|NHGRI Aims to Make DNA Sequencing Faster, More
New Grants Support Quest to Develop Next Generation of Sequencing
Bethesda, Md. – The National Human Genome Research Institute
(NHGRI), part of the National Institutes of Health (NIH), today
announced the latest round of grant awards totaling more than $13.3
million to speed the development of innovative sequencing technologies
that reduce the cost of DNA sequencing and expand the use of genomics
in medical research and health care.
“There has been significant progress over the last several years
to develop faster and more cost-effective sequencing technologies
and, we are committed to supporting these innovative efforts to
benefit scientific labs and medical clinics,” said NHGRI Director
Francis S. Collins, M.D., Ph.D. “These technologies will eventually
revolutionize the way that biomedical research and the practice
of medicine are done.”
Since 1990, NHGRI has invested approximately $380 million to develop
and improve DNA sequencing technologies. 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 project to sequence the human genome.
However, it still costs around $10 million to sequence 3 billion
base pairs – the amount of DNA found in the genomes of humans and
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 participating in 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 an individual’s
genome during 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 nine investigators developing revolutionary
technologies that may make it feasible to sequence a genome for
$1,000, as well as two investigators developing “near 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. Since 2004, NHGRI
has awarded $83 million to investigators to develop both “near
term” and revolutionary sequencing technologies.
“It is very important that we encourage and support the development
of innovative sequencing technologies. Many of these new approaches
have shown significant promise, yet far more exploration and development
are needed if they are to be useful to the average researcher or
physician," said Jeffery Schloss, Ph.D., NHGRI's program director
for technology development. "We look forward to seeing which of
these technologies fulfill their promise and achieve the quantum
leaps that are needed to take DNA sequencing to the next level."
“$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:
John Nelson, Ph.D., General Electric Global Research,
Niskayuna, N.Y. $900,000 (2 years) “Closed Complex Single Molecule
This team will use existing enzyme and dye-tagged nucleotide
resources, the building block of DNA, in a novel way that will
simplify the fundamental, front-end chemistry of massively parallel
sequencing-by-synthesis. This method uses the natural catalytic
cycle of DNA polymerase to capture just a single DNA base on
an immobilized primer/template. A fluorescence scanner will be
used to scan and identify hundreds of thousand of molecules at
once. Then the cycle will be repeated. This phased award will
increase if specific milestones are met in the initial experiments.
J. Michael Ramsey, Ph.D., University of North Carolina,
Chapel Hill $3.8 million (4 years) “Nanoscale Fluidic Technologies
for Rapidly Sequencing Single DNA Molecules”
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 2 nanometers in diameter) for use as DNA
sequence transducers and propose to detect an electrical, or
ionic, signal from individual DNA molecules. The goal of this
group is to fabricate nanoscale channels in which single molecules
of DNA will pass between nano-electrodes that are less than 2
nanometers apart, to measure an electric current that will identify
Xiaohua Huang, Ph.D., University of California, San
Diego, La Jolla $275,000 (1 year) “Genome Sequencing by Ligation
Using Nano-Arrays of Single DNA Molecules”
Using an experimental method for DNA sequencing called “single
molecule sequencing by ligation,” this project aims to develop
a method for fabricating high-density arrays of wells with sub-micrometer
dimensions for ordering single nanoparticles and DNA molecules.
The investigator will attempt to demonstrate that more than 1
billion individual DNA molecules can be sequenced in massive
parallel though a process involving cyclic sequencing by ligation,
a process where an enzyme is used to join pieces of DNA together.
This phased award will increase if specific milestones are met
in the initial experiments.
Amit Meller, Ph.D., Boston University, Boston $2.2 million
(3 years) “High-Throughput DNA Sequencing Using Design Polymers
and Nanopore Arrays”
This group will continue to implement a novel approach previously
funded through this program in which a nanopore is used to simultaneously
detect electrical and fluorescent signals from many nanopores
at one time. A novel sequencing instrument will be fabricated,
along with additional analysis tools, with the aim of producing
a viable, low-cost sequencing system.
Timothy D. Harris, Ph.D., Helicos Biosciences Corporation,
Cambridge, Mass. $2 million (3 years) “High Accuracy Single
Molecule DNA Sequencing by Synthesis”
This team of investigators has developed a fully automated instrument
capable of sequencing single molecules of DNA on a planar surface.
The group is now developing a high-throughput version of this
technology for the re-sequencing of whole human genomes. The
sequencing strategy involves obtaining short reads (about 25
DNA bases) from billions of strands of DNA immobilized on a surface
inside a reagent flow cell. The research plan aims to advance
this strategy to achieve high accuracy, re-sequencing of highly
variable genomes and assembly of never-before sequenced genomes.
