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FEATURE Vol. 20 / No. 11 / December 2021 (A SUBJECTIVE LIST) ALSO: 10 GIFTS FOR THE SCIENTIST IN YOUR LIFE
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CONTENTS NEWS FEATURES PERSPECTIVES 2 24 56 EDITOR'S NOTE BEST OF BMB IN 2021 THE JOYS OF DOING RESEARCH Our gift to you (A subjective list) WITH UNDERGRADUATES 3 30 58 MEMBER UPDATE HOLIDAY GIFT GUIDE MENTORING THE NEXT GENERATION 7 60 IN MEMORIAM SCIENCE IS A HUMAN ENDEAVOR 9 32 ASBMB ANNUAL MEETING SOCIETY NEWS 33 Michel strives to be a better mentor 10 34 Belfort strikes the right balance NEWS 35 Airola learns from failure 10 ASBMB public affairs 2021: 36 Toker recognized for ‘seminal The year in review contributions’ to lipid biology 56 12 ‘Fatty retina’: A root cause 37 Sharpee sees many ways of looking of vision loss in diabetes? at a tree 13 Democratizing calcium 38 Johnson wants every student visualization to feel they belong 15 Salivary proteins may hold key 39 Bollinger built a bioinorganic powerhouse to targeting tick-borne diseases 40 Provost makes chemistry 16 A new way of looking at HDL accessible in pregnancy 41 Farese and Walther find depth 17 What’s growing in your mouth in a droplet might change with your health 42 Wang’s work is fueled by interest 18 From the journals in cells 43 Smith unravels secrets of nature’s catalysts 58 44 Telomerase studies led Collins to discoveries in genetic elements 45 Fuchs goes boldly where no stem cell biologist has gone before 12 46 Taylor’s career began as med school detour 47 Boothroyd honored for Toxoplasma gondii research n 48 Career-development programming at the annual meeting 51 Pubs workshop to cover images, words and reach 17 60 52 Symposia session speakers 55 Interest groups at #ASBMB2022 DECEMBER 2021 ASBMB TODAY 1
EDITOR’S NOTE Vol. 20 / No. 11 / December 2021 Our gift to you THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY OFFICERS ANDCOUNCIL FOR BIOCHEMISTRY MEMBERS MOLECULAR BIOLOGY Suzanne Barbour Toni M. Antalis President Joan Broderick By Comfort Dorn OFFICERS COUNCIL MEMBERS Toyou! Charles Craik W Ann Stock Squire J. Booker Gerald Hart President-elect Matt Gentry Victoria J. DeRose President Susanna Blake Greer Hill hen my older sister and I were Wei Yang Jennifer DuBois Secretary Audrey AudreyLamb Lamb about seven and six years old, Secretary JamesM.M. Ntambi Joan Conaway James Ntambi respectively, what we really Toni Treasurer M. Antalis CeliaFelder Takita A. Shiffer Sumter Treasurer Takita Felder Sumter wanted for Christmas were Tammy Kelly Ten–Hagen Kelly Ten-Hagen dolls. Tammy was about the same size EX-OFFICIO MEMBERS JoAnn Trejo EX-OFFICIO MEMBERS ASBMB TODAY EDITORIAL as Barbie (and had almost as many Vahe Robert S. Bandarian Haltiwanger ADVISORY BOARDEDITORIAL ASBMB TODAY clothes), but she was considered a Martha Cyert Carla Koehler Co-chairs, 2022 Annual Meeting ADVISORY William BOARD J. Sullivan more wholesome toy for little girls. Co-chairs, 2020 Annual Chair Program Committee Rajini Rao Meeting Program Committee Jeanine ChairAmacher She had poofy hair and wore a little Cheryl Bailey Chair, Education Cheryl Bailey and Education Professionaland Paul Craig Floyd “Ski” Chilton turquoise romper. We were obsessed. ASBMB Today team’s gift to you, our Chair, René Fuanta Henrik Dohlman Development Committee Professional Development My sister was the enterprising one, members and readers. We are so grate- Danielle Peter J.Guarracino Kennelly DanielCommittee Raben Ken Beronda Montgomery Hallenbeck and she did a fair bit of snooping. ful for your unflagging interest and Chair, MeetingsDaniel Committee Raben A. Maureen Brian O’Flynn Rouhi A few weeks before the big day, she enthusiasm, especially over the past Chair, Meetings SoniaCommittee Flores JenMelissa Vaught Quick–Cleveland found the coveted dolls in their hiding two years. You’ve kept us motivated Chair, Minority Affairs Binks W. Wattenberg Sonia Flores Brandon Roy Committee Chair, Minority Affairs Binks Wattenberg place. I wanted to be surprised, but through these months of uncertainty. Nicole Woitowich Committee ASBMB TODAY she insisted on showing me and then So tucked into this issue is our Chair, Science Outreach and Qiou Wei Susannna Greer Angela Hopp Communication Committee Chair, Public Outreach Executive Editor swore me to secrecy. By Christmas roundup of some of the year’s most ASBMB TODAY Rick Page Committee ahopp@asbmb.org morning, I was an emotional wreck. interesting science and our annual gift Chair, Public Affairs Comfort Angela HoppDorn Matthew S. Gentry Advisory Committee Managing Executive Editor Editor But when we tore into our gifts, guide (does giving gift suggestions Chair, Public Affairs Ed Eisenstein Advisory Committee ahopp@asbmb.org cdorn@asbmb.org there were no Tammy dolls to be count as a gift?). We’ve got profiles of Chair, Membership Committee John Arnst Comfort Dorn found. My mother figured out we’d the ASBMB’s 15 big award winners Sandra Weller Science Writer SusanPublications Baserga Managing Editor Chair, jarnst@asbmb.org cdorn@asbmb.org unearthed them, so she took them to get you excited about the 2022 Chair, Women in Biochemistry Committee and Molecular Biology Laurel Oldach Laurel Oldach back to the store and replaced them annual meeting in April in Philadel- Lila Committee M. Gierasch Science Writter Editor-in-chief, JBC Science Writter loldach@asbmb.org with far more expensive and tasteful phia. We also offer two very different Sandra Weller loldach@asbmb.org A. L.Publications Chair, Burlingame Ed Marklin Madame Alexander dolls. You can see essays, by Adele Wolfson and Brooke Ed Web Editor Marklin Editor, MCP Committee Webemarklin@asbmb.org Editor where I got my obsession with the Morriswood, about the rewards of Nicholas Alex Toker O. Davidson emarklin@asbmb.org Allison Frick element of surprise — not to mention having undergraduates in the lab. And Editor, JBCJLR Editor-in-chief, Media Specialist A. L.Kerry-Anne BurlingameRye Allison Frick africk@asbmb.org my general anxiety around the giving we wrap it all up with a truly lovely Multimedia and Social Media Editor, MCPJLR Editor-in-chief, Barbara Gordon Content Manager and receiving of gifts. essay by Richard Levy on the pain and Executive Director Nicholas O. Davidson africk@asbmb.org bgordon@asbmb.org December is, of course, the big rewards of a life in research. Editor-in-chief, JLR Stephen F. MIller month for gifts, so I’m tamping down Thanks so much for reading. I Kerry-Anne Rye Executive Director Editor-in-chief, JLR smiller@asbmb.org my emotions and trying to get into hope your holidays overflow with joy the spirit. This month’s issue is the and surprises. For information on advertising, contact Pharmaceutical Media Inc. at 212-904-0374 or mperlowitz@pminy.com. CORRECTIONS: In November’s articles about symposia sessions at the 2022 ASBMB Annual Meeting, the names www.asbmb.org/asbmbtoday of several speakers were misspelled. A corrected list of speakers starts on page 52 of this issue. www.asbmb.org/asbmbtoday PRINT ISSN 2372-0409 PRINT ISSN 2372-0409 A sidebar in November’s feature on the ASBMB Undergraduate Poster Competition incorrectly Articles published in ASBMB Today reflect solely the authors’ views and not the official positions of the American Society for Biochemistry and identified Pamela Mertz of St. Mary’s College of Maryland. She is chair of the ASBMB Student Articles published in ASBMB Today reflect solely the authors’ views and not Molecular Biology or the institutions with which the authors are affiliated. the official positions of the American Society for Biochemistry and Molecular Mentions of products or services are not endorsements. Chapters Steering Committee. Biology or the institutions with which the authors are affiliated. Mentions of products or services are not endorsements. 22 ASBMB ASBMB TODAY TODAY DECEMBER 2021
