pear, and their genetic instruc-
tions for protein production are
altered. The Institute team —
consisting of Dr. Michael 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 transcription of DNA to RNA
— control of protein gene ex-
pression in Leishmania takes
place only after the RNA is
"This finding," Dr. Shapira
says, "gives us a basis for genet-
ically engineering a non-virulent
species of Leishmania that is
sensitive to body heat, which
could be used for vaccination
12 million victims
In 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
'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
ofleishmaniasis worldwide, with
700,000 new cases reported each
year. There is no effective vac-
cine against the disease, and
chemotherapy — based on drugs
such as Pentostam and Glucan-
time — is toxic and often harm-
Dr. Shapira holds the Helena
Rubinstein Career Development
Chair in Cancer Research for
Outstanding Women Scientists.
Her research is being supported
by the MacArthur Foundation,
the Nathan Fund for Dermato-
logical Research and the US-Is-
rael Binational Science
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