[net-gold] MEDICAL: DISEASES: MALARIA : MEDICAL: RESEARCH : MEDICAL GENETICS : BIOLOGY : INSECTS: Scientists Find Genetic Basis for Key Parasite Function in Malaria
- From: "David P. Dillard" <jwne@xxxxxxxxxx>
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- Date: Sun, 21 Aug 2011 09:09:57 -0400 (EDT)
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MEDICAL: DISEASES: MALARIA :
MEDICAL: RESEARCH :
MEDICAL GENETICS :
BIOLOGY : INSECTS:
Scientists Find Genetic Basis for Key Parasite Function in Malaria
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Date: Thu, 26 May 2011 12:48:48 -0400
From: "NIH OLIB (NIH/OD)" <olib@xxxxxxxxxx>
To: NIHPRESS@xxxxxxxxxxxx
Subject: Scientists Find Genetic Basis for Key Parasite Function
in Malaria
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U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Allergy and Infectious Diseases (NIAID)
http://www.niaid.nih.gov/
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Embargoed for Release: Thursday, May 26, 2011, Noon EDT
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CONTACT:
Anne A. Oplinger
(301) 402-1663
e-mail:
aoplinger@xxxxxxxxxxxxx
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SCIENTISTS FIND GENETIC BASIS FOR KEY PARASITE FUNCTION IN MALARIA
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NIH researchers show parasites create feeding ion channels in blood cells
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Snug inside a human red blood cell, the malaria parasite hides from the
immune system and fuels its growth by digesting hemoglobin, the cell's
main protein. The parasite, however, must obtain additional nutrients from
the bloodstream via tiny pores in the cell membrane. Now, investigators
from the National Institute of Allergy and Infectious Diseases (NIAID),
part of the National Institutes of Health, have found the genes that
malaria parasites use to create these feeding pores.
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The research was led by Sanjay A. Desai, M.D., Ph.D., of NIAID's
Laboratory of Malaria and Vector Research. In 2000, Dr. Desai
co-discovered the primary type of feeding pore on parasite-infected blood
cells, an ion channel known as the plasmodial surface anion channel (PSAC)
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http://www.niaid.nih.gov/news/newsreleases/2000/Pages/malariafeed.aspx
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Ion channels are pore-forming proteins that allow the movement of calcium,
sodium and other particles into or out of the cell. A report of the
team's new findings, which build on this original discovery, is now online
in Cell.
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"Despite recent progress in controlling malaria worldwide, the disease
continues to kill more than 700,000 people, primarily young children,
every year," said NIAID Director Anthony S. Fauci, M.D. "Dr. Desai and his
colleagues have discovered the genetic basis of a fundamental aspect of
malaria parasite biology, and in doing so, they have opened up potential
new approaches to developing antimalarial drugs."
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Scientists have known for decades that malaria-infected red blood cells
have greater nutrient uptake than non-infected cells, presumably to
support parasite survival and growth, noted Dr. Desai. But, he added, "It
was debated whether the parasite co-opts existing human channels or uses
its own proteins to remodel the red blood cell membrane."
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To answer this question, the NIAID team screened nearly 50,000 chemicals
for their ability to block nutrient uptake by cells infected with either
of two genetically distinct lines of Plasmodium falciparum malaria
parasites, HB3 and Dd2. Most chemicals were equally active against the two
lines, but one, ISPA-28, stood out because it was 800 times more active
against the nutrient channels of Dd2-infected red blood cells than against
those of HB3-infected cells.
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If the PSAC protein is made by the parasite, the scientists reasoned, the
strikingly different effects of ISPA-28 on the two lines may reflect
genetic differences. To explore this possibility, the investigators
measured how well ISPA-28 inhibited PSAC activity in daughter parasites
resulting from a genetic cross between the HB3 and Dd2 lines. They found
that most daughter parasites made channels that were identical to those of
one or the other parent, indicating that parasite genes play an important
role. The inheritance pattern of ISPA-28 action on channels led the
researchers to chromosome 3, where they found two parasite genes, clag3.1
and clag3.2, that appear to encode the PSAC protein.
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This genetic evidence was bolstered when they showed that individual
parasites express either the clag3.1 gene or the clag3.2 gene, but not
both simultaneously. They found that switching between the two genes
produced changes in PSAC behavior that could be predicted. Malaria
parasites use gene switching as a way to protect essential proteins from
attack by the immune system, Dr. Desai explained.
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"We were surprised to discover a role for clag genes in PSAC activity,"
said Dr. Desai. This family of genes, which do not look like other ion
channel genes, was previously thought to be involved in helping infected
cells adhere to the inner lining of blood vessels. Clag genes are found in
all species of malaria parasites, noted Dr. Desai, and this fact, along
with the discovery that the parasites can choose between one of two
channel genes to ensure nutrient uptake, strongly suggest that PSAC is
required for parasite survival within red blood cells.
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The discovery of parasite genes required for PSAC activity opens up
several new research directions, said Dr. Desai. For example, development
of antimalarial drugs that target these channels could be accelerated. The
NIAID team has already found PSAC inhibitors that kill malaria parasites.
Dr. Desai's team also is exploring how the PSAC protein is transported
from the parasite to the red blood cell membrane, as preventing this
transport may be another way to kill malaria parasites.
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In addition to funding from NIAID's Division of Intramural Research, this
study was supported by Medicines for Malaria Venture, a not-for-profit
public-private partnership headquartered in Switzerland.
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NIAID conducts and supports research -- at NIH, throughout the United
States, and worldwide -- to study the causes of infectious and
immune-mediated diseases, and to develop better means of preventing,
diagnosing and treating these illnesses. News releases, fact sheets and
other NIAID-related materials are available on the NIAID Web site at
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http://www.niaid.nih.gov
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About the National Institutes of Health (NIH): NIH, the nation's medical
research agency, includes 27 Institutes and Centers and is a component of
the U.S. Department of Health and Human Services. NIH is the primary
federal agency conducting and supporting basic, clinical, and
translational medical research, and is investigating the causes,
treatments, and cures for both common and rare diseases. For more
information about NIH and its programs, visit
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http://www.nih.gov
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REFERENCES:
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W Nguitragool et al.
Malaria parasite clag genes determine nutrient uptake
channel activity on infected red blood cells
Cell
DOI: TO COME
(2011)
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SA Desai et al.
A voltage-dependent channel involved in nutrient uptake by
red blood cells infected with the malaria parasite
Nature
406:1001-05
(2000)
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NOTE TO REPORTERS:
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A video abstract about the Cell paper will be available online at
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http://www.cell.com
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after Noon on May 26.
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##
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This NIH News Release is available online at:
http://www.nih.gov/news/health/may2011/niaid-26.htm
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Sincerely,
David Dillard
Temple University
(215) 204 - 4584
jwne@xxxxxxxxxx
http://daviddillard.businesscard2.com
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