The COVID-19 issue - THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY - American Society for Biochemistry and ...
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Vol.
Vol.19
19 // No.
No.54 // May
April2020
2020
TTHHEE MMEEMMBBEERR MMAG
AGAAZZIINNEE OOFF TTHHEE AAMMEERRIICA
C ANN SSOOCCIIEETTYY FO
FORR BBIIOOCCHHEEMMIIST
STRY
RY AANNDD MMOOLLEECCUULLAARR BBIIOOLO
LOGY
GY
The COVID-19
issue
A new career center
Browse jobs, post positions, have your
resume critiqued and more.
careers.asbmb.org
NEWS FEATURES
FEATURES PERSPECTIVES
PERSPECTIVES
2 22 50
EDITOR’S NOTE A LEGACY OF TYROSINE ON THE FRONT LINE:
Breaking the news PANDEMIC INSIGHT FROM
3 A HEALTH CARE WORKER
MEMBER UPDATE COVID19
52
7 30 A small army of researchers
races to build a coronavirus QUARANTINED THOUGHTS
IN MEMORIAM interactome
10 32 Could an old malaria drug
help fight SARS-COV02?
54
JOURNAL NEWS A NEW CITY, A NEW JOB
10 Yeast as a detective’s assistabt 34 Anatomy of a molecule: what AND A GLOBAL PANDEMIC
12 Cow born in Japan after removal, makes remdesivir promising?
replacement of placental cells
13 How is myelin made?
16 Review delves into
36 Slipping past the proofreader
59
proximity proteomics 44 Scientist uses community IS MORE SCIENCE THE MEDICINE
organizing skills to mobilize
17 From the journals
researchers against COVID-19
WE NEED TO CURE THE WORLD’S
2
STRUGGLING ECONOMY?
46 Researchers retool genomics
labs to provide virus
testing
12
48 “We are doers. We want to get
involved.”
22
13
54
MAY 2020 ASBMB TODAY 1
EDITOR’S NOTE
THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY
FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Breaking the news
OFFICERS
COUNCIL MEMBERS By Comfort Dorn
Gerald Hart Suzanne Barbour
President Joan Broderick
PHOTO BY MIKA BAUMEISTER ON UNSPLASH
Toni M. Antalis Matt Gentry
President-elect Blake Hill
Audrey Lamb
Wei Yang James M. Ntambi
Secretary Takita Felder Sumter
Joan Conaway Kelly Ten–Hagen
Treasurer JoAnn Trejo
EX-OFFICIO MEMBERS ASBMB TODAY EDITORIAL
ADVISORY BOARD
Robert S. Haltiwanger
Rajini Rao
Carla Koehler Chair
Co-chairs, 2020 Annual
Meeting Program Committee
Ana Maria Barral Protective masks, normally used for surgery, are now in use to fight the coronavirus, SARS-CoV-19.
T
Natasha Brooks
Cheryl Bailey Kelly Chacón
Chair, Education and Beronda Montgomery his month marks my third an- aware of an insidious new disease that
Professional Development Bill Sullivan niversary as managing editor of was sickening people in China. We
Committee Melissa Vaught
Daniel Raben Binks Wattenberg
ASBMB Today. If COVID-19 posted our first article about research
Chair, Meetings Committee restrictions continue, I’ll probably related to chloroquine and “the new
Sonia Flores ASBMB TODAY celebrate privately with an extra cup coronavirus” on Feb. 6, covering a
Chair, Minority Affairs Angela Hopp
Committee Executive Editor of coffee at my kitchen table/desk. paper published two days earlier.
Nicole Woitowich ahopp@asbmb.org Maybe even a doughnut. Since then, this job and my old
Chair, Science Outreach and Comfort Dorn As I’ve mentioned in this space jobs have felt increasingly similar as
Communication Committee Managing Editor
Terri Goss Kinzy cdorn@asbmb.org before, I worked for about 20 years we race to share news of COVID-19
Chair, Public Affairs Lisa Schnabel at daily and weekly newspapers research and how our members are
Advisory Committee Graphic Designer
before I came to the ASBMB to edit helping and coping. Our staff writ-
Ed Eisenstein lschnabel@asbmb.org
Chair, Membership Committee John Arnst
a monthly magazine. The change was ers, contributors and members have
Susan Baserga Science Writer stark, mostly in terms of pacing. I churned out articles and essays at
jarnst@asbmb.org
Chair, Women in Biochemistry spent much of my career hounding what, for us, is an astonishing pace.
and Molecular Biology Laurel Oldach
Committee Science Writter reporters to turn around daily stories Why am I telling you this?
loldach@asbmb.org
Sandra Weller in a matter of hours. Here, I found This issue of ASBMB Today
Chair, Publications Ed Marklin
Committee Web Editor that we had the luxury of working for reflects these recent changes. Here
Lila M. Gierasch
emarklin@asbmb.org weeks, even months, on articles and we have collected the best of the
Allison Frick
Editor-in-chief, JBC
Multimedia and Social Media
essays to get them exactly right for COVID-19 writing that we’ve posted
A. L. Burlingame Content Manager this magazine. Very little was urgent. on our website since February. We
Editor, MCP africk@asbmb.org
We moved at a stately and thoughtful tried to update articles wherever
Nicholas O. Davidson Barbara Gordon
Editor-in-chief, JLR Executive Director pace, rather like an ocean liner or a possible, but the story is evolving
bgordon@asbmb.org
Kerry-Anne Rye dowager countess. quickly. This is a snapshot, from the
Editor-in-chief, JLR
That changed this year. And it viewpoint of this magazine and this
changed fast. society, of a moment that comes once
For information on advertising, contact Pharmaceutical
Media Inc. at 212-904-0374 or mperlowitz@pminy.com. First, we moved to daily pub- in a century.
lishing on our website in January, Stay well and stay safe.
meaning we were posting fresh stories
every morning — often several a day.
This had been a longtime goal of the Comfort Dorn
www.asbmb.org/asbmbtoday ASBMB Today staff, and we were (cdorn@asbmb.org) is the
PRINT ISSN 2372-0409 managing editor of ASBMB
delighted with our fresh new website, Today. Follow her on Twitter
Articles published in ASBMB Today reflect solely the authors’ views and not
even though it meant major pivots in @cdorn56.
the official positions of the American Society for Biochemistry and Molecular
Biology or the institutions with which the authors are affiliated. Mentions of
our workflow.
products or services are not endorsements. Later that month, we became
2 ASBMB TODAY MAY 2020
MEMBER UPDATE
Three ASBMB members win Protein Society awards
Pictured, from left, are Protein Society award winners Catherine Drennan, Stephen Sligar and Karen Fleming.
