Malaria is one of the
world’s most insidious poverty-related diseases. Half a billion
people are infected every year, resulting in over a million fatalities
annually. A team of European researchers from Spain and the UK believes
that more insight into the biology of the parasite will allow for the
design of vaccines with a considerable likelihood of success. The study
has identified a new mechanism in the parasite to help it adapt to
Malaria is transmitted to people and animals by mosquitoes. More than a million people die from the disease every year. Image by Ute Frevert
Plasmodium falciparum is responsible for the most severe forms of human
malaria. Invasion of host red blood cells is an essential step in the
complex life cycle of this parasite. During the process of invasion, P.
falciparum, which appears in the stage of a "merozoite", is exposed to
antibodies from the immune system. As a result, the proteins of the
merozoite that interact with red blood cells are a possible weak point,
and thus a very clear target for the development of vaccines.
Researchers (including Alfred Cortes, who heads a research line in
molecular parasitology in the Genetic Translation Laboratory at IRB
Barcelona, together with a team from London’s National Institute
for Medical Research) have discovered that the parasite has the ability
to switch on and off the expression of some of the proteins it uses to
enter its victim's red blood cells.
They believe that this ability makes the parasite more adaptable when
attempting to invade the cells. Understanding which proteins can be
turned off is important, since vaccines based on single antigens of the
parasite that can be turned off without affecting its growth would have
little chance of inducing protective immunity.
The scientists have discovered that P. falciparum can activate and
deactivate the expression of 7 genes (of the 30 genes that are known to
be involved in the process of invasion), as well as their corresponding
proteins, without compromising the parasite’s ability to enter
normal or modified red blood cells.
Results have shown that the silencing mechanism operates at the
epigenetic level. This indicates that the parasite stops expressing a
certain gene without changing the underlying genetic information, and
that the mechanism is flexible, adaptable and easily reversible.
According to scientist Alfred Cortes, this indicates that the parasite
can re-express the proteins relatively easily when infecting another
individual, or silence them again in a different host.
'We are talking about a very sophisticated adaptation system to the
host and our challenge is to find out how this mechanism works at
molecular level; that is, we need to figure out which specific
epigenetic modifications are associated to activity or to silencing,'
'Thanks to this study we have been able to identify seven genes in four
different genetic families that may be silenced in a specific P.
falciparum strain; we suspect, however, that other genes may also be
silenced, and we'll follow this up with studies on wild strains of the
The research results have also shown that none of the proteins acting
alone would be suitable candidates in vaccine development, since the
parasite will continue to succeed in invading the red blood cell to
continue its life cycle. Although this is a promising breakthrough, the
team emphasises the need to harness more knowledge in order to reach
the ultimate objective of an effective vaccine.
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