Biotech News - NHGRI Aims to Make DNA Sequencing Faster, More Cost Effective
NHGRI Aims to Make DNA Sequencing Faster, More Cost Effective
New Grants Support Quest to Develop Next Generation of Sequencing
Technologies
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 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 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 Sequencing"
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 individual bases.
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 DNA
Sequencing"
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 Resequencing"
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 detection system.
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.
http://www.arizonabiotech.com/
http://tech.groups.yahoo.com/group/biotech-news/
http://www.azhttp.com/
New Grants Support Quest to Develop Next Generation of Sequencing
Technologies
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 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 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 Sequencing"
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 individual bases.
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 DNA
Sequencing"
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 Resequencing"
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 detection system.
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.
http://www.arizonabiotech.com/
http://tech.groups.yahoo.com/group/biotech-news/
http://www.azhttp.com/
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