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tacking internal organs in an of-
ten fatal form of the disease.
Upon moving from insects to
mammals, Leishmania must
adapt to an environment with a
radically different temperature
and chemical composition. In the
course of this adaptation their
lashlike appendages used for
motion — called flagella — dis-
appear, and their genetic in-
structions for protein production
are altered. The Institute team
— consisting of Dr. Michal Shapi-
ra, postdoctoral fellow Rady Aly
and doctoral student Miriam
Argaman of the Institute's De-
partment of Membrane Research
and Biophysics — has now pin-
pointed where and how these ge-
netic alterations occur.
The scientists focused on the
genes that encode for heat-shock
proteins, compounds endowing
Leishmania with tolerance for
the higher temperature of their
new mammalian environment as
compared to the temperatures
prevailing in sandflies. Through
genetic manipulation the Weiz-
mann team mapped the RNA se-
quences involved in regulating
the synthesis of these proteins.
They found that unlike heat-
shock gene expression in all oth-
er organisms — whose regulation
depends mainly on the tran-
scription of DNA to RNA — con-
trol of protein gene expression in
Leishmania takes place only af-
ter the RNA is formed.
"This finding," Dr. Shapira
says, "gives us a basis for genet-
ically engineering a non-virulent
species of Leishmania that is sen-
sitive to body heat, which could
be used for vaccination purpos-
es."
In a related study the re-
searchers designed a novel ap-
proach enabling them to
determine how the parasites con-
trol the expression of a set of
genes encoding for a small RNA
molecule well-known for its key
role in the parasites' regulatory
mechanisms.
"While gene regulation in non-
protozoan organisms has been
largely clarified in recent years,"
Dr. Shapira says, "very little is
known about this process in
Leishmania and parasitic proto-
zoa of the same family."
There are 12 million victims of
leishmaniasis worldwide, with
700,000 new cases reported each
year. There is no effective vaccine
against the disease, and
chemotherapy — based on drugs
such as Pentostam and Glucan-
time — is toxic and often harm-
ful.
Dr. Shapira holds the Helena
Rubinstien Career Development
Chair in Cancer Research for
Outstanding Women Scientists.
Her research is being support-
ed by the MacArthur Founda-
tion, the Nathan Fund for
Dermatological Research and the
US-Israel Binational Science
Foundation.
❑
Robert I. Gans, M.D.
Gary D. Bergman, M.D.
Jeffrey S. Katz, M.D.
David S. Grey, M.D.
Ronald H. Bergman, M.D.
Leonard H. Lerner, M.D.
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