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Magic with Single Molecules

  • Title: Assistant Professor of Bioengineering, University of California, San Diego
  • Education: PhD, University of Texas at Houston, 2003
  • Recommended by: George Church

If doing a postdoc puts you in the scientific trenches, doing a postdoc in George Church’s lab virtually guarantees a badge of honor. Kun Zhang just completed a whirlwind four years as a postdoctoral fellow with Church, and the experience made him a veteran in single-molecule analysis, DNA sequencing, and large-scale genomic scanning.

Zhang, who earned his PhD at the University of Texas, Houston, and the MD Anderson Cancer Center, spent his first two years in Church’s lab working on technologies at the single-molecule level. Working from individual molecules, Zhang was part of a team that used an in situ polony method and managed to characterize long-range haplotypes across an entire chromosome, compared to the hundreds of kilobases most groups had been able to accomplish. “By doing that, we were able to expand the range by about 1,000-fold,” he says. In parallel, Zhang worked on a project to demonstrate accurate genome amplification from a single cell. “Previously, people had been trying to do that, but it has been very difficult,” he says, mostly because researchers tended to amplify lots of DNA unrelated to the molecule of interest. Zhang was able to show highly specific DNA amplification, and then took that all the way through to genome sequencing from the original single molecule.

But that was just the first two years. Since then, Zhang rounded out his postdoc with a large-scale study of the exon regions in the human genome, and was joint first author on the resulting paper that came out this year in Nature Methods. Part of Zhang’s contribution involved figuring out a way to use microarrays to capture information from SNPs to transcriptome. The method proved successful at capturing “allele-specific gene expression in a digital way,” Zhang says. While there have been a number of analog ways to do this, he says, there’s been no large-scale “method to look at genome-wide, allele-specific gene expression.” He used the method to characterize gene expression patterns across different kinds of tissue, using samples from Church’s Personal Genome Project.

Today, Zhang hangs his hat in San Diego, where he is just setting up his lab as an assistant professor in UCSD’s bioengineering department. He’s still making use of the methods he developed in Church’s lab, but now his focus is on stem cells. That interest was the deciding factor in accepting the offer from UCSD, he says: “I came to California because I wanted to have the freedom to work on human embryonic stem cell lines that are not approved by NIH.” Zhang is looking specifically at examining transcription factors that are active in human embryonic stem cells and tracking their activity in other cell types.

Looking ahead

Zhang can’t wait to get going in his new department. Less than two months into his time on campus, he’d already struck up several collaborations with his new colleagues at UCSD. “It’s not like you’re just doing your own research here,” he says. “People are talking and helping each other.”

A geneticist by training, Zhang says he will have plenty to learn from his computer science and engineering counterparts. His own track is firmly in the stem cell realm, where he hopes that a better understanding of the genetics and genomics of these special cells will yield clues to how to manipulate and reprogram them for medical benefit.

While he’s grateful to be in an instrumentation-heavy department, Zhang sees holes in the technology landscape. For one thing, he says, his research could be greatly expedited if someone invented a tool that would perform “large-scale phenotyping assays” that would automatically collect and measure any number of phenotypes “in a very convenient way.”

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