The Protein Society has honored three members of lipid-membrane patches stabilized by a belt of mem-
the American Society for Biochemistry and Molecular brane-scaffolding proteins. For that work, he also won
Biology with 2020 awards. Karen Fleming of Johns the ASBMB’s 2016 Herbert A. Sober Lectureship,
Hopkins University, Stephen Sligar of the University of recognizing outstanding biochemical and molecular
Illinois at Urbana–Champaign and Catherine Dren- biology research, with a special emphasis on the devel-
nan of the Massachusetts Institute of Technology were opment of methods and research techniques.
set to receive their awards at the World Conference on The Anfinsen award is sponsored by the Protein
Protein Science in June, which was canceled in response Society. ASBMB members who have won it in the past
to the COVID-19 pandemic. include Anthony Kossiakoff, University of Chicago
Karen Fleming, a professor of biophysics at Hop- (2019); Sachdev Sidhu, University of Toronto (2015);
kins and a pioneer in the study of membrane-protein and Barry Honig, Columbia University (2012).
folding, won the Carl Brändén Award, which honors Catherine Drennan, a professor at MIT and a
a protein scientist who has contributed significantly to Howard Hughes Medical Institute investigator, won
science, education and/or service. the Dorothy Crowfoot Hodgkin Award for solving
Fleming is an associate editor for the Journal of high-resolution structures of proteins and protein
Biological Chemistry, served on the ASBMB Council complexes that enhance understanding of the biology of
from 2014 through 2017 and co-founded the Gordon metalloproteins.
Research Conference on Membrane Protein Folding. Hodgkin used X-ray crystallography to determine
She recently received the Society of General Physiolo- the structure of vitamin B12 and won the 1964 Nobel
gists’ inaugural Sharona Gordon Award. Prize in chemistry.
The Brändén award is sponsored by Rigaku Corp. The Protein Society, in its announcement, pointed
ASBMB members who have won it in past years to Drennan’s determination of the first structure of co-
include Billy Hudson, Vanderbilt (2017); C. Robert balamin-dependent ribonucleotide reductase, one of the
Matthews, University of Massachusetts (2015); Stephen three enzymes that catalyze the final step in production
White, University of California, Irvine (2014); Sheena of deoxyribonucleotides in all organisms.
Radford, University of Leeds (2013); Helen Berman, Drennan is a former member of the ASBMB
Rutgers University (2012); Michael Summers, Univer- Education and Professional Development Committee,
sity of Maryland, Baltimore County (2011); and Bruce a past ASBMB annual meeting session organizer, and a
Alberts, University of California, San Francisco (2010). past winner of the ASBMB–Schering–Plough Research
Stephen Sligar, who chairs the biochemistry depart- Institute Award.
ment at UIUC, won the Christian Anfinsen Award for The Hodgkin award is sponsored by Genentech.
methodological advances in the field of protein sciences. ASBMB members who have won it include Hao Wu,
Anfinsen received the Nobel Prize in chemistry in Harvard Medical School (2019); Susan Marqusee,
1972 for his work on enzyme structure. His namesake University of California, Berkeley (2018); Manajit Hay-
award recognizes “a technological achievement or sig- er–Hartl, Max Planck Institute of Biochemistry (2017);
nificant methodological advances in the field of protein Rachel Klevit, University of Washington (2016); Judith
sciences.” Frydman, Stanford University (2014).
Sligar discovered and developed nanodiscs,
MAY 2020 ASBMB TODAY 3
MEMBER UPDATE
University of Vermont names interrogate the protein machines and a Presidential Early Career for
Parise as dean involved in repairing DNA and Scientists and Engineers for his
Leslie Parise, maintaining genome integrity. metabolism research. In one line of
a biochemist who is The International Award — one inquiry, his lab uses novel systematic
currently chair of of 10 awards given each year by the screening to glean functional insights
the department of United Kingdom–based Biochem- into orphan mitochondrial proteins.
biochemistry and ical Society — recognizes research Other lines of inquiry concern the
biophysics at the that illustrates the importance of the synthesis of coenzyme Q and the role
University of North molecular biosciences in the advance- of phosphatases in regulating mito-
Parise Carolina, Chapel ment of life sciences and is given to chondrial activities.
Hill, and until recently was chair of early-career scientists of any nation- Since 2015, in addition to
the faculty at that university, will ality who are located outside the UK running his lab, Pagliarini has also di-
soon join the faculty of the Universi- and Ireland. rected the metabolism branch of the
ty of Vermont. There, she will serve “This certainly would not have independent Morgridge Institute for
as the dean of the College of Agricul- been possible without the hard work Research, a nonprofit institute affiliat-
ture and Life Sciences. and creativity of the members of ed with UW-Madison and located on
Parise’s lab focuses on the molec- my laboratory,” Eichman said of the its campus.
ular mechanisms of cancer and blood award in a statement. “I thank my BJC Investigators are funded
clot formation. One line of inqui- colleagues who made and endorsed by the St. Louis-based hospital and
ry focuses on the protein calcium the nomination and who have guided physician organization BJC (original-
and integrin-binding protein 1, or me over the years, and my family ly Barnes–Jewish/Christian) Health-
CIB1, which may be a drug target for their support and encourage- Care. They are selected by a search
in triple-negative breast cancer cells; ment. This award will help maintain committee of 42 professors at Wash-
a second research program has to do momentum within my research team, ington University School of Medicine.
with the role of a lipid deacetylase in so that we may continue to approach Pagliarini is the fifth of 10 professors
platelet aggregation. what we feel are important and in- the program is projected to recruit.
In addition to her service at teresting questions related to genome
UNC Chapel Hill, Parise was an maintenance.” Olzmann wins
associate editor for the journal Blood. presidential award
She has served as president of the Pagliarini to move University
Association of Medical and Graduate from Madison to Missouri of California,
Departments of Biochemistry and on Dave Pagliarini, Berkeley faculty
the American Society for Biochem- an associate profes- member James
istry and Molecular Biology’s public sor of biochemistry Olzmann was
affairs advisory committee. She is at the University of among the 315 re-
scheduled to start at UVM in May. Wisconsin–Madison cipients of the
best known for his Olzmann 2019 Presidential
Eichman wins award work on defining Early Career Award for Scientists and
Pagliarini
from Biochemical Society and functionalizing Engineers.
Vanderbilt Uni- mitochondrial proteins, has been Olzmann, an associate professor
versity biochemistry named a BJC investigator and will in the department of nutritional stud-
professor Brandt join the faculty at Washington Uni- ies and toxicology and an investigator
Eichman has won versity in St Louis in May. at the Chan Zuckerberg Biohub,
the Biochemical Pagliarini received the Earl and investigates the regulation of lipid
Society’s 2021 In- Thressa Stadman award from the droplets and the role that they play
ternational Award. American Society for Biochemistry in maintaining lipid homeostasis in
Eichman Eichman’s lab and Molecular Biology this year and conditions such as obesity and fatty
uses structural biology techniques has previously landed young investi- liver disease. He joined the faculty at
including X-ray crystallography to gator awards from the Protein Society UC Berkeley in 2013 after earning
4 ASBMB TODAY MAY 2020
MEMBER UPDATE
his Ph.D. from Emory University and Fuchs and Bissell win 2020 Gairdner awards
doing postdoctoral work at Stanford
University.
