Spotlight on Akhila Rajan

Discovering how fat cells communicate with the brain

Akhila Rajan, obesity researcher

Solving big challenges requires being willing to approach a problem from a variety of perspectives. This is why Dr. Akhila Rajan doesn’t like to slot her research into a specific discipline such as genetics, developmental biology or neuroscience.

“I found that these boundaries are not helpful in the way one can solve problems. I wanted to work on projects that had far-reaching implications," she said.

True to that sentiment, her lab studies how organisms regulate energy storage, which touches many areas of biology and has huge implications for our health. Everyone knows that maintaining a healthy body weight requires balancing the amount of food we eat with how active we are. But if the balance of energy input and output gets thrown off, there can be severe health consequences, including obesity. Among obesity’s many negative consequences on an individual’s well-being are its effects on cancer risk and progression.

While the basic equation for maintaining body weight is simple, the processes that occur in our bodies before and after our afternoon snack are anything but. A complex series of chemical signals sends information to and from our brain to determine our current energy status and direct our behavior. The complexity of this process is why questions related to energy storage can be difficult to answer: They require an understanding of cell biology, neuroscience, chemistry, genetics and behavior. Rajan hopes that by shedding light on the pathways that regulate energy signaling and balance, her research will help lead to a healthier population.

Dr. Akhila Rajan in her lab
“I wanted to work on projects that had far-reaching implications.” Robert Hood / Fred Hutch

Rajan got her start as an undergraduate in biology at the Birla Institute of Technology and Sciences in Pilani, India. She started out studying not how fat cells communicate with the brain, but how the brain communicates with muscles. Research “was innately attractive to me,” she said. “It’s just fun ... making observations no one’s made before.”

From there she traveled to Houston, Texas, to work on her Ph.D. at Baylor College of Medicine, where she studied how cells turn into neurons during development. While at Baylor, she first learned about the work of Dr. Bruce Edgar, a former researcher at Fred Hutch who studies growth and nutrition. Edgar’s work suggested there was a signal from the fat to the brain that conveyed information about nutrient stores in the fruit fly, though no one had identified it.

For her postdoctoral fellowship, Rajan wanted to solve this mystery. Her adviser was supportive but skeptical. Other researchers had looked and come up empty handed. Some even doubted that the signal existed.

It took Rajan three long years, but she found the signal, a hormone called Upd2. Released by fat cells, this hormone acts on neurons in the fly’s brain to tell the fly it can direct energy toward energy-consuming biological tasks like releasing more eggs. If the fly were starving, it would be risky to funnel limited energy reserves toward reproduction rather than a search for food.

Eventually, all this increased activity causes the fat stores to decrease and consequently the Upd2 signal to drop, which lets the fly know it’s time to look for more to eat. The proper balance between these signals helps maintain a healthy body weight.

“The tactile aspect of biology is so important to me. I need to be able to go collect some of the raw data myself.”

Despite Rajan’s major achievement in discovering the signaling molecule, a major question remains: How does Upd2 actually make it into the brain? The brain is different from other organs; it has a protective tissue layer around it called the blood-brain barrier. This helps protect the brain from infection but also makes it impossible for many pharmaceuticals to get through. The Upd2 hormone, however, makes it through the barrier and into the brain. If Rajan can figure out how this works, she’ll not only improve our understanding of fat signaling but also may help improve strategies to get other beneficial molecules into the brain.

This is one of Rajan’s main areas of research now that she has her own lab at Fred Hutch. In fact, the former resident of her office was Edgar, the same researcher who helped inspire her to study fat signaling.

She was drawn to Fred Hutch and the Basic Sciences Division because she knew they wanted her to focus on big questions and supported her vision of interdisciplinary work. Rajan said it’s the division’s investment in young scientists, such as herself, that makes her feel like she “has to do something big, something that puts our division on the map, and not the next most-obvious thing.”

As a scientist who likes to chart her own path of discovery, Rajan said she’s didn’t want to join an institution where she sits in her office all day while someone else does the research.

“The tactile aspect of biology is so important to me,” she said. “I need to be able to go collect some of the raw data myself.”
 

— By Matthew Ross, Jan. 21, 2020