{"id":241331,"date":"2017-06-29T19:00:53","date_gmt":"2017-06-29T22:00:53","guid":{"rendered":"http:\/\/revistapesquisa.fapesp.br\/?p=241331\/"},"modified":"2017-06-30T14:07:51","modified_gmt":"2017-06-30T17:07:51","slug":"boost-for-brazilian-science","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/boost-for-brazilian-science\/","title":{"rendered":"Boost for Brazilian science"},"content":{"rendered":"
\"\"

Fundecitrus<\/span><\/a> Genomic map of the 2.7 million base pairs of the X. fastidiosa chromosomeFundecitrus<\/span><\/p><\/div>\n

During the morning of May 1, 1997, biologist Fernando Reinach, who at the time was a professor at the Chemistry Institute of the University of S\u00e3o Paulo (IQ-USP), called physicist Jos\u00e9 Fernando Perez, then scientific director of FAPESP. Since the preceding year, they had been discussing new ways to invest in the scientific training of Brazilian researchers in the field of molecular genetics, considered key to the field of biotechnology. From the long conversation between the two, the first project for sequencing a genome in Brazil emerged: Xylella fastidiosa, <\/em>the bacterium that causes citrus variegated chlorosis (CVC), one of the worst orange pests in the state of S\u00e3o Paulo. Launched on October 14 of that year, the project involved 35 laboratories and 191 researchers from several state institutions and various disciplines, which were integrated virtually by the Organization for Nucleotide Sequencing and Analysis (ONSA) Network. In addition to initiating research on molecular genetics, the sequencing of the first plant phytopathogen in the world represented a new way of doing science in Brazil, and thus contributed to the education and training of a generation of young scientists. Many used the knowledge and experience they acquired to start their own firms. Others changed the focus of their research, established new scientific collaboration networks and advanced in their careers in universities and elsewhere.<\/p>\n

The mapping of the Xylella<\/em> genome brightened the outlook for genetic research in Brazil. Other sequencing endeavors followed, such as the Genoma Cana project, completed in November 2000, with the goal of sequencing selected parts of sugarcane DNA and identifying genes with economically important characteristics. Other projects sprang up at almost the same time, such as the Cancer Genome project, completed in March 2002, and the sequencing of the genetic code of the Xanthomonas citri<\/em> bacterium, which causes citrus canker, completed in August 2001. These scientific undertakings helped train researchers and improve the infrastructure of the largest laboratories in S\u00e3o Paulo, thus hastening the development of molecular biology in Brazil.<\/p>\n

\"\"<\/a>

Cover of the journal Nature<\/em>, which said that the sequencing of the phytopathogen was a success story for Brazilian bioscience<\/p><\/div>\n

The experience acquired by taking part in the project and the promising market for biotechnology products and solutions also motivated a number of researchers to go into business. In 2002, two years after the sequencing was completed, computer scientist Jo\u00e3o Paulo Kitajima left the Bioinformatics Laboratory (LBI) at the University of Campinas Institute of Computing (IC-Unicamp) where he worked to set up Alellyx with other project participants. Alellyx is a research and development company for biotechnology products that focuses on generating and marketing patents in applied genomics (see Pesquisa FAPESP<\/em> Issue n\u00ba 74<\/a>).<\/p>\n

Kitajima joined the bioinformatics team shortly after the Xylella<\/em> genome project began. \u201cI started as a bioinformatics analyst at LBI along with bioinformaticians Jo\u00e3o Meidanis and Jo\u00e3o Carlos Setubal. Then I started to assist with coordinating the bioinformatics part of the project, so I was the third leader named \u201cJo\u00e3o,\u201d he says. At the time, due to the need for speedy communication among the labs that were involved, the project managers decided to set up a centrally coordinated virtual network that was physically scattered over the research centers in the state of S\u00e3o Paulo. The ONSA Network went live in December 1997, connecting the laboratories and establishing links among the researchers so they could develop genetic protocols, share information, solve problems and adapt and adjust techniques.<\/p>\n

\"\"

Fundecitrus<\/span><\/a> Bacteria-transmitting insectFundecitrus<\/span><\/p><\/div>\n

The network had a bioinformatics system so researchers could incorporate information from the sequencing of the bacterium\u2019s genetic material. Setubal, Meidanis and Kitajima were in charge of maintaining the flow of information. \u201cWe were responsible for obtaining the sequencing data that the labs produce and processing them on computers to develop a complete genome,\u201d Setubal says. Meidanis, who came into contact with bioinformatics during his doctoral work at the University of Wisconsin-Madison in the United States in 1989, recalls that \u201cwe didn\u2019t know if the groups would have sufficient Internet bandwidth access to send us all the genomic information.\u201d<\/p>\n

