I magine a complex system of gears—each wheel turning with interlocking teeth.  Throw in a wrench, and everything stops.

Dr. Arnab Sengupta, an assistant professor of cell and molecular biology, mulls over that scenario every day.

Only, in his case, the wheels are cells and the wrench, stress.

If Sengupta and his team of undergraduate researchers can learn enough about cells and what causes them to shut down or keep producing, they could someday help stop cancer.

“From a cell’s perspective, stress is lack of food, lack of oxygen, acidity, lack of water molecules,” Sengupta said. “Food—small bits of what we eat—enter the cell. Cells need all kinds of nutrients and proteins to function.”

“Stress for a cell is basically anything that signals its resources are now going to be limited. It can no longer do everything it’s doing. In this condition, most cells shut down nonessential functions. Not cancer,” he said. “Under those conditions, cancer genes still function. Think of a tumor, an unregulated growth of cells. Your normal genes are not functioning, but your cancer genes are in overdrive. They’re thriving in those conditions and, despite the stress, they’re just blocking all the signals to stop growing, until a tumor forms and spreads.”

Cancer is a complex disease, not something any one scientist or lab can conquer. But Sengupta leans on his expertise in ribosome function to lead students in answering one particular aspect of the puzzle: how cells switch on or off.

When Sengupta started at Georgia College & State University in January 2022, it was his first faculty position. He interned at biotech companies after earning a biotechnology degree from Amity University in New Delhi, India. Then, Sengupta moved towards science, getting a Ph.D. in biotechnology at the University of Alabama in Huntsville and postdoctoral training at the University of North Carolina at Chapel Hill and North Carolina State University in research and teaching.

Sengupta was drawn to Georgia College because of its new Integrated Science Complex and the beauty of a public liberal arts education—where undergraduate research is valued, and he could continue to explore topics that interest him, like mRNA (messenger ribonucleic acid).

Some cancer genes are switched on or off at the stage when genetic information in mRNA is read to make proteins. In stressful conditions, cancer genes defy orders to stop functioning. They act as rebels—ignoring environmental triggers.

This is something we know little about.

If researchers understood how some mRNAs are controlled under stress, they could someday turn off cancer-causing genes and turn on cancer-fighting genes.

“I’m interested in a couple of these mRNAs that, under stressful conditions, still want to translate into proteins. They are the ones that tend to enable cancers,” Sengupta said. “My fascination centers on how the mRNA is doing it, not cancer genes in particular. This research could have a big impact. That is what drives me.”

He thinks the answer may lie in the way mRNA folds upon itself.

DNA (deoxyribonucleic acid) has two long strands, arranged like a twisted ladder, which support its structure. RNA has one strand and folds upon itself. Because of this, it can adopt a variety of shapes.

“At this point, I just want to know how they’re doing it!” he said, excitedly. “How are you defying these orders when you’re being told not to make proteins? How are you still going on and figuring out a way to do that? How are you defying the instructions? That is fascinating to me.”

Sengupta recruited four students in his lab to help unravel the mystery.

Their goal is to map folding patterns of certain mRNAs and build a structural model. To do this, they first extract RNA in test tubes. They’ll compare those results to live-functioning cellular RNA and, finally, to cellular RNA under stress.

Each student in Sengupta’s lab is tasked with researching a different gene related to cancer.

Jin Yeong Kim of Milledgeville is a senior biology major with a pre-med concentration and minor in philosophy. It’s her job to study p53, a tumor-suppressor gene. She’s trying to understand how mRNA is read to make the p53 protein.

Helping p53 work more efficiently could be one way to combat cancer.

It’s important work.

“There’s a lot of troubleshooting involved. All research is important because it gives you one less possibility,” Kim said. “Sometimes the results are not what we’re expecting, but Dr. Sengupta’s great. This research is so above my level as an undergraduate student. It’s Ph.D. level, but he’s able to explain it in a way I truly understand, which makes the work more engaging and interesting.”

Kim also maintains cell cultures in a biosafety cabinet for Sengupta’s lab. She grows human lung carcinoma cells for this research. To be put in charge of cell cultures was a little “nerve wracking” at first, she said. But her confidence grew as she daily washed and suspended, then cleaned cells again. To an outsider, it looks like a lot of sudsy-looking pink liquid swooshing through tubes.

Other students work with mRNAs that continue making proteins under stress.

Junior biology major Alexandra Furney of Johns Creek, Georgia, is getting a minor in Spanish. Last summer, she earned a Mentored Undergraduate Research and Creative Endeavors (MURACE) grant to work on a gene called Hypoxia-Inducible Factor (HIF)-1a.

