The Onsa Network
The São Paulo Virtual Genomics
Institute
These transparencies should be viewed as a complementary material to
the paper “ONSA, The São Paulo Virtual Genomics Institute” Nature
Biotechonology Vol.16, 795-796, 1998
Fapesp´s Genome:
from project to program - a Chronology
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MOTIVATION: BIOTECHONOLOGY
May 01.97 INITIAL IDEA
MEETINGS WITH SCIENTISTS
INTERNATIONAL CONSULTANTS
(A. Goffeau 06.13, S.Oliver)
INDUSTRIAL PARTNERS
CHOICE OF ORGANISM
10.13.97 CALL FOR APPLICATIONS
11.15.97 DEADLINE FOR APPLICATIONS
11.16.97 SELECTION OF LABS
ONSA
The Original Architecture
• DNA COORDINATOR
Andrew Simpson (Ludwig ICR - SP)
• TWO CENTRAL LABS
USP (Reinach) - UNICAMP (Arruda)
• 32 SEQUENCING LABS
• BIOINFORMATICS CENTER
UNICAMP (Setubal & Meidanis)
Chronology
•
•
•
•
•
11.17.97 PURCHASE OF EQUIPMENT
Dec.97 COPERSUCAR and Sugarcane
Jan. 98 CGAP and the Cancer Project
05.01.98 START SEQUENCING
07.98 APPROVAL OF A GENOME PROGRAM
FUNCTIONAL GENOMICS:
“UNDERSTANDING CVC FROM Xf´S
GENOME” : CALL FOR PROPOSALS
• 01/99 FUNCTIONAL GENOMICS - 21
PROJECTS
• 02.99 GENE PATENT SUBMISSION
• 03.99 BEGIN OF FUNCTIONAL GENOMICS
Number of participating labs: 21
• GENOME CONCLUSION:
INITIAL GOAL: JUNE 2000
ACTUAL CONCLUSION: JANUARY 2000
• NATURE VOL.406 JULY 13
Estimated genome size 2.1 Mb
Genome size: revised 2.7 Mb
Sugarcane EST Project
SUCEST
• Goal: sequence circa 50 000 genes of Sugarcane
by April 2001
• DNA coordinator: Paulo Arruda (Unicamp)
• Bioinformatics UNICAMP
• 03.99 Call for application
• 04.99 Choice of participant labs
HUMAN CANCER GENOME
PROJECT
• PARTNERSHIP LICR - FAPESP
• NOVEL METHODOLOGY:
ORESTES (OPEN READING FRAMES ESTs)
DNA COORDINATOR - SIMPSON
• Tumors: Colon, Stomach, Head, Neck, Cervix
• Call for applications: April 99
• Choice of labs: June 99
• Initial Goal: 500.000 SEQUENCES - June 2001
• Revised Goal: 1.000.000 SEQUENCES September 2000
BUDGET
• Xylella fastidiosa: US$ 13 mi
• Functional Genomics: US$ 4 mi
• CANCER: US$ 10mi (1999) + 10 mi (2000)
LICR + FAPESP
• SUGARCANE: US$ 6 MILLION
• Xanthomonas axonopodis citri: US$ 5 MILLION
The Enlarged ONSA
65 labs through out the State of São Paulo
300 researchers
ONGOING PROJECTS
• XANTHOMONAS CITRI (4.7 Mb)
Expected Conclusion December 2000
• GRAPEVINE´S Xf (USDA + AVF)
• CLAVIBACTER XYLI (SUGARCANE
CONSORTIUM)
MEDIA VISIBILITY
• NATURE
• NEWSPAPERS
• MAGAZINES
• RADIO
• TV SERIES - 5 PROGRAMS
Brazilian scientists team up for cancer genome project.
Ricardo Bonalume Neto
(SÃO PAULO) Brazilian researchers have entered the competitive
field of human genome sequencing with the signing of an
agreement between the state funding agency of São Paulo
(FAPESP) and US-based Ludwig Institute for Cancer
Research.
Each will contribute US$ 5 million to two-year Human Cancer
Genome Project. According to FAPESP, the programme is
"aimed at providing sequences from genes expressed in
tumours that are important within the context of public
health in the state of São Paulo".
