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UCSFSchool of PharmacyNews ArchiveAdam Abate receives NSF CAREER award

Adam Abate receives NSF CAREER award



Friday, March 1, 2013

Adam Abate, PhD

By David Jacobson

Physicist Adam Abate, PhD, who applies microfluidics technology to speedily process millions of encapsulated biological samples to discover drugs, engineer proteins, and diagnose cancers, has received a National Science Foundation (NSF) CAREER award.

The prestigious award, which provides $750,000 in funding over five years, supports junior faculty who “exemplify the role of teacher-scholars through outstanding research … and the integration of education and research.”

Abate’s awarded project will develop new technology—massively-parallel ultrahigh-throughput single-cell sequencing—to allow scientists to determine the genetic make-up (genomes) of each individual cell in samples as large as a million cells in just a few days. It will also allow researchers to analyze each cell’s transcriptome (transcribed RNA) which reflects which genes are active.

Abate is a faculty member in the Department of Bioengineering and Therapeutic Sciences, a joint department of the UCSF Schools of Pharmacy and Medicine, and is also affiliated with the Institute for Quantitative Biosciences (QB3).

Potential uses of massively parallel single-cell sequencing

Individual cell analysis is vital to understanding diseases such as cancer, Abate notes, since the cells that comprise a tumor are actually heterogeneous.

“Doing a transcriptome analysis of the cells in tumors,” he says, allows researchers to determine “which of those cells are actively replicating or expressing genes that are important for evading the immune system or inducing angiogenesis” (increasing blood supply for further tumor growth).

Differentiating among cancer cells’ genetic makeup and activity allows researchers to better understand the disease and target it with treatments.

Currently investigators may precisely dissect tumors but ultimately must mix the genomes and transcriptomes of thousands of cells for analysis. This loses key distinctions, such as the gene interactions within certain cells that render them resistant to chemotherapy.

Moreover, since it takes days to analyze the genetics and gene activity of one cell in a test tube, it would literally take centuries to sequence the genomes of a million cells, one by one.

But Abate’s lab will encapsulate each cell in a microdroplet of water (a tenth the diameter of a human hair) that flows in an oil emulsion channel at a rate of about 1,000 droplets per second. The cells will be broken open inside the droplets and treated to amplify (make additional copies of) portions of the genome or transcriptome for analysis.

You need JavaScript enabled and Adobe Flash Player 8 or newer to view this video. Watch on YouTube

A slow-motion Abate lab video captures picoinjection, in which about 10 picoliters (10 trillionths of a liter) of chemical reagent (such as might be used to amplify DNA) is added to microdroplets of water flowing in an oil emulsion at a rate of about 1,000 per second.

The new technology being developed will use this ultra-fast assembly line of what are, effectively, microscopic liquid test tubes to radically speed up the process. Ultimately, after DNA from a million microdroplets is subject to simultaneous en masse sequencing of their nucleobase makeup, each genome and transcriptome can be traced back to an individual cell.

For now, this kind of massively-parallel “single-cell sequencing capability doesn’t exist,” says Abate. “Once it does, there will be many applications we can’t even envision right now.”

Indeed, in an educational outreach component of the project, graduate students in Abate’s lab will lead expeditions of community college and high school students to collect wild bacteria samples—another mixture of diverse single-celled species that can be difficult to analyze for sub-types via current means. The students will learn lab skills and bioscience by genetically sequencing the bacteria using the new technology.

More:

Adam Abate - Faculty Profile - YouTube

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