Established in 1996, the PECASE
honors the contributions scientists
and engineers have made to the
advancement of science, technol-
ogy, education, and mathematics
education and to community service
as demonstrated through scientific
leadership, public education and
community outreach.
Outstanding investigator
award for UW’s Bornfeldt Mina Bissell and Elaine Fuchs
Karin Born-
feldt, a professor Elaine Fuchs and Mina Bissell are among the five scientists to receive
of medicine and a 2020 Canada Gairdner International Award.
pathology at the The award honors Fuchs, a pioneering cell biologist, for revealing the
University of mechanism by which skin cells make and repair tissues. Much of what
Washington and we know about human skin’s capacity to heal and regenerate — and, in
an associate editor cases of mutation, to succumb to diseases like epidermolysis bullosa — has
Bornfeldt of the Journal of been made possible by Fuchs’ work, from her first lab at the University of
Lipid Research and several other Chicago to her current position as the Rebecca C. Lancefield investigator
journals, has received an Outstanding at the Rockefeller University.
Investigator Award from the National The award honors Bissell, a distinguished senior scientist at the
Heart, Lung and Blood Institute. Department of Energy’s Lawrence Berkeley National Laboratory, for her
Diabetes can accelerate the pro- paradigm-shifting work in modeling the two-way interactions between
cess of atherosclerosis, wherein cho- normal and malignant cells in tumor microenvironments. This behavior,
lesterol-rich lesions form in arterial called “dynamic reciprocity,” revealed that tumor cells behave differently
walls. This puts people with diabetes in lab environments than in patients, led to 3D understanding of tumor
at heightened risk of heart attack and behavior and has had significant impacts on cancer therapies.
stroke. Bornfeldt’s lab studies the role The Gairdner Foundation was established by Canadian businessman
of lipids, lipoproteins and immune and philanthropist James A. Gairdner in 1957 with the goal of recognizing
cells in this process. In addition to and rewarding international excellence in fundamental research that im-
running a research lab, she directs pacts human health. The foundation has bestowed 395 awards on laureates
the Diabetes Complications Program from 35 countries, 92 of whom have gone on to receive Nobel prizes. This
and serves as associate director for re- year’s International award winners also include Roel Nusse, Rolf Kemler
search of the UW Medicine Diabetes and Masatoshi Takeichi.
Institute and as deputy director of the
UW’s Diabetes Research Center.
The Outstanding Investigator
Award mechanism provides substantial
flexible funding for a research program, Marion B. Sewer Distinguished
rather than supporting specific projects.
Scholarship for Undergraduates
Bornfeldt and her team will receive
$7.2 million over up to seven years to Deadline: June 1
pursue strategies for preventing cardio- asbmb.org/diversity/undergraduate-scholarship
vascular complications of diabetes.
MAY 2020 ASBMB TODAY 5
MEMBER UPDATE
Student chapter members land Goldwater scholarships
The recipients of this year’s Goldwater scholarships • Mark Hargrove, a professor at Iowa State Uni-
were announced in late March. versity, working with Behnia Rezazadeh Shirazi
The scholarships, named in honor of Senator Barry • Matthew Francis and Jennifer Doudna, pro-
Goldwater, offer $7,500 per remaining academic year fessors at the University of California, Berkeley,
to sophomore and junior students pursuing bachelor’s working with Casey Mogilevsky
degrees in the natural sciences, math or engineering. • Leslie Hicks, an associate professor at the
Many of this year’s recipients in the life sciences University of North Carolina at Chapel Hill,
are American Society for Biochemistry and Molecular working with Lauren Lim
Biology Student Chapter members. The ASBMB con- • Terry Hill, a professor at Rhodes College, work-
gratulates these promising sophomores and juniors: ing with Ramiz Somjee
• Furyal Ahmed, Agnes Scott College • Vincent Hilser, a professor at Johns Hopkins
• Chris Bragança, Villanova University University, working with Andrew Munoz
• Daniel Cheong, University of Oklahoma • Michael Jewett, a professor at Northwestern
• Landon Clark, University of Georgia University, working with Alexandra Wooldredge
• Madeline Farringer, Iowa State University • Henrik Kibak, a professor at California State
• Shellaina Gordon, Northeastern University University, Monterey Bay, working with Saman-
• Edena Khoshaba, Chapman University tha Miller
• Stella Ma, University of Wisconsin–Madison • Daniel Kraut, an associate professor at Villano-
• Eran Maina, The College of Wooster va University, working with Chris Bragança
• Emily Mahoney, Rochester Institute of Technol- • C. Martin Lawrence, a professor at Montana
ogy State University, working with Sheridan Brown
• Rishi Mehta, University of Cincinnati • Teresita Padilla-Benavides, a professor at the
• Mlana Lore, Eckerd College University of Massachusetts Medical School,
• Jessica Pierce, Salisbury University working with Shellaina Gordon
• Cynthia Schofield, University of Massachusetts • Tanya Paull, a professor at the University of
Boston Texas at Austin, working with Cassandra Bishop
• Ramiz Somjee, Rhodes College • Subbiah Pugazhenthi, an associate professor at
• Daniel Wieland, University of Arizona the University of Colorado Anschutz Medical
• Karen Zhang, University of Washington Campus, working with Anit Tyagi
• Jacob Schwartz, an assistant professor at the
As part of the application, students write an essay University of Arizona, working with Daniel
about their experience with their research mentors. Wieland
ASBMB salutes the many mentors of this year’s 287 • Vincent Tagliabracci, an assistant professor at
Goldwater scholars in the life sciences, who helped the University of Texas Southwestern Medical
ignite their students’ excitement about biology. Among Center, working with Patrick Nnoromele
the ASBMB members who mentored a Goldwater • Timothy Wencewicz, an associate professor at
scholarship recipient are: Washington University in St. Louis, working
• Jeanine Amacher, an assistant professor at Western with Michael Moore
Washington University, working with Min Gaoå • James West, an assistant professor at The Col-
• Pascale Charest, an associate professor at the lege of Wooster, working with Eran Maina
University of Arizona, working with Jamison • Crystal Young-Erdos, an assistant professor at
Takashima Eckerd College, working with Mlana Lore
6 ASBMB TODAY MAY 2020
IN MEMORIAM
Jerry Lingrel Bruce S. McEwen
Jerry Lingrel, a Neuroscientist
longtime associate Bruce S. McEwen, who
editor of the Journal of made important discov-
Biological Chemistry and eries about the effects of
a University of Cincinnati stress and sex hormones
College of Medicine fac- on the brain, died Jan. 2.
ulty member for almost He was 81.
