Cells may be microscopic but they have a lot of moving parts, and learning what guide them to develop the way they do has not been easy. That process became clearer with the discovery of microRNA by Victor Ambros and Gary Ruvkun, the two Nobel Prize laureates in Physiology or Medicine 2024.

“Their surprising discovery revealed an entirely new dimension to gene regulation. MicroRNAs are proving to be fundamentally important for how organisms develop and function,” stated the Royal Swedish Academy of Sciences after the announcement.

He and Ruvkun met as post-doctoral fellows at Massachusetts Institute of Technology (MIT) and exchanged information after they went on to do parallel work in separate labs.

Victor Ambros made the discovery of microRNA while studying mutations in the roundworm C. elegans 30 years ago at his lab at Harvard University. He and Ruvkun met as post-doctoral fellows at Massachusetts Institute of Technology (MIT) and exchanged information after they went on to do parallel work in separate labs.

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Gary Ruvkun: An out-of-the box thinker

More than three decades after their discovery of microRNA, Professor Gary Ruvkun received the “mythic call” from Stockholm to learn that he’d been awarded the Nobel Prize in Physiology or Medicine alongside his erstwhile colleague Victor Ambros.

A very active field

Ambros’ fascination with cell processes goes back to his undergraduate days at MIT, he says to NLS. 

“I got interested in biology, and I was doing work in labs, taking recordings from the brains of frogs and salamanders, and had a chance to publish some papers,” he says. “I had some great mentors, and the more I thought about it [cellular processes] the more mysterious it got. I liked the fact that I could use genetics to learn more about these processes and the effects of these processes inside cells.”

I had some great mentors, and the more I thought about cellular processes the more mysterious it got.

“The more we learned, the more we realized that cellular processes are very complex and nuanced,” he says. “This is a very active field and it is very exciting when people are discovering new aspects of gene regulating mechanisms.”

Detailed molecular mechanisms

This discovery and understanding of microRNA’s role has opened new opportunities for diagnosing and treating metabolic disorders and other diseases.

“There has been a lot of studies about the microRNAs that can be detected in body fluids, such as blood plasma,” says Ambros. “When we find microRNAs released into circulation, that can reflect that cells are being stressed or being replaced somewhere in the body. For example, liver damage from acetaminophen can be indicated by microRNAs in circulation that usually are only expressed in the liver. Research has also linked microRNAs in circulation to the presence of tumors.”

One of the recent revolutions has been the emergence of the CRISPR genome editing technology.

Ambros is continuing to use C. elegans in his research and a new gene editing tool has opened new opportunities, he says. “One of the recent revolutions has been the emergence of the CRISPR genome editing technology. We can design a mutation and identify parts of the gene that we want to mutate because,” he notes.

“We’re focusing on detailed molecular mechanisms and we’re interested in how microRNA and its partner proteins work together. When a microRNA binds to a messenger RNA target it brings with it a protein, Argonaute, which acts upon the messenger RNA to repress protein production. Mutations in human Argonaute proteins are involved with a class of neurodevelopmental disorders called Argonaute syndrome. While the number of people identified thus far with this condition is not large, many have come forward to participate in studies.” 

Ambros jokes at age 70, he doesn’t have long term goals so much as a desire to do what he can do over the next few years to investigate these and other new diseases.

“I’m fascinated by how Argonaute proteins work together with microRNAs,” he says. “Since there are human diseases traced to Argonaute mutations, these mutations can help scientists better understand Argonaute molecular mechanisms, and also better understand the Argonaute Syndrome condition. Remarkably, these patients are gifting to scientists these very informative mutations that we haven’t had access to before.”

Aspired to go to MIT

Ambros traces his interest in science and nature to growing up on a farm in Vermont. He was one of eight children and everyone had to pitch in to keep things running. “We always had to be doing something,” he says.

But when his chores were done, he had time to fish, hunt, and explore nearby areas, he says. He also liked working with his hands and learned from an early age that if he needed something, first try building it yourself – a philosophy he still follows in his work today.

Lee has worked as his Lab Manager since 1986 and she was part of the research team and the first author on the 1993 paper about microRNA that the Nobel Committee referenced.

In school Ambros excelled in math and science, and aspired to go to MIT for as long as he could remember. It was also at MIT that he met his wife and co-researcher, senior scientist Rosalind Lee, when they were undergraduates. Lee has worked as his Lab Manager since 1986 and she was part of the research team and the first author on the 1993 paper about microRNA that the Nobel Committee referenced.

Ambros marvels at her juggling abilities. “She carried in her head the needs of the family and all the people in the lab. Without her I wouldn’t be here,” he says. The couple is now looking forward to attending the Nobel Prize festivities in Stockholm with their three sons and their spouses.

Fuels for success

Ambros adds that he was fortunate with the way his career evolved, thanks to both circumstances and caring people.

“I view my career as lucky,” he explains. “Things happened, I didn’t make choices, I fell into labs and had supportive mentors.”

He urges those entering research to seek mentors and colleagues who are helpful to them and to collaborate as much as possible. “Share your findings, don’t be secretive,” he continues. “Some others might be emphasizing being secretive but the sharing of information was critical for me and Ruvkun going forward. Gary and I could have chosen to compete and we’d have been in a different place if we had made that decision. It would have taken much longer to make the discovery. When you share in a community, ideas pop up. Brainstorming and collaborating are fuels for success and that makes science fun.”

Some others might be emphasizing being secretive but the sharing of information was critical for me and Ruvkun going forward.

The science landscape in USA continues to look strong, according to Ambros. “The research community is steadily diversifying,” he notes.

“Scientists always say there is not enough funding and they must compete for grants. I’m grateful to have been funded my whole career. Right now, there is a lot of talent coming through the pipelines and people come from all over the world to the US to do science, and that is one of the most important things for us to maintain.” 

Victor R. Ambros
  • Age: 70
  • Born: Hanover, New Hampshire, USA
  • College: Massachusetts Institute of Technology
  • Personal: Married, three children, four grandchildren. “What I love most is hanging out with the little ones.”
  • Hobbies: Running, woodworking, astronomy, reading astrophysics magazines, restoring furniture.