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Research by Christina Fan '10 and Jianbin Wang '12 Named to Technology Review's TR10

ARTICLE BY: Ingfei Chen

Technology Review

September 12th 2011

Research by Christina Fan '10 and Jianbin Wang '12 was honored as one of the 10 Emerging Technologies of 2011 by MIT Technology Review.


Every year, Technology Review looks at the advances that have happened over the previous year and chooses 10 emerging technologies that we think will have the greatest impact. The ultimate criterion is straightforward: is the technology likely to change the world? This year’s group includes high-energy batteries that could make cheaper hybrid and electric vehicles possible and a new class of electrical transformers that could stabilize power grids. Some of our choices will alter how you use technology: you’ll be tapping into computationally intensive applications on mobile devices, or using gestures to command computers that are embedded in televisions and cars. Other choices could improve your health; for instance, doctors will craft more effective cancer treatments by understanding the genetics of individual tumors. But no matter the category, all 10 promise to make our lives better. 


Separating Chromosomes

A more precise way to read DNA will change how we treat disease

The clear rubber chip sitting under a microscope in Stephen Quake's lab is a complex maze of tiny channels, chambers, and pumps, hooked up to thin plastic tubes that supply reagents and control 650-plus minuscule valves. Using this microfluidic chip, Quake, a biophysicist at Stanford University, has engineered a way of obtaining data that's missing from nearly all human genome sequences: which member of a pair of chromosomes a gene belongs to.

Technology that makes it easier to identify the variations between chromosomes could have a huge impact on fundamental genomic research and personalized medicine. "This is definitely the next frontier," says Nicholas Schork, a statistical geneticist at the Scripps Research Institute. Right now, he says, "we're missing out on all sorts of biological phenomena that occur as a result of humans' having [paired chromosomes]."

When scientists sequence human genomes, they largely ignore the fact that chromosomes come in pairs, with one copy inherited from the mother and one from the father. (The Y chromosome, which determines gender, is the exception.) Standard techniques blend genetic data from the two chromosomes to yield a single sequence.

Quake's alternative is to physically separate chromosomes before genomic analysis. Cells are piped into the chip; when Quake spots one that's preparing to divide (a stage at which the chromosomes are easier to manipulate), he traps the cell in a chamber and bursts its membrane, causing the chromosomes to spill out. They are randomly distributed into 48 smaller chambers. While it is possible for more than one chromosome to end up in a single chamber, it's very unlikely that a chromosome will end up with its pair. Using standard techniques, the chromosomes are then sequenced or screened for genetic variants.

Other groups have pursued different strategies to sequence individual chromosomes. But Quake thinks his has an advantage because it doesn't rely on decoding and reconstructing chromosomes from a mixed pool of DNA fragments, as others do. "By the way we physically prepare the sample, we know [the result is] right," he says.

If costs can come down enough, Quake's technique will be widely used, says Meredith Yeager, a senior scientist at the National Cancer Institute's Core Genotyping Facility. The ability to routinely tell where genetic variants lie on different chromosomes "really is a big deal," Yeager says. "Context matters."

For example, if testing detects two separate mutations in a disease-related gene, it's now impossible to tell whether one chromosome has both mutations or each chromosome has one. A patient who has at least one good copy of the gene is much more likely to escape the disease or experience it in a relatively mild form. Whether the aim is to predict responses to an asthma drug or to find better matches for bone marrow transplants, the accuracy of personalized medicine could eventually hinge on understanding the variation between chromosomes.

Fluidigm, the South San Francisco company that Quake cofounded in 1999 to commercialize microfluidic chips, is now looking at ways to automate the chromosome separation chip so that it doesn't require so much expertise to use. Quake hopes to discover "something really interesting" about human diversity or the region of the genome that defines immune system responses. This region has been difficult to understand because it has so much genetic variation, and scientists lacked a tool to study it carefully—until now.

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