MEMBER UPDATE ASCB honors University in India and his Ph.D. in awards for young investigators molecular biology at Drexel Univer- from the International Ceramide Montgomery, Alahari sity. After postdoctoral research at the Committee. The American Society for Cell University of North Carolina, Chapel Biology has announced its 2021 slate Hill, he joined the faculty there. He Kadakia named of award recipients and fellows. Two has worked at the Louisiana State ASBMB members are on the list. University Health Sciences Center interim vice provost Beronda Montgomery, the MSU since 2004. Madhavi Kadakia, who served as Foundation Professor at Michigan He is a fellow of the American chair of the biochemistry and mo- State University, will give the Mentor- Academy for the Advancement of lecular biology department at Wright ing Keynote Lecture at the ACSB’s Sciences. State University in Dayton, Ohio, 2022 meeting. The from 2015 until June of this year, has lecture highlights Carr moves to UW been named the university’s interim “an individual who vice provost for research. exemplifies mentor- Rotonya Carr, a physician–scien- The Kadakia lab works on signal- ing by their impact tist who was until recently an assistant ing pathways in cancer research, on the training of professor of medicine and director of focusing on the tumor protein p63. scientists and schol- the liver metabolism and fatty liver Like the better-known p53, p63 is a ars who belong to program at the University of Pennsyl- transcription factor. Kadakia’s research MONTGOMERY underrepresented vania, has moved has focused on an N-terminally groups.” to the University of truncated protein isoform that is most Montgomery’s lab studies photo- Washington in Se- highly expressed in epithelial tissue. morphogenesis, or the growth and attle. Since Oct. 1, The protein is thought to act as a tu- development responses of photo- she has headed the mor suppressor, keeping cells adhered synthetic organisms such as plants, university’s division and preventing migration. Kadakia’s algae and cyanobacteria to light of gastroenterology. group has described microRNAs and cues. Simultaneously, Montgomery Carr cares for coding transcripts that p63 affects. CARR applies this line of thinking, investi- hepatology patients Kadakia has been associate dean of gating how individuals perceive and and leads a lab that studies the research affairs at Wright State’s medi- respond to their environments, to pathophysiology of fatty liver diseases. cal school since best practices in research mentoring Her team is particularly interested 2019. According and leadership. She is the author of a in the effects of alcohol on ceramide to a press release, recent book, “Lessons from Plants.” metabolism and in how proteins as- as head of the Suresh Alahari, a professor at Lou- sociated with lipid droplets affect the pandemic research isiana State University, is a member of development of disease. task force, she was the 2021 cohort of ASCB fellows. His After earning her M.D. at Cornell instrumental in lab studies cancer, University and completing a residency getting researchers with particular at Massachusetts General Hospital, KADAKIA back onto campus focus on a protein Carr spent four years as a practicing after operations called nischarin, physician before returning for fellow- shut down in 2020. which they identi- ship training in gastroenterology at After receiving bachelor’s and fied. They study Penn. She joined the faculty at the master’s degrees in microbiology at tumor cell migra- conclusion of that three-year training the University of Mumbai in India, tion and adhesion, period and has worked at Penn for the Kadakia earned a Ph.D. in infectious ALAHARI along with how next 10 years. disease and microbiology from the microRNAs are misregulated in breast She was a member of the first University of Pittsburgh. She shifted cancer. class of junior associate editors of the into cancer research as a postdoc at Alahari earned a master’s degree Journal of Lipid Research and of the the Pittsburgh Cancer Institute and in human genetics from Andhra first cohort of Lina Obeid memorial conducted further research at the DECEMBER 2021 ASBMB TODAY 3
MEMBER UPDATE Cancer Institute of New Jersey. She graduates, and its University, he cloned human actin has been on the faculty at Wright members include isoforms and investigated the differ- State since 2002 and was promoted to ASBMB member ences between skeletal and cytoplas- full professor in 2013. She has served and ASBMB Today mic versions of the proteins. (Prior to as a board member for the Association contributor Isha that, he studied gene expression in the of Medical and Graduate Depart- Verma, a postdoc, nervous system as a graduate student ments of Biochemistry since 2018. along with 10 other at Monash University in Melbourne graduate students and then neuronal differentiation at VERMA UMich honors Benore, and postdocs. Stanford.) Gunning is a member of numer- Verma’s group Gunning receives ous scientific societies, including Marilee Benore was one of three the American Society for Biochem- University of Michigan faculty President’s Medal istry and Molecular Biology and its members honored Peter Gunning, a professor at the Australian counterpart, also known as this year with University of New South Wales Medi- ASBMB, as well as the ANZSCDB the university’s cine and Health in Sydney, Australia, and the American Society for Cell Carol Hollenshead has received the highest honor of the Biology. He has served as president of Inspire Award for Australia and New Zealand Society the ASBMB (Australia) and as found- Excellence in pro- for Cell and Developmental Biol- ing editor of the journal Bioarchitec- moting equity and ogy, its President’s Medal. The award ture. He is the former deputy dean social change. recognizes Gunning’s career-long re- of research and head of the school of BENORE Benore is a pro- search on the regulation and function medical sciences at UNSW and was fessor of biochemis- of the actin cytoskeleton. the inaugural chair of the research try and molecular biology at UM- Gunning’s lab studies the actin division at the Children’s Hospital at Dearborn, where she studies vitamin cytoskeleton and filament proteins Westmead in