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FEATURE                             Vol. 20 / No. 11 / December 2021

             (A SUBJECTIVE LIST)
          ALSO: 10 GIFTS FOR THE SCIENTIST IN YOUR LIFE
(A SUBJECTIVE LIST) - FEATURE
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(A SUBJECTIVE LIST) - FEATURE
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
(A SUBJECTIVE LIST) - FEATURE
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
(A SUBJECTIVE LIST) - FEATURE
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
(A SUBJECTIVE LIST) - FEATURE
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
(A SUBJECTIVE LIST) - FEATURE
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
(A SUBJECTIVE LIST) - FEATURE
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
(A SUBJECTIVE LIST) - FEATURE
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
(A SUBJECTIVE LIST) - FEATURE
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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