Under stressful low-oxygen levels, HIF-1a doesn’t shut down. It’s triggered to make more protein.

Furney had never done scientific research before, but Sengupta’s easy explanations in genetics class helped her catch on quickly. Originally a political science major, Furney switched to biology to pursue veterinarian school. Working with cells and molecules was a complete turnaround.

Now, Furney wants to stay in research.

She follows daily protocols, squirting cells into test tubes, running experiments through a machine to get data and, depending on results, deciding what to do next. Furney is preparing to do the same experiments with actual cancer cells.

Like p53, HIF-1a is activated in cancer cells. Understanding how low-oxygen stress triggers HIF-1a to activate could help the team better understand how cancer develops.

“It’s a little technical,” Furney said, “but the general gist is we’re trying to build a model of the structure and, if we have the model, then we can see how it works, and that can be applied to the bigger picture.”

“The first big step in what we do is figuring out conditions that are going to work for the rest of our experiment,” she said. “It takes a lot—depending on temperature, how many cycles it runs, the amounts we add to the test tubes—then we go back and try to find a process that gives the best results.”

HIF-1a gene is involved with important, everyday body processes, like creating new blood vessels. It provides tumors with an adequate supply of blood. Figuring out a way to cut off that supply could help combat cancer.

“It feels good working on a project like this,” Furney said. “Even a little progress is a big victory. Science is about building knowledge. So, even though it might seem insignificant, our work may help another scientist somewhere else to build upon their work. It feels good contributing to all of that.”

Another student in Sengupta’s lab, junior Brittany Benner of Albany, Georgia, is a biology major with a pre-med concentration. Her piece of the research is studying an mRNA gene called FGF2 (fibroblast growth factor 2)—which is essential for all cells to grow.

Cancer cells use this gene to stimulate tumor formation and reproduce.

To understand how FGF2 works, Benner first looks at DNA, using a gel. Later, she’ll see how it works in different stress conditions.

“If my gene were to get out of whack at some point in the body,” Benner said, “it could continue to grow and cause a tumor and also provide blood vessels. It grows blood vessels. Hopefully, if we can figure out more, we can better describe that type of cancer.”

“It’s very interesting to work in this lab and do such high-level stuff,” she said. “It’s really neat to be trusted with this type of work.”
 
Benner’s confidence has grown enormously since joining Sengupta’s lab. At first, she didn’t know where things were kept or what to do. Now, she comes in during free time and works on her own.

The experience will help when Benner applies to medical school. It’ll show she can work independently and be trusted with important tasks.

Sengupta enjoys this aspect of teaching—sharing his research and giving students what they need to succeed.

Since arriving at Georgia College, he’s been amazed at the level of assistance from multiple department colleagues and university officials. Dr. Jordan Cofer, associate provost of Transformative Learning Experiences, used MURACE funds to support Furney’s summer research. Support from GC Journeys helped secure basic and cutting-edge lab equipment.

Currently, the team sends gene samples to the University of Georgia for “next-generation sequencing,” which determines the building blocks of DNA and RNA. To ensure high-quality samples are sent from Georgia College, the university secured funding for Sengupta to purchase an Agilent TapeStation which tests purity through the movement of charged particles. Students in Sengupta’s lab courses for Genetics and Molecular BioTechniques are also trained to operate the TapeStation.

Few universities have a TapeStation. It’s something mostly seen at large research schools.

When Sengupta tells associates at research-intensive universities what his students are doing—and the kind of equipment they’re working with—his friends are “flabbergasted.”

Someday, Sengupta would like Georgia College students to do their own next-generation sequencing. He applied for a $500,000, three-year research grant from the National Science Foundation (NSF) that includes funding for a sequencer.

He doesn’t believe in dreaming small.

“To be able to analyze molecules and prepare samples all the way through inhouse next-generation sequencing—would speak volumes to their ability and open doors for students in higher studies and biotech industry careers,” he said.

As undergraduates, Sengupta’s students are at levels of research seen in graduate school.

It’s complex work and takes a lot of self-motivation. Undergraduates might go a little slower at first, but they’re moving quickly now and doing as well as any student earning a master’s degree.

“What’s motivating them to come? They have a choice,” Sengupta said. “They keep doing this because, they are driven by curiosity. That’s only possible if you’re pursuing a meaningful project.”

“If you can spark a curiosity in their minds about pursuing research, then that changes their direction. You’ve opened a door for them” he said. “That’s what I like to do.”