Dmitri V. Vezenov, Ph.D., Lehigh University, Bethlehem,
Penn. $905,000 (3 years) “Force Spectroscopy Platform for Label
Free Genome Sequencing”
This team will apply force spectroscopy, a technique used to
understand the mechanical properties of polymer molecules or
chemical bonds, to DNA undergoing arrested polymerization to
initially demonstrate one-molecule-at-a-time analysis of changes
in molecular mechanics at a resolution of a single base. Using
optical, near-field probes, the methods of force spectroscopy
can be advanced into techniques having massively parallel format,
where millions of single DNA base additions can be followed at
the same time. The identification of bases will be done exclusively
on the basis of changes experienced by the molecule as a whole.
The team aims to fabricate a low cost table-top setup suitable
for use in a majority of biological, chemical and hospital laboratories.
Peiming Zhang, Ph.D., Arizona State University, Tempe,
Ariz. $895,000 (3 years) “Fabrication of Universal DNA Nanoarrays
for Sequencing by Hybridization”
Expanding the performance of the sequencing-by-synthesis technology,
this group will develop a cost-effective method to fabricate
universal DNA nanoarrays using nano-contact printing. The current
photolithography technology can cause damage to DNA probes, which
the group will strive to avoid by using nano-contact printing.
With the nano-sized features, a DNA nanoarray can also improve
throughput by offering the ability to accommodate billions of
DNA molecules in a small area. Hybridization will be detected
by atomic force microscopy.
Carlos H. Mastrangelo, Ph.D., Case Western Reserve University,
Cleveland $815,000 (3 years) “Large-Scale Nanopore Arrays for
This team will aim to develop highly integrated arrays of nanopores
that can be fabricated by lithographic methods, along with on-chip
silicon-based electronic circuits and circuit techniques that
amplify and isolate their various electrical signals. This group
will also design a dipole-sensing methodology, which in principle
can distinguish signals from each of the DNA bases. Arrays of
nanopores will be constructed on silicon substrates using a self-aligned
compositional approach. Quadrature dipole moment detectors will
be constructed that yield a signal independent of the rotation
of the DNA molecule relative to the electrodes.
Jens Gundlach, Ph.D., University of Washington, Seattle
$605,000 (2 years) “Engineering MspA for Nanopore Sequencing”
The passage of single-strand DNA through a nanopore using electrophoresis,
a method using an applied electric field to analyze molecular
structures, has the potential to become an inexpensive, ultrafast
DNA sequencing technique. Most current research in nanopore sequencing
involves the protein pore, a-hemolysin; or artificial pores in
inorganic materials. This investigator will explore the use of
a different protein pore, Mycobacterium smegmatis porin
A (MspA), as a new tool for nanopore sequencing.
“$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 is possible today. There is strong potential
that, in less than five years, several of these technologies will
be at or near commercial availability. Grant recipients in the
current cycle and their approximate total funding are:
Michael L. Metzker, Ph.D., Human Genome Sequencing Center,
Baylor College of Medicine, Houston $500,000 (1 year) "Ultrafast
SBS (Sequencing by Synthesis) Method for Large-Scale Human
This team has developed a novel type of fluorescent nucleotide
that is modified for sequencing by synthesis. Their goal is to
improve the chemical subunits, called reversible terminators,
for use in a system that will ultimately be used to sequence
DNA templates in high-density arrays, using a sensitive fluorescence
Steven Jeffrey Gordon, Ph.D., Intelligent Bio-Systems,
Inc., Worcester, Mass. $425,000 (1 year) “High-Throughput DNA
Sequencing by Synthesis Platform”
The main goal of this project is to develop a high-speed, massively
parallel DNA sequencing system using unique base analogues with
cleavable dye and reversible terminator groups and the sequencing
by synthesis approach. This application is focused on the development
of the subsystems required to construct high-density sample arrays
on glass chips and to run sequencing by synthesis reactions on
them in an automated, high-throughput fashion.
For more details about the NHGRI sequencing technology development
grants, go to http://www.genome.gov/10000368.
NHGRI also just announced the next round of funding under the genome
sequencing technology program. The deadline for applying is Nov.
24, 2006, and information about the application process can be
found at http://genome.gov/10000990.
Editor’s Note: NHGRI Director Francis Collins
will participate in a press conference to announce a $10 million
prize offered by the X Prize Foundation for the creation
of rapid genome sequencing technology. The prize is designed
to stimulate competition to speed up the use of genome sequencing
in research and medicine. The press conference will be held
at 10 a.m. Wednesday, Oct. 4, 2006, in the 13th floor ballroom
of the National Press Club, 529 14th Street NW, Washington, D.C.
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.