Funds fuel genome sequencing research

ASU’s Biodesign Institute has received new funding to continue in its development of novel DNA sequencing technologies to help usher in the era of personalized medicine.

Looking ahead to a time when each person’s genome can be sequenced as a routine part of medical research and health care, the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), awarded more than $15 million in grants to support development of innovative technologies with the potential to dramatically reduce the cost of DNA sequencing.

Biodesign Institute researcher Stuart Lindsay was one of eight investigators in the country who received funding to develop revolutionary technologies that would make it possible to sequence a genome for $1,000. Lindsay’s three-year, $890,000 award will integrate biochemistry, chemistry and physics with engineering to enhance the national effort to develop the next generation of DNA sequencing and analysis technologies.

“Innovative sequencing technologies are critical to our efforts to move advances in genomic knowledge into the clinic,” says NHGRI director Francis S. Collins. “The era of personalized medicine will demand more efficient and cost-effective approaches to DNA sequencing.”

The NHGRI, part of the National Institutes of Health (NIH), has set an ambitious target of $1,000 or less – a cost 10,000 times lower than current technology – to make genome sequencing a routine diagnostic tool in medical care. The reduced cost could allow doctors to tailor medical treatments to an individual’s genetic profile for diagnosing, treating and ultimately preventing many common diseases such as cancer, heart disease, diabetes and obesity.

“We believe that rapid DNA sequencing is a unique application for combining single-molecule electronics and chemical recognition, areas in which our Biodesign lab has significant expertise,” says Lindsay, director of the Center for Single Molecular Biophysics at the institute and ASU Carson Professor of Physics and Chemistry.

He leads a team that is developing nanopores (holes about 2 nanometers in diameter) that may be able to recognize individual DNA bases by their electrical or ionic signals to achieve high-accuracy sequencing of individual DNA molecules.

Lindsay will be advised by Gregory Timp from the University of Illinois-Urbana Champaign to develop a high-throughput, high-accuracy, DNA sequencing technology. The research team seeks to develop molecular wires that are sufficiently flexible and sensitive to enable this type of sequencing.

“The Biodesign Institute is a uniquely broad interdisciplinary research environment, and this allows us to bring together tools from physics, chemistry and nanoscale engineering for this challenging project,” Lindsay says.

DNA sequencing costs have fallen more than 50-fold over the past decade, fueled largely by tools, technologies and process improvements developed as part of the effort to sequence the human genome. However, it still costs around $10 million to sequence 3 billion base pairs accurately – the amount of DNA found in the genomes of humans and other mammals.

Lindsay’s effort also joins two other ASU research teams, led by Biodesign’s Peiming Zhang and colleague Jian Gu, and Peter Williams, who have more than $3 million in other DNA sequencing projects funded by the NHGRI.

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 as part of studies to identify genes that contribute to common, complex diseases.

Williams, a professor of chemistry and biochemistry, is working on a $100,000 genome project, part of the five-year goal of the NHGRI to drop the price to a hundredth of the cost. His goal is to selectively sequence genes known to be involved in disease in a matter of hours, and for a few hundred dollars.

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.

In Zhang and Gu’s $1,000 sequencing project, billions of base pairs of genomic DNA could be sequenced on a cookie-crumb-sized, 1-by-1-centimeter chip. The technique uses hybridization, a process of joining two complementary strands of DNA, to sequence DNA by applying a sample to single stranded DNA probes attached to a chip.

For the complete details about the NHGRI sequencing technology development grants, visit the Web site www.genome.gov/10000368.