The project will sequence and analyse short DNA fragments
created from the central coding portions of human genes.
Although a US patent is being sought for the technique used
to generate these expressed sequence tags (ESTs), the
sequences will be freely available on the Internet. "No
sequences will be patented. All the data will be promptly
published", says Ed McDermott Jr., president of the Ludwig
Institute, who visited Brazil to sign the agreement.
The programme follows on from the Organization for Nucleotide
Sequencing and Analysis (ONSA), a network of 30
laboratories in the state of São Paulo now in the final steps
of sequencing the complete genome of the plant pathogen
Xylella fastidiosa. The groups will build upon their
experience with this pathogen, which causes many
economically important plant diseases, notably citrus
variegated chlorosis, which poses a major threat to São
Paulo's orange farming (see Nature 389, 654; 1997).
ONSA is a "virtual" institute that links the sequencing
laboratories, keeping down costs and red tape. The acronym,
which sounds like the word onça (jaguar) in Portuguese,
mimics the Institute for Genomic Research (TIGR),
according to José Fernando Perez, FAPESP's scientific
director.
Five centres will carry out the sequencing, each helped by four
other labs. The centres will be at the chemistry institute, the
faculty of medicine at São Paulo, and the faculty of
medicine at Ribeirão Preto, all from the University of São
Paulo; at the Paulista School of Medicine, São Paulo; and at
the Hemocentro of the University of Campinas. The
programme aims to generate between 500,000 and 750,000
EST sequences, and about 200 million bases of human
genome sequence.
The project will be monitored by a four-member steering
committee, composed of Marcelo Bento Soares of the
University of Iowa, John Sgouros of the Imperial Cancer
Research Fund in Londo, and Webster Cavenee and Richard
Kolodner of the Ludwig Institute in San Diego.
Brazil to sequence ´first plant pathogen´
Ricardo Bonalume Neto
São Paulo. The creation of a network of laboratories in São Paulo
state, Brazil, to sequence the complete genome of a
microorganism was announced last week by the Foundation
for the Support of Research of the State of São Paulo
(FAPESP),
The Organisation for Nucleotide Sequencing and Analysis will
first tackle the bacterium Xylella fastidiosa, the causal agent
of many economically important plant diseases, particularly
citrus variegated chlorosis, which poses a major threat to
São Paulo's orange cultivation. This is thought to be the first
plant pathogen genome to have been sequenced.
Citrus variegated chlorosis, first reported in 1987, has been found
only in Brazil and Argentina. São Paulo and Florida are the
two most important citrus-growing areas in the world, São
Paulo producing 87 per cent of Brazil's -- and 30 per cent of
the world's -- citrus crop. According to FAPESP, the total
cost of the project is US$11.6 million, to be spent over two
years. Sequencing completion is predicted by 2000.
Xylella fastidiosa was chosen because sequencing might help in
the control of the pest, with obvious gains to the state's
economy. It will also help to forge links between research
centres and the private sector, which is contributing to the
cost of the project.
The state says that it is keen to create a network of laboratories
that will "significantly increase the number of laboratories in
the state capable of using modern molecular biology
techniques".
The project will be overseen by a five-member steering committee
onsisting of three international experts in genome
sequencing and two researchers from São Paulo state. Two
of the experts, André Goffeau of the University of Louvain
in Belgium and Steve Oliver of the University of Manchester
Institute of Science and Technology, helped to set up the
project, and were also involved in the sequencing of the
Saccharomyces cerevisiae genome.
The committee will select one laboratory to house a
bioinformatics centre. Two large central sequencing
laboratories will be chosen to generate a large part of the
sequence data. These laboratories will also act as training
and support centres for other members of the network.
