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Sep 16, 2010

NHGRI Fortifies Third-Generation Sequencing Development with $18M

NHGRI Fortifies Third-Generation Sequencing Development with $18M

Boston University and Scripps, studying single-molecule nanopore techniques, receive the largest grants. [Amit Meller, Boston University]

  • National Human Genome Research Institute (NHGRI) is giving out more than $18 million in grants to spur the development of third-generation DNA sequencing technologies. The grants will fund 10 investigative teams with the aim of driving the cost of genome sequencing down to $1,000.

    Grant recipients and their approximate funding are:
    • Adam Abate, Ph.D., GnuBIO; $240,000 (1 year); Microfluidic DNA Sequencing
    • Amit Meller, Ph.D., Boston University; $4.1 million (4 years); Single Molecule Sequencing by Nanopore-Induced Photon Emission
    • Dean Toste, Ph.D., University of California, Berkeley; $430,000 (2 years); Base-Selective Heavy Atom Labels for Electron Microscopy-Based DNA Sequencing
    • Javier A. Farinas, Ph.D., Caerus Molecular Diagnostics; $500,000 (2 years); Millikan Sequencing by Label-Free Detection of Nucleotide Incorporation
    • Jeremy S. Edwards, Ph.D., University of New Mexico Health Sciences Center; $2.7 million (3 years); Polony Sequencing and the $1000 Genome
    • M. Reza Ghadiri, Ph.D., Scripps Research Institute; $5.1 million (4 years); Single-Molecule DNA Sequencing with Engineered Nanopores
    • Murugappan Muthukumar, Ph.D., University of Massachusetts; $800,000 (3 years); Modeling Macromolecular Transport for Sequencing Technologies
    • Steven J. Gordon, Ph.D., Intelligent Bio-Systems; $2.6 million (2 years); Ordered Arrays for Advanced Sequencing Systems
    • Stuart Lindsay, Ph.D., Arizona State University; $860,000 (3 years); Tunnel Junction for Reading All Four DNA Bases with High Discrimination
    • Xiaohua Huang, Ph.D., University of California San Diego; $800,000 (2 years); Direct Real-Time Single Molecule DNA Sequencing
    • Dean Toste, Ph.D., University of California, Berkeley; $430,000 (2 years); Base-Selective Heavy Atom Labels for Electron Microscopy-Based DNA Sequencing

    Dr. Meller from Boston University and his team report that they have already demonstrated the first use of solid-state nanopores—four-nanometer-wide holes in silicon chips that read DNA strands as they pass through—to optically sequence the four nucleotides that encode each DNA molecule.

    "We are the first to employ optical detection from individual nanopores, and this allows us to probe multiple pores simultaneously using a single high-speed CCD camera," Dr. Meller remarks. "As a result, our method can be scaled up vastly, ultimately allowing us to probe thousands of nanopores and obtain unprecedented DNA sequencing throughput."

    Dr. Meller says that by combining optical detection capability with the ability to analyze extremely long DNA molecules with superior sensitivity, his team's solid-state nanopores are uniquely positioned to compete with current, third-generation DNA sequencing methods for cost, speed, and accuracy. Unlike those approaches, the new nanopore method does not rely on enzymes whose activity limits the rate at which DNA sequences can be read. Instead, readout speed is restricted only by current optical detection limits.

    "This puts us in the unique advantageous position of being able to claim that our sequencing method is as fast as the rapidly evolving CCD/CMOS technologies," said Dr. Meller. "We currently have the capability of reading out about 100 bases per second, which is already much faster than other commercial third-generation methods. This is only the starting point for us, and we expect to significantly increase this rate in the next year."

    Licensing intellectual property from Boston University and Harvard University, Dr. Meller and his collaborators founded NobleGen Biosciences last February to develop and commercialize nanopore sequencing based on the new method. Researchers from the University of Massachusetts Medical School in Worcester are also working on the current project.

    "Given the aggressive research and development effort that's now under way, I estimate that it will take less than five years to bring highly competitive and cheap DNA sequencing to the medical marketplace," Dr. Meller predicts.


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