\u201cAt Alellyx I had the opportunity to coordinate the applied research and specialize in the field of regulatory processes for transgenic organisms,\u201d says biologist Jesus Aparecido Ferro of the School of Agricultural and Veterinary Sciences at S\u00e3o Paulo State University (Unesp) in Jaboticabal, and one of the founders of the company. Ferro was also one of the coordinators of the Xylella<\/em> Functional Genome program, launched in June 1999. The purpose of the project was to investigate the function of the genes identified during the sequencing, and thus to understand how Xylella<\/em> triggers CVC.<\/p>\n

\"\"

Eduardo Cesar<\/span><\/a> Ana Cla\u00fadia Rasera, Jo\u00e3o Kitajima, Jesus Ferro, Paulo Arruda and Jo\u00e3o Setubal at the launch of biotechnology company Alellyx, in 2002Eduardo Cesar<\/span><\/p><\/div>\n

Alellyx was sold along with CanaVialis in 2008 to multinational Monsanto for $290 million (the equivalent of R$980 million today). \u201cIn 2009, I went into the field of human health,\u201d Kitajima says. \u201cI worked as a bioinformatician at the Israel Institute of Education and Research at Albert Einstein Hospital until 2011.\u201d More recently, he and other partners founded Mendelics An\u00e1lise Gen\u00f4mica, a customized genetic testing company.<\/p>\n

For Meidanis, the project was a major turning point in his life. \u201cI became a hybrid of academic and company manager,\u201d he says. Today he divides his time between his position as professor at Unicamp and entrepreneur at Scylla Bioinform\u00e1tica, a software company he founded that works in the fields of genomics and proteomics.<\/p>\n

\"\"

Adri Felden\/Ag. Argos <\/span><\/a> Award ceremony for the S\u00e3o Paulo Medal of Scientific and Technological Merit…Adri Felden\/Ag. Argos <\/span><\/p><\/div>\n

Ambitious project<\/strong>
\nThe Xylella<\/em> genome project was launched at a time when research was having a considerable impact on the field of molecular biology. But this science was brand-new in Brazil. \u201cPerez realized that scientific production in this area was growing in other countries, and that Brazilian researchers had to be trained for us to boost our position on the international science scene,\u201d Reinach says at his office at the Pitanga Fund, which raises money from investors interested in technology-based endeavors. That was the start of a lengthy scientific effort to develop the project. \u201cThe older researchers weren\u2019t convinced,\u201d he says. \u201cIt was an ambitious and risky project that would involve large sums of money,\u201d according to Reinach, who at the time was one of the few Brazilian researchers with experience in the field of molecular biology and scientific entrepreneurship (he founded the first company in Brazil that performs paternity tests, Genomic Engenharia Molecular).<\/p>\n

The choice of which microorganism would be sequenced was made weeks before the project was launched. \u201cThe genome had to be large enough to involve many researchers and small enough for us to be able to complete it,\u201d says Perez in his office at Recepta Biopharma, a biotechnology firm he founded in 2005 that performs research and develops compounds that have the potential to fight cancer.<\/p>\n

\"\"

Adri Felden\/Ag. Argos <\/span><\/a> …given by the government of S\u00e3o Paulo State to the 191 researchers involved in the genome projectAdri Felden\/Ag. Argos <\/span><\/p><\/div>\n

At that time, the organism that best met these prerequisites was Thiobacillus ferrooxidans<\/em>, used in biomining; however, no Brazilian groups had succeeded in growing the Xylella<\/em> bacterium. \u201cIn September 1997, the Citriculture Defense Fund (Fundecitrus) expressed interest in participating in the project if Xylella<\/em> was chosen,\u201d Perez says. \u201cI mentioned the difficulties involved in selecting the bacterium, but they replied by saying that a French researcher knew how to grow it.\u201d They were referring to Joseph Bov\u00e9 of the National Institute of Agricultural Research (INRA in French), in Bordeaux, France. Bov\u00e9 was working in molecular genetics and was able to provide the bacterium, while Fr\u00e9d\u00e9ric Laigret, from Bordeaux 2 University, would support the establishment of a DNA bank for the bacterium to supply the fragments to be sequenced. \u201cThey convinced us and we chose Xylella,<\/em>\u201d Perez says.<\/p>\n

The project was launched with a $12 million investment from FAPESP and $400,000 more from Fundecitrus. This was the largest sum to date for a scientific project in Brazil. Of the 70 laboratories that applied to take part in the project, 35 were selected by an international committee consisting of Steve Oliver of the University of Manchester in England, Andr\u00e9 Goffeau of the Catholic University of Leuven in Belgium, and John Sgouros of the Imperial Cancer Research Foundation in England. This committee was placed in charge of supervising and running the project.<\/p>\n

\"\"

