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August 22, 2005

UCSC researchers awarded grant to develop faster, cheaper DNA sequencing

By Tim Stephens

A team including researchers at UCSC has received a major grant from the National Human Genome Research Institute (NHGRI) to develop new technology for genome sequencing.

The grant is part of an NHGRI program to develop "revolutionary genome sequencing technologies" that will enable a human-sized genome to be sequenced for $1,000 or less.

The UCSC researchers are working with collaborators at other institutions to develop electronic sequencing in nanopores. David Deamer, research professor of chemistry and biochemistry and acting chair of biomolecular engineering, and Mark Akeson, associate adjunct professor of biomolecular engineering, are pioneers in the development of nanopore technology for DNA analysis.

They will be working with Harvard University researchers Jene Golovchenko (principal investigator of the project) and Daniel Branton and University of New Orleans researcher Stephen Winters-Hilt, who earned his Ph.D. in bioinformatics at UCSC in 2003.

The three-year, $5.2 million grant includes about $1.5 million for UCSC's part of the project. Deamer said about six researchers at UCSC will be involved in the effort. The objective of this project is to develop a general utility instrument to provide inexpensive sequencing that can also be used for projects to recognize genome variation. The group will design novel nanopores articulated with probes to sequentially, and directly, identify nucleotides in very long fragments of genomic DNA based on their unique electronic signals.

NHGRI, part of the National Institutes of Health (NIH), announced the grant August 8 as part of an expanded effort to advance the development of innovative sequencing technologies by awarding a dozen new grants totaling more than $32 million. The program is intended to reduce the cost of DNA sequencing and expand the use of genomics in biomedical research and health care.

"The efforts are aimed at speeding the rate at which the next generation of sequencing technologies become available in the scientific lab and the medical clinic," said NHGRI director Francis Collins. "Not only will these technologies substantially reduce the cost of sequencing a genome, but they will provide a quantum leap in the scope and scale of research aimed at uncovering the genomic contributions to common diseases, such as cancer, heart disease, and diabetes."

Over the past decade, DNA sequencing costs have fallen more than 50-fold, 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 about $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, which would enable 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 balance NHGRI's sequencing research portfolio by supporting more investigators working on technologies that would make it feasible to sequence a genome for $1,000. The majority of researchers who received NHGRI's initial sequencing technology grants, issued in October 2004, are working on 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.

"It is very important that we encourage and support the variety of sequencing technology projects that hold the most promise for revolutionizing genome sequencing. Each research team brings a unique set of skills and expertise to solving difficult scientific and engineering problems," said Jeffery Schloss, NHGRI's program director for technology development. "The different approaches will likely yield several successful and complementary technologies. It is going to be interesting to see how each technology progresses and which of them can ultimately be used by the average researcher or physician."

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