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Collaboration on latest technology leads to new vista on viruses

Biochemistry majors Ben Ryan, left, and Tyler Rollman, with the MinION computer they'll be using to do genetic research as part of a project looking at the life and genes of viruses in insect vectors.In the lifecycle of viruses, it’s typically only the endgame that gets any attention: people, animals or plants become hosts to the virus, sicken and sometimes die.

But the vectors — insects and other organisms — that spread viruses often live with these infectious agents for a much longer period than the final hosts, and are thus able to spread the virus farther and wider.

“A virus can live in a mosquito for much longer than it lives in a human being,” said Carol Fassbinder-Orth, PhD, a Creighton University associate professor of biology specializing in avian immunology and zoonotic diseases. “If we’re going to understand how outbreaks happen, we have to know more than just what happens in the end.”

For several years now, Fassbinder-Orth has been researching the life of viruses in vectors like mosquitoes, their genetics and structures, all in the interest in hoping to intercept major outbreaks of insect-borne diseases like zika and West Nile. As a means of persisting, a virus will delete portions of its genetic code, thus allowing it to escape detection in its host and making it difficult for researchers to pinpoint.

A new project taking the research of Fassbinder-Orth and the innovative capacities of the Creighton RaD Lab has come together to build a computer capable of sequencing whole genetic structures of viruses and comparing them to a base reference genome. The procedure allows researchers to do a comparison of the genetic code and determine what’s being deleted — essentially mining massive amounts of a genetic haystack to find a few needles.

The MinION Computer RaD Lab analysts and student interns have fashioned, based on designs from Oxford Nanopore Technologies, is capable of computin large data files in a single sequencing experiment.

“It’s a hot rod,” said Ryan Cameron, RaD Lab senior director of innovation and research and development. “Primarily, to compute quickly while working in a traditional data center, you bolt on more and more servers. But in this instance, we needed a desktop computer to gather field research data in a lab environment. So what we have essentially built is an insanely fast number cruncher.”

In Fassbinder-Orth’s lab, the focus will be on the RNA sequencing of viruses in the swallow bug, a relative of the human bedbug which prefers to feed on avian species. While experiments documenting virus’ deletions of its genetic code have been done before, it’s been more than 40 years since the last examinations. Since then, technology has surged and the emphasis on RNA sequencing will be unique to the work in Fassbinder-Orth’s lab.

Biochemistry majors Tyler Rollman, a sophomore, and Ben Ryan, a senior, will be taking on two crucial components of the study. Rollman will be looking at what are called “squiggles” — that’s small amounts of genetic data — and comparing them to base genetic strands, while Ryan will be looking at how the genetically altering virus continues to kill cells in its host.

“It’s quite amazing to see what’s happening, how these deletions take place,” Rollman said. “Even more incredible is that, with this machine, we’re going to be able to do a real-time comparison to see what’s being cut off and from there, trying to figure out how the deletion occurs and how the deletions relate to one another and how they relate between genotype (genetic structure) and phenotype (how the genetic structure manifests in an organism).”

With the latest in processor technology and a four-terabyte server, the MinION is still accessible via USB devices, and technology is being developed to allow for data collection on a high-powered cellphone.

The technology has not been out long — about nine months — but Fassbinder-Orth said Cameron, the RaD Lab and the Department of Biology have all convened to create “access to a pipeline of understanding” with the powerful new tools.

“We needed this kind of power and a lot of data storage, so we could not have done any of this without this collaboration,” Fassbinder-Orth said, citing several of her colleagues who have also undertaken projects with help from the RaD Lab. “It was a matter of knowing what we needed and having the vision to see how we could do this kind of sequencing and Ryan and the RaD Lab helped show us the way. It’s been a fabulous partnership.”

With grants from the Institutional Development Award Program (IDeA) Networks of Biomedical Research Excellence (INBRE) project and from the RaD Lab, Fassbinder-Orth was able to secure funding for the MinION.

Cameron said the RaD Lab was only too happy to engage this project. By the time most of the raw materials from Oxford Nanopore arrived, he said, analysts and interns couldn’t wait to take off on a spree build.

“It’s been just as much an opportunity for us as it is for Dr. Fassbinder-Orth and her lab,” Cameron said. “This is so cool! Our students were excited to participate in something with lasting impact. Of course, we love our video games and our virtual reality projects, but to be involved in something where technology can improve global health, it was something we jumped at.”

As researchers and RaD Lab analysts become more familiar with the MinION technology, Cameron and Fassbinder-Orth are hopeful more projects might germinate from the use of this computer which, in an echo of its name, is colored with a bright yellow swatch to conjure images of the DreamWorks Animation’s yellow Minions.

“Fingers crossed,” Cameron said. “This effort creates new research potential. As usual at the RaD Lab, we’re curious and eager to see what we can do next.”


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