60 years, died Feb. 22. McEwen, the Alfred
He was 84. E. Mirsky professor
In a 2007 and head of the Harold
autobiographical and Margaret Millikin
paper, Lingrel wrote that as a child he “spent a lot of time Hatch Laboratory of Neuroendocrinology at The Rockefeller
watching things grow and being fascinated by the complexity University, worked at the intersection of neurobiology, endo-
of the structure of different flowers, trying to understand how crinology and behavioral science. His research changed the
engines worked … I had a real curiosity about science, but had way scientists conceived of the brain.
no idea what real experimental science involved.” Encouraged “When he began his career in the 1960s, most scientists
by an enthusiastic biology teacher, he went to Otterbein Col- believed that the brain ceases to change when it becomes fully
lege where he majored in biology and chemistry, then earned a developed, at which point its basic architecture becomes sta-
Ph.D. in biochemistry from The Ohio State University followed ble,” explained Rockefeller writer Katherine Fenz. “Research of
by a postdoc at the California Institute of Technology. the day focused largely on ion movements and the transmis-
Lingrel joined the faculty of the University of Cincinnati in sion of chemical signals across synapses. But McEwen, along
1962 and became a professor of biochemistry and molecular with a few other scientists, recognized that the brain is in fact
biology in 1972. He served for 27 years as chair of the depart- malleable and can be modified by circulating hormones.”
ment of molecular genetics, biochemistry and microbiology. McEwen discovered adrenal steroid-binding sites in
After stepping down in 2008, he returned to serve as the the brain, showed that brain regions not previously linked to
department’s interim chair from 2014 to 2017. hormone or stress regulation, including the hippocampus and
Lingrel was known for taking a biochemical approach to prefrontal cortex, selectively bind radiolabeled corticosterone,
physiological problems. Recently, his research had focused and studied glucocorticoid influences on neuroplasticity.
on a zinc finger transcription factor called Kruppel-like factor McEwen was born in Fort Collins, Colorado, on Jan. 17,
2, or KLF2, that is required for vascular integrity and might 1938. He grew up in Ann Arbor, Michigan, where his father was
play a protective role against atherosclerosis. In years past, a professor at the University of Michigan.
his lab cloned the Na,K-ATPase, a major transport protein, and He earned his bachelor’s degree in chemistry at Oberlin
identified specific amino acids involved in binding sodium and College in Ohio and then his Ph.D. in cell biology from Rockefeller
potassium as well as those necessary for binding the cardiac University in 1964. He did postdoctoral work in Sweden and took a
stimulant molecule ouabain. faculty position for a short time at the University of Minnesota.
Lingrel’s career spanned disciplines, he wrote, and He returned to Rockefeller as a faculty member in 1966.
“while biochemistry has been a very important aspect of this He was promoted to professor in 1981 and served as associate
work, I think my research has always had as a focus the use dean and then dean of the graduate training program between
of chemical principles to understand physiological function.” 1985 and 1993. He was named the Mirsky professor in 1999.
He also stressed the impact of working with others, writing, McEwen won many awards and honors during his career. He was
“we probably have more influence on the individuals we train elected to the National Academy of Sciences, the National Academy of
than we anticipate and clearly mentoring should be taken very Medicine and the American Society of Arts and Sciences.
seriously.” He is survived by his wife, neuroimmunologist Karen
Bulloch, with whom he collaborated; his former wife, Nancy,
and their two daughters, Carolyn and Sarah; stepchildren,
Kimberly McGrath and Scott Muryasz; and eight grandchildren.
7 ASBMB TODAY MAY 2020
IN MEMORIAM
Michael Wakelam James C. Hu
Michael Wakelam, a James C. Hu, a
professor at Cambridge longtime professor
University and an in the Texas A&M
associate editor for the University department
ASBMB’s Journal of Lip- of biochemistry and
id Research, died March biophysics, died in
31 of respiratory failure, his home in College
likely from COVID-19 Station, Texas, on Jan.
infection. He was 64. 23 from complications
Wakelam studied of liver disease. He
lipids’ structural, meta- was 66.
bolic and signaling roles and pioneered the use of high-sensi- Born April 3, 1953 in Berkeley, California, Hu grew up
tivity liquid chromatography–mass spectrometry to measure in Palo Alto. He earned a B.S. in biology at Stanford Univer-
lipid levels in various cell and tissue types. sity and a Ph.D. in molecular biology from the University
He had been director of the Babraham Institute, a life of Wisconsin. He worked as a postdoctoral fellow at the
science research center near Cambridge, since 2007 and a Massachusetts Institute of Technology before establishing his
JLR associate editor since 2013. lab at Texas A&M.
In a joint statement, JLR’s editors-in-chief, Kerry-Anne In his research, Hu worked to develop biological
Rye and Nicholas O. Davidson, said this about Wakelam’s ontologies, sets of standardized controlled vocabularies for
personal qualities and work for the journal: “Those who had annotation. Most recently, his lab worked with other groups on
the privilege of knowing him enjoyed his generous spirit as well the Ontology for Microbial Phenotypes, a resource for reuse
as his passion for science. Michael maintained the highest and analysis of microbial genetics data. His group worked
standards of objectivity in his role as an (associate editor) and with the Gene Ontology Consortium on annotation of gene
was an exceptional judge of scientific merit.” functions and developed systems for integrating annotation
Wakelam was born in 1955. He earned his undergraduate with education in the Community Assessment of Community
and doctoral degrees at Birmingham University in 1977 and Annotation with Ontologies. They also worked on systems for
1980, respectively. He went on to complete postdoctoral building model organism databases for community annotation,
training at Glasgow University and worked in Germany and including EcoliWiki, which uses and modifies the open-source
London before joining Glasgow as a lecturer in 1985. In software built for Wikipedia to provide specialized scientific
1993, he returned to Birmingham as a professor of molecular data resources.
pharmacology. Along with his work in microbial genomics and commu-
The director position lured him to Babraham in 2007. nity annotation, Hu was known as a supportive colleague who
There, he oversaw a team of researchers engaged in preclinical was generous with his time and energy. He loved teaching and
and clinical studies of the cellular and molecular details of interacting with students. He mentored undergraduate and
aging. graduate students in the lab, at meetings and in collaborative
He is survived by his wife, Jane, and their two grown projects.
children. Hu is survived by his wife, Deborah Siegele, a professor
Editor’s note: In May 2019, ASBMB Today science writer in the biology department at Texas A&M. Generations of
Laurel Oldach wrote a cover story about efforts to harmonize students and colleagues have known them as the rare couple
lipidomics. For that story, she interviewed Wakelam and others who collaborated at work and at home, in symbiosis yet with
involved with the Lipid Metabolites and Pathways Strategy, fierce independence.
known more commonly as LIPID MAPS. Read the story.
