RESEARCHERS DISCOVER HOW MALARIA PARASITE DISPERSES FROM RED BLOO D CELLS

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U.S. Department of Health and Human Services 
NATIONAL INSTITUTES OF HEALTH 
NIH News 
National Institute of Child Health and Human Development (NICHD)
http://www.nichd.nih.gov/

EMBARGOED FOR RELEASE: Monday, September 19, 2005; 12:00 p.m. ET 

CONTACT: Robert Bock or Marianne Glass Miller, 301-496-5133,
bockr@xxxxxxxxxxxx

RESEARCHERS DISCOVER HOW MALARIA PARASITE DISPERSES FROM RED BLOOD CELLS 

Researchers at the National Institute of Child Health and Human Development
have determined the sequence in which the malaria parasite disperses from
the red blood cells it infects. The National Institute of Child Health and
Human Development is one of the National Institutes of Health. 

The study appears in the September 20 "Current Biology". 

"It's extremely important to learn about all aspects of the malaria
parasite's life cycle," said Duane Alexander, M.D., Director of the NICHD.
"The parasite is growing resistant to the drugs used to treat it, and new
information is essential for developing strategies to protect against the
disease." 

The study supplants earlier theories on how the malaria parasite spreads
from the red blood cells it infects. 

According to the World Health Organization, malaria kills more than 1
million people a year. (See
http://mosquito.who.int/cmc_upload/0/000/015/372/RBMInfosheet_1.htm.) 

Malaria is caused by four species of the parasite "Plasmodium", the most
common and deadly of which is "Plasmodium falciparum". "P. falciparum"
spends part of its life cycle in the salivary glands of mosquitoes and is
transmitted to human beings through the bite of infected mosquitoes. The
parasite infects red blood cells. Called a merozoite at the stage of its
life when it infects red blood cells, the parasite multiplies inside the
cell, until the cell ruptures and releases them. The newly released
merozoites infect still other cells, and the process begins again. 

To conduct the study, the researchers stained red blood cells infected with
"P. falciparum" with two kinds of dye, explained the study's senior author,
Joshua Zimmerberg, M.D., Ph.D., Chief of NICHD's Laboratory of Cellular and
Molecular Biophysics. One dye stained the blood cells green, the other
stained the parasites red. 

In the first stage of the merozoites' release, which the researchers dubbed
the "irregular schizont" stage, the red blood cell resembles a lop-sided
fried egg, with the parasites visible as a sphere near the center of the
cell. (A diagram of the entire sequence appears at
http://www.nichd.nih.gov/new/releases/malaria_graphic.cfm.) The cell's
lop-sided appearance probably results from destruction of the cytoskeleton,
the molecular scaffolding that helps the cell to maintain its rounded shape.


In the next stage, called the "flower" stage, the red blood cell assumes a
roughly spherical shape, covered with rounded structures that resemble the
petals of a flower. Shortly thereafter, the blood cell's membrane appears to
break apart. At roughly the same time, cellular compartments, called
vacuoles, which encase the newly formed merozoites, also break apart. The
entire process has an explosive appearance, dispersing the merozoites some
distance from the cell. 

During the release, Dr. Zimmerberg explained, the cell membrane appears to
collapse inward upon itself and fragment into pieces. 

One previous theory held that the red blood cells and the
merozoite-containing vacuoles inside them swelled and then burst like a
balloon containing too much air. 

"The swelling was an artifact of too much light from the microscope," Dr.
Zimmerberg said. "The cell membrane was light sensitive. When we turned the
light down, we didn't see the swelling." Rather, he said, upon release of
the merozoites, the cell membrane appeared to contract in upon itself. 

Another theory held that the merozoite-containing vacuoles would fuse with
the cell membrane, and then release their contents. 

"But we didn't see any fusion," Dr. Zimmerberg said. 

The third theory held that the cell membrane ruptured, expelling
merozoite-containing vacuoles. Again, however, the researchers observed that
this theory also offered an inaccurate picture, as the vacuoles ruptured at
roughly the same time as the cell membrane. 

Each step in the release process is a potential avenue for new therapies to
treat the disease, Dr. Zimmerberg said. By first understanding how the
parasite brings about each of these steps, it may be possible to find ways
to prevent each step from occurring. 

The NICHD is part of the National Institutes of Health (NIH), the biomedical
research arm of the federal government. NIH is an agency of the U.S.
Department of Health and Human Services. The NICHD sponsors research on
development, before and after birth; maternal, child, and family health;
reproductive biology and population issues; and medical rehabilitation. 

The National Institutes of Health (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. It is the primary Federal agency
for conducting and supporting basic, clinical, and translational medical
research, and investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs, visit
http://www.nih.gov.
  
##
 
This NIH News Release is available online at:
http://www.nih.gov/news/pr/sep2005/nichd-19b.htm.

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