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Advanced Work

National Genome Program concludes sequencing of the bacterium

ARQUIVO WALTER COLLI /Q-USPTrypanosoma is a subject for research in ParanáARQUIVO WALTER COLLI /Q-USP

The sequencing of the Chromobacterium violaceum bacterium by the Brazilian Genome Project (BRGene), which unites 160 researchers in 25 laboratories scattered over the country, has been concluded. The bacterium is found in tropical regions like the Negro river, for example, in the Amazon. It is believed that it may be used in the treatment of some diseases like Chagas’s disease and leishmaniosis. “The definition of a possible continuation of the work will depend on decisions of a technical/scientific Nature”, says Ana Lúcia Assad, the coordinator-general of the National Biotechnology Program of the Ministry of Science and Technology (MCT).

This is the first result of the research carried out by the National Network of the Brazilian Genome Project, launched in December 2000, which covers 480 teaching and research institutions and gathers together 240 scientists in the area of biotechnology nationwide. Generally speaking, there have been significant advances in the other regional networks that are part of the project. “The networks have now been consolidated, as far as the participation of the groups, the processes and procedures of group work, and the qualification of human resources are concerned”, says Ana Lúcia. Integrating the networks is making it possible to build a huge database, which, in future, may contribute towards very significant reductions in the time it takes to show results in genomic research.

According to Ana Lúcia, some of the institutions involved in the regional projects are still awaiting the arrival of imported equipment, but many of them are now working at full steam ahead, and, in some cases, are even negotiating possible partnerships with private enterprise. “The first round of monitoring in loco will be carried out at the beginning of this year, when we will be verifying whether there are any needs not yet covered”, she says. From then on, she notes, the possibility of further funds being brought in will be analyzed.

Of the seven regional networks, four are working in the area of health, researching new medicines and alternatives for the prevention of endemic diseases. The other three have directed their focus towards the agriculture, with the aim of fighting diseases and increasing quality and productivity in the countryside. In all, the seven networks are receiving investments of R$ 13 million from the MCT and another R$ 13 million from various sources. “The major part of the supplementary funds is coming from state research support foundations”, Ana Lúcia explains.

Crinipellis perniciosa
Among the jobs at an advanced stage is the project for the expansion of the network for genomics in the state of Bahia, which is targeted on theparasitic fungus Crinipellis perniciosa, which causes the witch’s broom disease that is laying waste the cacao plantations in Bahia and has brought about losses of US$ 1.6 billion since 1989. “This amount only takes into account the sales that failed to be carried out”, observes Gonçalo Amarante Guimarães Pereira, the coordinator of the Genomics and Expression Laboratory of the State University of Campinas (Unicamp) and of the project. “Considering other aspects, such as the level of employment, the losses exceed US$ 10 billion easily.”

Pereira also says that leaving cacao plantations idle, as a result of the witch’s broom, has had a strong environmental impact on the stretch of the Atlantic Rain Forest in the south of Bahia. The cacao plantations held back deforestation, since they need the shade of the forest. The disease is the biggest problem from a plant pathogen in the cacao producing regions on the American continents, and also affects the states of Pará, Rondônia, Amazonas, Mato Grosso and Acre. To date, no fungicide has proved effective in the combat Crinipellis perniciosa, which has been studied with conventional techniques for about a hundred years.

“After defining the basic characteristics of the molecule we needed to contain the advance of the witch’s broom, we started to look for it in the market”, says Pereira. This molecule, supplied by a company that works in the area of agro-chemicals, but had never been used in fighting witch’s broom, has shown excellent results in the laboratory. “The field tests started in December.”

The project received R$ 1.3 million from the MCT and R$ 1.2 million from the government of Bahia, and it enjoys the participation, besides Unicamp, of the Center for Cacao Research, of the State University of Santa Cruz (Uesc), of Embrapa Recursos Genéticos e Biotecnologia, of the State University of Feira de Santana (UEFS), of the Federal University of Bahia (UFBA) and of the Catholic University of Salvador (Ucsal). “One of the important aspects of the project is the dissemination of genomics”, says Pereira.

Schistosoma mansoni
The Genome Network of the State of Minas Gerais uses as a model the expressed genome of Schistosoma mansoni, which causes schistosomiasis. A similar project is being developed by a group of six laboratories from São Paulo, under the coordination of Sérgio Verjovski. Half of the 120,000 ESTs expected in the project have already been sequenced. Minas already has a tradition in the study of this parasite – the first studies in the state involving Schistosoma, carried out at the Institute of Biological Sciences of the Federal University of Minas Gerais (UFMG) and in the Renê Rachou Research Center (CPQRR/Fiocruz), date from the beginning of the Nineties.