8 ASBMB TODAY MAY 2020IN MEMORIAM
Manford K. “Bud” Patterson Jr. Paul Starr Sypherd
Manford K. Paul Starr Sypherd,
“Bud” Patterson Jr., a microbiologist who
a former officer of held leadership roles
the Samuel Roberts at the University of
Noble Foundation and California, Irvine and the
former president of the University of Arizona,
Oklahoma Academy of died Jan. 18. He was 83.
Science, died Jan. 22 in Born Nov. 16,
Edmond, Oklahoma. He 1936, in Akron, Ohio,
was 93. Sypherd moved to Arizo-
Born Aug. 20, na at age 6. He earned
1926 in Muskogee, Oklahoma, Patterson served in the a B.S. in microbiology at Arizona State (College) University, an
U.S. Navy Air Corps after high school, then earned a B.S. in M.S. in microbiology at the University of Arizona and a Ph.D. at
chemistry and an M.S. in biochemistry from the University of Yale University. He was a postdoctoral fellow at the University
Oklahoma. He worked for several years in the soils lab of the of California, San Diego and later said he believed his training
Noble Foundation, an agricultural research institution, before and experiences at UCSD set him on his academic trajectory.
earning a Ph.D. in biochemistry from Vanderbilt University. He Sypherd began his career at the University of Illinois; he
served as a consulting biochemists for the Interdepartmental had a fully funded research laboratory and obtained tenure
Committee on Nutrition for National Defense before returning there before he was recruited to the University of California,
to the Noble Foundation in 1973 as vice president and direc- Irvine where he served as chairman of the department of
tor of the biomedical division. Following his retirement from microbiology and molecular genetics for more than a decade,
the foundation, he joined IMTEC Corporation as a senior vice director of the medical scientist program, vice chancellor for
president of research and development. research and dean of graduate studies. He returned to the
Patterson played a role in developing L-asparaginase, a University of Arizona in 1993 as executive vice president and
drug used to treat acute lymphocytic leukemia in children. provost, leading development of an integrated learning center.
He developed a quality control system that enabled IMTEC to As provost, he focused on improving staff and faculty working
market in the U.S. He co-edited a book, “Tissue Culture: Meth- conditions. One of his lasting contributions was closing the
ods and Applications,” contributed chapters to other scientific campus between Christmas and New Year’s, so employees
books, published more than 60 articles in scientific journals could spend time with their families. He retired in 2002 and
and held three patents. He was an adjunct professor at was designated provost emeritus and professor emeritus of
Oklahoma University and served the American Tissue Culture molecular and cellular biology at the UA.
Association as an officer and editor-in-chief of its journals. He Over the course of his 35-year research career, Sypherd
played an active role in many scientific and civic organizations and his students published more than 150 articles in peer-re-
and served as a judge at numerous international science and viewed journals, many on protein synthesis and nucleic acid
engineering fairs. metabolism in bacteria and fungi. He was also a pioneer in
Patterson is survived by his wife of 66 years, Beverly; a ribosome research. He was a founding editor of the Journal
daughter, Shelley Goetz, and her husband, Dan; and a grand- of Molecular and Cellular Biology and editor for the Journal
son, Manford Goetz, and his wife, Julie. of Bacteriology, and he served on the National Institutes of
Health study section for microbial chemistry for two terms
and on the National Research Council committee on medical
education.
Sypherd is survived by his wife, Linda; his daughter,
Denise; sons David, Sean and Scott; his grandchildren; and
many other relatives.
MAY 2020 ASBMB TODAY 9JOURNAL NEWS
Yeast as a detective’s assistant
Susan Henry’s work on inositol-containing phospholipids
By Martin J. Spiering
M
ASBMB TODAY
acromolecules such as proteins, “Yeast is almost like the Esche-
lipids and carbohydrates often richia coli of the eukaryotic world,”
have complex structures that Henry said, adding that yeast helped
underpin their cellular functions. researchers “to figure out exactly
The sugar alcohol myo-inositol is where the metabolic components are
a notable exception — its simple coming from.”
six-carbon structure looks unremark- The fully sequenced S. cerevisiae
able but is used in countless cellular genome did not become available
processes in all domains of life. until 1996, so earlier studies of the
According to Susan Henry, a genetics and biochemistry of even
professor of molecular biology and this simple organism required skilled
genetics at Cornell University, inosi- detective work to find all the players
tol is absolutely essential in cells. “It’s involved in a molecular pathway.
a major phospholipid precursor as At Albert Einstein College of Susan Henry’s work on the regulation of inositol
well as a signaling molecule,” Medicine in the mid-1970s, Henry and phospholipids in yeast enabled numerous
she said. and Ph.D. student Michael Culbert- studies of the same pathways in humans and
Henry has studied inositol me- son used the mutagenic agent ethyl other eukaryotes.
tabolism in the yeast Saccharomyces methanesulfonate to generate more
cerevisiae since the 1970s. “I focused than 50 S. cerevisiae mutants de-
on the phospholipids and the metab- fective in inositol biosynthesis. This the late 1980s and early 1990s and
olites that regulate their formation,” mutant strain collection provided a now recognized as Classics, Henry
she said. “Inositol turned out to be resource to launch investigations into and colleagues at Albert Einstein
the strongest regulatory metabolite the genes involved in inositol and College and at Carnegie Mellon
of these pathways.” phospholipid metabolism. University reported the sequence
Early in her career, Henry chose In a 1981 JBC paper, Henry and genetic analysis of the INO1
to work with S. cerevisiae, she said, and co-author Thomas Donahue gene along with its regulation by a
because it is easier to study inositol reported the first purification and transcriptional repressor and two
and phospholipids in this organism characterization of yeast myo-inosi- transcriptional activators.
than in more complex eukaryotes. tol-1-phosphate synthase, or Ino1, In the first of these papers,
an enzyme that catalyzes a reaction Henry and Margaret Dean–Johnson
Making a mutant resource that yields inositol 1-phosphate, an sequenced the cloned INO1 gene
Yeast species have been a work- immediate precursor to free inositol. and also determined the amino acid
horse for scientists since the dawn of The two scientists also mapped sequence of the purified protein. This
modern research. Their widespread its gene to a locus called INO1 in analysis uncovered an open reading
use in fermentations led to the coin- the yeast genome and developed frame, or ORF, as a prime candidate
age of the term “enzyme” (Greek for antibodies for specific detection for encoding the entire enzyme.
“in yeast”). S. cerevisiae grows rap- of Ino1, laying the groundwork When they disrupted the pre-
idly in culture as single cells, a boon for more detailed biochemical and dicted INO1 ORF in yeast cells, the
for investigating eukaryotic biochem- genetic studies. researchers found that the cells did
istry. The species can be maintained not express the Ino1 protein and
stably in the haploid state, and its The first classic grew only when supplied with inosi-
genes can be manipulated easily. In three JBC papers published in tol from the growth medium.
