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PhD student grabs international headlines for her work on the Zika structure



Devika Sirohi is huge in India.

Dubbed the “Zika Decoder Girl” by her home country’s many, many media outlets, Sirohi was one of the key faces of this spring’s Zika virus structure discovery by a team led by Biological Sciences professors Richard Kuhn and Michael Rossmann. Video of her at the hood in a Hockmeyer Hall of Structural Biology wet lab and still photos of the PhD student working in a biosafety hood with a pipette were posted worldwide.

Sirohi worked with her professors and postdocs Zhenguo Chen, Lei Sun and Thomas Klose, but she also had to handle late night media requests much like Kuhn and Rossmann have had to do in their illustrious, respective careers.

“When it all started, there were so many news channels from India that called me in the middle of the night requesting for an interview,” recalled Sirohi, with a laugh now. “It was too much, too soon. It was very humbling but also overwhelming.  ”

Zika is a devastating, grotesque infection that is in the same family of flaviviruses that are prominent in India and many other countries around the world. Kuhn’s lab has had recent breakthroughs on this cluster of viruses, including the landmark visualization of the dengue virus in 2002 and West Nile virus in 2003.

What about a vaccine?

Field studies for a Zika vaccine should begin soon – by the end of 2016 or beginning of 2017, Sirohi said.

The main roadblock is perhaps the antibody cross talk between closely related flaviviruses in vaccine recipients. Pre-existing flavivirus antibodies could prevent the development of neutralizing antibodies to Zika (or vice versa) or even exacerbate the disease. This will make the many hoops to jump through in releasing a vaccine more difficult.

The Zika visualization gives scientists across the globe a way to better understand the virus, which causes debilitating birth defects. The work done by Sirohi and her colleagues could eventually lead to a vaccine and cure.

Recruited by the head

Born and raised in Meerut, India, Sirohi earned her bachelor’s degree in biochemistry from University of Delhi and a master’s at Tata Institute of Fundamental Research in Mumbai. She learned a variety of disciplines spanning immunology, cell biology, molecular biology and developmental neuroscience. 

It was in Mumbai where Sirohi met Kuhn, who organized a joint Indo-US conference on infectious disease at TIFR. She read about the head of Purdue Biological Science’s work with dengue virus and was quick to accept an offer to come to West Lafayette, Indiana.

“Dengue is still more prominent than Zika and is more problematic,” Sirohi stated.

Sirohi’s broad bioscience background helped her fit into Kuhn’s lab, even though Kuhn’s work with viral diseases was a new field for her.

“I did lot of protein biochemistry and enzymology related work for my master’s thesis, not infections agents,” Sirohi said.

The big picture science at the interface of basic and applied biology appealed to her the most.

A fast, critical decision

Sirohi perhaps surprised her media interviewers when she said she was in on the decision to investigate Zika and that decision was only made in December. Work started in January as soon as the group could receive the virus to work on. That means it was only a little more than three months to research Zika and only two months of lab work to find the virus’ structure before the landmark March 31 announcement of the Zika visualization.

“Research on Zika is a hot area with intense competition,” Sirohi said. “If you don’t do it quick, before you can blink somebody else has done it.”

Once samples arrived at the Hockmeyer lab, work was intense with long hours. Kuhn and Rossmann knew that many other researchers were investigating the Zika structure so they had to work fast.

Devika Sirohi with Zika samples
Sirohi with samples of the Zika virus

“A lot of us were working around the clock,” Sirohi said. “As a group, we were working at least 18 to 20 hours a day. There was a lot to be done and it had to be done yesterday.

“The day we got the samples was the day we first infected the cells.”

Sirohi’s lab duties were crucial to the discovery. She decided on what cells to grow the virus in and she experimented with different purification methods to get the best preparation for homogeneous samples for single particle reconstruction.  She also helped in data analysis and writing of the manuscript.

“It took more than a month to get the cells ready, grow and purify the virus” Sirohi remembered.

Along the way, Chen took thousands of pictures with the state of the art multimillion-dollar FEI Titan Krios electron microscope to create a three-dimensional map of Zika virus.

Those Eureka! moments

Along the line of long days, long weeks and long months in the lab, Sirohi and team celebrated each step that brought them closer to the Zika structure: successful purification and first images of the virus, the discovery that the Zika looked similar to other flaviviruses, the subtle differences between the viruses, and each time the virus structure became clearer and clearer.

“Something or the other was always happening. We were making progress and there was continuous excitement,” Sirohi said.

Straight from the head

Kuhn recognized Sirohi’s potential early and recognized her pre-Purdue accomplishments.

“She’s a very smart, articulate person,” he said. “She is passionate about science and really, really dedicated and really engaged.”

Kuhn credited Sirohi’s work in the trenches, both at bench creating samples and at the computer deciphering data. He gave her credit for knowing that work on Zika is a sprint to the finish. Work would have to be done day and night. Yet, she and her fellow researchers would have to stay sharp and not get burnt out.

“She jumped headlong into preparting the virus,” Kuhn recalled, noting that Sirohi had been working on croyo-EM reconstruction before the Zika project. “There was so much to do and so little time. She had her hand on every aspect.

“Devika was up on everything on Zika. Everything we needed to know, she was aware of it. Not just bench work, it was who’s doing what and what makes sense and how do we interpret the data.”

Kuhn is proud how Sirohi has taken on the science spotlight, along with the rest of his team of postdocs and research scientists.

“She’s gained some recognition in the lay and scientific communities,” said Kuhn, adding that a recent meeting he attended of the American Society of Virology had many of his peers congratulating him and his team on the work. “She’s a senior author on there. She’s on the front edge of that.”

Much more to be done

Sirohi expects to receive her PhD from Purdue Biological Sciences in December. Until then, she will continue her work on Zika and dengue viruses.

“This is just the beginning,” Sirohi explained. “Having the structure opens the door for many hypothesis-driven questions.  What regions of the virus are important for receptor binding? What epitopes on the virus will bind antibodies that will help neutralize the virus?

“We continue to work with Zika, further exploring the antigenic structure of the virus and.collaborating with many groups in Purdue to develop inhibitors that block Zika infection in cells. We are also studying the impact and mechanism of infection both in cell culture and in an animal model. ” 

And she will continue to field media requests and lecture bookings as well as manage a full e-mail inbox.

“I’m still getting a steady stream of e-mail with resumes on them to see if I can hire them,” Sirohi laughed. “I’m a graduate student. I cannot hire you!”

For now, at least. The next level -- and discovery -- is coming soon.

Devika working

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