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Bacillus bacteriophage PZA (Illustration: Ben Darby) Bacillus bacteriophage PZA (Illustration: Ben Darby)
 


Going Viral

Fresh faces at SDSU’s Viral Information Institute are bringing diverse backgrounds and fearless experimentation to the fast-moving world of microbial research.
By Michael Price
 

“There are so many interesting questions being asked that I could imagine fruitful collaborations with everyone in the group.”

This story appears in the summer 2016 issue of 360: The Magazine of San Diego State University.

It's a recent trend in superhero movies: Studios make films for individual heroes, then team them up for a blockbuster extravaganza. San Diego State University’s Viral Information Institute (VII) follows a similar formula. Over the past several years, the institute, led by microbial ecologist Forest Rohwer, has been assembling a super-team of diverse, highly skilled researchers to combat problems too big for any single scientist or discipline to solve.

Like their celluloid superhero counterparts, these new hires are sometimes oddballs—scientifically speaking—with unique research interests that made it initially difficult for some to find the right fit within academia. Take Nicholas Shikuma, who joined the VII last year. He studies how bacteria play an essential role in the lifecycle of marine life like tubeworms, sea urchins and corals.

It turns out that these animals need a nudge from bacteria to undergo metamorphosis, turning from larvae into juveniles. Bacteria do this using a kind of modified, headless virus particle as a spear that prods the animals into a metamorphic state.

“Some bacteria form a flower-like matrix of interlinking virus tails,” Shikuma explained. “It’s really quite beautiful.”

Interestingly, these virus-spears are also used to attack other bacteria in a sort of microbial jousting match. This process raises several evolutionary questions: Did bacteria first modify viruses to use as weapons, which later became incorporated into tubeworms’ lifecycles? Do bacteria get anything out of this arrangement?

Out-there ideas

Within the microbiology community, Shikuma is virtually alone in asking these questions. But at the VII, he’s working alongside people who recognize his work’s importance to larger questions about the poorly understood role microbes play in practically every facet of life.

“I study something pretty weird,” Shikuma said. “I’m not mainstream, and neither is SDSU, so we kind of met at that level.”

While Shikuma works with organisms that spend their whole lives in the water, fellow VII newbie Marina Kalyuzhnaya studies some who often don’t see enough of it. The biologist who joined SDSU in 2015 specializes in microbes that consume methane. In addition to work exploring methane’s potential as a biofuel or in biotech, she’s also exploring a fairly radical application: using methane-eating microbes to reduce methane emissions and to produce water.

Water is a byproduct of certain kinds of methane consumption. Kalyuzhnaya wondered whether you could deprive a plant of external hydration but supply it with methane so that microbes within the system produce their own water. It’s an admittedly crazy idea, but preliminary trials reveal plants thriving in a dry, methane-filled environment while their equally dry, methane-less peers shrivel. Scaled up, this process could help farmers understand how to adjust the organic carbon content of their soil to make their crops grow with less water.

“From the very moment I came here, everyone has been very open in such a way that if you have a crazy idea, they’re excited to look into your crazy idea,” said Kalyuzhnaya.

Structured thinking

Sometimes looking into a crazy idea means being able to visualize what’s normally invisible to the human eye. That calls for the expertise of chemist Manal Swairjo, hired in 2015. She harnesses the power of crystallography to explore the miniscule structures of microbes.

Within the world of viruses, Swairjo is interested in the biochemical pathways that bacteriophages (viruses that replicate within bacteria) use to defend their genetic matter when invading a bacterial host, as well as how phages change their protective coats in response to different environments. A better understanding of these processes could reveal new antiviral strategies, new techniques for using specialized viruses to deliver drugs to targets within the body, and the ability to use phages as environmental indicators. Bridging all of these disciplines and research focuses are the common languages of physics and math. That’s where Antoni Luque comes in. Trained as a biophysicist, he likes “to make abstract thoughts specific,” as he puts it.

He applied to work at SDSU after seeing Rohwer deliver a research talk at the University of Barcelona, where Luque earned his doctorate. He was intrigued by Rohwer’s deep knowledge of viruses combined with a commitment to incorporating unique viewpoints. Wanting to find a practical application for his biophysics background, he joined SDSU and the VII last year. He coordinates the math department’s weekly biomath meetings, which frequently include VII collaborators who throw out ideas and discuss their mathematical underpinnings.

“In interdisciplinary science, you get to solve problems, not just use the most advanced mathematical techniques,” Luque said.

Microbial mysteries

One of those problems he’s working on is figuring out the molecular and biophysical properties of double-stranded bacteriophages, which account for about 95 percent of all known phages.

“If we get these guys down, we’ll have gotten a pretty good chunk of the whole ecology,” Luque said.

The opportunity to apply broad practical knowledge to really big, sometimes bizarre ideas is a big reason the VII is quickly gaining a reputation as a hotspot for up-and-coming researchers.

“The institute brings together a broad range of expertise to study one of the planet's most ubiquitous, yet most mysterious, life forms,” Swairjo said.

But the chance to work alongside other brilliant, unconventional scientists might be the VII’s biggest selling point.

“Forest is known for his visionary ideas,” Shikuma said. “That he brought together such an interdisciplinary group is what attracted me here. There are so many interesting questions being asked that I could imagine fruitful collaborations with everyone in the group.”

The fruits of these collaborations, university leaders hope, will in turn seed further achievements across campus and advance SDSU's goal of becoming a top-50 public university.

"The VII is a cornerstone investment for SDSU research which we believe will serve as a catalyst for future growth and achievement," said Stephen Welter, vice president of research and dean of graduate affairs. "Its recent success in hiring bright minds with proven records of success underscores the university's commitment to recruiting top talent and becoming a premier research destination."