10 ASBMB TODAY MAY 2020JOURNAL NEWS
Their findings showed that the OPI gene in the yeast genome, uncovering how phospholipid syn-
INO1 gene encodes myo-inosi- cloned and sequenced it, and identi- thesis is regulated in eukaryotes.
tol-1-phosphate synthase in yeast and fied several features of the predicted
made available the full-length nucleo- Opi protein sequence, including a A ladder for research
tide and amino acid sequences of this leucine repeat and polyglutamine Looking back, Henry says that
pivotal phospholipid enzyme. stretches present in many other regu- mentorship by Seymour Fogel and
In keeping with earlier findings latory proteins. Alec Keith laid the foundation for her
of the Henry lab that expression of The paper defined an important career. Besides sharing their expertise
the Ino1 enzyme is transcriptionally regulatory mechanism controlling in genetics and biochemistry, they
regulated, their work revealed several INO1 expression. It also provided gave Henry critical material support
conserved short DNA motifs in the critical momentum for identifying an to get her work off the ground.
5’ promoter region of the INO1 gene important regulatory DNA element, “I was really lucky that they were
that likely were bound by transcrip- the inositol-sensitive upstream not the kind of people who wanted
tional regulators. activation sequence. This element is me to (work exclusively) on their hot
Henry next set her sights on present in the promoters of genes for project,” she said. “They were willing
deciphering the regulation of INO1 biosynthesis of phospholipids and the to let me come into the laboratory
expression by inositol and another lipid triacylglycerol. and use their materials to do the
phospholipid precursor, choline. The third Classics paper further things that I wanted to do.”
Using various INO1 promoter con- elucidated the regulatory circuit that Moreover, although she was
structs fused to the E. coli lacZ gene controls phospholipid biosynthe- working with yeast, she secured fund-
to measure the promoters’ activities, sis in yeast. Henry and colleagues ing through agencies that typically
her team pinpointed the main regula- demonstrated that the yeast proteins support mainly medical research.
tory regions in the INO1 promoter. Ino2 and Ino4 form a heterodimeric “I didn’t have any trouble getting
In particular, the team found a complex that binds and activates support from the National Institutes
region that appeared to be bound by the INO1 promoter and delineated of Health, because of the connec-
a transcriptional repressor, Opi1, they the binding sites of the Ino2–Ino4 tion with lipid metabolism in other
had previously identified. complex on this promoter. eukaryotic organisms,” she said.
The paper was the first to describe This investment paid off. “Many
The regulatory circuit a basic helix-loop-helix, or bHLH, of the genes that I worked on were
In the second Classics paper, heterodimeric transcription factor in homologous to those in other eu-
Henry and colleagues mapped the yeast and represented a milestone in karyotes, providing a ladder for other
people to find the (corresponding)
genes in other organisms,” Henry
ASBMB TODAY
said.
Martin J. Spiering
(mspiering@asbmb.org)
is the technical editor at
the Journal of Biological
The sugar alcohol myo-inositol is a signaling compound and a ubiquitous precursor to phospholipids Chemistry. Follow him on
Twitter @spieringmj.
and many other important structural and signaling metabolites.
MAY 2020 ASBMB TODAY 11JOURNAL NEWS
Cow born in Japan after removal,
replacement of placental cells
By John Arnst
R
esearchers at Hokkaido Universi-
COURTESY OF NANAMI KOHRI/ HOKKAIDO UNIVERSITY
ty have found that cow embryos
from which placenta-forming
cells had been removed can regrow
those cells, form a placenta and
successfully gestate. The scientists
recently published their results, which
provide insight into the regenerative
capacity of mammalian embryos, in
the Journal of Biological Chemistry.
All mammalian embryos follow
the same blueprint in the first week of
development: After being fertilized,
a zygote divides into two cells, which Scientists in Japan removed placenta-forming cells from a bovine embryo, but it was able to regrow
quickly become four, eight, then 16 those cells, form a placenta and successfully gestate. It is now this healthy 23-month-old cow. The
cells that specialize into an inner cell researchers named the cow Matoryona because as an embryo it resembled a Russian matryoshka
mass and outer cells that are known nesting doll.
individually as trophoblasts and col-
lectively as the trophectoderm. Laboratory of Animal Breeding and the weaker regenerative capacity.
Nanami Kohri, the lead author Reproduction previously had isolated Kohri and colleagues plan to
on the paper, was intrigued by the bovine inner cell masses from embry- investigate what drives the differenc-
fact that mouse embryos in which the os at the early blastocyst stage to find es in embryonic protein expression
trophoblasts — which differentiate where the genes that give rise to the among mammals as they continue to
to form the placenta — had been trophectoderm were being expressed. monitor their calf, which is now 23
removed were much less successful in Other groups had shown that cells months old and healthy.
regenerating a placenta than bovine positioned at the outer margin of “It has been suggested that the
embryos that also had trophoblasts the inner cell mass could be trans- molecular basis of determining
removed. formed into trophectoderm in mouse cellular divisions and localization in
“Although isolated inner cell embryos. development differs among species,”
masses in both mice and cattle To understand why the bovine Kohri said. “In the future, we will
underwent trophectoderm regenera- embryos had more success regener- have to use our experimental system
tion, they were significantly different ating placental cells than the murine to evaluate trophectoderm regener-
in terms of regeneration efficiency, embryos, the researchers at Hokkaido ation from the reformed inner cell
marker protein distribution and University investigated the expression masses in mice and cattle.”
expression status of key genes,” he of the gene SOX17, which creates a DOI: 10.1074/jbc.RA119.010746i
said. “Surprisingly, a calf was success- protein that regulates cell specializa-
fully delivered after the transfer of tion in development. They found that John Arnst (jarnst@asbmb.
the reformed inner cell mass to the the expression of SOX17 varied sig- org) is an ASBMB Today
science writer. Follow him
surrogate mother, but no descendants nificantly between the two species and on Twitter @arnstjohn.
were obtained from reformed inner was localized to the trophectoderm
cell masses in mice.” cells that had been originally absent in
Kohri and his colleagues at the murine embryos, which might explain
12 ASBMB TODAY MAY 2020JOURNAL NEWS
How is myelin made?
Understanding the protective coating on neurons may inform future therapies
By Nuala Del Piccolo
M
JENNIFER SIOW
yelin is the protective lipid
sheath wrapped around a
nerve. It functions as an insula-
tor, akin to the protective coating on
a wire, speeding up electrical trans-
mission of signals along a neuron.
Myelin also plays a role in maintain-
ing the health of neurons. Myelin
function is dysregulated in many
neurological disorders, including
multiple sclerosis.
