NEW YORK, Nov. 12 (Genome Technology) - Had the GT All-Stars contest been around 20 years ago, George Church could have won as easily then as now: In 1984 he developed the first direct genomic sequencing method in Wally Gilbert's lab at Harvard, he helped plan the Human Genome Project, and he was one of 11 participants in the first Human Genome Institute Workshop.

Between those old days and now, Church also helped found genome centers at Stanford, MIT, and Genome Therapeutics Corp., and took a faculty position at Harvard where he is now a professor of genetics at Harvard Medical School and director of the Lipper Center for Computational Genetics. Among his credits are the formulation of the concepts of molecular multiplexing and tags, homologous recombination methods, and an array DNA synthesizer.

To be sure, Church would be a good candidate for a lifetime achievement award in genome sequencing, but as far as we know, it was his current work, not his past, that earned him the 2003 GT All-Star Award for Sequencing.

The 49-year-old scientist acknowledges of his lab, "We've published a fair amount recently." His team's latest developments have earned widespread attention from other genomics scientists, some of whom have published follow-on research employing one particular new technology that has emerged from the Church lab.

The method is known as polony sequencing - a process by which PCR colonies, or polonies, generated from acrylamide-coated single molecules and grown on a glass microscope slide are spotted on a gel so that one DNA strand can be immobilized and annealed by a sequencing primer. High-throughput sequencing would be conducted by adding one fluorescence-labeled base at a time. (The polony technology was described in more detail in Genome Technology's July 2003 issue, and Church himself was profiled in the April 2003 magazine.)

While the technology is already in use for exon typing, haplotyping, alternative splicing, and sequence tagging, Church and others are still working to refine polonies for sequencing applications. So far, they have succeeded in sequencing small numbers of bases with the technology.

Church says his main focus now is on reducing the size of the polonies and shrinking the individual sequencing particles with beads. His original experiments relied on 100-micron particles; he has now achieved success sequencing with one-micron particles. Explains Church: "The benefit with one-micron particles is that you can fit 2 million per slide. With 30-base reads, that's enough to cover one human genome."

Researchers outside of Harvard who are now using the polony approach for applications including genotyping and expression profiling are Jeremy Edwards at the University of Delaware and Rob Mitra at Washington University, both former postdocs of Church, and Bert Vogelstein at HHMI. Edwards, whose lab studies systems biology, has published several papers employing the technology for gene expression profiling.

"We're interested in systems biology, and the technologies George is developing are perfect. No others provide the quantitative precision that polony technology does," Edwards says. Plus, he adds, at only a couple of dollars per data point, it's far cheaper than the expensive gold-standard expression profiling method, qPCR, which can run closer to $100 per data point.

Church says the polony approach has captured attention by being "down-to-earth yet exotic enough." Indeed, that combination seems to be the secret to Church's success. Edwards describes the lab where he spent one year as an environment that encourages wild creativity: "George has tremendous people come through his lab, and he gives people the freedom to explore their ideas."

And yet Church reveals his practical side when asked to describe his dream technology: He simply wishes for an inexpensive, high-resolution scanner that would let him transfer the data he generates into a computer.

This is the second in a series of profiles of our 2003 All-Stars. To read now about the rest of the winners - for gene expression, proteomics, bioinformatics, databases, SNPs/genotyping, and dealmaking, as well as the best institute and technology of the year - check out the current issue of Genome Technology.