Los Alamos National Laboratory

High-Throughput Laboratory Network

Every influenza virus has the potential to mutate its way past molecular defenses such as vaccines, so the key to having control over influenza is to understand how it evolves. “Rendering a virus harmless means honing in on the exact sequences that are being changed though mutations,” says Gary Resnick, the Bioscience Division leader.

The first node of that network will be UCLA’s Global Bio Laboratory. Nearly operational, the lab will consist of several automated or semiautomated stations for inventorying samples gathered from influenza hot spots, preparing the samples for analysis, and screening them to make sure they contain influenza A.

The High-Throughput Laboratory Network project's sequencing team leader, Lance Green.

An influenza sample will typically contain anywhere from a thousand to 100 million viruses per milliliter, not enough to sequence the whole genome. In the past, researchers would infect embryonated chicken eggs with the virus, let the virus reproduce, then harvest their RNA—a rather cumbersome and limiting technique. The project is already moving toward harvesting viral RNA using nextgeneration cultured cell lines to grow the viruses. After being harvested, the viral RNA will be sequenced at the genotyping station.

Built to Los Alamos specifications by Agilent Technologies and about the size of a compact car, each automated genotyping station will perform “all the functions needed to first amplify then sequence viral gene segments,” says Lance Green, leader of the project’s sequencing team. The data will then be analyzed and pieced together to obtain the sequence of all 13,588 RNA bases of influenza’s genome, which will be accessible to researchers anywhere in the world. Finally, interesting samples will be sent to a refrigerated archive that can hold up to a million strains, which will be available for further studies.

Once it becomes fully operational at UCLA, the high-throughput genotyping station can begin sequencing up to 160 samples per 11-hour run. In an emergency mode, up to 10,000 samples per day will be processed to obtain enough identifying information to follow the course of an outbreak.

Technologist Cheryl Gleasner attends to matters in the Los Alamos-designed automated genotyping station.

“Just imagine that you have 10,000 influenza strains come into the system a year,” says Resnick. “After screening them, you sequence the ones that are interesting and archive the ones that are still interesting to you after you sequence. So now you’re starting to have this temporal, spatial archive of strains from all around the world. You’ll have a huge capability to do comparative studies, get to the heart of host-pathogen interactions, and generate knowledge that can be readily applied to designing more-efficacious medical countermeasures.”

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