Philip Santangelo has a cold. Santangelo, an assistant professor in the Department of Biomedical Engineering, doesn’t know where it came from, but he has a guess. Several of his graduate students have been sick, and so he figures one of them must have transmitted the virus to a door handle, which Santangelo then touched with his hand, which he then brought to his face, allowing the the virus to worm its way into his skin and into a cell where it set up shop churning out more of its kind, which then spread all throughout his system.
Thus, his cold.
Santangelo’s familiarity with virus transmission stretches back beyond his current sniffle. A mechanical engineer by training, he researches the way that viruses move inside a host. And by tracking virus RNA at the single-molecule scale, he’s helping to find new treatments to fight viruses.
Much of Santangelo’s focus is on the RSV virus, a leading cause of bronchitis and pneumonia in children. Each year, hundreds suffer from it in Atlanta alone. And there’s no treatment.
While scientists have long understood the basics of how viruses spread inside the body, they haven’t been able to study viruses in their smallest form—as RNA moving inside individual cells.
And so Santangelo has created probes, each about four or five nanometers in size, that attach to RNA. When a certain wavelength of light shines on the probes, they light up a different color. That allows the probes—and the RNA—to be tracked as they move.
“We want to see the genome enter the cell,” Santangelo says. “Where does the genome go? Where does it replicate?”
His engineering background helped in the creation of the probes, which called for math more than biology. The probes utilize Watson-Crick pairings to target RNA and have organic fluors (a fluorescent dye) attached to them. The pairings are chemically altered to have a high affinity for RNA.
Santangelo’s big breakthrough was creating a brighter probe that holds more fluors, which has allowed scientists to observe RNA for days on end. Other probe types last less than a minute.
That level of knowledge is crucial because, even though cells are tiny, they’re vastly complex. “The cell is a horribly nonlinear system, and it’s hard to even quantify the number of elements,” Santangelo says.
The hope is that by developing a thorough understanding of what the virus RNA does inside the cell, researchers can create a plan to fight the virus. Like most viruses, RSV sequesters virus-fighting proteins. Santangelo hopes to find a way to prevent the virus from overpowering that innate immune response.
The research also could lead to new discoveries related to cancer. When cancer develops, the body’s messenger RNA “gets very messed up,” Santangelo says. He’s working to track that RNA and see what’s going wrong.
There’s also the potential to take biopsies and learn beforehand whether certain types of chemotherapy will be effective for a given case. Currently, patients often have to go all the way through treatment to learn if it will help.
The National Cancer Institute’s Innovative Molecular Technologies Analysis Program provided a grant for Santangelo’s research into cancer RNA.
“Understanding these things at the single-cell level is really important,” he says. “The problem now is people are looking for downstream effects. I tend to want to get as close as possible.”
Although one assumes his current encounter with a virus is a little too close for comfort.
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