Here’s a science riddle: “What does sonar have to do with aging?” The answer is new biology assistant professor Nicola Neretti, whose intellectual path from physics graduate student in 1997 to new tenure-line faculty member at Brown has been interdisciplinary to say the least.
In his studies, first in Bologna, Italy, and then at Brown, Neretti focused on signal processing, the science of extracting relevant information from an incoming flood of data. Cell phones use it to tune in just your conversation. Submarines use it to figure out which reflected sounds came from a distant object of interest.
Neretti hadn’t studied much biology, but that changed when he joined the lab of Leon Cooper, professor of physics. There he found a team studying sonar not just in transducers and microprocessors but also in the animal brain.
“It turns out that bats and dolphins do a much better job at locating and classifying objects than man-made devices can do,” said Neretti, assistant professor of biology in the Department of Molecular Biology, Cell Biology and Biochemistry. “There was a lot of interest, especially from the Navy, to develop models inspired by biology.”
By the time Neretti was a postdoc at Brown in 2001, he was working closely with Jim Simmons, professor of neuroscience, to create a computer model of the neural circuitry of bat echolocation.
At about the same time, biologists were rapidly gaining access to new tools that produced reams of data. They were excited by expression microarrays. The little chips would, by means of a grid of tiny glowing dots, display the specific gene expression of different cells under different circumstances.
“This required some pretty sophisticated signal processing in order to make any sense of it,” Neretti said.
With his skills as a computational modeler of biology, Neretti became involved with molecular biologists at Brown who were hoping to do just that.
With work culminating in a 2005 paper in the Proceedings of the National Academy of Sciences, Neretti had moved from physicist to neuroscientist to molecular biologist, all the while staying true to his computational and signal processing interests. Among Neretti’s co-authors was John Sedivy, a prominent cancer researcher who in 1998 has begun to study aging at the level of the body’s cells.
In 2007, with Sedivy, Mark Tatar in ecology and evolutionary biology, and Charles Lawrence in applied mathematics, Neretti won a five-year grant from the National Institutes of Health to study how diet affects an organism’s processes for handling genes associated with aging. Working mostly in fruit flies and mice, they set out to explain why organisms that eat about 40 percent fewer calories live longer than peers who eat what they’d like.
“It feels like starving,” Neretti said. “There are humans that do that voluntarily and they say that they are constantly hungry. The idea is not to suggest this as a solution for an increased lifespan, but to use this as a tool to identify what are the genes and changes that are induced by this lower level of calories.”
And so for years as a research professor, Neretti and his colleagues have been using computer analyses of microarray data to zero in on which genes are important to longevity and what difference low-calorie diets make in either expressing or silencing them.
“When you calorie-restrict an animal, you change thousands of genes,” he said. “But not all of them have an impact on lifespan. You want to find the key ones.”
In the last two years, Neretti’s team has published a couple papers in the journal Aging that provide important insights in the area. In a 2010 paper, in collaboration with Stephen Helfand in molecular biology, cellular biology, and biochemistry, they identified about 30 genes and focused on one, ironically bearing the dining-related name “Takeout,” as having a role in regulating lifespan.
This summer, the researchers published a largely mathematical advance that allowed them to track genes of interest in both insects and mammals. One of their findings was that calorie restriction and the compound resveratrol seem to operate similarly on genes in both kinds of creatures.
At about the same time all this research was underway, Neretti was thinking about his next career move. He had been at Brown for more than a decade, after all, and other institutions have presented him with other offers.
But Brown has kept up with his interests. Last year the University beefed up its gene sequencing capabilities with a new high-throughput Illumina machine and recently the University also partnered with IBM to build out a powerful supercomputing facility.
“They give me all the tools I need for my research to move forward,” he said.
His next project will be to study how the three-dimensional physical structure of DNA changes with age and how that correlates with how genes are expressed.
It’s the next step in a journey that has blended physics with biology at Brown.