Adri Felden\/Ag. Argos <\/span><\/a> Former governor of S\u00e3o Paulo State M\u00e1rio Covas giving biochemist Andrew Simpson (at left<\/em>) the award for his leadership in coordinating the projectAdri Felden\/Ag. Argos <\/span><\/p><\/div>\n

Since the Brazilian researchers had little experience in the field of molecular biology, the decision was made to have DNA and bioinformatics coordinators for the project as well as central sequencing laboratories to train the researchers and generate the necessary sequences. Biochemist Andrew Simpson, from the Ludwig Institute for Cancer Research in S\u00e3o Paulo, was placed in charge of coordinating the DNA. The central sequencing laboratories were the Molecular Biology Laboratory at IQ-USP, which Reinach headed up at that time, and the Center for Molecular Biology and Genetic Engineering (CBMEG) at Unicamp, coordinated by biologist Paulo Arruda. The laboratories that were chosen were given automatic DNA sequencers, reagents and technical assistance. Xylella<\/em> would be mapped using 99 cosmids, which are fragments of DNA that carry and multiply parts of the genome to be studied.<\/p>\n

Less than a year after the project was launched, 90% of the Xylella<\/em> genetic code had been sequenced. There were still a few gaps in the total sequence of the genome. To bridge the gaps and confirm the order of the cosmids, Simpson developed alternative experimental approaches at the Ludwig Institute laboratories while he attempted to connect the cosmids to those that were contiguous to them so as to order the sequences and describe the genome completely.<\/p>\n

\"\"

Gilberto Alves<\/span><\/a> Group of scientists responsible for sequencing Xylella<\/em>, meeting with Fernando Henrique Cardoso, former president of Brazil (in beige suit<\/em>), at the Alvorada PalaceGilberto Alves<\/span><\/p><\/div>\n

New opportunities<\/strong>
\nGeneticist Anamaria Camargo joined Simpson\u2019s team at the Ludwig Institute in 1998 while she was a postdoctoral researcher. Her work consisted of bridging the gaps in the Xylella<\/em> genome with researchers Cl\u00e1udia Monteiro-Vitorello, Elizabeth Martins, Mariana Cabral de Oliveira, Marie-Anne Van Sluys, Marilis do Valle Marques and Ana Cl\u00e1udia Rasera. \u201cToday I am working in the area of cancer genomics, using much of what I learned in the Xylella <\/em>project,\u201d says Camargo, coordinator of the Molecular Oncology Research Center at the S\u00edrio-Liban\u00eas Institute of Education and Research in S\u00e3o Paulo. Her colleague, biologist Marilis do Valle Marques, was invited to join the project by physicist Suely Lopes Gomes, a professor at IQ-USP. \u201cI took part in the analysis and assembly of the sequences and the assembly and annotation of the pXF51 plasmid, which proved to be challenging because it has a duplicate region, making it difficult to assemble the sequence,\u201d explains Marques, a professor in the Microbiology Department of the Institute of Biomedical Sciences (ICB) at USP.<\/p>\n

The project was completed in January 2000 and consisted of sequencing 2.7 million base pairs of the Xylella<\/em> chromosome. On July 13 of that year, Nature<\/em> dedicated the cover of the journal to this work. In Brazil, the researchers received awards and tributes, such as the S\u00e3o Paulo Medal of Scientific and Technological Merit, awarded by the government of S\u00e3o Paulo State (see Pesquisa FAPESP<\/em> Issue n\u00ba 51).<\/p>\n

\"\"

Eduardo Cesar | L\u00e9o Ramos Chaves<\/span><\/a> Van Sluys and Oliveira acquired experience in Brazil and led projects in the United StatesEduardo Cesar | L\u00e9o Ramos Chaves<\/span><\/p><\/div>\n

For Simpson, thanks to the success of the Xylella<\/em> genome project, he was able to lead other projects, such as the Cancer Genome. \u201cAs a result of that work, I was promoted to the position of scientific director of the Ludwig Institute in New York,\u201d he says. Years later he returned to Brazil as chief executive officer of Orygen, a biotechnology company that develops, produces and sells therapeutic antibodies and vaccines.<\/p>\n

The Xylella<\/em> genome project turned into an opportunity for many young scientists to become independent researchers. After participating in the project, biologist Marcelo Briones from the Microbiology Department of the Federal University of S\u00e3o Paulo (Unifesp) became one of the coordinators of the Cancer Genome project along with Simpson. At that time, the equipment used in his laboratory to sequence the Xylella <\/em>cosmids helped him sequence genes expressed in cancers that have a high incidence in Brazil, such as cervical cancer and cancer of the head and neck. In 2000, after completing the two projects, Briones obtained funding from the Howard Hughes Medical Institute in the United States to conduct research on infectious and parasitic diseases in Brazil. \u201cI would not have obtained the funding without the equipment and knowledge I acquired during the Xylella<\/em> and Cancer projects,\u201d he notes.<\/p>\n

\"\"