Sydney. transport using a flock of chickens called tropomyosins, which in The award consists of a medal and with a mutation in riboflavin binding muscle cells help to build the actin– a talk presented at the recent virtual protein. The mutation, which is lethal myosin sarcomere. ANZSCDB meeting in Melbourne. to embryos unless supplementary Tropomyosins in riboflavin is injected into eggs, has the nonmuscle cells can Johnson delivers interesting secondary effect of turning affect how strongly egg whites completely transparent. actin-binding pro- Greenberg lecture Benore also conducts social teins bind to actin Elizabeth Johnson, an assistant research in women’s persistence in filaments and the professor in the division of nutritional science, technology, engineering and activity of myosin sciences at Cornell University, deliv- mathematics and has published peda- GUNNING motors. Because ered the 2021 Judith Greenberg Early gogical studies as well. She is the for- the cytoskeleton Career Investigator Lecture at the mer chair of the American Society for changes dramatically as a normal National Institutes Biochemistry and Molecular Biology’s cell transforms into a cancerous cell, of General Medi- Student Chapters subcommittee and tropomyosins are also possible targets cal Sciences in late is a member of the society’s Women for chemotherapy, and this has led September. in Biochemistry and Molecular Biol- Gunning to form a company develop- The lecture series ogy Committee. ing drugs that target tropomyosins. highlights the work In addition to honors for UM In an interview with his university’s of early-career professors, an educational outreach press office, Gunning said, “I cannot grantees at the organization led by grad students and believe we have gone so far in my life- JOHNSON NIGMS and was postdocs called Developing Future time from understanding cytoskeletal named for Judith Biologists received recognition. The organization and function through Greenberg, a former deputy director group focuses on making develop- to drug development.” In the 1980s, of the institute who retired in 2020 mental biology accessible to under- as a postdoctoral fellow at Stanford after working at the National Insti- 4 ASBMB TODAY DECEMBER 2021
MEMBER UPDATE HHMI names new investigators The Howard Hughes Medical Institute announced 29 proteins that can be incorporated into one or more in September a class of 33 new investigators. Three of the complexes within the SWI/SNF family are found members of the American Society for Biochemistry in over 20% of human cancers, and and Molecular Biology were on the list. some of them serve as the key mo- Shingo Kajimura is a professor at Beth Israel lecular drivers of select pediatric and Deaconess Medical Center/Harvard Medical School adult cancers. and the Broad Institute who studies the roles As a graduate student at Stanford mitochondria-rich brown and University, Kadoch found that these beige adipose cells play in organ- proteins are altered in cancers, af- ismal metabolism. These tissues fecting oncogenic gene expression. are well known to metabolize fat KADOCH She later joined the faculty at Dana– to generate heat; Kajimura’s lab Farber, where her lab now works on of clinicians and basic scientists disruption of SWI/SNF complexes and recently solved has shown that they can do more. the structure of one multisubunit SWI/SNF complex Beige cells can modulate blood and its nucleosome substrate. KAJIMURA sugar and circulation of other Vincent Tagliabracci is an associate professor at metabolites in a way that suggests the University of Texas Southwestern Medical Center implications for diabetes. Kajimura is also interested who is interested in discovering novel kinases. His lab in adipose tissue development and whether it might studies unusual protein modifications, such as glu- be possible to reprogram white adipose cells, which tamylation and AMPylation, by proteins that resemble store energy, into brown or beige cells, which are kinases. They also have a related line of research into more metabolically active. The lab identified a master how Legionella lipid kinases alter the host cell mem- regulator for brown and beige fat development and brane as well as other interactions also studies intracellular nutrient trafficking. between bacterial effectors and host Kajimura earned his Ph.D. at the University of cells. Tokyo. He was a postdoc at Harvard Medical School Tagliabracci earned his Ph.D. in before joining the faculty at the University of Cali- biochemistry and molecular biology fornia, San Francisco. He returned to Boston with at Indiana University, where he stud- his lab in the spring of 2020. ied the role of glycogen phosphate in Cigall Kadoch is an associate professor at the Lafora disease, a form of epilepsy. He Dana–Farber Cancer Institute and at Harvard Medi- TAGLIABRACCI conducted postdoctoral research in cal School and a member of the Broad Institute. Her Jack Dixon’s lab at the University of lab studies ATP-dependent chromatin remodeling California, San Diego, studying the mysterious kinase complexes, macromolecular machines with a dozen that phosphorylates the protein casein in the Golgi or more protein components each. The remodeling apparatus. (It turned out to be a protein called Fam20c, complexes — also called switch/sucrose nonferment- which governs many other secreted phosphoproteins able, or SWI/SNF, complexes — can alter DNA as well.) He joined the faculty at UT Southwestern in accessibility and gene expression by moving nucleo- Dallas in 2015. Learn more about his work in a talk somes along a DNA strand, changing the compac- he will present at the 2022 ASBMB annual meeting tion and organization of chromatin. Mutations in the session on signaling. tutes of Health for 45 years. how lipids from human milk influ- man College and earned her Ph.D. Johnson studies how compounds ence microbial metabolism and the at Princeton University, working on from the gut microbiome become part effects that interplay goes on to have cell-cycle transcriptomics. She was a of host physiology. Specifically, she on infant health. postdoc with Ruth Ley and worked on works on sphingolipids, investigating Johnson studied biology at Spel- lipid-dependent host–microbe interac- DECEMBER 2021 ASBMB TODAY 5
