Hijacking The Virus: The Schmitt Laboratory
Phuong Schmitt was only supposed to work in principal investigator Tony Schmitt’s virology lab for two years.
She wanted to help her husband get his newly formed Penn State research laboratory off the ground in 2005, so she took a break from her career as a clinical pharmacist. The Schmitts, however, never looked back, and the pair still works together studying viruses.
“Two years turned into 14 years,” Phuong Schmitt said.
Dr. Tony Schmitt met his wife 27 years ago at UCLA while completing a summer Ph.D. rotation project that investigated the genetics of Tay-Sachs disease. Phuong Schmitt, meanwhile, had recently earned her undergraduate degree from UCLA and had aspirations of attending pharmacy school in Chicago after a research stint in the same lab.
The couple moved to Illinois, where Tony Schmitt began studying virology while completing his postdoctoral training at Northwestern University. He has been focused on understanding the life cycle and possible medical application of viruses ever since.
The Schmitt Laboratory is currently interested in studying a class of viruses called paramyxoviruses, which include the well-known viruses measles and mumps, along with recently emergent zoonotic viruses like Nipah and Hendra. These zoonotic viruses naturally infect bats, but can cause deadly illnesses when they infect humans. The lab focuses on how these viruses work at the molecular level so that new antiviral strategies can be developed.
“We mainly study one step of the virus life cycle — the particle formation step. How do viruses cause infected cells to release hundreds of virus particles that can then transmit infection to new hosts? Different scientists study different bits of the virus life cycle so that in the end we can try to understand the entire picture of what the virus needs to do and figure out which of these steps can be blocked to inhibit viruses,” Tony Schmitt said.
In addition to studying how the virus particles are formed, the lab also studies how these particles — Tony Schmitt calls them “biological delivery vehicles” — transfer their genetic information to new cells, thereby spreading the infection.
“That’s the goal of a virus particle. It’s a tiny container that holds the virus genome and transfers it to the next cell so that it can become infected,” he said.
Virus particles are about 1000 times smaller than the cells they inhabit. They attack these cells and hijack their machinery, so that the cells unknowingly become factories dedicated to producing more of the virus.
“It’s going to dump its contents — its genome — into a cell. The cell is going to follow all of the instructions that are on the viral genome, and this results in the cell making viral proteins and doing all sorts of things that it’s not normally supposed to do,” Tony Schmitt said. “In the end, the goal of the virus is to make it so that this cell makes lots and lots of new virus particles that can spread the infection to the next cell.”
But again, the cells do not willingly participate in this cycle. The process is a bit more complicated for a virus to accomplish than it seems.
“This is actually one of the most difficult things for a virus to do…to take its contents and deliver it into the cytoplasm of the cell because a cell is surrounded by a membrane that is meant to keep things like viruses away,” Tony Schmitt said.
Knowing this, the Schmitt Laboratory is studying ways to manipulate the mechanism of viral transfer.
“We’re working on ways where we could replace what goes inside the virus particle — what normally goes inside is the virus’ genome — with other useful things. So that now the virus particle becomes a tool that you can use to deliver beneficial proteins into cells and into people who might need those proteins,” Tony Schmitt said.
To be more specific, there is a mechanism by which the infectious viral genome is incorporated into the virus particle. That’s because if the particle was empty, it would be a waste of resources for the virus, since it would have produced a non-infectious particle.
According to Tony Schmitt, viral genomes are covered with a protein called NP. Another viral protein called M is located in the places where virus particles form. The binding of these two proteins together is what directs the genome into the virus particle, thus allowing it to become infectious.
One of the lab’s undergraduate researchers, Jeff Lorenz, is conducting a project to better understand M and NP interaction. This understanding could lead to the successful manipulation of viruses to become useful bodily delivery vehicles.
“One of the projects in our lab aims to understand the interaction that causes the genome to go into the particle, because if you can understand it then maybe you can manipulate it,” Tony Schmitt said. “Whatever it is that makes the viral protein bind to M protein, if you can figure it out, then maybe you can change it so that other proteins would be able to bind to M proteins in the same way…then you could use the particle to deliver the beneficial protein into cells.”
One of the lab’s graduate students, Sabahat Gazal, leads another study. Her project examines how viruses hijack the cells’ machinery to cause particle formation by viral budding. The budding portion of the viral life cycle involves the viral particle exiting the cell by pinching off from the cell membrane.
Gazal is studying strategies that can be used to block the virus from using host cell machinery in the first place.
“If you manipulate the host cell machinery that the virus recruits for its use, then it will not be able to come out of the cell,” Gazal said.
Phuong Schmitt fills many roles for the lab. Not only does she conduct her own pilot experiments, but she also works closely with the lab’s undergraduate students.
Tony Schmitt said he feels fortunate that his wife ultimately chose to work at Penn State.
“She had to choose between the pharmacy route, which makes considerably more money, or helping my lab. She’s very skilled at all the molecular biology techniques and when starting out the lab it’s especially important to have someone like that to get those first papers and data,” he said. “It was my great fortune that she decided to help my lab get started, and we’ve been working together ever since.”
After spending many years working with undergraduates, Phuong Schmitt realizes the importance of assigning projects that can produce tangible results before her students graduate. One trait she looks for in prospective lab students is the ability to commit time to the lab.
“I think if you’re an undergraduate and you seriously want to work in a lab, pick a lab and talk to them. Try to schedule your classes so that you have the top or bottom part of the day open. That way you have a stretch of 3-4 hours to come in,” she said.
Although Tony Schmitt’s fascination in understanding and manipulating these viruses is immense, he didn’t begin studying them until he started his postdoctoral training. While he was at UCLA, his Ph.D. work focused on researching stress responses in yeast. That’s why he believes that a career in science requires an open mind.
“What my story illustrates is that there isn’t one path that is necessarily the best one or the one that leads you to being successful and happy,” Tony Schmitt said.
“There are many possible routes I could have gone. Had I not studied viruses, I’m sure I would have found something else that I would be really excited about and been successful at. I’m lucky that I found one of them — one of the possible paths for me.”
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