Case School of Medicine faculty member wins AAAS Young Scientist
Award for ‘Holy Grail’ discovery
Valadkhan identified “a relic from the
RNA world” and
proved its catalytic potentiald
March 1, 2005 | For more information: George
Stamatis 216-3635
 It was a molecular riddle that had baffled scientists for two decades,
but Saba Valadkhan, M.D., Ph.D., solved it. Valadkhan, an assistant
professor in the Case Western Reserve University School of Medicine’s
Center for RNA Molecular Biology, correctly identified “a relic
from the RNA world” and proved its catalytic potential, earning
the 2004 Young Scientist Award from the American Association for the
Advancement of Science (AAAS) in the process. The $25,000 award, supported
by GE Healthcare and the journal Science, was presented Feb. 11 at the
annual meeting of the AAAS, the world’s largest general science
society and publisher of Science.
“Saba’s discovery was akin to finding the Holy Grail of
the splicing catalysis field,” said James L. Manley, Ph.D., JC
Levi Professor of Biological Sciences at Columbia University in New
York City, where Valadkhan initiated her research as a graduate student;
Manley supervised her work. “Obtaining catalytic activity from
purified small nuclear RNAs had been attempted many times over the years
in many of the major splicing labs around the world, which underscores
the significance of her accomplishments,” he said.
Timothy W. Nilsen, Ph.D., professor and director of the Case School
of Medicine’s Center for RNA Molecular Biology where Valadkhan
is on faculty, said, “This award is particularly significant because,
from a worldwide pool of talented investigators, it recognizes a single
junior scientist.”
DNA, life’s genetic blueprint, drives most modern biological
events, along with proteins, and generally is considered the primary
repository for genetic information. Many scientists, however, believe
that DNA’s modern-day messenger, RNA, played a far more dominant
role in ages past, before handing over most of its biological functions
to DNA and proteins.
To rule the biological world, RNA needed to serve as an enzyme, capable
of catalyzing a wide range of chemical reactions, explained Valadkhan.
In fact, pre-messenger RNA splicing plays an important role in many
aspects of cell growth control, differentiation and disease. This splicing
reaction is catalyzed by the most complex cellular machine known, the
spliceosome, a big ribonucleoprotein particle located within the cell
and composed of some 300 proteins and five RNAs.
But where and how does the spliceosome’s catalytic activity occur?
For two decades, scientists had been investigating
two of the spliceosome’s
small nuclear RNAs (snRNAs), called U2 and U6,
as the most likely candidates —without
any proof until Valadkhan’s relentless quest for the answer.
Her graduate research involved building the spliceosome’s active
site from scratch, by bringing together U2 and U6, then proving their
catalytic action by producing a novel RNA species, RNA X. More recent
study has yielded another interesting product, RNA Y, which still is
being characterized. Collectively, Valadkhan said, her findings “proved
that the spliceosome is an RNA enzyme and a relic
from the RNA world.”
Valadkhan “is an enormously talented young scientist with all
the qualities — intelligence, dedication and imagination — that
it takes to make significant and meaningful discoveries in the field
of molecular biology,” Manley said of his former student. “Strikingly,
with careful planning, experimentation and persistence,
Saba succeeded in establishing that purified U2 and U6 snRNAs do indeed
have catalytic activity and can promote a reaction related to the first
step of splicing.”
While finally proving the catalytic potential of the two spliceosomal
snRNAs, Valadkhan also developed a powerful new tool for further investigations
of this crucial cellular machine and its evolution.
Valadkhan was born and raised near Tehran, Iran. She attended medical
school at the Iran University of Medical Sciences from 1989 to 1996
and in 1993 placed fourth in the country in the nationwide Basic Sciences
Medical Board Exam.
She switched to science partly in hopes of increasing the impact of
her contributions. “If you want to have a real impact on health
care, you can be a doctor and treat people, one by one,” she said, “or
you can become a scientist and make discoveries
that could someday tell us something about disease, for example. So
I thought that I could potentially have an impact on many more people
as a scientist.”
Valadkhan moved
to the United States in 1996 to attend graduate
school at Columbia. While there, she received awards for both teaching
and research. Her thesis was recognized with a Harold Weintraub Award
from the Fred Hutchinson Cancer Research Center in Seattle. In 2004,
the same year she joined Case Western Reserve University, she was named
a Searle Scholar.
“The science prize, together with Dr. Valadkhan’s Searle
Scholar award, attest to her remarkable accomplishments as a graduate
student,” said Nilsen of the RNA Center. “We are truly fortunate
to have her on our faculty, where I am sure she
will continue to make fundamental and important
contributions to understanding basic mechanisms of gene expression.”
The Young Scientist Award recognizes exceptional thesis work by molecular
biologists in the early stages of their careers.
Applicants for the 2004 award earned their Ph.D.s
in 2003 and submitted 1,000-word essays based on their dissertations.
The essays were judged on the quality of research and the applicants’ ability to articulate how their
work would contribute to the field of molecular biology, which investigates
biological processes in terms of the physical and chemical properties
of molecules in a cell. A panel of judges selected Valadkhan’s
essay, “Construction of a Minimal, Protein-Free Spliceosome,” as
the 2004 grand prize winner and also selected four
regional winners, in North America, Europe, Japan,
and All Other Countries categories.
An extended interview with Valadkhan is available online
at http://www.aaas.org/news/releases/2005/0210ys-Valadkhan.shtml.
About Case Western Reserve University
Case is among the nation's leading research institutions. Founded in 1826
and shaped by the unique merger of the Case Institute of Technology and Western
Reserve University, Case is distinguished by its strengths in education, research,
service, and experiential learning. Located in Cleveland, Case offers nationally
recognized programs in the Arts and Sciences, Dental Medicine, Engineering,
Law, Management, Medicine, Nursing, and Social Work. http://www.case.edu.
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