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Wellcome Trust Spinoff Beowulf Genomics Completes First Sequence Of C. jejuni

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LONDON--Beowulf Genomics, a nonprofit initiative established in February by the Wellcome Trust, has released its first complete sequence. The project sequenced the microbial pathogen Campylobacter jejuni, a major cause of diarrhea. Said to be the world's largest medical research charity, the trust established Beowulf with initial funding of £7million to coordinate efforts on sequencing microbial pathogens related to human and animal health.

Most initial work is being undertaken at the Sanger Centre, part of the Wellcome Trust Genome Campus at Hinxton, where a third of the human genome is also being sequenced. Julian Parkhill, a computer biologist in Sanger's pathogen group, explained that the coding sequence of C. jejuni is being made available annotated with predicted proteins. Database searches will also be offered for each of the numbered proteins. "This will provide users with a direct source of structural information on the proteins, including, for example, the kinds of motifs involved. In this way we hope to encourage meaningful dialogue among users," he said.

The trust seeks to ensure that genome sequences are widely distributed, and committed Beowulf at the outset to making its sequence data freely available to all scientific users.

"The more people who are endowed with the latest information, the faster science will progress," observed Celia Caulcott, Beowulf's program manager.

But, she added, that arrangement wasn't palatable to potential commercial collaborators. "We were very keen at the outset to involve industry in the venture, but the issue of public access led to a lukewarm response. Companies we approached also wanted to see some evidence of results before committing themselves," Caulcott observed.

Of the philosophy behind Beowulf, Caulcott explained, "Beowulf will increase our understanding of the genetics of pathogens. But this is not an end in itself, more a set of tools with which to work. Short-term benefits will include improved targets for vaccine development, testing, and treatment of disease, but in the longer term we are seeking a far better understanding of the host-pathogen interaction and the associated insights this may bring to new kinds of intervention."

Beowulf will support sequencing of up to 10 microbial genomes during the coming year. In addition to C. jejuni, Caulcott said, "good progress is being made with Bordetella pertussis (whooping cough) and Yersinia pestis (plague), for which the shotgun is complete. Salmonella typhi and Clostridium difficile (gut pathogens) are next on the list," she added.

Pilot projects have been launched to sequence parts of the genomes of the human pathogens Leishmania major Freidlin, a tropical health hazard, and Trypanosoma brucei, which causes sleeping sickness and is a major cattle parasite in Africa.

Caulcott said criteria such as a disease's burden, the capacity of the genetics community to exploit the data, and the sequencing status of the organism elsewhere are considered when choosing subjects for study at Beowulf. Sequences claimed by industry are not necessarily excluded. "So far we have only funded the sequencing of organisms we know are not being sequenced elsewhere. But, along with the US National Institutes of Health, we see no reason to limit the field in this way indefinitely. Although industry has funded the sequencing of many pathogens, there is absolutely no evidence so far of them sharing these data," she noted.

Beowulf has also entered a collaborative venture with the UK Biotechnology and Biological Sciences Research Council to sequence Streptomyces coelicolor, a model organism for antibiotic production. Another area of potential interest involves those veterinary pathogens that could most beneficially be sequenced, but there is a question about the successful exploitation of such data, according to Caulcott."We would dearly like to raise the profile of genome sequencing within the veterinary community," she said. "Although a number of possible targets have been identified, it's not clear at the moment to what extent the veterinary science community will benefit from such sequencing projects."

The Wellcome Trust recently announced another £10 million in funding for Beowulf and more support is anticipated in the future. Caulcott was optimistic about finding additional financing. "We are still interested in developing further collaborations, commercial and academic, to maximize the quantity and quality of microbial genome sequence data that could be obtained in the next five years," she concluded.

--Paul Wymer

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