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Feminine contribution

Disguise unveiled

Studies on the parasite that causes Chagas’s disease give the 2004 L’Oréal-Unesco award to a Brazilian woman

MICHELINE PELLETIERDedication and luck: in 25 years of researches, Lucia Previato has unveiled the Trypanosoma’s camouflageMICHELINE PELLETIER

In November 2003, unexpected correspondence arrived at room C-42 of the Carlos Chagas Filho Biophysics Institute, on the campus of the Federal University of Rio de Janeiro (UFRJ) on Fundão Island. Biologist Lucia Mendonça Previato opened the envelope coming from Paris and did not believe what she saw.  “I read it and reread it, trying to find between the lines whether some stage was still missing”, the researcher says.  The content justifies the initial distrust.  The text of just half a page announced the coordinator of UFRJ’s Glycobiology Laboratory as the winner in Latin America this year of the 2004 L’Oréal-Unesco Award for Women in Science 2004.

Granted annually by the French cosmetics manufacturer L’Oréal and the United Nations Educational, Scientific and Cultural Organization (Unesco), the Women in Science award is recognition for the contribution of five prominent women researchers towards improving people’s living conditions, and an encouragement for women to carry on with a scientific career. In this edition of the prize, the sixth since its creation in 1998, other winners include molecular biologist molecular Jennifer Thomson, from the University of Cape Town, South Africa; neurobiologist Nancy Ip, from the Hong Kong University of Science and Technology, China; geneticist Christine Petit, from the Pasteur Institute, France; and molecular biologist Philippa Marrack, from the Howard Hughes Medical Institute, United States.

Lucia is the second Brazilian amongst the 29 researchers now honored with the award, an indication of the importance of Brazilian research. In 2001, geneticist Mayana Zatz, from the University of São Paulo, was given the prize for her work related to neuromuscular dystrophy, which led to the detection of at least three genes associated with the appearance of this hereditary disease, which causes degeneration of the muscles and progressive loss of the capacity for movement.

In almost 25 years of research, Lucia and her collaborators from UFRJ have discovered and revealed in detail one of the tricks that allows the causer of Chagas’s disease – the Trypanosoma cruzi protozoon, a parasite that contaminated about 18 million people in Latin America – to escape from the immune system. Soon after invading the bloodstream, transmitted by the feces of the kissing bug, the Trypanosoma puts on a disguise. With molecular sleight of hand, the protozoon steals a signaling molecule – a sugar called sialic acid – present on the external part of human cells, and exposes it on its own surface, in a sort of camouflage that allows the protozoon to pass unnoticed by the human defense cells.

The news of the award – worth US$ 100,000 – gave the team from Rio one more reason for commemorating.  Recently, the researchers from the Glycobiology Laboratory found that a single gene, which exists in a copy, also unique, in the genome of the Trypanosoma, controls the beginning of the formation of the molecule that will receive the sialic acid, as they reveal in a study to be published in the next few months. In Lucia’s opinion, this is the perfect target for new drugs against the parasite, since this chemical reaction – the bonding of Alpha-N-acetyl-glucosamine with the threonine amino acid – is exclusive to the Trypanosoma. In theory, a medicine that prevents this bonding, never observed in mammal cells, would only affect the protozoon, leaving the human cells intact.  This would mean that fewer side effects would appear, frequent in the current treatment.

“These results open up the prospects for producing new remedies, less toxic and capable of combating the protozoon in the chronic stage of the disease as well”, the biologist comments. Lucia is now seeking the partnership of chemists and pharmacologists specialized in designing artificial molecules, in order to arrive, in a few years, who knows, at a specific compound, capable of blocking only this chemical reaction typical of the parasite and preventing its camouflage. The medicines currently used in combating Chagas’s disease, based on nitroimidazoles or nitrofurans, act only in the initial or acute stage of the infection, when the protozoon still runs free in the bloodstream and the person shows a high temperature, swelling at the place of the bite, and a feeling of tiredness.

Should the Trypanosoma not be combated soon after contamination, the situation may get complicated. Without treatment, from one quarter to one third of the people infected develop the chronic form of the disease: the protozoon penetrates the cells of organs like the heart, the intestines, and the esophagus, causing progressive damage, and possibly the malfunctioning of these organs. More common amongst the rural population, which takes longer to seek treatment, the chronic form of the disease leaves few ways out: in general, the sick organ is removed, or, when possible, a transplant is done, since the parasite in the interior of the cells is not affected by medicines.

Political choice
Hours of work on end, and, of course, a bit of luck, led Lucia and her husband, José Osvaldo Previato, also from UFRJ’s Glycobiology Laboratory, to discover the protozoon’s strategy of robbery back at the beginning of the 1980s, as a result of work started, in part, by a political issue. The couple had hardly returned from postdoctoral studies abroad, when Lucia had to take up the laboratory headed up by physician Luiz Rodolpho Travassos, who was moving to the Federal University of São Paulo. Two programs for funding research into endemic diseases were to give them the opportunity for raising the necessary funds to keep the laboratory working and to apply the knowledge acquired abroad in studying the parasite of Chagas’s disease, which affects 8 million Brazilians.

Three years after the initial contact with the Trypanosoma, Lucia and José Osvaldo had already identified the parasite’s strategy, described in 1985 in an article in Molecular and Biochemical Parasitology. Incapable of producing the actual sialic acid, the protozoon uses a special protein, an enzyme called transialidase, to steal it  from human cells. “It was a discovery that gave new bearings for research into Trypanosoma cruzi in Brazil and abroad”, comments the researcher from Alagoas, who in 1955, at the age of 5, moved from Maceió to Rio de Janeiro.  Lucia’s team was to spend almost a decade prying in detail into the structure of the sugar and the protein of T. cruzi to which the sialic acid binds itself, until, in 1994, they identified the special connection between the protein and the sugar (the binding of Alpha-N-acetyl-glucosamine with the threonine amino acid), that is exclusive to Trypanosoma cruzi and a possible target for new medicines.