|New Grants Bolster Efforts to Generate Faster
and Cheaper Tools for DNA Sequencing
NHGRI Seeks to Advance Next Generation of
Looking ahead to a future in which each person’s genome can be
sequenced as a routine part of medical research and health care,
the National Human Genome Research Institute (NHGRI), part of the
National Institutes of Health (NIH), today awarded more than $15
million in grants to support development of innovative technologies
with the potential to dramatically reduce the cost of DNA sequencing.
"Innovative sequencing technologies are critical to our efforts
to move advances in genomic knowledge into the clinic. The era
of personalized medicine will demand more efficient and cost-effective
approaches to DNA sequencing,” said NHGRI Director Francis S. Collins,
DNA sequencing costs have fallen more than 50-fold over the past
decade, fueled in large part by tools, technologies and process
improvements developed as part of the successful effort to sequence
the human genome. However, it still costs as much as $5 million
to sequence 3 billion base pairs — the amount of DNA found in the
genomes of humans and other mammals.
NHGRI’s near-term goal is to lower the cost of sequencing a mammalian-sized
genome to $100,000, allowing researchers to sequence the genomes
of hundreds or even thousands of people as part of studies to identify
genes that contribute to common, complex diseases. Ultimately,
NHGRI’s vision is to cut the cost of whole-genome sequencing to
$1,000 or less, which will enable the sequencing of individual
genomes as part of routine medical care. The ability to sequence
an individual genome cost-effectively could enable health care
professionals to tailor diagnosis, treatment and prevention to
each person’s unique genetic profile.
The new grants will fund eight investigators to develop revolutionary
technologies that would make it possible to sequence a genome for
$1,000, as well as three investigators developing nearer-term technologies
to sequence a genome for $100,000. Both approaches have many complementary
elements that integrate biochemistry, chemistry and physics with
engineering to enhance the whole effort to develop the next generation
of DNA sequencing and analysis technologies.
"The different approaches will likely result in several successful
and complementary technologies. We will monitor carefully to see
how each technology progresses and which of them can ultimately
be used by the average researcher or health care provider,” said
Jeffery Schloss, Ph.D., NHGRI's program director for technology
development. "Each research team brings a unique set of skills
and expertise to solving difficult scientific and engineering problems."
“$1,000 Genome” Grants
NHGRI’s Revolutionary Genome Sequencing Technologies grants have
as their goal the development of breakthrough technologies that
will enable a human-sized genome to be sequenced for $1,000 or
less. Grant recipients and their approximate total funding are:
Richard B. Fair, Ph.D., Duke University, Durham, N.C.
$3,686,000 (3 years)
Continuous Sequencing-by-Synthesis, Based on a Digital Microfluidic
This group has already shown the potential of droplet-based
microfluidics in sequencing-by-synthesis. Their new goals are to
extend read length, minimize reaction volume and increase throughput
to 10,000 reactions in a very small area. Separating the chemistry
and detection steps makes this technology more efficient, and the
droplet-based microfluidics system solves many of the difficulties
involved with complicated fluid handling on a very small scale.
Stuart Lindsay, Ph.D., Arizona State University, Tempe
$877,000 (3 years)
Sequencing by Recognition
A nanometer is one-billionth of a meter, much too small
to be seen with a conventional lab microscope. Several groups are
developing nanopores (holes about two nanometers in diameter) that
may be able to recognize individual DNA bases by their electrical
or ionic signals to achieve high-accuracy sequencing of individual
DNA molecules. This research team seeks to develop molecular wires
that are sufficiently flexible and sensitive to enable this type
Xinsheng Sean Ling, Ph.D., Brown University, Providence,
$820,000 (3 years)
Hybridization-Assisted Nanopore DNA Sequencing
Investigating further the potential of nanopore technology,
these researchers intend to use solid-state nanopores to detect
the location, along a DNA strand, where another short, known DNA
sequence attaches by hybridization (base-pairing). By doing this
experiment many times with many different short, known sequences,
the sequence of long DNA strands would be determined.
Wlodek Mandecki, Ph.D., University of Medicine and Dentistry
of New Jersey, Newark
$1,672,000 (3 years)
Ribosome-Based Single Molecule Method to Acquire Sequence Data
This researcher and his team will modify key components
of the ribosome — the translation system that cells use to build
proteins on messenger RNA templates — to read out the sequence
of nucleotide building blocks along that message. Any DNA molecule
can be converted to such a message, so by “sequencing” the messenger
RNA, the sequence of the DNA itself could be determined.
