The National Human Genome Research Institute (NHGRI) has awarded a $1.1 million
grant to researchers in the Jack Baskin School of Engineering at UC
Santa Cruz to support their work on nanopore technology for analyzing DNA.
 | | This image of the nanopore used by UCSC researchers shows a double-stranded DNA molecule superimposed on the channel of the nanopore. The DNA molecule, 2.2 nanometers in diameter, fits into the pore vestibule but not through the pore, which is 1.5 nanometers wide. Image courtesy of M. Akeson. |
Led by biomolecular engineers Mark Akeson and David Deamer, the UCSC nanopore
group has pioneered a technology based on a tiny pore in a membrane, called
a "nanopore" because it is just 1.5 nanometers wide at its narrowest
point. The nanopore is formed by a self-assembling protein complex called an
ion channel and is just big enough to allow a single strand of DNA to pass through.
Researchers use the nanopore device to obtain precise measurements of DNA structure
and dynamics as the molecule passes through the pore.
A primary goal of the project is to develop nanopore technology as a fast and
inexpensive method for DNA sequencing. Medical diagnosis and treatment is being
revolutionized by tools that enable doctors to quickly obtain detailed genetic
information about their patients. That genetic information is encoded in the
sequence of nucleotide subunits in DNA molecules. Despite many advances in sequencing
technology, however, DNA sequencing is still too expensive and time-consuming
for routine clinical use.
Akeson, a professor of biomolecular engineering, said the UCSC nanopore group
has made progress recently by coupling DNA-binding enzymes to the nanopore.
DNA polymerases are enzymes involved in the replication of DNA in cells. When
coupled to the nanopore, the enzymes control the movement of the DNA molecule
through the pore.
"We are borrowing from nature, which has developed this molecular machinery
to replicate DNA in cells," Akeson said. "The polymerase controls
the rate at which the DNA is processed through the nanopore sensor, operating
in the range of 1 to 100 milliseconds per nucleotide. It also regulates the
distance the DNA molecule moves, so that it advances one nucleotide at a time."
In the work funded by the NHGRI grant, the researchers are focusing on experiments
to measure the effects of voltage and other variables on how efficiently the
nanopore system can control and process long DNA molecules (up to 2,500 nucleotides
in length). The new grant was funded through the economic stimulus bill (the
American Recovery and Reinvestment Act).
Since its beginnings in 1996, the UCSC nanopore project has grown into a large
collaborative effort within the Baskin School of Engineering. In addition to
Akeson and Deamer, a research professor of biomolecular engineering, the group
now includes William Dunbar, assistant professor of computer engineering; Hongyun
Wang, professor of applied math and statistics; and senior investigators Kate
Lieberman, Felix Olasagasti, and Robin Abu-Shumays. Graduate students Noah Wilson,
Daniel Garalde, and Nick Hurt are also associated with the nanopore group, as
are six undergraduates.
"Some of the most promising work we do is coming from the undergrads in
our lab," Akeson said. "One of our laboratories and four of our state-of-the-art
nanopore devices are currently devoted to experiments by these students."
The nanopore technology developed at UCSC has been licensed by Oxford Nanopore
Technologies of Oxford, U.K., which is developing nanopore technology for DNA
sequencing and other potential applications. The UCSC Office for Management
of Intellectual Property was instrumental in negotiating a favorable agreement
with the company, Akeson said.
Posted October 14th, 2009
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