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Home > ARRA Stories > Dr. Stephen Turner: Creating DNA Sequencing Solutions
Dr. Stephen Turner: Creating DNA Sequencing Solutions

By Alison Davis

December 21, 2009

Stephen Turner, Ph.D., Chief Technology Officer, Pacific Biosciences, Inc.

Photo of Stephen Turner

For many, the most dramatic triumph of modern biology has been the sequencing of the human genome. But although scientists can now read the human DNA language letter-by-letter, countless individual dialects remain to be discovered and explored. Physicist-turned-DNA sequencer Dr. Stephen Turner has a plan.

The Problem: The Human Genome Project spelled out the three billion DNA letters of the human genome. This provided researchers with a "reference genome," the ordered sequence of DNA sampled from just a few different people. The same work must be repeated for thousands of individual genomes, an effort that is time-consuming, labor-intensive and costly.

Re-sequencing the genome of many individuals for whom there is only a reference genome available will let scientists dig deeper to find genetic hot spots that serve as disease signatures. New tools and technologies are emerging to reduce the cost of DNA sequencing such that, ultimately, it can be a routine part of both research and medicine.

Finding a Solution: Dr. Turner and his team at Pacific Biosciences Inc., in Menlo Park, Calif., are working toward the goal of slashing the cost of DNA sequencing to $1,000 per genome; that's 100 times cheaper than currently possible. They invented a technique called Single-Molecule Real-Time (SMRT) DNA sequencing. This DNA-reading method is unique in that it actually mimics what happens in the body as cells divide and copy their DNA with a cellular protein machine called DNA polymerase. SMRT sequencing uses a lab-made version of this DNA-making engine and adds a few twists to make the process fast.

As the DNA-making machine tracks along the DNA, it adds a fluorescent tag to each of the four DNA letters, creating a burst of light that is recorded by a computer. Just as quickly, the tag falls off and the reading continues without delay. Although it is very fast, the process is extremely precise, Dr. Turner says, because it focuses on only one DNA letter at a time.

In addition to the funding received for SMRT sequencing, Pacific Biosciences also received a Recovery Act grant to adapt the SMRT process for specific uses. Using this funding, Dr. Turner custom-designed DNA polymerase to sense slight, subtle "rhythm" changes–like syncopation in a jazz piece–in a DNA strand as it is being made. These changes signify the presence of chemical tags called methyl groups. Detecting these chemical tags allows researchers to identify these changes, which are known to be central in both healthy development and diseases like cancer, on DNA.

How This Funding Helps: Dr. Turner's Recovery Act funding could lead to a $1,000 genome and much more. He predicts that if SMRT DNA sequencing technology works as expected and becomes commercially available to the broader scientific community, it will bring hundreds of new jobs to Silicon Valley as well as a revolutionary tool for researchers to understand the role of epigenetics in health and disease.

"Having government funding in an economic downturn revived a crucial project that would have been shelved. Maintaining this technology is important not just for us, but for the future of personalized medicine."

Dr. Turner is especially excited about the promise of his SMRT DNA methylation approach. In addition to giving scientists a powerful tool for mapping the "topography" of an individual's DNA, he explains, it may ultimately enable fingerprinting of disease-specific markings in tumors and other tissues.

After Two Years ... The Pacific Biosciences project is one of seven projects, each with a different technological strategy, funded by the Recovery Act to achieve a $1,000 genome. Dr. Turner notes that he doesn't see it as a race, but as a brute-force attack on the obstacles to reach the goal. The multiple approaches will likely complement each other, and having several people working on the problem ensures that after two years, "someone will cross the finish line."

According to Dr. Turner, current gene tests cost about $2,500 on average, and they read the sequence of only one gene. With a $1,000 price tag or less for reading an entire genome of 20,000 genes in a matter of minutes, Dr. Turner explains, DNA information can become a routine part of medical care. Just like a simple blood test, an inexpensive whole-genome DNA scan could help health care providers choose effective, personalized treatments in an office or clinic setting.

Recovery Act Investment: "Real-Time Multiplex Single-Molecule DNA Sequencing," $714,406 for FY 2009; "Direct Single Base-Pair Real-Time DNA Methylation Sequencing," $595,011 for FY 2009 (both from the National Human Genome Research Institute)

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