Oligodendrocytes are the my-
elin-producing cells of the central
nervous system. The myelin sheath
around a neuron is part of an oligo-
dendrocyte’s plasma membrane, and
a single oligodendrocyte can myelin-
ate as many as 50 neurons. During
myelination, an oligodendrocyte
stretches out tubes of membrane in
search of a neuron. When it finds
one, it sends the necessary building
materials down the tubes and, still
operating from a distance, assembles
a myelin sheet around the neuron.
Composition, number of wraps and
total coverage all matter. A myelin-
ated neuron that loses its coating
cannot transmit electrical signals
properly, leading to loss of mus-
cle control and other neurological
problems.
The myelin sheath is mostly
made of lipids, including sphingo-
lipids, which are critical to myelin’s
structure and function. The enzyme
serine palymitoyltransferase, or SPT,
produces the backbone of all sphin-
golipids, and the membrane-bound
protein ORMDL monitors sphingo- This artist’s rendition shows neurons with (bottom) and without (top) a myelin
lipid levels and regulates SPT activity. sheath. The neuron with a myelin sheath functions at full capacity, while a neuron
ORMDL’s activity must be precise: without myelin is unhealthy. Oligodendrocytes are depicted in red.
MAY 2020 ASBMB TODAY 13JOURNAL NEWS
Too little sphingolipid production during myelination, Wattenberg and measurable, but the team deduced
impedes myelination, and too much Sato–Bigbee’s team worked with that ORMDL isoform expression
can be toxic. newborn rat brains, because peak varies over time. These findings pave
Binks Wattenberg, a professor of myelination occurs directly after the way for future experiments.
biochemistry and molecular biology birth. Only one in five cells in the “The control of sphingolipid
at Virginia Commonwealth Univer- brain is an oligodendrocyte, so the biosynthesis is key to myelination,
sity, studies membrane biogenesis team isolated these myelin-produc- and understanding how this process
and now focuses on lipid biogenesis. ing cells for their experiments. works will enable us to alter it in
“I am very curious about how the The researchers found that a future treatments,” Wattenberg said.
cell knows when to make sphingo- large portion of the sphingolipids “Our pie-in-the-sky goal is to under-
lipid and when to stop,” Wattenberg present in oligodendrocytes during stand sphingolipid biosynthesis so
said. “I think ORMDL might be the myelination have an atypically long well that we can reprogram oligoden-
key to answering that question.” backbone — an 18-carbon chain drocytes and reverse demyelination
Wattenberg’s next-door lab instead of a 16-carbon chain. “The in degenerative myelination diseases
neighbor, Carmen Sato–Bigbee, a 18-carbon chain backbone points to like MS.”
professor in the same department, a change in lipid composition during DOI: 10.1194/jlr.RA120000627
studies myelination, with a focus on myelination, which might explain
oligodendrocytes. The two joined the insulating properties of myelin,”
forces to study the role of sphingo- Wattenberg said. “In future work, we Nuala Del Piccolo is a
lipid biosynthesis in myelination in want to look at the role of each type postdoctoral scholar in the
biomedical engineering
developing brains. They report their of sphingolipid in myelination.”
department at the
recent results in the Journal of Lipid The study also found that SPT University of California,
Research. activity increases for the first few Davis. She earned her
Ph.D. in materials science
To uncover the dynamics of days of myelination and then begins and engineering at Johns
sphingolipid content and synthesis to decrease. ORMDL activity is not Hopkins University.
Upcoming ASBMB events and deadlines
MAY
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14 ASBMB TODAY MAY 2020MAY 2020 ASBMB TODAY 15
JOURNAL NEWS
Review delves into proximity proteomics
By Laurel Oldach
I
n a recent review article in nearby proteins with a chemical tag The second enzyme family, the
Molecular & Cellular Proteomics, that then can be purified. After puri- peroxidases, evolved to convert
Payman Samavarchi–Tehrani and fication, mass spectrometry identifies hydrogen peroxide to water by redox
colleagues in the Gingras lab at Sinai the tagged proteins. chemistry. In the presence of a bio-
Health Systems and the University Most often, the chemical tag is bio- tin–phenol substrate and hydrogen
of Toronto offer an introduction to tin, a cofactor that is key to carboxylase peroxide, they can make a short-lived
proximity-dependent biotinylation, a enzyme activity in several metabolic free radical that reacts with certain
key first step in proximity proteomics. pathways. Two types of enzyme are amino acid side chains, once again
The authors give researchers who are used for proximity-dependent bioti- tagging nearby proteins for later
new to the field information about nylation: peroxidases, used for methods identification.
the natural history of biotinylation such as APEX, and biotin ligases, used As proximity proteomics has
enzymes. They also offer insights into for methods such as BioID. grown in popularity, both types of
the mechanisms of these enzymes and Ordinarily, biotin ligases append enzyme have been the targets of
new perspectives on future proximity biotin to the carboxylases that need extensive engineering and molecu-
SAMAVARCHI–TEHRANI ET AL./MCP
A schematic diagram shows the proximity proteomics workflow. A bait protein is tagged with a biotinylation enzyme (center of concentric circles),
which allows for covalent labeling of proteins in its vicinity with a reactive biotin intermediate. Then the researcher lyses the cells and uses streptavidin
to extract biotin-tagged proteins, digests those proteins and uses mass spectrometry to determine their identity.
proteomics experiments. it as a cofactor. Biotin ligases found lar evolution to coax them toward
Traditional proteomics can pro- in cells have high specificity for the activity profiles users want. The
vide information about the quanti- their substrate proteins, but certain authors review the available enzymes
tative contents of a cell or tissue, but mutations reduce that specificity by and discuss experimental design con-
it sacrifices much information on the decreasing the ligase enzyme’s affinity siderations, such as choice of control
spatial organization of proteins with- for a reactive intermediate. Such conditions and how to get rid of what
in cells. Since protein activity often mutants lose their grip on the cofac- they call “frequent flyer” proteins that
depends on location and interactions tor and can release a reactive biotin often are isolated nonspecifically.
with other proteins, researchers have that can bind the next amine group DOI: 10.1074/mcp.R120.001941
developed approaches such as prox- it encounters — often on a nearby
imity proteomics to obtain informa- protein. When researchers pull down Laurel Oldach (loldach@
tion about the environs of a protein biotin after this reaction occurs, they asbmb.org) is a science
writer for the ASBMB. Follow
of interest. Proximity proteomics can determine what proteins were her on Twitter @LaurelOld.
methods developed in the past 10 localized in the neighborhood of the
years depend on fusing the protein of biotin ligase and, by extension, the
interest to an enzyme that will label protein it was tethered to.