Andre Marziali, Ph.D., University of British Columbia,
$746,000 (3 years)
Nanopore Array Force Spectroscopy Chip for Rapid Clinical Genotyping
These investigators will develop solid-state, nanopore-based
force spectroscopy for rapid electronic detection of sequence variation.
The project builds on the team’s previous demonstration of the
ability to detect sequences at single base resolution using organic
nanopore force spectroscopy.
John S. Oliver, Ph.D., NABsys, Inc., Providence, R.I.
$498,000 (2 years)
Hybridization-Assisted Nanopore Sequencing
This team will work with collaborators at Brown University
to develop the biochemical and algorithmic components of a method
for sequencing by hybridization. By designing tagged probes and
novel reconstruction algorithms, the team expects to get around
the resolution limits that have prevented nanopores from being
used for sequencing.
Robert Riehn, Ph.D., North Carolina State University,
$439,000 (2 years)
Sequencing DNA by Transverse Electrical Measurements in Nanochannels
This group proposes to stretch long DNA molecules by passing
them through nanofluidic channels. Nanoelectrodes will be built
into those channels to detect each DNA base’s specific electrical
H. Kumar Wickramasinghe, Ph.D., University of California,
$2,184,000 (3 years)
High-Throughput, Low-Cost DNA Sequencing Using Probe Tip Arrays
This group has proven the feasibility of accelerating and miniaturizing
the conventional Sanger method of DNA sequencing by relying on
nano-scale electrophoretic separation of DNA fragments along the
surface of an Atomic Force Microscope probe tip. This method reduces
volume of materials, potentially accelerating and reducing the
cost of sequencing. Researchers plan to demonstrate these very
challenging separations and to implement them on a massively parallel
sequencing platform containing hundreds of probe tips.
“$100,000 Genome” Grants
NHGRI’s Near-Term Development for Genome Sequencing grants will
support research aimed at sequencing a human-sized genome at 100
times lower cost than was possible when this initiative was announced
in 2004. In part through the efforts of this NHGRI-led program,
several technologies have either recently been commercialized,
or are expected to be released during the next few months, that
have great potential to achieve this goal. These additional grants
aim to make improvements that could be implemented in the near
future to further improve sequencing at this dramatically-lowered
cost. Grant recipients and their approximate total funding are:
Jeremy S. Edwards, Ph.D., University of New Mexico School
of Medicine, Albuquerque
$900,000 (3 years)
Polony Sequencing the Human Genome
The ultimate goal of this team is to use established polony genome
sequencing technology to re-sequence a human genome within a week
for less than $10,000. To meet their goal, they will continue improving
the quality of sequencing data and further develop the computational
tools needed to assemble a human genome sequence.
Jingyue Ju, Ph.D., Columbia University, New York (Two Grants)
$644,000 (2 years)
3’-O-Modified Nucleotide Reversible Terminators for Pyrosequencing
This investigator will design a library of synthetic molecular
tools designed to optimize the pyrosequencing method to overcome
the difficulties deciphering repetitive regions of DNA templates.
The current pyrosequencing method utilizes unmodified DNA base
pairs and polymerases to synthesize DNA and a firefly enzyme to
generate a chemiluminescent signal.
$2,217,000 (2 years)
An Integrated System for DNA Sequencing by Synthesis
This team will continue its development and optimization of a
novel set of fluorescent nucleotide reversible terminators for
sequencing by synthesis. A new method for preparing DNA-beads for
attachment to a substrate will also be developed. The goal is to
increase the length of the DNA sequencing reads while maintaining
high data quality.
David C. Schwartz, Ph.D., University of Wisconsin, Madison
$882,000 (3 years)
Sequence Acquisition from Mapped Single DNA Molecules
The focus of this project is to create a system capable of analyzing
large amounts of human genome data that ties the location of sequence
elements to longer-range map information. This would include information
such as structural variations and aberrations associated with cancer
genomes. The resulting data could be linked to information produced
by other emerging sequencing platforms.
For more details about the NHGRI sequencing technology development
grants, go to: http://www.genome.gov/10000368.
NHGRI is one of the 27 institutes and centers at NIH. The NHGRI
Division of Extramural Research supports grants for research and
training and career development at sites nationwide. Additional
information about NHGRI can be found at www.genome.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.