Sunday 24 August 2008

New Grants Drive Development Of Rapid, Cost-Effective Sequencing Technologies

�The National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), has awarded more than $20 million in grants to develop modern sequencing technologies inexpensive and efficient sufficiency to episode a person's DNA as a routine part of biomedical research and health care.



"The ability to comprehensively sequence whatsoever person's genome is the type of quantum leap needed to usher in an age of personalised medicine where healthcare providers can use an individual's genetic code to keep, diagnose, and treat diseases," said Alan E. Guttmacher, M.D., playing director of the National Human Genome Research Institute.



DNA sequencing costs have fallen dramatically over the past decade, fueled in big part by tools, technologies and sue improvements developed as part of the successful try to episode the human genome. NHGRI subsequently launched programs in 2004 to accelerate the development of sequencing technologies and the rate of reduction of genome sequencing cost. Significant progress has been made towards the goal of producing high quality genome sequence of 3 1000000000 base pairs - the amount of DNA ground in humans and other mammals - for $100,000. Ultimately, NHGRI's vision is to cut the cost of whole-genome sequencing of an individual's genome to $1,000 or less, which will enable sequencing as part of routine medical care.



"A unexampled generation of sequencing technologies is stepping in front end of the already impressive technologies that enabled initial sequencing of the human genome," aforementioned Jeffery Schloss, Ph.D., NHGRI's program director for technology development. "We continue to seek further innovation to enable routine sequencing of genomes to advance scientific knowledge and healthcare."



The new grants will fund vIII investigator teams to train revolutionary technologies that would make it possible to sequence a genome for $1,000, as well as troika investigators developing nearer-term technologies to sequence a genome for $100,000. The collective approaches incorporate many complementary elements that integrate biochemistry, chemical science and physics with technology to heighten the whole effort to develop the next contemporaries of DNA sequencing and analysis technologies.



"$1,000 Genome" Grants




NHGRI's Revolutionary Genome Sequencing Technologies grants have as their goal the development of find technologies that will enable a human-sized genome to be sequenced for $1,000 or less.

Grant recipients and their approximative total financial backing are:



Daniel Branton, Ph.D., Jene A. Golovchenko, Ph.D., Harvard University, Cambridge, Mass.

$6.5 million (4 years)

Electronic Sequencing in Nanopores



Several groups are developing nanopores (holes about 2 nanometers in diameter) that may be able to recognize individual DNA bases by their electrical or ionic signals to reach high-accuracy sequencing of individual DNA molecules. The goal of this group is to design and optimize nanopore engineering using novel electronic control and perception methods to eventually lead to a nanopore detector chip subject of sequencing a mammalian genome inside a day on a single instrument.



Stephen Y. Chou, Ph.D., Princeton University, Princeton, New Jersey

$920,000 (3 years)

Nanogap Detector (Arrays) Inside Nanofluidic Channels for Fast Real-Time DNA Sequencing



A nanometer is one-billionth of a meter, much excessively small to be seen with a conventional research lab microscope. This group testament explore exploitation a nanochannel that includes a nanogap detector sensitive enough to identify DNA base pairs by their electrical signals as a single DNA molecule is moved through the device, eliminating the costly stone's throw of amplifying or labeling the DNA. The stress of the initial work is to develop techniques for fabricating nanogap detectors with improved sensitivity and functionality.



Marija Drndic, Ph.D., University of Pennsylvania, Philadelphia

$820,000 (3 years)

DNA Sequencing Using Nanopore-Nanoelectrode Devices for Sensing and Manipulation



This team of researchers will address several current obstacles to achieving nanopore-based DNA sequencing by using nanoelectrodes to sense and manipulate molecules passing through the nanopore, and by integrating microfluidics to actively transport DNA molecules to the nanopore. Developments will be made available to other groups working to create nanopore-based DNA sequencers.



Di Gao, Ph.D., University of Pittsburgh, Pennsylvania

$370,000 (2 years)

DNA Sequencing-At-A-Stretch



This team will position the foundation to demonstrate basic principles for a technology where DNA strands are pulled away from a solid surface when stretched by an electric field. When the stretching force exceeds a certain value, which is proportional to DNA length, the DNA strand would be released from the aerofoil and detected by fluorescence. The order in which strands ar released allows the legal instrument to place the sequence of root pairs.