GENOMES 2000:
Intimate Portraits of Bacterial Nemeses
Michael Hagmann
A Genome Cinderella Story
This coup earned the Brazilian scientists ample praise from their
In 1987 orange growers in the Brazilian state of São Paulo first
international peers. Raves biochemist André Goffeau of the
noticed the telltale signs of a new disease: conspicuous yellow
École Normale Superieure in Paris: "The quality [of the
patches on individual leaves. The fruits on these spotted trees
sequence] is superb. It's incredible how fast they've done it,
turned out to be small, hard, and gave little juice, rendering
given that 2 years ago they didn't even have the [sequencing]
them commercially useless. Today, citrus variegated chlorosis
machines." The X. fastidiosa genome "is quite a big deal,"
(CVC)--as the disease is known--threatens the entire citrus
says Edwin Civerolo, a plant pathologist with the U.S.
industry in São Paulo state, the world's largest exporter of
Department of Agriculture (USDA) who works at the
concentrated orange juice. The disease affects more than 30%
University of California, Davis. Indeed, the work is so
of all trees and causes losses estimated at $100 million each
impressive that the USDA and the state of California have just
year.
enlisted--to the tune of $250,000--the Brazilian team to
Now scientists have a new tool to attack this devastating microbe.
sequence a related strain of X. fastidiosa that causes Pierce's
On 12 April a team reported at the meeting that they had
disease and is threatening vineyards across California.
deciphered the 2.7-million-base-pair genome of Xylella
The X. fastidiosa genome project was conceived in 1997 when
fastidiosa, the causative agent. X. fastidiosa is the first bacterial
Fernando Perez, scientific director of the State of São Paulo
plant pathogen ever to be fully sequenced. What's more, the
Research Foundation (FAPESP), a state-run public funding
feat was pulled off not by one of the sequencing superstars in
agency, became concerned about the lack of genomics
the United States or Europe but by a consortium of some 30
research in Brazil. After consulting some of Brazil's top life
labs in São Paulo state--groups with little or no previous
scientists, Perez and his scientific advisers decided that Brazil
genomic expertise.
should embark on its own genome project. But what to
sequence?
EUROPEAN MOLECULAR BIOLOGY NETWORK - EMBNET
Brazil, a new Mecca for genomics?
Historical perspective
The agency settled on Xylella fastidiosa, a bacterium that infects orange
High-throughput sequencing is a highly specialised trade, practised
trees, a major source of income in São Paulo, and causes Citrus
in a very limited number of laboratories in the developed
Variegated Chlorosis. This choice also brought in additional funding
world. It can be estimated that a dozen labs are contributing
from the citrus growers' association (Fundecitrus).
over half the total sequence data currently being deposited in
the public databases, with another 50 or so accounting for the
bulk of the rest. All of these labs are located in North America, ONSA
the larger European countries, Australia and Japan. It may thus A major goal of this first genome project was to bring sequencing
come as a surprise that the latest entrant in this select club
technology to as many laboratories as possible, thus propelling them
hails from Brazil, and more specifically the state of São Paulo.
into the genome age. Therefore, the concept of setting up a single
São Paulo has a law stating that 1% of the tax revenue collected by
sequencing centre was rejected from the start. Instead, bids were put
the state has to be given to an independent agency that supports
up for laboratories interested in participating in the project, and those
scientific research, known as FAPESP (Fundação de Amparo à
that were selected received equipment (ABI370 sequencers),
Pesquisa do Estado de São Paulo). As São Paulo is the richest
reagents, and ample technical advice. In total, 30 labs were selected
state in Brazil, this amounts to a considerable amount of
for the Xylella project, dispersed geographically throughout the state
money (USD 250 Mio in 1998). By law, FAPESP is also
of São Paulo. In addition to the sequencing labs, the project steering
forbidden to spend more than 5% of its money on
committee designated a DNA co-ordinator (for the handling and
administrative costs. The combination of ample funding and
distribution of clones) and a bioinformatics centre. The
political independence gives the Foundation a lot of freedom to
bioinformatics group, located at the University of Campinas (about
develop innovative scientific programs.
80 km from São Paulo), was made responsible for all of the data
handling, from base calling to final assembly verification. The
In 1997, FAPESP decided that Brazil should not miss out on the
sequencing labs submitted trace files only, and were paid on the
scientific and economic opportunities that can be derived from
basis of the amount of non-vector, high-quality sequences (based on
genome sequencing, and should be able to produce its own
phred scores) that could be extracted from their data. The entire
data, analyse them, and use the results for local scientific
process was automated using Web pages, and enabled the
projects. To start off, it was decided that a good target rganism
bioinformatics group to keep very close tabs on the daily progress of
should be bacterial, and of interest to the local economy.
the project as a whole.