MEMBER UPDATE tions before starting her lab at Cornell energy imbalance as a cow mobilizes in dairy nutrition and biochemistry at in 2018. Her NIH biography noted nutrients to feed her calf faster than Michigan State University, studying that she “finds much inspiration from it can eat new food; this can lead a cell-free protein synthesis system her two small gut microbiome sample to the breakdown of fats and serum isolated from udders, Beitz took a generators.” ketosis, which can cause fatty liver faculty position at Iowa State in 1967 disease and other health problems. and has remained a professor there for Beitz named a fellow Beitz has studied dietary changes more than 50 years. He is a mem- and other interventions, such as the ber of numerous scientific societies, of Sigma Xi hormone glucagon, aimed to prevent including the American Society for Donald Beitz, a distinguished these disorders from developing. Biochemistry and Molecular Biol- professor in the animal science and He also studies the effects of dietary ogy, the American Association for biochemistry de- interventions on milk composition the Advancement of Science, and partments at Iowa and collaborates on a project look- the American Society for Nutrition, State University, ing for ways to reduce emission of of which he is also a fellow. He has has been named a greenhouse gases such as methane served as president of both the Ameri- fellow of the scien- and hydrogen sulfide from bovine can Dairy Science Association and the tific research honor digestive tracts. His research has Council for Agricultural Science and society Sigma Xi. been supported over the years by Technology. Preventing the United States Department of Sigma Xi is a society for science BEITZ metabolic disorders Agriculture, the Wisconsin Milk and engineering, founded in the in dairy cows is Marketing Board and other agricul- 19th century, which today has about a focus of Beitz’s research. Calving tural trade associations. 60,000 members in chapters around and early milking are apt to cause an Soon after earning his doctorate the world. CALL FOR SUBMISSIONS Meeting Connections Have you made a connection, forged a collaboration, gleaned insight or had another meaningful experience at a scientific meeting? If so, tell us about it. We invite you to write about your own meeting connection in 300–500 words. We will publish the best stories in the March issue of ASBMB Today. Email your submission to asbmbtoday@asbmb.org with the subject line “Meeting connections.” Deadline extended to Dec. 30! And there will be prizes: FIRST PLACE: Free ASBMB membership, free registration to the 2022 ASBMB annual meeting and a $100 Amazon gift card SECOND PLACE: Free registration to the 2022 ASBMB annual meeting and a $50 Amazon gift card THIRD PLACE: $25 Amazon gift card 6 ASBMB TODAY DECEMBER 2021
IN MEMORIAM Gertrude Forte By Courtney Chandler G ertrude “Trudy” Forte, former Recognition Award in 1999. She was editor-in-chief of the Journal also the first recipient of the annual of Lipid Research and leading American Heart Association Mentor lipoprotein researcher, died June 9. of Women Award in 2001. She was 84. Forte was editor-in-chief of the Forte was born Feb. 25, 1937, Journal of Lipid Research from 1999 in Wayne, Pennsylvania. According to 2003 and was the first woman to her obituary from the Berkeley to serve in this role. She also served Lab, she grew up in the countryside, as director of research for Lypro which fostered her love of plants and Biosciences, a therapeutic develop- animals. She attended Immaculata ment company focusing on develop- College in Chester County, Penn- ing nanotechnology for better drug sylvania, and graduated magna cum delivery, from 2008 to 2017. laude with a Bachelor of Arts in biol- Laura Knoff, a former senior ogy. She received a National Science Gertrude Forte research associate who worked with Foundation predoctoral fellowship Forte from 1992 to 2000 at Berke- award to pursue a Ph.D. in zoology at density lipoprotein, which shuttles ley, remembered her intelligence and the University of Pennsylvania. cholesterol from the bloodstream to mentorship. During graduate school, Forte met the liver, changes shape as it matures. “(I was) in awe of her intellec- and married her husband, John, now After joining CHORI, Forte tual abilities and personal stamina,” deceased, and had two of their three moved her research in a new direction Knoff said. “I learned so much from children. In the 1960s, Forte and her to take a more applied approach. She her. She was truly a role model for family moved to California, and she developed and tested lipid nanoparti- women in science and will be sorely began her postdoctoral training at the cles to be used for drug delivery. One missed.” University of California, Berkeley. She of her projects focused on synthesiz- According to a family obituary, had her third child shortly after. ing nanoscale particles of low-density Forte was a music enthusiast. She Forte remained at Berkeley for lipoprotein to deliver anticancer drugs played the piano and sang in the nearly 30 years and was a senior safely and effectively to tumors in a choir of the Saint Mary Magdalen scientist from 1978 to 2004. She then certain type of brain cancer. Parish in Berkeley. She also enjoyed moved to the Children’s Hospital Throughout her career, Forte was supporting local performing arts and Oakland Research Institute, where awarded more than 30 National Insti- attending live performances. she worked from 2004 to 2017. tutes of Health research grants and co- Forte is survived by her three During her tenure at Berkeley, published over 230 research works. children, their spouses and seven Forte researched the roles lipids and Forte received numerous awards grandchildren. proteins play in cardiovascular disease. and honors in recognition of her She helped develop electron micros- research and professional accom- copy techniques used to determine plishments, including the Lawrence Courtney Chandler (courtneyec19@gmail.com) the structural features of lipoprotein Berkeley Laboratory Outstanding is a postdoctoral researcher particles and applied these techniques Performance Award in 1992, the As- at the University of Maryland, to study serum lipoproteins from sociated Western Universities honor of Baltimore, and an industry careers columnist for ASBMB human samples. She also used model distinguished lecturer in 1994 and the Today. Follow her on Twitter: systems to demonstrate how high- American Heart Association Special @CourtneyCPhd. DECEMBER 2021 ASBMB TODAY 7
IN MEMORIAM Jean Wilson William Whelan Jean Wilson, a renowned William “Bill” Joseph Whelan, endocrinologist, died June 13. a renowned biochemist who Wilson was born on Aug. 26, 1932, embodied his own discovery (he in Wellington, Texas. After graduating was, by nature, a primer), died at from the University of Texas at Austin his Miami home on June 5. with a bachelor’s degree in chemistry Whelan was born in Lancashire, in 1951, he completed medical England, on Nov. 14, 1924. His school and a residency in internal mother was a homemaker and his medicine at the University of Texas Southwestern Medical Center, father, from Ireland, made skins for sausages. conducted postdoctoral research for two years at the National Heart Whelan was the first in his family to go to university; he earned Institute under biochemist Sidney Udenfriend, then returned to UT three degrees at the University of Birmingham and was appointed Southwestern as a faculty member. There he continued his research as faculty while a graduate student. He then joined the University for more than 60 years until retiring in 2011. of North Wales, the University of London Lister Institute, and later Wilson's research centered around male sex hormones the Royal Free Hospital. called androgens. He discovered