M\u00e1rcia Minilo <\/span><\/a> Perez and Reinach: focusing on new ways of training Brazilian researchersM\u00e1rcia Minilo <\/span><\/p><\/div>\n

\u201cMy entire career is based on the study of Xylella,<\/em>\u201d says biologist Alessandra Alves de Souza from the Sylvio Moreira Citrus Research Center at the Agronomic Institute of Campinas (IAC) in Cordeir\u00f3polis, in inland S\u00e3o Paulo State. De Souza received her undergraduate degree in Pernambuco State and then went to S\u00e3o Paulo where she began work on her master\u2019s degree at the Luiz de Queiroz College of Agriculture (ESALQ) at USP. In her PhD work at Unicamp, she conducted comparative analyses of the expression of Xylella <\/em>genes associated with pathogenicity and the formation of a biofilm that connects the community of microorganisms that attack plants. This led her to study a molecule known as N-acetilcisteine (NAC) as a possible alternative for controlling CVC. NAC is a compound used to clear respiratory tracts and reduce biofilms formed by bacteria that cause disease in humans. In preliminary testing, NAC proved effective in breaking through biofilms produced by Xylella<\/em>, lessening the symptoms of CVC. Recently, de Souza and biologist Simone Picchi, also from IAC, opened CiaCamp, a research firm that develops NAC-based fertilizers (see Pesquisa FAPESP<\/em> Issue n\u00ba 247<\/a>). Today de Souza is working on a project funded by the European Commission to fight a variant of Xylella <\/em>that is destroying olive trees in the Puglia region of Italy.<\/p>\n

In her postdoctoral research at Michigan State University, biologist Cl\u00e1udia Monteiro-Vitorello had already worked on the mitochondrial DNA sequencing of a fungus that causes diseases in chestnut trees in the United States. When she returned to Brazil in 1998, she was invited to join the team of agronomist Luiz Lehmann Coutinho of the Animal Science Department at ESALQ-USP. \u201cDuring the Xylella<\/em> project, I studied at the National Scientific Computing Laboratory (LNCC) in Rio de Janeiro,\u201d she says. There she met Amos Bairoch, coordinator of Swiss-Prot, a Swiss database of proteins. \u201cAs a result of that meeting and the Xylella<\/em> project, I was hired to work at Swiss-Prot on annotations for bacterial genomes,\u201d she recalls. In 2008 Monteiro-Vitorello returned to academia as an assistant professor of microbiology at the Federal University of the ABC in Santo Andr\u00e9, S\u00e3o Paulo State. In 2009 she went to ESALQ-USP, where she works in the field of genomics on the plant-pathogen interaction involving diseases of sugarcane.<\/p>\n

\"\"

Francisco Tanakae Elliot Kitajima\/ESALQ-USP<\/span><\/a> Microscopic image of biofilms formed by Xylella inside plantsFrancisco Tanakae Elliot Kitajima\/ESALQ-USP<\/span><\/p><\/div>\n

For biologist Marie-Anne Van Sluys, from the Botany Department of the Biosciences Institute (IB) at USP, the Xylella<\/em> genome project was an opportunity to turn her studies on the interaction between bacteria and plants into the main focus of her research. After completing the sequencing of the Xylella <\/em>genome, Van Sluys and biologist Mariana Cabral de Oliveira, also from IB-USP, headed a project to decode the genomes of a strain of Xylella<\/em> responsible for the destruction of grapevines in the United States and the Leifsonia xyli subsp xyli <\/em>bacterium, which attacks sugarcane stalks. \u201cWe joined a network headed up by the Joint Genome Institute in the United States to unlock the DNA of two more strains of Xylella<\/em> that attack almond trees and that live in a plant called oleander,\u201d she says.<\/p>\n

\u201cIt was a time of much interaction with researchers from a variety of fields,\u201d says Oliveira, who took part in every stage of the Xylella <\/em>genome project, from sequencing to the macrostructural and comparative analysis of the genomes. Later, this paved the way for her to transfer the techniques of large-scale sequence analysis to her study of algae. For Perez, the project showed that Brazil is capable of conducting collaborative research that involves the scientific community, the government and private initiative. \u201cEven more, with this project, Brazil changed its perception of its capabilities and its place in the world of science.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"The paths of researchers who sequenced the genome of Xylella","protected":false},"author":346,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[1204],"tags":[200,237,241],"coauthors":[662],"class_list":["post-241331","post","type-post","status-publish","format-standard","hentry","category-careers","tag-environment","tag-genetics","tag-history"],"acf":[],"_links":{"self":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/241331","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/users\/346"}],"replies":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/comments?post=241331"}],"version-history":[{"count":0,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/241331\/revisions"}],"wp:attachment":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media?parent=241331"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/categories?post=241331"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/tags?post=241331"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/coauthors?post=241331"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}