Xiaohua Huang, Ph.D., University of California, San Diego, La Jolla

$2.5 million (4 years)

Genome Sequencing by Natural DNA Synthesis on Amplified DNA Clones



Building on late advances in sequencing by synthesis in several laboratories, and this lab's advances in preparing very large numbers of sequencing templates on a surface, this project aims to develop an instrument and protocols to ameliorate DNA sequence quality and speed while lowering cost, and develop methods for genome assembly from little sequence reads.



Jiali Li, Ph.D., University of Arkansas, Fayetteville

$830,000 (3 years)

Exploration of Solid-state Nanopore Reading Labeled Linear DNA Sequence



The goal of most nanopore-based sequencing platforms is to be able to succession DNA without having to label or copy the nucleotides. However, this squad will conduct basic research to develop a nanopore sensing organization that labels nucleotides with a bulky group that is loose to discover, to better differentiate the electrical signal difference among DNA bases. The short-run goal of the method acting is to determine the sequence of a piece of DNA about grand base pairs in length using solid-state nanopores.



Stuart Lindsay, Ph.D., Arizona State University, Tempe

$370,000 (1 year)

Sequencing By Recognition



This team will test a method in which molecules that are tethered to electrodes will tie transiently to DNA. Binding would dispatch an electron tunneling circuit, signaling the presence of a especial base - A, C, G or T - within the DNA. If successful, this method would be deployed in a nanopore with different binding molecules for each of the four nucleotide bases.



Predrag S. Krstic, Ph.D., Oak Ridge National Laboratory, Oak Ridge, Tenn.

$720,000 (2 years)

DNA Transport and Sequencing Through a Quadrupole Gate



This investigator is partnering with Mark Reed, Ph.D., of Yale University to develop a nanoscale device that would enhance control of localisation and movement of a DNA molecule based on the idea of a quadrupole Paul trap, a component of a bulk spectrometer that confines and analyzes ions using an intermixture of AC and DC electric fields. Ultimately, this research would combine improved manipulation of the DNA with nucleobase signal detection and could potentially lead to a cheaper alternate to 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 multiplication lower cost than was possible when this opening move was announced in 2004. In voice through the efforts of this NHGRI-led program, several technologies take recently been commercialized or are expected soon, that achieve or nearly attain this goal. These additional grants get for improvements that could be implemented in the near future to farther enhance sequencing at this dramatically lowered cost. Grant recipients and their close together total g are:



Steven A. Benner, Ph.D., Foundation for Applied Molecular Evolution, Inc., Gainesville, Florida

$1.1 million (3 years)

Near-Term Development of Reagents and Enzymes for Genome Sequencing



This laboratory testament apply modern nucleic acid analogs and enzymes that accept them to piecemeal diminish the cost of whole genome sequencing. These technologies, supported by bioinformatic workbenches, enable paths round cost-generating steps by increasing the number of reactions that ar run in parallel, to prepare genomic DNA for the sequencing process.



Jingyue Ju, Ph.D., Columbia University, New York

$950,000 (2 years)

DNA Sequencing with Reversible dNTP and Cleavable Fluorescent ddNTP Terminators



This team will develop a hybrid strategy that uses a salmagundi of chemically modified DNA constituents called nucleotides, along with newfangled methods to restart the sequencing reaction, to improve the length and timber of DNA information produced by sequencing-by-synthesis.



Mostafa Ronaghi, Ph.D., Illumina Inc., San Diego, Calif.

$5.1 zillion (3 years)

Development of a 10Gb Pyrosequencer



The principal investigator of this team is an discoverer of pyrosequencing, which uses unmodified nucleotides to synthesise DNA and generate chemiluminescent signals. Researchers plan to further develop a highly integrated and parallel format with improved equipment for detection of the chemiluminescent signals resulting in an approach that will enable human genome sequencing at a lower place $100,000.





For more details around the NHGRI sequencing engineering science 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 ontogeny at sites nationwide. Additional information around NHGRI bottom be establish at http://www.genome.gov/.



The National Institutes of Health - "The Nation's Medical Research Agency" - includes 27 institutes and centers, and is a constituent 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, inspect http://www.nih.gov/.



Source: Geoff Spencer

NIH/National Human Genome Research Institute




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