the enzyme 5-alpha-reductase, Whelan moved to the then 15-year-old Miller School of which converts testosterone into the hormone he identified as Medicine at the University of Miami in 1967, remaining its chair dihydrotestosterone. He demonstrated that dihydrotestosterone is of biochemistry until 1991 and retiring as one of its longest- critical for male sexual maturation and function in many animals. serving faculty in 2019. Wilson also discovered that unchecked dihydrotestosterone Whelan worked on important storage molecules in animals production can cause a condition of prostate enlargement. His and plants, glycogen and starch, respectively. When your research contributed to development of the first treatments for stomach is empty, you check the body’s metaphorical cupboards, prostate disease, a class of pharmaceuticals known as 5-alpha- where you can thank glycogenin for putting aside a condensed reductase inhibitors. He also developed methods to quantify form of glucose for just such a time. cholesterol in the body, contributing to our understanding of how But catalyzing requires raw materials. In the late 1980s, cholesterol is made and degraded. when funding was dry, his wife, Margaret, suggested he use a Wilson was elected to the National Academy of Sciences of the newly released pension from his U.K. faculty positions. Whelan U.S. in 1983 and to the National Academy of Medicine in 1994. expanded his lab and was elected a fellow of the Royal Society in He received the Oppenheimer and Koch awards of the Endocrine 1992 in part due to a discovery of how to make use of glycogen Society, the Amory Prize of the American Academy of Arts and stores — by glucosyltransferase reactions, in case you were Sciences, and the Kober Medal of the Association of American wondering. Physicians. Glycogenin is known for drawing things together. Knowing the Wilson’s legacy has been memorialized at UT Southwestern. The draw of Florida in winter, Whelan launched a winter conference Jean D. Wilson Center for Biomedical Research and the J.D. and attracting Nobel laureates, now enjoying its 53rd year. Glycogenin Maggie E. Wilson distinguished chair in biomedical research were fast-tracks; it is a catalyst. Whelan started an acclaimed program established to promote endocrinology, developmental biology and in response to medical shortages, giving Ph.D. students — like genetics research with support from Wilson and his sister, the late glycogen itself — condensed coursework to complete an M.D. Margaret Sitton. The Jean D. Wilson, M.D. Award also was created faster. And glycogenin is a self-starter; it self-phosphorylates. So, to recognize excellence in research mentorship. too, was Whelan. He started the journals Trends in Biomedical In addition to more than 340 scientific publications, Wilson Science and Federation of European Biochemical Society Letters, authored an autobiography titled “The Memoir of a Fortunate Man”; and he remained an editor-in-chief of the journal IUBMB Life he described growing up in the Texas panhandle, his scientific (and president of the International Union of Biochemistry and research and his many hobbies, including ice cream making, bird Molecular Biology) until 2020, stating he wanted biochemistry to watching and a passion for opera. be presented in “crystalline prose.” — Courtney Chandler — Renae Crossing 8 ASBMB TODAY DECEMBER 2021
SOCIETY NEWS Get involved Brady, Coulson and Strahl Give the gift with the ASBMB join JBC in 2022 of ASBMB We encourage all ASBMB Donita Brady, Elizabeth Coulson and Brian Strahl will membership members to engage in become associate editors for the Journal of Biological society activities — big or Give a colleague, student or friend Chemistry in January. All three are current editorial board small. Use our advocacy members. a full year of exceptional resources toolkit to communicate and enriching experiences. Visit Brady is a faculty member at with lawmakers. Start a the Perelman School of Medicine asbmb.org/gift-membership. student chapter at your school. Watch an on-demand at the University of Pennsylvania. webinar. Contribute to our She also serves as assistant dean diversity scholarship fund. for inclusion, diversity and equity in Learn all the ways you can research. Her areas of specialty are BRADY benefit and help at asbmb. cell signaling and protein kinases in org/membership/get- cancer. In 2016, she was named a JBC Herbert Tabor Early involved. Career Investigator Award winner. Also, in April, she will give a talk at the 2022 ASBMB Annual Meeting session on signaling titled “Tracing copper utilization Nominations by kinase signal transduction for the ASBMB pathways: Implications for cancer ASBMB welcomes Honor Society cell processes.” new undergraduate due Jan. 31 Coulson is a group leader at the Clem Jones Centre for Ageing education Student chapter members are eligible for election into Dementia Research and a professor coordinator COULSON the ASBMB Honor Society, at the Queensland Brain Institute. In October, the ASBMB ΧΩΛ. The honor society She also serves as deputy head of the school of biomedical welcomed Tejiri Olafimihan as recognizes juniors and seniors sciences. Her lab studies the degeneration that occurs in its new undergraduate education demonstrating exceptional cholinergic neurons in the brain and coordinator. In this role, she achievement in academics, spinal cord. She has been a member will support research and science outreach. the society’s of the ASBMB since 2013. For more information and student Strahl is a professor at the to apply, visit asbmb.org/ chapters, University of North Carolina School education/student-chapters/ undergraduate of Medicine, where he also serves as poster honor-society. STRAHL vice chair of the biochemistry and competition biophysics department. His areas of at the annual specialty are chromatin biology and histone modifications. meeting, degree-accreditation He has been a member of the society since 2005. He won the program and certification exam. ASBMB Young Investigator Award in 2006. “I have been an educator for the past five years, and stepping into this role from the classroom as a STEM educator, I’m excited to Advocating for open science and security continue to champion diversity in in the American research enterprise the scientific community as well In early October, the U.S. House Committee on Science, Space and Technology held an as provide students with different resources and opportunities that important hearing on balancing open science and research security within the U.S. will empower them to contribute The ASBMB public affairs staff submitted testimony on this issue urging members of to the next generation of great Congress to pass legislation harmonizing disclosure requirements, defining procedures for scientists,” Olafimihan said. “I handling allegations of research misconduct violation and providing the scientific com- look forward to helping bring munity with evidence-based reports on research integrity violations. Read the testimony about incredible change in the at asbmb.org/advocacy/position-statements. field of life sciences.” DECEMBER 2021 ASBMB TODAY 9
