Stockholm: The Nobel Assembly has awarded the 2024 Nobel Prize in Physiology or Medicine to Victor Ambros and Gary Ruvkun for their groundbreaking discovery of microRNA and its role in post-transcriptional gene regulation.

This year's Nobel Prize celebrates two scientists who uncovered a key principle that controls gene activity. The information stored in our chromosomes acts like an instruction manual for all cells in our body. 

While every cell contains the same chromosomes and genes, different cell types, such as muscle and nerve cells, have unique characteristics. This diversity arises through gene regulation, which allows cells to activate only the necessary instructions for their specific function, ensuring the right set of genes is active in each type of cell.

What did Victor Ambros and Gary Ruvkun do?

Victor Ambros and Gary Ruvkun explored how different cell types develop. Their discovery of microRNA, a class of small RNA molecules, unveiled a new mechanism of gene regulation that is critical for multicellular organisms, including humans. 

Their work revealed that the human genome encodes over a thousand microRNAs, highlighting a previously unknown layer of gene regulation. MicroRNAs are now recognized as essential for the development and proper functioning of organisms.

Who is Victor Ambros?

Victor Ambros was born in 1953 in Hanover, New Hampshire, USA. He completed his PhD at the Massachusetts Institute of Technology (MIT) in Cambridge, MA, in 1979, followed by postdoctoral research at MIT from 1979 to 1985. In 1985, Ambros became a Principal Investigator at Harvard University. He served as a professor at Dartmouth Medical School from 1992 to 2007 and currently holds the position of Silverman Professor of Natural Science at the University of Massachusetts Medical School in Worcester, MA.

Who is Gary Ruvkun?

Gary Ruvkun was born in 1952 in Berkeley, California, USA. He earned his PhD from Harvard University in 1982, after which he conducted postdoctoral research at MIT from 1982 to 1985. In 1985, he became a Principal Investigator at Massachusetts General Hospital and Harvard Medical School, where he now serves as a Professor of Genetics.

A New Layer of Gene Regulation

This year's Nobel Prize in Physiology or Medicine celebrates the discovery of a crucial cellular mechanism used to regulate gene activity. Genetic information flows from DNA to messenger RNA (mRNA) during transcription, and the mRNA then guides protein production. 

These processes, foundational to biology, explain how different cell types, despite having identical DNA, can express distinct sets of proteins. Gene regulation ensures that the right genes are active in each cell type, enabling specialized functions in cells like muscle, intestinal, and nerve cells.

Fine-tuning gene activity is vital for adapting cellular functions to environmental changes. Errors in gene regulation can lead to diseases such as cancer, diabetes, and autoimmune disorders. Understanding how gene regulation works has been a key goal of molecular biology for decades.

The Journey Towards MicroRNA Discovery

In the 1960s, researchers identified transcription factors—specialized proteins that control the flow of genetic information by determining which mRNAs are produced. This discovery was thought to explain the principles of gene regulation. However, in 1993, Victor Ambros and Gary Ruvkun made an unexpected breakthrough, revealing an additional level of regulation involving a new class of molecules, microRNAs, which turned out to be evolutionarily conserved across species.

In the late 1980s, Ambros and Ruvkun worked in the lab of Robert Horvitz, a Nobel laureate, studying the roundworm C. elegans. This tiny worm, though simple, possesses many specialized cells, making it an excellent model for studying tissue development in multicellular organisms. Ambros and Ruvkun focused on how certain genes controlled the timing of cell development.

Their research centered on two mutant strains of worms, lin-4 and lin-14, which exhibited defects in genetic program timing. Ambros had previously demonstrated that lin-4 negatively regulated lin-14, but how this occurred was a mystery.

After completing his postdoctoral research, Ambros investigated the lin-4 mutant in his new lab at Harvard University. His research revealed that the lin-4 gene produced a tiny RNA molecule without a code for protein production. Meanwhile, in his lab at Massachusetts General Hospital and Harvard Medical School, Ruvkun showed that lin-4 blocked protein production from lin-14 at the mRNA level.

Their collaboration led to a groundbreaking discovery: the lin-4 microRNA binds to complementary sequences in the lin-14 mRNA, preventing the production of the lin-14 protein. This revealed a previously unknown principle of gene regulation, where microRNAs play a key role. Their findings were published in two landmark articles in Cell in 1993.

A Breakthrough in Gene Regulation

Initially, their discovery of microRNA received little attention, as scientists believed the mechanism was unique to C. elegans and irrelevant to more complex organisms. However, in 2000, Ruvkun’s group discovered another microRNA, encoded by the let-7 gene, which is highly conserved across species. This discovery sparked widespread interest, and soon hundreds of microRNAs were identified. Today, scientists know that the human genome encodes over a thousand microRNAs, underscoring the importance of this regulatory mechanism in multicellular life.