New core member welcomed to the Broad

By Leah Eisenstadt, Broad Communications, October 31st, 2011
  • Paul Blainey, an expert in single-molecule and
    single-cell approaches, will join the Broad as a core
    faculty member in 2012.

The Broad Institute of MIT and Harvard proudly welcomes scientist Paul Blainey, who will join the institute as a core faculty member in early 2012. He brings expertise in analytic systems at both the single-molecule and single-cell levels.

“Paul is a real visionary in how to study biology at the single-cell and single-molecule levels,” said Broad Institute Director Eric Lander. “I'm thrilled that he has chosen to join the Broad, and extend a warm welcome to him on behalf of our entire community.”

At the Broad, Blainey plans to continue developing new applications of microfluidics in single-cell and single-molecule science. He will also hold an appointment as Assistant Professor in the Department of Biological Engineering at MIT.

“We’re thrilled that Paul’s appointment will bring an even closer partnership with our colleagues in the Biological Engineering Department at MIT,” said Broad core member David Altshuler, who also serves as the Institute’s Chief Academic Officer. “Paul is an extraordinary scientist, and I can’t wait for him to join us.”

A native of Seattle, Blainey studied math and chemistry at the University of Washington. He then pursued graduate study with Xiaoliang Sunney Xie and Broad associate member Greg Verdine in Harvard’s Department of Chemistry and Chemical Biology, with a focus on how proteins interact with DNA. He is currently completing postdoctoral research at Stanford University in the laboratory of Stephen Quake, where he has pioneered novel methods to perform single-cell microbial sequencing.

Blainey will further explore this emerging technology at the Broad. “The real bottleneck in microbial genomics has been the need to grow pure isolates of the organisms you want to study,” he said. At Stanford, he developed a microfluidic platform to physically segregate single cells that scientists don’t know how to culture in the lab, and directly sequence the genome. The technique is useful for identifying and characterizing unknown microbes. In his future work Blainey plans to use the technique to study organisms that humans face everyday in a biomedical context to get a deeper understanding of the population structure of human pathogens and unravel fundamental aspects of microbial evolution.

“Paul's approach is a game-changer in how individual microbes and microbial communities are studied and, ultimately, understood,” said Bruce Birren, co-director of the Genome Sequencing and Analysis Program and director of the Genomic Sequencing Center for Infectious Diseases at the Broad. “I'm thrilled that he will bring his remarkable expertise to bear on key challenges in infectious disease.”

He will also develop and apply single-molecule assays, the focus of his doctoral work. Some cellular proteins, such as those that influence gene activity, need to bind very specific sites in the genome to exact their function. Blainey and his colleagues wanted to understand how these proteins accomplish this impressive task. “The proteins face a real needle-in-a-haystack problem,” he said, “in finding these rare cognate sites among a vast excess of DNA that’s irrelevant to their locus-specific function.”

Scientists hypothesized that the proteins first bind a random site on the genome, and then move along DNA searching for their target site, with the proteins either hopping or sliding along the genome. Blainey and his fellow researchers devised a system to measure how the proteins moved along DNA, using simple microfluidics to stretch DNA and fluorescent protein labels to monitor the movement. The team discovered that the proteins stay in contact with DNA as they slide along it, and that they follow the DNA helix, spinning around it as they move.

In his new role, Blainey plans to develop microfluidic technology to make these single-molecule assays easier to perform, in addition to searching for new kinds of protein molecules and peptides that move along DNA by sliding. “I think there are more interesting molecules with sliding activity out there that we don’t know about yet.”

He also plans to develop and apply a microfluidic platform to connect high-resolution image data with molecular data at the microscale. Building upon the single-cell methods developed during his postdoctoral work, he wants to allow researchers to remove very small samples of microbes, guided by imaging data, and then perform molecular analyses.

Although imaging techniques are sophisticated enough to probe cells at the microscale, molecular biochemical techniques lag behind. “We have all these wonderful genome-wide techniques that give a systems-level perspective,” he said. “But what’s been difficult is addressing systems where the biology is spatially heterogeneous.” With current methods, a scientist must collect a sample of cells, grind it up, and then perform molecular analyses such as sequencing RNA. “You’ve mixed together and washed away all of the microscale heterogeneity, which is really important to the biology of these types of microbial communities.” Blainey aims to synchronize the molecular and imaging techniques, something he thinks will be increasingly valuable for more complex systems, such as those involving both mammalian and infectious microbial cells.

Blainey said he looks forward to joining the Broad, where the diversity of expertise matches that of his research interests. He hopes his work at the Broad and MIT will allow these technologies to find a broad range of important applications quickly. “It’s the best place in the world to do this kind of work.”