NIH award supports research on nanopore DNA sequencer

NIH award supports research on nanopore DNA sequencer
NIH award supports research on nanopore DNA sequencer
Wednesday, September 27, 2006

William Dunbar, an assistant professor of computer engineering at UC Santa Cruz, has received a career development award from the National Institutes of Health. The Mentored Quantitative Research Career Development Award is designed to encourage researchers with backgrounds in quantitative science and engineering to focus on questions relating to health and disease.

Dunbar, whose expertise is in the area of feedback control, will be working with faculty in the Department of Biomolecular Engineering to develop nanopore technology for high-speed DNA sequencing. He will be applying feedback control to probe and enhance the ability of a nanopore device to obtain sequence information from individual DNA molecules.

UCSC's nanopore project, funded by a major grant from the National Human Genome Research Institute (NHGRI), is part of an NHGRI program to develop revolutionary genome sequencing technologies that will enable a human-sized genome to be sequenced for $1,000 or less (see earlier story).

"Such capability would lead to efficient reading of human genetic variations. This would in turn lead to disease treatments and preventions based on information from the patient's own genome," Dunbar said.

NHGRI is sponsoring Dunbar's $690,000 grant, which will support him for five years of supervised study and research under the guidance of three faculty mentors. His primary mentor is David Haussler, professor of biomolecular engineering, and co-mentors are David Deamer, research professor of chemistry and biochemistry, and Mark Akeson, associate adjunct professor of biomolecular engineering. Deamer and Akeson have pioneered the development of nanopore technology for DNA analysis.

Dunbar's research will include the use of feedback control to probe and characterize enzymes coupled to the nanopore. The nanopore is large enough to thread single-stranded nucleic acids (DNA and RNA) through it, but enzymes are too large to pass through the pore. By pulling DNA and RNA molecules into the nanopore while they are being acted on by an enzyme, the nanopore serves as a "sensor" that can monitor the dynamic state of the enzyme, which remains on top of the nanopore as it processes the molecule, Dunbar said.

"Feedback voltage control can be used to hold the enzyme in place for monitoring purposes or to alter the enzyme's dynamic state," he said. "From an engineering perspective, enzymes are the nanomotors of the biological world, and they are amazingly robust and efficient. The possibility of being able to probe a single enzyme while it is functioning is very exciting."

Additional information about the nanopore project at UCSC is available online at http://www.cbse.ucsc.edu/research/research_nano.shtml.