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Watch: A cellular biologist animates the life cycle of HIV in this hypnotic video

2018-4-27 12:02 Science 305 0 0
Watch: A cellular biologist animates the life cycle of HIV in this hypnotic video

While the musical soundtrack is wholly a product of the imagination, everything else in this spellbinding animation of the HIV virus — created by Janet Iwasa — was based on the findings of researchers.

University of Utah cellular biologist Janet Iwasa has spent much of the past four years engaged in discussions with dozens of HIV researchers. The usual product of these endeavors would be a paper in an academic journal, or maybe a textbook, but for Iwasa, a Senior TED Fellow (Talk: How animations help scientists test a hypothesis) … it became a video animation that shows, for the first time, the life cycle of HIV at molecular scale.

“Most of the knowledge that scientists produce is locked away in jargon-filled publications, difficult to read even for people slightly outside of their field,” she says. “In general, science needs better ways of communicating our research, in ways accessible to everyone.” Her work is an attempt to bring microbiology into the mainstream, and to showcase the information synthesized from many labs working on different aspects of the same disease.

The HIV capsid (the protein shell of a virus) enters a T cell.

Why HIV? Iwasa became interested in animation while getting her PhD at UC San Francisco. After graduating, she took a 10-week course in animation in Hollywood. Since then, she has created visualizations of many scientific processes, including the origins of life, the workings of CRISPR, the contents of dust, the motility of bacteria, and how proteins detangle other proteins. “I chose HIV for this particular project because it has been well-funded and is very well-studied, so there is a vast amount of information available to create a reasonably accurate interpretation,” she says.

But there’s no central clearinghouse of knowledge about the biology of HIV. “Different researchers study different aspects of the biology — how the virus enters and exits a cell, what’s happening in the nucleus, what’s happening in the cytoplasm, how the RNA moves around, and so on,” she says. Through involvement with CHEETAH, an NIH-funded research center based at the University of Utah that studies HIV structural biology and similar groups, she talked to “about 30 HIV researchers at length” about her project, gathering ideas about what to show. Then she used Autodesk software to build her animation.

The HIV capsid moves towards the nucleus of the T cell, using the cell’s microtubules as a kind of highway system.

Her animation marries artistic license and scientific fact. “Since most molecules and cells are colorless, the colors I selected were arbitrary,” Iwasa says. “I generally made my choices to maximize both aesthetics and clarity. For example, I tried to visually cluster proteins of related functions by using hue, but changed the saturation to differentiate between them.” The shapes and locations of the molecular components are true to life, based on data from the scientists she spoke to. “Structural biologists can figure out the shapes of proteins using X-ray crystallography and cryo-electron microscopy,” Iwasa says. “Cell biologists look for where proteins are located in a cell, using light microscopy and fluorescence. With those methods, we can figure out that they’re in a particular part of a cell and how many there are. Then, biochemists can tell us how proteins connect.”

However, the precise motions depicted inside the cell are a best guess. While advanced technologies allow us to view these tiny proteins, “such methods take only a snapshot, frozen in time. Unfortunately, you can’t use these methods to look at proteins in action in a living cell.” As a result, scientists rely on indirect experimentation to start visualizing what exactly occurs at each stage of the HIV life cycle. “We can only say what we think is going on, based on the best evidence we have,” says Iwasa. She compares the process to a CSI, where researchers gather various pieces of data that they piece together to form a picture that tells a story.

Different RNAs begin leaving the nucleus of the T cell.

Another creative choice: setting the animation to music. She tapped cellist, composer and TED Senior Fellow Joshua Roman (Watch: On violin and cello, Johan Halvorsen’s “Passacaglia”) to provide a musical accompaniment that would offer a sense of familiarity in the strange molecular environment. “Looking at a molecular animation can feel very alien. I hoped to be able to give people a sense of space and rhythm, and Joshua provided a soundscape for the different environments,” says Iwasa. “When you’re outside of the cell, it sounds one way, and when you’re inside a cell, there’s a different sound, more like a machine — proteins moving around. And then when you’re inside the nucleus, it’s a little bit more hushed, but you still have this constant sound of the machinery.

With this work, Iwasa wants to show what scientists have learned about HIV. In particular, she’d like to correct one misconception: that we don’t know much about HIV because we don’t yet have a cure. She says, “It’s a shame the general public doesn’t realize how much we do already understand about HIV and how much progress has been made.” With her vivid depiction, she also wants to show how insidious the virus is. “Retroviruses like HIV work by gluing their own viral DNA with the cellular DNA,” Iwasa adds. “That’s why HIV is so hard to cure: it’s integrated into the cell’s genome.” While she has shared her work in progress with “hundreds of researchers” to get their notes and tweak her efforts, she is just starting to share the clip with the general public. She mentions receiving an email from someone who is HIV-positive. Upon seeing an early clip, they wrote, “The video is so simple, but it’s so powerfully graphic. I never thought that this is what must be going on inside me. I was awestruck.”

The HIV cell proteins cause the membrane of the T cell to bulge until fission occurs and the viral bud is released into the bloodstream.

That combination of perspective and information is what Iwasa wants to bring to people’s understanding of science. “We scientists have an obligation to communicate what we do, because the vast amount of it is publicly funded. This knowledge really should belong to everyone,” she says. “This project is an attempt to try and make it more accessible for those who are interested.” In addition to instructing the lay public, the video could also help scientists to connect with other people and organizations that can help move their research forward.

Iwasa is already busy on other videos related to this project. “My next animations will show how antiviral drugs work to stop the virus from either infecting an individual — or, once someone is infected, how it keeps the viral population in check,” she says. “I’ll also show different ways scientists are hoping to develop a cure.” In addition, she is currently collaborating with TED Fellows Kellee Santiago and Jimmy Lin to create Project Quorum, a game that will allow anyone to help researchers analyze image data and make discoveries. They plan to release it later this year.

Watch the full video below, and for additional information on the project, go to Iwasa’s Science of HIV site:


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