NEWS ASBMB public affairs 2021: The year in review By Sarina Neote F rom advocating for sustainable science funding to supporting junior scientists, the American Society for Biochemistry and Mo- lecular Biology public affairs team put together this roundup of our policy accomplishments in 2021. Here are the highlights. Supporting early-career scientists and the research enterprise The ASBMB took the lead on a bipartisan "dear colleague" letter (a document used by members of Con- gress to encourage their colleagues to support specific issues) in the House of U.S. Customs and Immigration Ser- Improving scientific vices outlining significant barriers, Representatives advocating for targeted such as visa processing delays, that integrity policies relief for junior scientists affected by the pandemic. Reps. Jamie Raskin, international students and scholars President Joe Biden’s administra- D-Md.; Bill Foster, D-Ill.; and David face when trying to study or work in tion has focused on restoring trust McKinley, R-W.Va., sent the letter to the U.S. in science in the federal govern- the House leadership in late May. The society also submitted for- ment and strengthening integrity In addition to this effort, the mal testimony for a congressional policies at the science agencies as ASBMB public affairs staff worked roundtable, “Researching While outlined in his January presidential with the society’s Public Affairs Chinese American: Ethnic Profiling, memo. Per his request, in June, Advisory Committee to advocate for Chinese American Scientists and a the White House Office of Science the passage of the Research Investment New American Brain Drain.” In its and Technology Policy published to Spark the Economy Act, which, testimony, the ASBMB emphasized a notice of request of information if passed, would provide support for that recent efforts by the Depart- to improve the effectiveness of research disrupted by the COVID-19 ment of Justice targeting Chinese federal scientific integrity policies to pandemic. and Chinese American scientists and enhance public trust in science. The those who collaborate with Chinese ASBMB submitted formal com- institutions have had a chilling effect ments recommending the OSTP Supporting international on international scientific collabora- strengthen whistleblower protec- collaboration tion, undercutting the U.S.’s role tions, refine conflict-of-interest poli- The ASBMB public affairs staff as the global leader in science and cies, encourage preprints and media wrote and submitted comments to technology. engagement, and study and remedy 10 ASBMB TODAY DECEMBER 2021
NEWS not fuel racial profiling of Chinese, Chinese American, Asian and Asian The end of an era at the NIH American scientists. The longtime director of the National Institutes of Health, Francis Collins, announced in the fall that Commenting on the NATIONAL INSTITUTES OF HEALTH he plans to step down as director and return to running his lab, which proposal for ARPA-H focuses on cystic fibrosis. Collins, President Biden called for the a physician–scientist, has run the creation of the Advanced Research agency for 12 years, serving under Projects Agency for Health, or three presidents. Before that, he was ARPA-H, dedicated to researching the director of the National Human human diseases and focusing on Genome Research Institute for 15 innovative research to address the years, presiding over the completion nation’s greatest health challenges. of the Human Genome Project. Reps. Diana DeGette, D-Colo., and Francis S. Collins has served as the Fred Upton, R-Mich., released the Collins’ signature projects as NIH director of the National Institutes of discussion draft of the bill establish- director have included efforts to Health since August 2009. address structural racism and sexual ing this new agency and requested harassment, rolling out data-sharing policies, and leadership through feedback from the scientific com- the first two years of the COVID-19 pandemic. In a statement, the munity. The ASBMB advocated for ASBMB wrote, “Francis Collins has served admirably through some keeping ARPA-H autonomous and of the most challenging times in the NIH’s history. ... a steadfast separate from other federal funding leader showing grace, tenacity and — on a lighter note — a skill with agencies and advocated for ARPA- a guitar unmatched by any other agency leader.” H to create an inclusive research ecosystem that attracts a diverse talent pool. funding inequities. recommend that federal agencies Shortly after it published this harmonize conflict-of-interest and RFI, the OSTP also began creat- conflict-of-commitment disclo- Sarina Neote (sneote@ ing implementation guidance for sure requirements, be transparent asbmb.org) is the science federal agencies on clear rules for about investigative processes on policy manager for the ASBMB advocating for diversity in research security and researcher violations of research integrity, STEM, sustainable funding responsibility. The ASBMB and ensure that the Department for scientific research and the STEM workforce. strongly encouraged the OSTP to of Justice’s China Initiative does New stories online every day. asbmb.org/asbmb-today DECEMBER 2021 ASBMB TODAY 11
LIPID NEWS ‘Fatty retina’: A root cause of vision loss in diabetes? By Clay F. Semenkovich & Rithwick Rajagopal V ision loss in diabetes, one of the like in the liver, the diabetic retina does most feared complications of not develop intracellular lipid droplets this disease, is caused by a pro- and does not possess any significant gressive pathogenic process known as triglyceride stores. Moreover, in com- diabetic retinopathy, or DR. Elevated prehensive surveys of membrane lipids blood glucose is the predominant risk in the retina, we found only modest factor for DR, so many people believe disease-associated changes. Instead, that glucose toxicity is the major palmitate could elicit pathological contributor to the development of signaling either through lipid second this disease. Yet, to date, no pharma- messengers or via lipidation of protein ceuticals specifically targeting glucose- messengers. Our group is investigating dependent pathways exist for DR. Diabetic retinopathy, shown here, causes vision these possibilities actively. Diabetes is a disease of broadly loss in patients with diabetes. Our results shed some light on a disordered metabolism that affects puzzling feature of human DR: Though how cells handle lipids, amino acids building block for many lipids. This glucose is the major risk factor for vi- and signaling networks that regu- shift in lipid production was likely sion loss in diabetes, it explains only a late growth and proliferation — in due to elevated glucose alone, as fraction of the variability in disease pro- addition to its impact on glucose. isolated retinal tissue exposed to high gression. Differences among individuals Accordingly, abnormalities of lipid glucose showed the same increase in in terms of their retinal