16 ASBMB TODAY MAY 2020JOURNAL NEWS
From the journals
By Latavia Hill, Kian Kamgar-Parsi & Anand Rao
We summarize a selection of various iron pathways to acquire iron HDL have failed. According to Ka-
recent papers from the Journal of and effectively compete with other trin Niisuke and a joint team from
Biological Chemistry, the Journal bacterial species. Tufts University and the Centers for
of Lipid Research and Molecular & DOI: 10.1074/mcp.RA119.001829 Disease Control and Prevention, our
Cellular Proteomics. limited knowledge of the composi-
A new therapeutic target tion–function relationship in HDL
How a pathogen for inflammatory CRMO particles could be a reason for those
adapts to survive The autoinflammatory bone failures. In new research published
Pseudomonas aeruginosa, a disease chronic recurrent multifocal in the Journal of Lipid Research,
Gram-negative opportunistic patho- osteomyelitis, or CRMO, is mediated the researchers sought to elucidate
gen, causes burn wound infections by the inflammatory cytokine inter- better the role of lipid composition
and pneumonia. It produces sidero- leukin 1 beta, or IL-1beta, a known in HDL function.
phores to acquire iron for survival driver of bone lesions in CRMO. Using samples from CHD
and can express various iron-uptake To develop effective therapies for patients and healthy controls,
pathways with specific TonB-depen- the treatment of CRMO, research- Niisuke and colleagues were able to
dent transporters, or TBDTs, which ers need to better understand the separate out large and small HDL
allows it to use exosiderophores pro- signaling events that result in high particles and characterize their
duced by other bacterial species. levels of IL-1beta. Tejasvi Dasari lipid compositions. Compositional
Quentin Perraud of the Uni- and colleagues at St. Jude Children’s differences were found between the
versity of Strasbourg and a team of Research Hospital used mutant large and small particles in all patient
researchers in France recently pub- mouse strains, immunoblotting groups, but differences in both lipid
lished work in the journal Molecular and microcomputed tomography composition and the function of
& Cellular Proteomics focused on to reveal a role for the nonreceptor apoA-1 between healthy subjects and
understanding how P. aeruginosa se- spleen tyrosine kinase, or SYK, in the CHD patients were primarily in the
lects, regulates and adapts its expres- signaling cascade, resulting in elevat- large particles. These large particles
sion levels of iron-uptake pathways ed IL-1beta levels. influence cholesterol control through
in response to environmental stimuli. Their work, published in the the scavenger receptor class B type
In this study, the researchers showed Journal of Biological Chemistry, 1 pathway; thus, this research not
that P. aeruginosa uses different suggests that SYK may be a thera- only provides a deeper understand-
siderophores at different chelating peutic target for the treatment of ing of the composition–function
efficiencies, with catechol sidero- CRMO. relationship of HDL but also could
phores being the most powerful. DOI: 10.1074/jbc.RA119.010623 inform development of treatments
They also showed that expression of for CHD.
the TBDTs varied when P. aeruginosa Good cholesterol gone bad DOI: 10.1194/jlr.RA119000258
was grown in three different media, in coronary heart disease
which suggests that different pheno- High-density lipoprotein, com- A new drug’s role in
typic patterns exist. This work also monly called HDL, often is referred cholesterol trafficking
shows that P. aeruginosa can detect to as “good cholesterol” for the Niemann–Pick type C disease,
the presence of epithelial cells and beneficial role it plays in maintaining or NPC, is a fatal genetic disorder
adjust gene expression accordingly. cholesterol balance in the body. HDL that results in the accumulation of
These findings show that P. aerugi- also has been shown to mediate cor- excess cholesterol in lysosomes, a key
nosa senses changes in its environ- onary heart disease, or CHD, but so waste disposer in cells. While there
ment and alters the expression of its far clinical trials of drugs that target are no approved drugs to treat NPC,
MAY 2020 ASBMB TODAY 17JOURNAL NEWS
Shedding light on lipid raft formation
A major recent advance in our understanding of cellular mem- team from Stony Brook University led by Guangtao Li write that they
branes is the discovery of so-called lipid rafts or nanodomains. These were able to circumvent this common shortcoming. The researchers
domains are membrane regions enriched for certain lipids and proteins used a technique called Förster resonance energy transfer, which
and are predicted to be important for a range of biological processes. sensitively can detect low nanometer distances between labeled lipids
With many questions outstanding on their function, structure and otherwise undetectable by normal microscopy. With this technique, the
formation, nanodomains are the subject of significant research in the researchers detected nanodomain formation in GPMVs at temperatures
field of lipid membranes. at least as high as 38 degrees, where larger-scale separations disappear,
Attempts to study these nanodomains, however, have been ham- confirming that nanodomains occur at physiological temperatures. Li
pered by difficulties in detection, leading many studies to use model and colleagues also were able to modulate the lipid and cholesterol
membranes called giant plasma membrane vesicles, or GPMVs, at compositions of their GPMVs, confirming that differing membrane
low temperatures (0°C to 20°C). These conditions induce larger-scale compositions could influence domain formation.
membrane ordering that can be detected by basic light microscopy With the importance of nanodomains in normal cellular function,
techniques. While such studies have been valuable, researchers remain the ability to study these domains under more biologically relevant con-
concerned that low temperature studies on these large-scale phase ditions is invaluable. Future research not only could expand our scientif-
separations do not represent accurately the behavior of smaller nano- ic knowledge of nanodomain behavior but potentially allow scientists to
domains in human cells under physiological conditions. target and manipulate these domains for new drugs and treatments.
In a recent paper published in the Journal of Lipid Research, a DOI: 10.1194/jlr.RA119000565
— Kian Kamgar–Parsi
ARTUR JAN FIJAŁKOWSKI/WIKIMEDIA COMMONS
Lipid bilayers often are
separated into disordered
regions (1) and ordered
nanodomains (2), with
these relatively poorly
understood nanodomains
serving important biological
functions.
2-hydroxypropyl-beta-cyclodextrin, with CD. occurred. These findings provide a
or CD, is a promising molecule In a paper published in the Jour- more complete picture of CD’s role
currently in human trials. However, nal of Lipid Research, Feltes and in mediating cholesterol homeostasis
researchers know little about the her colleagues were able to confirm in NPC and could prove useful in
details of CD’s mechanism of action. CD-dependent decrease in lysosomal CD’s continued development as a
Previous studies have shown CD to cholesterol levels. Rather than re- drug for this disease.
decrease lysosomal cholesterol ac- moving this cholesterol from the cell,
cumulation but also have shown no however, CD promoted transfer of Using a fusion protein
effect on total cellular cholesterol. To lysosomal cholesterol to the plasma to make fat levels fall
reconcile these seemingly disparate membrane. From there, cholesterol Lipoprotein lipase, or LPL, is an
findings, McKenna Feltes and a team either would exchange with lipopro- enzyme that metabolizes circulating
from Washington University labeled tein-bound cholesterol or be routed triglycerides. When LPL activity is
cholesterol and tracked its movement to the endoplasmic reticulum for compromised — as is the case in
through model NPC cells treated processing if excess accumulation familial chylomicronemia syndrome,
18 ASBMB TODAY MAY 2020You can also read