Los Angeles Times
By Melinda Fulmer
April, 15, 2000
Cinderella Genes
Brazil was the poor sister of genome research, until its scientists pulled of two world-class coups
By Mac Margolis
NEWSWEEK INTERNATIONAL
August 6 - Brazilian biochemist Sandro de Souza, 32, ha landed a dream job at Harvard University.
His boss was physicist and Nobel laureate Walter Gilbert, practically a deity in the world of DNA
sequencing. Then the phone rang. A friend asked Souza to join a new genome research project - in
Brazil, of all places. To his surprise, Souza took a deep breath and accepted. "I wondered what
would become of me," he recalls.
THAT WAS TWO whole years ago, before Brazil, a
backwater of genetic research, metamorphosed into an
international powerhouse. Last month researchers at Sao
Paulo's fapesp research institute announced that they had
cracked the DNA code of Xylella fastidiosa, a bacterial
pest that destroys a third of Brazil's orange crop each year.
It is the first time scientists had ever mapped the structure
of the genome of a plant pathogen - a "landmark
achievement," as the British journal Nature put it.
As if that weren't enough, a week later Souza's own group
announced that it had successfully mapped the structure of
some 500,000 human expressed-sequence tags (EST) in
malignant tumors. ESTs are tiny bits of DNA that scientists
use to piece together the far longer sequence of base pairs
that make up a gene. The more ESTs you know for a
particular tumor, the better your chance of being able
to decode the entire structure of its genome and eventually to
"The Brazilian find a cure. Only the United States and Britain have
team has shown identified more human ESTS. Ali of a sudden, Souza and his
that engineering fellow Brazilians are sitting pretty at the top of an important
nations can
field of research. "This is the leading edge," said Richard
particpate as
equals in cutting- Klausner, president of the National Cancer Institute, who works
edge research." closely with the Brazilians. "TheBrazilian team has shown that
RICHARD
emerging nations can participate as equals in cutting-edge
KLAUSNER
research.”
president of the
National Cancer
Institute
How did Brazil pull off such a feat? Slowly at first, then all at
once. The slow part was Fapesp's rise to the research big
leagues. Fapesp takes a 1 percent share of Sao Paulo's
state tax revenues, which has allowed the 50-year-old institute
to nourish a fat endowment and fund quality research into
everything from airplane dynamics to weather prediction.
The Economist
July 22nd-29th, 2000 - Ed. no. 8180
Brazilian science
Fruits of co-operation
Peter Collins
SAO PAU L O
SAMBA, football and...genomics. The list of things for which Brazil is renowned has suddenly got longer. Only a
few days after publishing, on July 13th, the first-ever sequence of the genome of a plant pathogen, scientists at Sao
Paulo’s state research agency, Fapesp, were due to announce, on July 21st, another success—the composition of
279,000 human expressed-sequence tags, small pieces of DNA that allow genes to be located along chromosomes.
Only in America and Britain have more than that number of human ESTs been identified.
Though they are of global significance, both of these advances are also of particular interest to Brazilians. A number
of the ESTs in question are derived from genes linked to cancer of the head and neck, which for some reason is
unusually common in Brazil. And the plant pathogen sequenced, Xylella fastidiosa, is an insect-borne bacterium
that has been ravaging Brazil’s orange groves, causing their trees to produce shrivelled fruit and costing growers an
estimated $100m a year.
As if sequencing X. fastidiosa were not enough of an achievement in itself, the project was finished two months
ahead of schedule and $2m under its original $15m budget, even though it involved co-ordinating a "virtual
institute" made up of 35 laboratories scattered across the state. The man who did that co-ordinating, Andrew
Simpson, says there were two reasons for arranging things this way. The alternative, building a giant, bricks-andmortar institute would have been costly and time-consuming. And dividing the work between many laboratories
maximised the sharing of know-how among Sao Paulo’s scientists.
The Economist
July 22nd-29th, 2000 - Ed. no. 8180
This sudden leap in scientific expertise has had a long run-up. Ever since the 1960s, Fapesp has been
guaranteed, by law, a fixed share of all the tax collected in Sao Paulo (first 0.5%, later 1%) and independence
from the political meddling that is endemic in Brazilian public institutions. And whereas other states’ research
agencies have such guarantees routinely ignored, Fapesp’s growing prestige over the years has made it
increasingly hard for local politicians to interfere or pinch its money. By late 1997 it was possible for the agency
to decide that, although there had until then been only some limited sequencing of individual genes, the state’s
laboratories were ready to jump into a huge project and sequence a complete organism.
