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Inside research
A researcher’s quest for a cure: inside the Virtual Parasite Project
At first glance, the Virtual Parasite Project appears to be a modern-day video game with Virginia Commonwealth University researchers entering a virtual world and using a host of tools and test tubes.
However, their goals are greater than a mission to find a gold ring or to defeat a cybervillain. Here the adventure is of real consequence and the quest is for a cure.
Led by Tarynn Witten, Ph.D., senior fellow and director of research and development at VCU’s Center for the Study of Biological Complexity, the team is gaining a deeper understanding of Trypanosoma cruzi, T. cruzi, the deadly parasite at the root of Chagas’ disease, which kills some 50,000 people each year and is the causative agent for the third-most deadly parasitic disease worldwide.
“The Virtual Parasite Project provides a working environment for our researchers in the form of a virtual or in silico laboratory. The laboratory is in the computer and that’s where the researchers perform their experiments,” Witten explained.
“We want to gather more biological data on T. cruzi and find out more about how it functions. The goal is to move toward developing therapeutic strategies or even a cure for infections caused by T. cruzi,” she said.
The parasite is found mainly in rural, poverty-stricken areas of Latin America and is transmitted to animals and humans through insect vectors. The parasite alone does not cause Chagas’ disease. It must first gain passage into the bloodstream through an open wound or break in the skin. It can then alter muscle tissue to develop into Chagas’ disease. The infectious disease wreaks havoc on the body, affecting the nervous and digestive systems and the heart.
Limited treatment options exist for Chagas’ disease, making the development of alternative therapies critical. That’s where Witten and her team come in.
For more than 30 years, Witten has created mathematical and computer models of how living things work. A leader in her field, Witten was determined to create a model that had never before been designed in the virtual world. Recently, Witten became VCU’s principal investigator on a National Institutes of Health grant to train next-generation physicians in computational modeling of heart and lung behavior.
While a number of virtual models already exist for understanding the heart, human anatomy, biomechanics and genomics, none existed for the investigation of parasite behaviors. That model was uncharted territory, until now.
The Virtual Parasite Project is housed in the Center for the Study of Biological Complexity and allows researchers to select the parameters they would like to specifically test. For example, what would happen if gravity was turned off? Could the parasites swim? Would they know where they are? How would they react? Would the parasites still swim downward toward the host cells, as they do now?
“We attempt to design the models as realistically as possible and use the best known biological data for computing. We’ll see if they match up and if they don’t we try to understand why,” Witten said. “For example, is it because we don’t have enough biological data? Or is it because the models of T. cruzi aren’t good enough?”
After just five years, the project has already unlocked one of T. cruzi’s secrets. Witten’s team made an important discovery last year that led to a patent application for a potential therapeutic intervention against the parasite.
The team observed the parasites swimming around in the test tube and noticed that they did not collide with each other. They hypothesized that the parasites must sense each other’s electromagnetic field. To test their theory, the team placed nanoballs with electric charges to the solution. Then they put the parasites in the solution with the host cells at different concentrations to produce different electric field strengths and see if the parasites would bind to the host cells.
They discovered that the more electric fields present in the environment, the less likely the parasites were to bind to the host cells, which typically results in infection.
“Our findings may one day lead to a potential therapeutic intervention. If we put biologically inactive or inert vesicles into a human that are highly charged, we could theoretically slow its progression and the infection enough so that another therapy may work at a lower dose,” Witten said.
“This work was based on a theory we had — nobody knew any of this before. Creating the model actually led to an unknown biological result and new, critical information about this parasite,” she added.
The focus on T. cruzi is because VCU has expertise in this area and the best biological data for use in the computational modeling. However, Witten has plans to expand the project’s scope to allow researchers to study other organisms. Researchers would have an opportunity to create their own experimental in silico environments, enter biological data into the computer program and perform necessary simulations.
“It’s truly at the bleeding edge of how to do what we call multi-scale modeling. It is an example of a computationally intense and mathematically difficult model,” Witten said of the Virtual Parasite Project. And the computer-science world has taken notice.
Sun MicroSystems has awarded the project access to its national grid of more than 100,000 nodes and an academic educational grant to purchase additional equipment. This past year, it was highlighted at an IBM deep computing booth at the International Super Computer Conference. VCU received a Deep Computing award from IBM for the Virtual Parasite Project based on the intense computing capabilities, the amount of data and the amount of computation involved.
More recently, the director of computing at Argonne National Laboratories invited Witten and her group to benchmark the Virtual Parasite Project on their largest supercomputing grid.
To run experiments and make predictions in the virtual world, Witten’s team draws on expertise from a multidisciplinary group of professionals, including biologists, microbiologists, physicists and mathematicians. Since the project’s inception, more than 35 experts, undergraduate, doctoral and master’s students have worked on it.
“It’s generating not just research, but degrees. It has a broad student impact now,” she said.
Witten and her group are collaborating with a number of universities to optimize the speed of the Virtual Parasite Project to make it even faster. Witten’s next goal is to develop it into a national center for parasitic modeling and simulation.
The work at the Virtual Parasite Project is supported by awards from the Center for the Study of Biological Complexity, Apple, IBM and Sun MicroSystems, and Argonne National Labs.