A team of researchers led by Jingyue Ju, Samuel Ruben-Peter G. Viele Professor of Engineering at Columbia University's Fu Foundation School of Engineering and Applied Science, has won a three-year $5.25 million grant from the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), to develop a novel integrated miniaturized system for real-time single molecule electronic DNA sequencing.
The award is the largest of NHGRI’s most recent $17 million initiative to support development of innovative technologies with the potential to dramatically reduce the cost of DNA sequencing, so that sequencing an individual’s genome can become a routine part of medical research and health care.
The team includes researchers from Columbia University and its collaborative institutions: Harvard University, Genia Technologies, Inc., and the National Institute of Standards and Technology (NIST). Under the direction of Ju, who is also Professor of Chemical Engineering and Pharmacology and Director of Columbia Engineering’s Center for Genome Technology and Biomolecular Engineering, the team aims to use nucleic acid chemistry, electronics, and protein engineering to develop a NanoTag single molecule electronic DNA sequencing approach, which includes the design and synthesis of four nucleotide analogs (modified building blocks of DNA) labeled at the 5’-terminal phosphate with distinct polymer tags. These tagged-nucleotides will elicit well-differentiated electrical current blockade signals as they enter nanopores under an applied voltage during polymerase reaction for DNA sequence determination. The investigators will assemble large arrays of the nanopores, each with an attached polymerase, to create DNA sequencing chips. The addition of the primed DNA template and the four tagged-nucleotides to the nanopore-chip will allow high accuracy single molecule electronic sequencing by synthesis in real time.
“Our research and development efforts in DNA sequencing technologies have been generously supported by the NIH for over a decade. This has led to the development of a four-color DNA sequencing by synthesis platform using cleavable fluorescent nucleotide reversible terminators, which is the dominant approach used in the next generation DNA sequencing systems,” says Ju. “This new NHGRI grant provides timely support for our consortium to develop the NanoTag single molecule electronic DNA sequencing approach into a robust miniaturized platform that will eventually allow the entire human genome to be deciphered for about $100. The enhanced accuracy, scalability, and flexibility of this technology will make it an ideal platform for personalized medicine and basic biomedical research.”
The other key researchers for the Columbia Engineering-led research consortium include George Church, Professor of Genetics, Harvard University Medical School; James Russo, Associate Director of the Center for Genome Technology and Biomolecular Engineering, and Ken Shepard, Professor of Electrical and Biomedical Engineering, both at Columbia; John Kasianowicz, fellow of the American Physical Society, at NIST; and Stefan Roever, CEO of Genia.