register incredible success rates, send- help address these needs, I started ambassadors to represent us and be ing both girls and boys to school. to save and frequently wired money our eyes and ears. Most schools in Burkina lack for my family to support those who With Teêbo, we have built pro- basic teaching supplies. In 2016, I struggled to survive. In 2011, I went grams to engage, equip and empower co-founded EDEN School with my home for the rst time since moving Burkinabés in rural areas. Our End wife, Wendpagnanda Christiane.
52 ASBMB TODAY NOVEMBER 2019 TEÊBO
We aim to advance knowledge using my scienti c research. My indelible the impact of the implemented the 5E model (engage, elaborate, long-term goal always has been to programs, we can report back to explain, evaluate and examine) that improve human health through partners and donors; this is the pub- I learned at the Science Education improving quality of life and saving lication stage for us. Partnership and Assessment Labora- lives. is is constant whether I am I have been able to use my tory at San Francisco State Univer- wearing the hat of a social entrepre- research skills to help grow Teêbo sity. Our curriculum and teaching neur or a scientist. and EDEN School. I look forward strategies encourage teamwork with I regularly apply the scienti c to a future when I’ll contribute pre- and post-lecture assessments. method as founder and executive actively to enriching lives not just in We plan to implement STEM edu- director of Teêbo. Our strategies to my naturalized and birth countries cation through collaborations with help the Burkinabés are intertwined but other countries as well, making scientists and teachers in the eld with the scienti c process of making our world a better place through my and here at Hopkins. discoveries. It starts with background experiences in biomedical research research, collecting data in a new and social innovations. Weaving science and service village. From that preliminary data, Pingdewinde Sam ([email protected]) is a In my research lab, my mind my team and I meet and launch a Ph.D. candidate in the department of cellular often leads me to ask how my exper- pilot program, which we then closely and molecular physiology at the Johns Hopkins University School of Medicine and iments can have a positive social im- monitor to assess its e ectiveness. the founder of Teêbo.org. Follow him on pact. My service work is woven with rough measuring and analyzing Twitter @samestry.
Pingdewinde Sam, a Ph.D. candidate in the department of cellular and molecular physiology at the Johns Hopkins University School of Medicine, founded Teêbo, a nonprofit organization, to help people in need in his native Burkina Faso.
NOVEMBER 2019 ASBMB TODAY 53 NEW! ASBMB Today call for submissions
ASBMB Today is publishing a new essay series in 2020 SERVICE BEYOND SCIENCE A career in the life sciences is demanding, but some researchers find time to give back to their communities — often in surprising ways. Do you do volunteer work that is unrelated to your life in the lab? Tell us about what you do and why. Email [email protected] for more information, or submit at asbmb.org/asbmbtoday. Want to see an example? Pingdewinde Sam’s essay, “Weaving social innovation and scientific methods for a bright future,” is on page 50 of this issue.
Upcoming ASBMB events and deadlines
1 Proposals for 2021 symposia due 3 Student Chapters northeast regional meeting 14 Deadline for abstracts for 2020 annual meeting 16 Student Chapters Outreach Grant deadline 18–24 U.S. Antibiotic Awareness Week
NOVEMBER 20 Student Chapters renewal deadline 27 Deadline for 2020 annual meeting travel award applications
2–8 National Influenza Vaccination Week 5 ASBMB–Deuel Conference on Lipids early registration deadline DECEMBER
1–31 National Mentoring Month 30 Deadline for last-chance abstracts for 2020 annual meeting 30 Deadline for scientific outreach abstracts for 2020 annual meeting 31 Deadline for Student Chapters Honor Society applications JANUARY
54 ASBMB TODAY NOVEMBER 2019 T-SHIRT CONTEST
All ASBMB members are eligible to submit a T-shirt design related to biochemistry and molecular biology.
The winning T-shirt will be sold at the 2020 ASBMB Annual Meeting in San Diego.
Submit your shirt design by Jan. 27. There will be one winner from ASBMB Student Chapters and one winner from all other member types.