“Now, we are looking for new drugs to inhibit the action of the parasite, and, possibly, a vaccine to prevent contamination”, explains Naftale Katz, the coordinator of the project and scientific director of the Research Support Foundation of Minas Gerais (Fapemig). According to Katz, schistosomiasis affects around 7 million people in Brazil, with a strong concentration in the coastal regions of the northeast and in the state of Minas Gerais. “With the migratory flow from the rural environment to urban regions, focuses of schistomosiasis have appeared in metropolitan areas.” Katz says that, over the last two years, two new medicines with few collateral effects, developed on the basis of discoveries made by Brazilian researchers, have made it possible to control the form of the disease that affects the liver and the spleen, which affects between 5% and 10% of the carriers of the parasite and can lead to death.

Recontamination, though, continues to be a serious problem – even the blandest manifestations of schistomosiasis can, for example, disable a person for work. In the whole world, about 200 millions of individuals are carriers of the disease.”The project received R$ 1.8 million from the federal government and R$ 2 million from Fapemig, in one of its first initiatives to induce demand”, Katz says. Some 40 researchers are working on the project. “We are glimpsing the possibility of establishing interesting partnerships with companies”, says Katz. “We are patenting everything.”

Paracoccidioides brasiliensis
The Center-West Network Project wants to map the differential functional genome of Paracoccidioides brasiliensis, the fungus responsible for paracoccidioidomycosis, an endemic mycosis that can be fatal in children. The idea is to develop new medicines. According to estimates, the number of person infected in Latin America comes to 10 million, 80% of the cases being in Brazil.

The Implementation Program of the Institute of Molecular Biology of Paraná, is working with the functional genome of the process of cellular differentiation of Trypanosoma cruzi, which causes Chagas’s disease. It is looking for the genes with expression regulated during the cellular differentiation of the parasite (metacyclogenesis), and to select and characterize new genes and to analyze innovating chemotherapic targets. The experience built up in the process may be transferred to other genome projects.

Herbaspirillum seropedicae
Then there is the Genome Program of the State of Paraná, the subject of which is the structural and functional genome of Herbaspirillum seropedicae, a nitrogen fixing bacterium that, when interacting with plants, can bring benefits to both sides. In this regard, the case of rice is a good example: in some samples of seeds, Herbaspirillum seropedicae supplies as much as 54% of all the nitrogen accumulated in the plant. The project aims to build new strains of the bacterium, with even higher levels of efficiency. Its authors believe that the use of these organisms by farmers can generate savings of R$ 840 million with nitrogenated fertilizers.

Gluconic acid
With similar objectives, the Implementation Program of the Genoma Network of the State of Rio de Janeiro (RioGene) has the target of sequencing the genome of Gluconacetobacter diazotrophicus, another endophytic nitrogen fixing bacterium. Present in such crops as sugar cane, coffee and sweet potatoes, the bacterium may also significantly reduce the use of nitrogenated fertilizers, bringing about savings estimated at R$ 60 million, just in the sugar cane crops. The bacterium also produces substances that stimulate plant growth and metabolisms of industrial interest, like gluconic acid.

Northeast deciphers protozoan genome

With R$ 8.2 million in hand, 20 research groups from the nine states of the northeast, united in the Northeast Genome Program (Progene), are working to overcome the first great genetic challenge of the region by the middle of this year: the sequencing of Leishmania chagasi, a protozoan that transmits visceral leishmaniasis. The disease afflicts 5,000 people a year in Brazil – 95% of them in the northeast. In the world, 500,000 new cases are recorded every year, particularly in India, Pakistan and Bangladesh.

Three sequencing machines are fully operational – two in Pernambuco and one in Alagoas. Piauí and Maranhão have now purchased the equipment, which will immediately boost the production of the regional network to 5,000 sequences a week. To meet the target of processing 150,000 sequences of the protozoan swiftly, the other states will be equipped by March, with their own resources and those of the National Council of Scientific and Technological Development (CNPq), which handed out R$ 1.7 million in July last year for the purchase of machines and supplies.

“Once the ideal structure is set up, we will be able to fly high”, are the plans of researcher Paulo Paes, from the Federal University of Pernambuco (UFPE), Progene’s coordinator. The next step will be the sequencing of a microorganism of agricultural importance for the northeast, as the scientists from São Paulo did with the Xylella fastidiosa bacterium that causes disease in orange plantations.

Progene’s research groups have opted not to work with the complete genetic code of Leishmania, but only with the expressed genes, those that actually carry out functions in the parasite. Some 4,000 of them should be studied. “Sequencing the whole genome would be a long job, for which we do not yet have the technology”, Paes explains.

The developments are being negotiated. The scientist sent the CNPq a R$ 3 million project to purchase equipment and to go further in the studies with the protozoan of leishmaniasis, going on to analyze the functions of the proteins existing in the DNA. A further R$ 250,000 will be invested in the creation of transgenic parasites, necessary for the detailed identification of the genetic activities.