Daniel Colón-Ramos Reveals the Mysteries of Worms’ Memories
Daniel Colón-Ramos Reveals the Mysteries of Worms’ Memories

Daniel Colón-Ramos Reveals the Mysteries of Worms’ Memories

The Yale neuroscientist seeks to understand the brain’s architecture and function using C. elegans.

Claudia Lopez-Lloreda
May 1, 2020

ABOVE: © Christopher Beauchamp

As a Harvard undergraduate, Daniel Colón-Ramos explored the forests of Panama and Honduras, listening closely as indigenous people described how they use medicinal plants to treat ill individuals. The interactions, he says, left him with many more questions than answers. “The questions that kept coming to my mind were molecular questions about what the bioactive agents were and how they worked,” he says. Sitting there in the forest, he realized he wanted to contribute knowledge to science, instead of just learning facts. 

After earning his bachelor’s degree in biology in 1998, he moved to Duke University, where he began a post-baccalaureate program that gave him his first experiences at the lab bench. “That was transformative in my ability to imagine myself as a scientist,” he says. He then applied to and was accepted as a PhD student at Duke, where he joined the lab of Sally Kornbluth, who studies cell suicide, a process called apoptosis. Colón-Ramos identified viral peptides that inhibited translation of RNA into host cell proteins that would otherwise induce apoptosis, revealing a potential mechanism that viruses use to continue their cell-to-cell spread.

Those experiments, together with attending talks and reading papers outside of his comfort zone, helped Colón-Ramos pinpoint what sparked his scientific curiosity: how cellular organization shapes the way an organism behaves. Colón-Ramos wanted to explore this connection in an animal model that could easily be modified genetically, which led him to the worm Caenorhabditis elegans. As a postdoctoral researcher, he also shifted his research focus from cell death to developmental neuroscience, joining Kang Shen’s lab at Stanford University. There, Colón-Ramos showed that non-neuronal cells called glia guide synapse formation and coordinate neural connectivity.

Less than a year after publishing the discovery, Colón-Ramos opened his lab at Yale University to further explore how synapses form, persist, and govern behavior. He’s using C. elegans to dissect cell biology, “but also he has stayed true to himself and expanded his interest in behavior,” Shen says. In 2018, Colón-Ramos’s postdoc Josh Hawk reported that a single cell in the worm’s nervous system serves as a logic system controlling how the animal senses temperature and responds to it based on a memory it made before. “We’re showing that these neurons can be molecular computers,” Colón-Ramos says. “They’re capable of pretty sophisticated integration.”

For Colón-Ramos, though, studying a single neuron is not enough. He wants to understand all of the neuronal connections of the brain, what’s called the connectome. In a multi-institutional effort, he and colleagues traced C. elegans connectomes to see which cells interact during development. “From that work emerged all sorts of circuits, some of which we knew, but [also] others which we had overlooked,” Colón-Ramos says. Delving into the developmental connectomics of C. elegans is not an easy feat, says Hari Shroff, a biophysicist at National Institute of Biomedical Imaging and Bioengineering who is part of the connectome collaboration. But Colón-Ramos has this “willingness to be fearless and try new technology, while also being critical and honest about limitations,” Shroff says.

That honesty has paid off in Colón-Ramos’s research as well as in his advocacy for representation of minorities in the sciences. Born and raised in Puerto Rico, Colón-Ramos became acutely aware of the lack of diversity in science as an undergraduate. “Not only did I not see myself represented in the sciences, but a lot of people had not met people from my background,” he says.

Colón-Ramos founded CienciaPR, a non-profit organization that brings Hispanic and Latinx communities together to promote scientific research and education. “He actually does want to make science a diverse place,” Shroff says. Shen adds that Colón-Ramos’s incredible passion for outreach is part of what sets him apart, along with his ability to establish collaborations and his outstanding science. “He seems to have this sort of energy to get it all done,” Shen says. “[His] success already speaks for itself.”