Targeting the biology of the malaria parasite
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 infected individuals.
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,' says Cortes.
'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 parasite.'
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.