Spotty fish may hold man's key

April 21, 2000

Jane Marshall concludes our focus on France with reports on the genome project mapping project.

A garden weed, a small spotted fish and the number 14 have something in common: they are vital components of research projects at the laboratories of Genoscope, France's national centre for gene sequencing.

The brassica Arabidopsis thaliana is the model plant under scrutiny in an international sequencing programme in which the centre is collaborating. It is hoped that the fish, Tetraodon nigroviridis, will play a part in deciphering human DNA. The laboratories are working two shifts a day, seven days a week, to meet a deadline to decode chromosome 14 for the international Human Genome Project.

Genoscope is part of Evry Genopole, 34 km south of Paris - France's "genetics valley". The government's top research priority for life sciences, especially genomics, has focused attention on Evry, which is at the forefront of the national effort to climb out of the doldrums into a dominant position in a field where less than a decade ago France was a pioneer.

Evry's evolution into France's most advanced genome research community dates back to a charitable initiative. In 1987, the French association of neuromuscular dystrophy, the Association Francaise contre les Myophathies (AFM), organised its first telethon for research funds. The huge success of the appeal enabled the AFM to set up Genethon, a laboratory dedicated to researching genetic causes of diseases. It became internationally known in 1992 when it produced the first human genome maps; and it contributed to identifying 400 genes responsible for serious illnesses.

In 1996, the AFM switched Genethon's research efforts to concentrate on gene therapy for rare diseases, and France subsequently lost its leading role to the United States and the United Kingdom.

But Genethon's success had already been attracting other institutions and companies with interests in genome research to Evry. Following renewed government interest, France's first genopole, which brings together public and private gene research, was inaugurated in 1998 by the then minister for research, Claude All gre, and the minister for the economy, Dominique Strauss-Kahn.

Under its director, Pierre Tambourin, former life sciences director at the National Centre for Scientific Research (CNRS), the role of Evry Genopole is to promote research and its transfer to real-life applications in medicine, agriculture and the environment, and to coordinate the activities of public and private bodies in the university, research and industry sectors Today, as well as the AFM and Genethon, Evry genopole brings together:

* The University of Evry-Val d'Essonne - established in 1990, as part of its commitment to genopole, its life sciences programmes lead to degrees in sequencing techniques, molecular biology and physiology

* Genoscope - a government-funded research unit set up in 1997 to extend Genethon's pioneering work, it provides high-quality sequencing data for human, animal, plant and microbial genomes with a scientific, medical or economic interest. Among Genoscope's in-house projects are the 1.7 million-base sequence of Pryocossus abyssi, a deep-sea bacterium that lives at a temperature of 100C, which was finished in January 1999 and the results publicly released; and the sequence of the spotted fish, Tetraodon nigroviridis.

* Centre National de Genotypage - dating from 1997, a government-funded centre for genotyping that identifies and characterises genes related to specific diseases and can establish millions of genotypes each year

* Infobiogen - founded in 1995, the national centre for applied computer science of genomics and molecular biology. Its database relevant to the study of biotechnology and is available to all scientists

* Cerma - a technological resource centre that designs, produces and develops equipment, machines and processes, specialising in complex equipment involving mechanics, electronics, special sensors and industrial computing

* Genoplante - a public-private partnership studying plant genomes to improve seed quality, nutrition, food safety and the environment.

There are also 14 public research groups run jointly by various partnerships involving university departments and national research centres, including the CNRS, the INRA (agronomic research), Inserm (health and medicine) and the CEA (nuclear energy), in areas including bio-informatics, nanotechnologies, robotics and post-genomics.

On the industrial and commercial side, Evry's purpose-built business park accommodates a growing number of private companies. An incubator offers support, including specialised equipment for biotechnology start-up enterprises. Companies at the site include:

* Genset, a biotechnology group that started with three employees in 1995 and now has 400. It supplies genome information to pharmaceutical laboratories

* The genomics department of Aventis Pharma, formerly Rhone-Poulenc Rorer, which identifies regions of the human genome containing genes susceptible to illness and sequences and clones genes for therapeutic programmes

* Neurotech, a developer of gene-therapy products for diseases of the central nervous and ophthalmic systems

* UroG ne, which is concerned with prostate cancer

* ESGS/Cybergene, which provides service and production activities in the DNA field.

As the spotted fish swim around their aquarium in Genoscope's basement, scientists and technicians are working in the laboratories upstairs. Nearby, robots and rows of computerised sequencers carry out such operations as injection of bacteria clones with DNA, colony-picking and decoding fragments of DNA, which are displayed on the screens in brilliant twists of red, green, blue and yellow.

Once the Genoscope project of sequencing the brassica Arabidopsis thaliana is completed this year, the laboratory will start genomic analysis of rice.

But for now, Genoscope is working round the clock to meet the extremely tight deadline - shortened from 2010 to 2003, then to this May - to complete the international Human Genome Project (deciphering all 24 pairs of human chromosomes). The eight laboratories in the countries of the Bermuda Club - the US, the UK, Germany and Japan, as well as France, which joined in 1996 - are striving to beat US microbiologist Craig Venter, who will patent the results if he finishes first. A Bermuda Club rule is open accessibility to such knowledge.

Under future plans, Evry will head a federation of new genopoles, each structured around an area of research composed of public laboratories and international companies, a university specialising in genetics, bio-informatics, genomics and technological aspects, with a business creation centre to encourage new start-up companies.

Last year the government announced the first ones would be set up in Lille, Strasbourg, Montpellier, Toulouse and Paris; a second phase could add Aix-Marseille, Lyon-Grenoble and Bordeaux to the list.

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