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To ensure that the data would be publicly accessible and that no group or company would have a competitive advantage, the consortium created a unique workflow for its projects. SGC is a not-for-profit organization funded by the Canadian and Swedish governments and by a few nonprofits and pharmaceutical companies. Although these funders nominate and choose
Researchers with the Structural Genomics Consortium (SGC) have been toiling away in their labs for ∼4 years now, solving and depositing hundreds of protein structures in public databases. To date, they have deposited 15% of the human protein structures solved so far and have published >100 papers on their findings. Yet, many scientists still don’t know what SGC does. Communication is a challenge, says Aled Edwards, who is at the University of Toronto and is the chief executive of the consortium. “We haven’t spent a lot of time on communication because we wanted to spend the time on science and scientific publications, but we appreciate that if we want our scientific output to be used to its maximum, we need to let more people know what we’ve been up to,” he explains. Proteins in 3D. An example of structures solved by SGC. Unlike the better-known Protein Above is an image of poly-(ADP-ribose)polymerase 3 Structure Initiative (PSI) funded (known as PARP-3), a nuclear protein, in complex with an by the U.S. National Institutes of inhibitor (yellow structure). Health, SGC members prioritize the proteins they study by relevance to human health. And the proteins that are on the SGC Target whereas PSI researchers are interested List, they “do not know about the in figuring out the relationship beprogress of any of those targets until tween a protein’s sequence and its [the structure] hits the public datastructure, SGC’s “mandate is to probases,” Edwards points out. He says mote the science of drug discovery by that SGC is viewed as a trusted intermaking fundamental information mediary between academia and indusabout human proteins freely available,” try because the group does not seek says Edwards. patent protection on anything that is The term “drug discovery” often discovered. conjures up images of secretive comIn that spirit, SGC researchers depanies working in competition with posit structures well before they start academic scientists, but this is not the writing papers on their work, and the case for SGC, according to Edwards. structures are freely available with no SGC began as a concept in the late restrictions. SGC protocols, reagents 1990s, when many scientists in the gesuch as clones and small-molecule innomics and pharmaceutical communihibitors, and sometimes even purified ties were rallying against the patenting versions of the proteins, also are free. of gene sequences. This sentiment Work on target proteins is divided helped shape the philosophy of SGC. among investigators at three sites: the “The pharma community felt it would University of Toronto, the University of be better to have [structural] informaOxford (U.K.), and the Karolinska Instition free and accessible [rather] than tute (Sweden). Scientists at each site kept as a trade secret or sequestered in specialize in the analysis of particular a patented state,” says Edwards. protein families. For example, enzymes
10.1021/pr800882w
2008 American Chemical Society
involved in nucleotide metabolism are studied at the Karolinska, whereas protein kinases are investigated at Oxford. Edwards says that by divvying up the work in this way, SGC researchers have the opportunity to become experts in certain areas of protein science. Most target proteins are of human origin, but SGC also studies proteins expressed by human parasites, such as those that cause malaria and toxoplasmosis. Edwards proposed parasites as a secondary focus in 2003. “I felt that if we were going to engage in a large-scale protein project, we, [as] rich countries, should have an impact in that area,” he says. The parasite projects have been centered at the Toronto site, but the Karolinska scientists also are joining the effort.
JOHAN WEIGELT
The Structural Genomics Consortium makes its presence known
The main SGC goal is to determine protein structures, but consortium scientists occasionally pursue related functional studies. “Inasmuch as we can maintain our structural output, which is our top priorityswe need to do, for example, 160 structures every yearsour scientists are highly encouraged to do as much as they can on a functional level, either by themselves or by identifying key collaborators,” says Edwards. In addition, ongoing projects include the generation of chemical inhibitors and binders, such as antibodies, for target proteins. Edwards points out that all of these research areas touch on proteomics. In his view, once a list of interesting proteins is obtained, proteomics scientists should integrate structural, subcellular, and temporal data to more fully understand a system. Graduate students, postdocs, and principal investigators who are interested in collaborating with SGC or conducting research at one of the SGC sites should contact Johan Weigelt at the Karolinska (
[email protected]) or Susanne Mu ¨ ller-Knapp at Oxford (
[email protected]) for more information. —Katie Cottingham PR800882W
Journal of Proteome Research • Vol. 7, No. 12, 2008 5073