lipid biosyn- metabolism are common in diabetes. palmitate production. thetic flux could account for some of For example, patients with diabetes Mechanistically, high glucose the variance in glucose response. often suffer from nonalcoholic fatty levels increased enzymatic activity of Future pharmacotherapy to finely liver disease, which is characterized two regulatory enzymes: acetyl Co-A tune retinal lipid biogenesis in DR by chronic positive energy balance carboxylase and fatty acid synthase, or could offer a novel approach to the causing increased lipid synthesis and FAS. Mice with partial FAS loss-of- treatment of an increasingly common elevated levels of hepatic triglycerides. function in rod photoreceptors — the cause of visual disability. Thus, we reasoned that the retina predominant cell type of the retina might switch its lipid metabolic — were spared from vision loss due to Clay F. Semenkovich programming in response to an abun- diabetes even though they developed (csemenko@wustl.edu) is a professor and division chief of dance of fuel in diabetes. severe systemic metabolic disease on endocrinology at Washington To test this possibility, our group par with control mice. Conversely, University in St. Louis. He studies studied the pathways that govern mice with FAS gain-of-function lipid metabolism in diabetes, obesity and related disorders. retinal lipid biogenesis (the process developed vision loss in half the time of synthesizing fatty acids from small as wild-type mice after induction of precursors) during experimental dia- diabetes. Taken together, our results Rithwick Rajagopal (rajagopalr@ wustl.edu) is an assistant betes in mice. In multiple models of implicate increased retinal FAS activ- professor of ophthalmology at diabetes, we observed a roughly 70% ity and elevated palmitate as root Washington University in St. increase over controls in the synthesis causes of vision loss in diabetes. Louis. His research focuses on abnormalities of neural of retinal palmitate — a ubiquitous The mechanisms for palmitate tox- metabolism as contributors to saturated fatty acid that forms a basic icity in the retina remain elusive. Un- vision loss in diabetes. 12 ASBMB TODAY DECEMBER 2021
JOURNAL NEWS Democratizing calcium visualization by Laurel Oldach A t a time when cloning a gene was a feat worthy of a high- impact publication, someone asked Roger Tsien why he studied calcium. “His somewhat flippant answer was, ‘Because it cannot be cloned,’” Nonprotonated structures of BAPTA recalled Joseph Kao, who was a post- (top) and Fluo3 (right). When Ca2+ is present, the carboxylic acid groups doc in Tsien’s lab and is now a profes- in each molecule coordinate the JOSEPH KAO sor at the University of Maryland. cation. “Early on, he was actually somewhat dismissive of molecular biology.” Tsien, who died in 2016, is best remembered for his contributions to developing a molecular biology icon: green fluorescent protein. His group’s concentration that could be used in four carboxylate groups. work helped transform the protein cells. At the University of California, from a coelenterine curiosity to a lab- Tsien began to pursue an inter- Berkeley, Tsien led a lab that devel- oratory staple and earned Tsien a third est in calcium signaling early in his oped the calcium probes fura-2 and of the 2008 Nobel Prize in chemistry. scientific career. The ion already was indo-1, which are elaborations of the Prior to launching that project in the known as an important signal car- BAPTA architecture. Both of these 1990s, Tsien already had revolution- rier central to muscle contraction, molecules are intrinsically fluorescent, ized the field of calcium sensing. synaptic transmission and many other but upon binding Ca2+, the shapes of In the 1970s, Kao said, measur- physiological functions. their fluorescence spectra change. The ing calcium was “a very rarefied, “Calcium was central to every- ratio of the fluorescence intensities arcane art” that depended on a deep thing — but it was very difficult to at two different wavelengths can be knowledge of electrophysiology. measure,” Kao said. Tsien considered calibrated into actual Ca2+ concen- Today, researchers can use a variety of electrophysiology as an undergradu- tration. Because such ratiometric fluorescent indicators to visualize the ate, but by the time he started his measurements are insensitive to the activity of calcium and other second graduate research at Cambridge, he concentration of indicator in the messengers in living cells. Many mod- was focused on chemical approaches. sample, some common experimental ern indicators derive from a series of The first Ca2+ chelator Tsien artifacts are minimized. Still, Tsien probes that Tsien’s lab developed. developed, 2-bis(o-aminophenoxy) was disappointed that they required In one Journal of Biological ethane-N,N,N′,N′-tetraacetic acid, or long-wavelength ultraviolet excitation, Chemistry Classic article on such BAPTA, remains widely used because which potentially can harm cells and probes, “Ca2+ indicators based on of its rapid binding kinetics, high excite autofluorescence. Tsien was ini- fluoresceins and rhodamines,” Akwasi selectivity for calcium and insensitiv- tially reluctant to publish on the new Minta, Kao and Tsien introduced ity to pH changes in the physiological indicators, Kao said, but ultimately several fluorescent indicators of Ca2+ range. BAPTA binds calcium through yielded to persuasion by postdoc DECEMBER 2021 ASBMB TODAY 13
JOURNAL NEWS over again.” They found that cells took up the in- JOSEPH KAO Some molecules he generated failed dicators through incubation with the to fluoresce or were protonated at corresponding acetoxymethyl esters near-physiological pH. Minta tweaked and confirmed a dazzling increase in and adapted, adding and modifying fluorescence when they applied Ca2+- functional groups until he had two mobilizing agonists. chimeric molecules, derived from the Fluo-3 quickly was adopted for fluorophores rhodamine and fluo- many uses. By 1995, researchers had rescein, that were weakly fluorescent reported watching waves of Ca2+ on their own but lit up dramatically activity pass through connected when Ca2+ bound. The lab dubbed networks of neurons in mouse brain the probes fluo-3 and rhod-2. slices, observing cell-cycle initiation Ordinarily, when a molecule in fertilized egg cells, and detect- absorbs light, the energy is dispersed ing “Ca2+ sparks” — microscopic, Three-dimensional model of Fluo3 binding a Ca2+ quickly as molecular motion, or elementary Ca2+ signals generated ion (purple). The structure shows the participation of the two nitrogens (blue) and six oxygens (red) heat. Fluorescence — the release of by the coordinated opening of small that bind to Ca2+, causing the ion to be enveloped captured light energy as a photon — clusters of Ca2+-release channels — on by the chelator. requires special circumstances. the sarcoplasmic reticulum in heart “When a molecule absorbs light, an cells. Kao said the new technologies Martin Poenie. electron is promoted from a lower- “made