Embargoed until 2:00 p.m. EDT
NSF PR 01-47 - May 30, 2001
Media contact:
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Tom Garritano, NSF
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(703) 292-8070
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tgarrita@nsf.gov
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Program contact:
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Monica Nadler,
BIDMC/HMS
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(617) 667-3705
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mnadler@caregroup.harvard.edu
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This material is available primarily
for archival purposes. Telephone numbers
or other contact information may be out
of date; please see current contact information
at media
contacts.
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Secret Channel Holds Key to Metabolic Mysteries
Researchers use cloned gene to reveal how cells transmit
vital elements
Biologists have discovered a "channel" that allows
key elements such as calcium and magnesium to enter
living cells. The research, published in the May 31
issue of the journal Nature, provides new insight
into the link between metabolic activity and a cell's
ability to regulate its levels of key elements. This
connection has been poorly understood despite its
importance to human health.
The work was possible because Monica Nadler of Beth
Israel Deaconess Medical Center (BIDMC) and Harvard
Medical School (HMS) in Boston cloned a particular
gene while supported by a grant from the National
Science Foundation's (NSF) Professional Opportunities
for Women in Research and Education (POWRE).
Three separate teams of scientists, led by Nadler's
BIDMC/HMS colleague Andrew Scharenberg, studied activity
in the product of a gene called LTRPC7, which they
found permits calcium ions to enter cells. In collaboration
with Reinhold Penner of the University of Hawaii,
they discovered that the channel is sensitive to the
presence of a chemical complex of magnesium and a
molecule called ATP. ATP has long been recognized
as the primary energy carrier in living cells. The
channel's sensitivity to the magnesium-ATP complex
reveals a direct link between the LTRPC7 channel's
ability to conduct calcium ions and the cell's energy
level. The discovery of this relationship could have
long-term implications for human conditions such as
hypoxia (oxygen deficiency) and hypoglycemia (sugar
deficiency).
"We had hoped the channel might be capable of passing
calcium ions," Nadler said. "That proved to be the
case. In collaboration with Tomohiro Kurosaki's group
at Kansai Medical University in Osaka, Japan, we discovered
that the gene has another surprising characteristic
-- removing it proves 100 percent lethal to cells."
This is a further indication that the researchers are
onto something important, because lethality shows
that the gene is somehow essential to every cell's
life. The Nature paper is important in part
because it will stimulate a race to determine the
gene's precise functions, and why no cell can live
without it.
"LTRPC7 represents a new family of ion channels that
have yet to be explored," Nadler said. "Importantly,
we don't yet understand how ion channels transmit
elements in relation to metabolic function. LTRPC7's
lethality when lost means it has fundamental importance,
so we need more research to explain it."
The NSF POWRE award helped Nadler keep her research
active while raising two young daughters -- now ages
two and three. "This grant gave me a chance to pursue
my work while I was striving to achieve a critical
balance between building my career and starting my
family," she said.
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