For more details visit asbmb.org/meeting2020/ tshirt/ 2020 ASBMB-Deuel Conference on Lipids
IMPORTANT DATES Dec. 5: Early registration deadline Feb. 4: Abstract-submission deadline Feb. 19: Registration deadline
2020 ASBMBDEUEL CONFERENCE HAVEL LECTURE
Dynamics of membrane tra cking, sorting and compartmentalization within eukaryotic cells
Jennifer Lippincott–Schwartz, HHMI Janelia Research Campus
asbmb.org/deuelconference/
56 ASBMB TODAY NOVEMBER 2019 CLASSIFIEDS
University of Calgary Kennesaw State University Canada Research Chair (CRC) Tier II Dean of the College in the area of Chemical Lipidomics of Science and Mathematics
The Departments of Biological Sciences and Chemistry in the Kennesaw State University invites applications and nominations for Faculty of Science at the University of Calgary invite applications the position of Dean of the College of Science and Mathematics. for a Canada Research Chair (CRC) Tier II in the area of Chemical The Dean of the College of Science and Mathematics acts as its chief Lipidomics. The successful candidate will be appointed at the rank academic and administrative ocer, charged with fostering growth and of Assistant Professor (tenure-track) or in exceptional cases as development of students, faculty and sta to advance the College. The an Associate Professor (with tenure) and will be nominated for an next Dean will have a body of high impact, peer-reviewed scholarship NSERC Tier II Canada Research Chair. The candidate’s program is supported by extramural sources such as federal agencies, national/ expected to combine recent advances in analytical technology and international foundations, and/or recognized corporate entities. big biological data analysis via biochemical techniques, including The selected candidate will have a strong track record of fruitful high-resolution mass spectrometry to radically expand the practical collaborative initiatives comprising varied constituents. The search committee is seeking an individual who will be a powerful advocate scope of Lipidomics analyses of the complex molecular phenotypes for the quantitative and natural science departments of the College, that contribute to health or disease. The anticipated start date for the both within and beyond the university. position is September 1, 2020. https://www.asbmb.org/Careers/Jobs/81754/ http://www.asbmb.org/Careers/Jobs/81758/
University of California, Santa Cruz Montana State University Physical and Biological Sciences: Postdoctoral Fellows Biomedical Sciences – Assistant Professors
The Division of Physical and Biological Sciences at the University of Postdoctoral positions are available in three areas concerning redox California, Santa Cruz invites applications for tenure-track Assistant and metallobiochemistry: Professors in global and community health who conduct basic and/ or translational research that addresses human health and disease, (1) An interdisciplinary study has been funded to describe the sym- and have interests in promoting diversity, equity, and inclusion. Four biotic relationships between the gut microbiome and the animal host positions will be lled in 2020. that allow both to metabolize dierent forms of iron. This project is a collaboration between faculty in the biochemistry and microbiology Successful candidates will be invited to join one of the following departments, and oers opportunities in sophisticated informatics, departments: Molecular Cell & Developmental Biology; Chemistry & Biochemistry; and Microbiology & Environmental Toxicology. Areas of computational, gnotobiotic mouse-model, and molecular biochemical particular interest are: 1) Stem Cell Biology, including the biology of studies. stem cells in development and cancer; 2) Cell and Molecular Biology (2) An interdisciplinary collaboration is in place involving the National of Parasitic and Infectious Diseases, with emphasis on diseases Renewable Energy Lab (NREL) and U. Portsmouth, UK. It has been that impact large disadvantaged populations or on development of formed to study the bioconversion of natural and man-made (plastic) chemical methodologies that lead to better treatments; polymers. Collaborative partners span the disciplines of biocatalysis, 3) Structural Biology, with emphasis on cryo-electron microscopy; and 4) Microbiology, with emphasis on the microbiome and the structural biology, genetic and enzymatic engineering, in vitro evolu- mechanisms by which it inuences host physiology and the immune tion, and informatics. system, or how the microbiome is inuenced by environmental, (3) A DOE-funded study of Fe metabolism pertinent to the origins chemical, and genetic factors. In addition to these specic areas, we of life on earth and astrobiology is at its inception. This project is a will consider all candidates with interests in human health and disease collaboration with the Boyd group at MSU. who can make exceptional contributions to leadership in diversity, equity and inclusion and whose research interests t within the https://www.asbmb.org/Careers/Jobs/81751/ broader subject areas encompassed by the participating departments. https://www.asbmb.org/Careers/Jobs/81755/
To see a full list of jobs, please visit asbmb.org/careers ANNUAL MEETING SAN DIEGO | APRIL 4-7, 2020
Community Binds Us Take your place among a diverse network at the 2020 ASBMB Annual Meeting. Attend high-caliber lectures, participate in hands-on workshops and team up with the best minds in your fi eld to strengthen your life’s most important work. Discover your common bond.
Regular abstract deadline: Nov. 14 Submit your abstract today! asbmb.org/meeting2020