The US National Human Genome Research Institute has awarded a total of more than $38 million in two sets of grants to 18 companies and laboratories, with the goal of producing new technologies to reduce the cost of sequencing a typical mammalian genome by 100-fold within five years, and by 10,000-fold in later years, from its current rate of about $10 million.
The first set of grants, which total $31.5 million, was awarded to 11 groups that will pursue technologies capable of sequencing 3 billion base pairs for $100,000 or less. The second set of grants, totaling $6.75 million, were awarded to groups hoping to bring the cost of sequencing down to $1,000 per genome.
“These grants will open the door to the next generation of sequencing technologies. There are still many opportunities to reduce the cost and increase the throughput of DNA sequencing, as well as to develop smaller, faster sequencing technologies that meet a wider range of needs,” said NHGRI Director Francis Collins in a statement announcing the grants last week.
The “$100,000 Genome” grants are:
- $6.1 million over three years to Stevan Jovanovich of Microchip Biotechnologies in Fremont, Calif., to develop the benchtop, automated Sanger technology-based “Microbead Integrated DNA Sequencer System.” The device labels and processes DNA fragments from individual microbeads, and utilizes “microfabricated” capillary electrophoresis channels.
- $5.4 million over three years to Gina Costa of Beverly, Mass.-based Agencourt Bioscience. The group’s “Bead-based Polony Sequencing” uses a “highly parallel” sequencing approach, which detects the single-nucleotide extension of DNA fragments attached to magnetic beads.
- $2.0 million over two years and $5.0 million over three years to Kenton Lohman and Marcel Margulies, respectively, both of 454 Life Sciences in Branford, Conn. The grants support further development of the company’s “Massively Parallel System.”
- $2.5 million over three years to John Williams of LI-COR in Lincoln, Neb. to support “Single-Molecule DNA Sequencing Using Charge-Switch dNTPs.” The technology will “detect the release of reaction products” from nucleotides as they are incorporated into growing DNA strands.
- $2.0 million over three years to Michael Metzker of the Baylor College of Medicine Human Genome Sequencing Center in Houston. This team is pursuing an “Ultrafast Sequencing by Synthesis Method for Large-Scale Human Resequencing.” The approach uses fluorescent, photolabile nucleotide terminators and “improved” DNA polymerases.
- $1.8 million over three years to Stephen Quake of Stanford University in Palo Alto, Calif., for “High-Throughput, Single-Molecule DNA Sequencing,” using sequencing by synthesis technology coupled with the detection of fluorescence resonance energy transfer with a total internal reflection microscope.
- $1.8 million over three years to Mostafa Ronaghi of the Stanford Genome Technology Center in Palo Alto, Calif. The group will develop a “Pyrosequencing Array for DNA Sequencing,” which incorporates a chemiluminescent signal-producing firefly enzyme into ordinary DNA synthesis.
- $1.8 million over three years to Jingyue Ju of Columbia University in New York. Ju’s team is working with an “Integrated System for DNA Sequencing by Synthesis,” which includes detection of fluorescent nucleotides after their addition to growing DNA strands. The group also hopes to produce a high-throughput system involving “thousands” of DNA molecules attached “site specifically,” that will be used in sequencing by synthesis.
- $1.7 million over three years to Peter Williams of Arizona State University in Tempe, Ariz. His group’s “Multiplexed Reactive Sequencing of DNA” will use fluorescein-labeled nucleotides and commercially available detectors in a “practical” multiplexed sequencing-by-synthesis system.
- $800,000 over three years to Steven Benner of the University of Florida in Gainesville. This grant will support development of “Polymerases for Sequencing by Synthesis,” an approach using DNA polymerase engineered for “optimal” sequencing by synthesis using chemically altered nucleotides.
- $600,000 over two years to Amit Meller of the Rowland Institute at Harvard University in Cambridge, Mass., for development of an “Ultra-fast Nanopore Readout Platform for Designed DNAs.” The team will work on the detection of simultaneous electrical and fluorescent signals from “many” nanopores as DNA molecules pass through them.
The “$1,000 Genome” grants are:
- $2.0 million over two years to Michael Ramsey of the University of North Carolina in Chapel Hill. The group will explore single-DNA-molecule sequencing using devices built by combinations of fabrication technologies, as well as simulation and modeling focused on the understanding of basic physics at the single-molecule level.
- $700,000 over three years and $750,000 over three years to James Weifu Lee of Oak Ridge National Laboratory in Oak Ridge, Tenn. Lee’s group will develop computational modeling to be used in the fabrication of a “novel” nanotechnology sequencing device that will use electron tunneling to detect stretched DNA molecules as they pass between electrodes.
- $850,000 over two years to Scott Collins of the University of Maine in Orono to develop electrode-equipped nanopores that detect DNA molecules using electron tunneling.
- $800,000 over three years to Steven Benner of the University of Florida in Gainesville. The second grant to this group will support work on “DNA Sequencing Using Nanopores,” which involves DNA detection using gold-coated conical nanopores.
- $650,000 over three years to Andre Marziali of the University of British Columbia in Vancouver, Canada, to support the group’s research on the use of “Nanopores for Transmembrane Biomolecule Detection.” It will attempt to “extend the use of nanopore sensors into living cells” and understand better how nanopores interact with single molecules.
- $550,000 over three years to Stuart Lindsay of Arizona State University in Tempe. His grant will support research into a “Molecular Reading Head for Single-molecule DNA Sequencing,” which uses a “chemical ring” to detect DNA by friction as it passes through a nanopore.
- $450,000 over two years to Ronald Davis of Stanford University in Stanford, Calif., which will research “Single Molecule Nucleic Acid Detection with Nanopipettes.”