The success of the X. fastidiosa project seems to be breeding more success—and more money. The Brazilian
citrus growers’ association, which helped to finance the project, is now offering to pay to decode the bug that
causes another serious disease, citrus canker. The Ludwig Institute, in Switzerland, is contributing half of the
$10m cost of the team’s human-cancer project. Brazilian sugar growers are helping to finance another new
project, to sequence the genome of sugarcane. And the American Department of Agriculture is to pay for a team
to sequence a strain of X. fastidiosa that causes
Pierce’s disease in grapevines, which is currently afflicting California’s vineyards.
The lesson of all this is that there is no reason why countries such as Brazil cannot compete in leading-edge
science if they put their minds to it. Brazil’s share of the scientific papers published in international journals has
risen from 0.4% to 1.2% over the past 15 years. With its largest state having now demonstrated the benefits of
co-operation and a secure source of financing, and with more than 200 young geneticists trained as a result of
the X. fastidiosa project alone, that share may well
go on rising.
July 18, 2000
Agriculture Takes Its Turn in the Genome Spotlight
By CAROL KAESUK YOON
In a scientific first, and a coup for science in Brazil, a team of more than
200 researchers there has for the first time deciphered the complete DNA
sequence of an organism that causes a plant disease.
Though other genome sequencing efforts -- for example, in humans or the
laboratory staple fruit fly -- have attracted more attention, the Brazilian
target, an odd little bacterium known as Xylella fastidiosa, distinguishes
itself as the first to be decoded of the countless nasty species that together
cost farmers and foresters many billions of dollars each year. This particular
organism can cause diseases in oranges, grapes, almonds, plums, peaches,
alfalfa, oaks, elms and other plants.
Xylella fastidiosa Genome Project
An electron micrograph of the
bacterium Xylella fastidiosa.
"Everyone is quite thrilled," said Dr. Andrew Simpson, a molecular biologist at the Ludwig Institute
for Cancer Research in São Paulo, Brazil, and one of the team leaders. "It's probably the biggest ever
scientific project in Brazil."
The team has been feted by the president of Brazil and serenaded by orchestras, and a new scientific
prize was invented just to be given to the team. It was an achievement for developing nations' science
as well, Dr. Simpson said, as this was the first complete sequence to come from outside the United
States, the United Kingdom or Japan.
LE FIGARO
Jeudi 13 Juillet, 2000
GÉNÉTIQUE Décryptage du génome d’une bactérie ravageant les agrumes brésiliens
Les mécanismes de la virulence dévoilés
L'annonce du décryptag complet du génome de la bactérie Xylella fastidiosa constitue un double
événement. Non seuloment, c'est la première fois qu'un micro-organisme pathogène pour les
végétaux est sequencé, mais, surtout, ce travail remarquable, publié aujourd'hui dans la revue
Nature, est 1'ceuvre d'un consortium de laboratoires brésiliens. Le fait que ce pays émergent
dans le domaine de la bio1ogie se soit impliqué dans ce projet, avec le soutien de I'Institut
national de la recherche agronomique, ne doit rien au hasard:la bactérie séquencée est un
redoutable ravageur des agrumes et le Brésil, qui produit le tiers des oranges vendues dans le
monde, compte bien utiliser ces connaissances pour maîtriser ce fléau.
LE FIGARO
Jeudi 13 Juillet, 2000
Le Brésil parmi les grands
En parvenant à séquencer le génome de la bactérie Xylella fastidiosa, le Brésil se hisse au niveau
des puissances << biologiques>> de la planète: Etats-Unis, Grande-Bretagne, France, Japon,
Allemagne. L'nitiative est venue, il y a trois ans, de la Fondation pour le soutien de la recherche
scientifique et technique de I'Etat de San Paolo (FAPESP). Soucieuse de développer la biologie
moléculaire, cette institution qui gère le produit de l'impôt destiné à la recherche, lançait par ce
biais une sorte de plan keynesien de relance appliqué à la seience. La FAPESP a fourni à chacun
des trente laboratoires qui ont répondu à son appe1 d'offres un séquenceur dont le prix unitaire
avoisine les 700 000 francs. Ces efforts ont payé. Mieux, les Etats-Unis viennent de commander
aux Brésiliens le séquençage d'une souche de X.fastidiosia qui s'attaque à leurs vignobles. Et qui
pourrait bien un jour menacer l'Europe et la France. Pas étonnant que ce grand pays ait été invité
aux côtés de la Chine, de l'Inde et du Mexique à participer, fin juin, à Bordeaux, à la réunion des
ministres de la Recherche du G8.