calcium measurement acces- Tsien was intent on developing a energy level into a higher-energy level, sible to essentially anyone with a fluorescent Ca2+ indicator with excita- leaving a vacancy in the lower level,” microscope.” tion in the visible range. Perhaps it Kao said. Emission of a photon de- Tsien was disappointed, however, could be done by combining BAPTA pends on the excited electron return- that the new probes changed only in with the visible fluorescence of already ing to its normal lower-energy state. If intensity, not in excitation or emission available fluorophores? He recruited an electron elsewhere in the molecule wavelength, upon Ca2+ binding; he postdocs Minta, a chemist, and Kao, a is free to slip into that lower orbital, had hoped to be able to do ratiomet- biophysicist, to work on the project. he said, the excited electron’s energy ric imaging. First, the molecules had to be syn- ultimately is lost as heat instead of “Roger was almost always dissatis- thesized. An early synthetic strategy being emitted as light, a phenomenon fied with any product that you made,” involved a long pressurized incuba- known as fluorescence quenching. Kao said. “He had a perfect concep- tion in an aluminum instrument that In the chimeric molecules, the fluo- tion of how they should behave, and resembled an old-fashioned coffee rophore can be quenched by electrons then they would fall short on one or urn. Kao recalled a time when the in lone pairs on the BAPTA moiety. another aspect, and he’d be a little chemists left a reaction to run over the But when a positively charged Ca2+ rueful: ‘If only we had discovered how weekend, hoping to improve its yield. ion is present, it forms bonds with to do this.’” “When we came back … there was those electrons, lowering their energy Tsien finally got his visible ratio- an imprint where the lid handle had and making it energetically unfavor- metric Ca2+ sensor about 10 years smashed into the ceiling. Somewhere able for them to fill the vacancy left later. It was based on GFP and the else, we found the lid completely flat- by the excited electron. Without com- calcium-binding protein calmodulin; tened.” The reaction also had shattered petition for the vacated orbital, the though calcium could not be cloned, an internal glass ampule, leaving glass excited electron can relax back into it, cloning turned out to be useful in its dust all over the lab. emitting a photon. study after all. “Subsequently, they found better “Calcium allows it to fluoresce ways to do that reaction,” Kao said. beautifully,” Minta said. In a test tube, Laurel Oldach (loldach@ Even after the molecules were syn- fluo-3’s brightness increased by 40- to asbmb.org) is a science writer thesized, the work was not complete. 100-fold when calcium was added. for the ASBMB. Follow her on “Roger was a perfectionist,” Minta In a second paper in the same issue Twitter: @LaurelOld. said. “If I did a dye and it had certain of JBC, Kao and several colleagues imperfections, he made me start all tested the probes for live-cell imaging. 14 ASBMB TODAY DECEMBER 2021
JOURNAL NEWS Salivary proteins may hold key to targeting tick-borne diseases By Nivedita Uday Hegdekar lated BaSO4-adsorbing protein 1, or SCOTT BAUER, U.S. DEPARTMENT OF AGRICULTURE W BSAP1, from tick saliva and described hen Ingrid Dijkgraaf ’s its anticoagulant activities. However, research group was search- its structure was yet undetermined, ing for molecules that could and Dijkgraaf saw this as an excellent inhibit chemokines, a group of small research opportunity. signaling proteins involved in the Denisov, by then a postdoctoral development of atherosclerosis, they fellow in Dijkgraaf ’s lab, had extensive stumbled upon an unusual source: experience in structural biology and tick saliva. undertook the project. As blood-sucking parasites, ticks “After Dr. Mans gave us the transmit more than a dozen serious sequence, we were able to synthesize Ixodes scapularis, commonly known as the deer diseases, including Lyme disease, this protein chemically,” Denisov said. tick or black-legged tick, is a vector for Lyme and typhus and tick-borne meningo- “Once we elucidated the structure, other diseases. encephalitis, to both animals and we carried out additional studies to humans. They also produce proteins characterize its activity.” nism by which the salivary proteins in their saliva that help them avoid Denisov discovered that parts of inhibit the host immune system and being spotted by the host’s immune the BSAP1 protein were similar to potentially use these proteins for system. others, such as tick salivary lectin development of anti-tick vaccines. Several years ago, Dijkgraaf ’s complement pathway inhibitor, or Her collaborator Joppe W. group, including then–graduate TSLPI, Salp14. He carried out assays Hovius, an infectious disease special- student Stephen Denisov, found that to distinguish TSLPI Salp14 and ist at the University of Amsterdam, is evasins, a family of those proteins that BSAP1on a functional level and found an expert on the TSLPI protein. help ticks skirt detection, also could that the BSAP1 and TSLP1 proteins “His work has shown that the neutralize chemokines involved in both inhibit the lectin complement TSLPI protein helps Borrelia bac- atherosclerosis. pathway and thus prevent the host’s terium to move from the ticks to “Tick saliva contains chemokine- immune system from recognizing the host and cause Lyme disease,” binding compounds,” said Dijkgraaf, an invasive tick bite. However, the Dijkgraaf said. “Hence, if we could an associate professor at the Univer- Salp14 protein has a double function inhibit this protein by antibodies or sity of Maastricht. “Millions of years — it is an inhibitor of both the lectin some medication, then maybe we of evolution have already developed, complement pathway and the host co- can also inhibit the transmission of probably, the most ideal compound to agulation cascade, which means it also the Borrelia bacterium from tick and target atherosclerosis. This shows how prevents clotting of the host’s blood at host.” nature could help researchers unravel the site of the bite. DOI: 10.1016/j.jbc.2021.100865 molecular mechanisms. They can be Denisov’s data collectively support the starting point for development of a mechanism by which tick saliva Nivedita Uday Hegdekar therapeutics and chemical agents.” proteins can evade the host immune (nivedita.hegdekar@ umaryland.edu) is a graduate Dijkgraaf began investigating other system. The findings recently were student at the University of proteins in the saliva of ticks. Several published as a research paper in the Maryland working toward a years ago, one of her collaborators, Journal of Biological Chemistry. Ph.D. in biochemistry and molecular biology and an M.S. Ben Mans, a professor at the Uni- For next steps, Dijkgraaf wants to in patent law. Follow her on versity of Pretoria, South Africa, iso- study the precise molecular mecha- Twitter @NiveditaHegdek1. DECEMBER 2021 ASBMB TODAY 15
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