Graduate student Ipsita Saha likes physics because it explains the small details of daily life—the science behind how a car works or the mechanics of opening a window. She also likes that physics allows scientists to visualize mathematical equations.
Saha received a bachelor’s degree from St. Xavier's College, Kolkata, India, and obtained a master’s degree from the Indian Institute of Technology in Bombay. During her studies, she harbored a secret desire to become an astronomer but eventually realized she was more interested in the ability of physics to answer intricate biological questions. When she came to the U for graduate studies, she joined a biophysics lab.
Today she studies the Human Immunodeficiency Virus (HIV). “Viruses are entities that are unable to replicate on their own,” said Saha, “so they hijack the cellular machinery to replicate, turning the cell against itself.” Budding is the process when the virus assembles on the cell membrane with its necessary proteins and genome that have been synthesized within the host cell and is then released from it. The released virus is immature and isn’t yet ready to infect other cells. The virus has to undergo maturation to become fully ready to infect other cells.
Saha’s work is trying to find the mechanism that leads to the maturation of HIV. Gag, the major structural protein, forms the spherical lattice of the HIV. When Gag is synthesized within the host cell, a ribosomal slippage or biological phenomenon occurs that results in the production of multiple, unique proteins from a single mRNA, called GagPol. In HIV there are about 2,000 Gag and 120 GagPol. One of the enzymes embedded in GagPol is protease, which plays the key role in the maturation process. Protease is embedded as half the molecule in a GagPol and has to become dimerized (the process when two molecules of the same compound react with each other) to become active and trigger the maturation process. This maturation encloses the viral genome within the capsid. Saha along with her supervisor have hypothesized that the HIV lattice is not a stuck structure—instead it probably diffuses on the viral membrane so the enzymes can actually find each other to become dimerized.
All of this is difficult to show because the virus is 140-180nm in diameter, so Saha has used super-resolution microscopy to reconstruct the lattice of the HIV in high resolution. While still a work in progress, Saha is confident her research will provide meaningful insights into the behavior of HIV to help find inhibitors to block maturation of the virus.
Saha’s research is under the supervision of Dr. Saveez Saffarian, associate professor of Physics & Astronomy and adjunct assistant professor, Biology. “Saveez is very supportive and has provided me with a lot of opportunities to explore a variety of things in my research, even when it didn’t align exactly with his interests,” said Saha. “He also has taught me to ignore useless things that divert my attention from my work. I hope to continue with his support as I move forward in my career.”
Movement of Molecules in Real Time
Last December Saha and Saffarian’s research was featured in a study published in the journal PLOS ONE. The study focused on a way to visualize how different molecules interact and behave within human cells in real time.
The new method uses interferometry to capture extremely high-resolution visualizations of millions of molecules moving across viscous gels or a plasma membrane. Saha, the lead author of the study, developed a correlation analysis that theoretically explained how the interferometry microscope could distinguish between two types of movement—flow and diffusion—and she and Saffarian verified it experimentally. The method brings scientists one-step closer to visualizing how molecules interact in an actual living cell. The development of this technique led the University to file a provisional patent and they are moving forward to file a full international patent.
Saha loves to read and watch movies, web-series, talk shows, and interviews. “I also read Bengali and English novels,” she said. The films she sees are mostly in Bengali, Hindi and English. She also enjoys traveling. She has learned the importance of avoiding negative people and situations. “I try hard not to behave badly even if others do. That attitude really keeps me calm so I can feel good at the end of the day,” she said.
She expects to complete her Ph.D. in 2021 and plans to do postdoctoral research.