( and fluorescent signals from many nano...)NHGRI aims to make DNA sequencing faster, more cost effective

• Timothy D. Harris, Ph.D, Helicos Biosciences Corporation, Cambridge, Mass.,$2 million (3 years),"High Accuracy Single Molecule DNA Sequencing by Synthesis"

This team of investigators has developed a fully automated instrument capable of sequencing single molecules of DNA on a planar surface. The group is now developing a high-throughput version of this technology for the re-sequencing of whole human genomes. The sequencing strategy involves obtaining short reads (about 25 DNA bases) from billions of strands of DNA immobilized on a surface inside a reagent flow cell. The research plan aims to advance this strategy to achieve high accuracy, re-sequencing of highly variable genomes and assembly of never-before sequenced genomes.

• Dmitri V. Vezenov, Ph.D., Lehigh University, Bethlehem, Penn. ,$905,000 (3 years),"Force Spectroscopy Platform for Label Free Genome Sequencing"

This team will apply force spectroscopy, a technique used to understand the mechanical properties of polymer molecules or chemical bonds, to DNA undergoing arrested polymerization to initially demonstrate one-molecule-at-a-time analysis of changes in molecular mechanics at a resolution of a single base. Using optical, near-field probes, the methods of force spectroscopy can be advanced into techniques having massively parallel format, where millions of single DNA base additions can be followed at the same time. The identification of bases will be done exclusively on the basis of changes experienced by the molecule as a whole. The team aims to fabricate a low cost table-top setup suitable for use in a majority of biological, chemical and hospital laboratories.

• Peiming Zhang, Ph.D., Arizona State University, Tempe, Ariz.,$8
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