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The Virus Mechanic

The Virus MechanicArmed with a prestigious Pew research grant, Tufts' Ekaterina Heldwein is parsing viruses to uncover the mysteries of their structure.

Boston [08.13.07] For Ekaterina Heldwein, or Katya as she prefers to be called, science is all about structure, a notion she developed as a young chemistry student in Moscow. "I was always interested in understanding how things worked on a basic level, what they're built out of, the make-up of things," the Tufts School of Medicine assistant professor of molecular biology and microbiology explains.

Heldwein has parlayed that curiosity into a career in structural virology, and in the process earned a coveted spot among this year's 20 inductees into the Pew Charitable Trust, winning a research grant worth $240,000 over four years.



Heldwein sees her role as a structural virologist much like that of a mechanic.

"[Understanding virus structure] is like knowing how an engine works. You need to understand the different components and how they come together," she says. "Without seeing that, you can't hope to completely understand what's going on."

While an engine powers only one car, what's going on in the Heldwein laboratory could drive medical innovations across disciplines."Structural knowledge is important in all fields of biology," she says. "More questions always arise, but knowing about the structure of [viruses] is a really good starting point for a myriad of different studies... bringing our understanding to a much deeper level. You can really see the details."

The Secret Lives of Viruses

Heldwein's current project, for which she was awarded the grant, is studying the process by which herpesviruses enter into host cells. The large family of viruses, encompassing those causing chicken pox, mononucleosis and some cancers, as well as their sexually transmitted cousins affects the body differently than most viruses.

"They stay in the host forever in a very surreptitious way," explains Heldwein. By studying their cell entry, Heldwein hopes to learn how to get rid of them for good.

"We don't know how they get inside the body in the first place," she says. "If we did, we could stop them and stop all their downstream effects, ranging from unpleasant, to painful, to deadly."

Heldwein often describes the virus anthropomorphically, referring to them "traveling,""hiding," and "subverting" inside the human body, but she's careful to avoid the word "living." She explains that viruses "can't reproduce by themselves, which is the classical definition of living, so they're not alive as such, but they're not dead, either."

This grey area captivates Heldwein. Like living things, they have the drive to reproduce, yet they need assistance: a juicy problem that would interest philosophers as well as biologists.

"It's interesting because viruses don't have that many genes but they can accomplish these amazing things. They're fascinating entities," Heldwein says carefully. "I want to say 'beings' but I can't call them that." The scientist's research is driven by dual motives. "On the one hand, I want to know more about these fascinating viruses, and on the other, I want to be able to help the people they affect."

The Next Step

The knowledge gained from Heldwein's study could help accomplish the latter by aiding in the development of vaccines or other preventive methods.

While most viruses use only one protein to help them enter host cells, herpesviruses use three-imagine them sticking out of the virus's outer coat like porcupine's needles, she suggests. Heldwein has already discovered the shape of one protein, gB, and after determining the others, "the next step is to understand how they work together."

"We don't know if it's like the passing of the torch in the Olympics like in a relay race," she speculates with a laugh, "or if they all come together and work at the same time."

To determine the way the proteins cooperate, Heldwein is producing a "molecular movie" of the process to document and preserve her results for use by other scientists.

Once her "viral documentary," as she calls it, is completed, "the third step would be to use that information to design antivirals," interrupting cell entry at its most vulnerable stage. "The goal," she says, "is to understand in such a level of detail that we can pinpoint the time and place when the viruses are the most vulnerable."

The Reward Cycle

Heldwein was honored to win the Pew grant, which she views as important to her study and to the Tufts community.

"It's encouraging to get such a prestigious award early in one's career and be recognized for having promising research," she says. "It's a huge boost to one's confidence."

One of the notable features of a Pew grant is that, unlike some other funding agencies, the Pew Charitable Trust leaves "no strings attached."

"The Pew grant leaves one with more options on how to use the money," she says, noting it could be used to pay the salaries of Tufts students she'd like to recruit for the project.

However, Heldwein says the real honor is being a part of such "a vibrant community of scientists," representing all aspects of biology, and the opportunity it provides to network.

Just completing her first year at Tufts, Heldwein recognizes a similar community here and hopes to continue branching out.

"I'm mostly familiar with my department because I'm so new here, but I really like the intellectual environment," she says, noting the possibilities for collaborations to come. "You can learn so much in the fields outside your own."

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