Wednesday, 12 July, 2000, 18:01 GMT 19:01 UK
Brazil hails scientific first
Xylella fastidiosa was first identified in 1987
By BBC News Online's Jonathan Amos
South American researchers have decoded the first genome for a bacterium that causes disease in
plants.
Xylella fastidiosa infects citrus crops and has been known to devastate plantations in Brazil
where one third of the world'soranges are now produced.
Wednesday, 12 July, 2000, 18:01 GMT 19:01 UK
"The bacteria thrive in the xylem, which are like the veins of the
plant transmitting the sap from the roots to the leaves," Dr
Simpson said. "Basically, they clog up these tubes so that the
extremities and leaves of the plant get undernourished and don't
get enough water.
"The fruits become very small and hard, and have no
juice in them."
This disease results in
smaller, less juice fruit.
This disease is known as citrus variegated chlorosis (CVC). It was first identified
in Brazil in 1987 but it was another six years before X. fastidiosa was shown to be
the cause.
Farmers are keen for scientists to develop new ways of combating the disease. In
the Sao Paulo region alone, 400,000 people are involved in the citrus business,
exporting orange concentrate valued at over $1.5bn a year.
Wednesday, July 12, 2000
“Genes of Plant Disease Mapped"
By JEFF BARNARD, Associated Press Writer
For the first time, scientists have reported mapping the genes of a plant disease, an
advance that could lead to new approaches to fighting a bacterial scourge that
ravages orange groves and other crops.
The work also sheds light on the way bacteria infect both humans and plants and
thwart their defenses.
“This sort of information is going to open up crop protection strategies the way
genome sequencing is opening up new pharmaceutical strategies to control
infectious diseases" in people, said Charles J. Arntzen, president of the Boyce
Thompson Institute at Cornell University.
New York Times - July 12, 2000
Genes of Plant Disease Mapped
By The Associated Press
For the first time, scientists have reported mapping the genes of a plant disease, an
advance that could lead to new approaches to fighting a bacterial scourge that
ravages orange groves and other crops.
The work also sheds light on the way bacteria infect both humans and plants and
thwart their defenses.
``This sort of information is going to open up crop protection strategies the way
genome sequencing is opening up new pharmaceutical strategies to control
infectious diseases'' in people, said Charles J. Arntzen, president of the Boyce
Thompson Institute at Cornell University.
Sponsored by the State of Sao Paolo Research Foundation in Brazil, 200 scientists
in 34 molecular biology labs worked for two years to sequence the genome of the
bacteria Xylella fastidiosa.
Editorial
There is a common misconception that only advanced industrialized nations have the
wherewithal and skilled human resources needed to achieve cutting-edge science. This
misconception is fanned by the number of researchers from developing countries who find
it necessary to obtain their research training abroad - and frequently decide not to return,
citing a lack of scientific opportunity. But it is given the lie by a paper published in this
issue which describes the result of a project carried out by a consortium of research centres
in the state of São Paolo in Brazil to sequence the bacterium Xylella fastidiosa. This
bacterium causes a disease that affects citrus fruit and other important crops, resulting in
many millions of dollars of damage each year.
As the first public sequence of a free-living plant pathogen, the paper represents a
significant scientific milestone. But it also sends a clear political signal, namely both the
desire and ability of countries such as Brazil to play in the big league. The sequencing
project was deliberately chosen by the project's main funding agency, FAPESP, to play a
catalytic role in helping research teams equip themselves for the challenge of the postgenome era. It was also intended to send a signal to Brazil´s young scientists that they do
not need to leave the country to engage in world-class science. In both respects, it appears
to have succeeded.