Nobel Prize for Medicine out: What exactly have the winners worked on

What is microRNA?

MicroRNA are molecules that help cells control their protein production. The proteins that cells produce play vital roles in almost all biological processes of living organisms. In human bodies, for example, the protein haemoglobin transports oxygen, insulin helps absorption of glucose from blood, etc. Thus, anything that impacts protein production can have consequences for human health.

MicroRNA works by binding with another type of molecule called messenger RNA (mRNA). As an article on the Ohio State University’s website explains, “microRNA controls gene expression mainly by binding with messenger RNA (mRNA) in the cell cytoplasm. Instead of being translated quickly into a protein, the marked mRNA will be either destroyed and its components recycled, or it will be preserved and translated later.”

What did Ambros and Ruvkun do?

According to the Nobel Prize website, in the 1980s, Ambros and Ruvkun were postdoctoral fellows in the laboratory of Robert Horvitz, who won the Nobel in 2002. The two were studying a tiny roundworm called C. Elegans, which possessed some cell types also found in more complex animals.

“They studied two mutant strains of worms, lin-4 and lin-14, that displayed defects in the timing of activation of genetic programs during development,” the website says.

Ambros had shown in previous work that the lin-4 gene hindered the lin-14 gene, but how this happened was not known. Through his studies, Ambros found that the lin-4 gene produced an unusually short RNA molecule, which was inhibiting lin-14. This turned out to be microRNA.

Meanwhile, Ruvkun studies lin-14. Back then, the common understanding was that to regulate a gene, its production of mRNA has to be targetted. “Ruvkun showed that it is not the production of mRNA from lin-14 that is inhibited by lin-4. The regulation appeared to occur at a later stage in the process of gene expression, through the shutdown of protein production,” the website says.

“Experiments also revealed a segment in lin-14 mRNA that was necessary for its inhibition by lin-4. The two laureates compared their findings, which resulted in a breakthrough discovery. The short lin-4 sequence matched complementary sequences in the critical segment of the lin-14 mRNA. Ambros and Ruvkun performed further experiments showing that the lin-4 microRNA turns off lin-14 by binding to the complementary sequences in its mRNA, blocking the production of lin-14 protein.”

While these results were published in 1993, they didn’t attract much attention then, as this gene regulation was thought to be limited to the roundworm C. Elegans. However, subsequent research has established that microRNA is found in all multi-celled organisms, including humans.

Why is their work important?

As the Nobel Prize website says, if “gene regulation goes awry, it can lead to serious diseases such as cancer, diabetes, or autoimmunity. Therefore, understanding the regulation of gene activity has been an important goal for many decades.”

“Gene regulation by microRNA, first revealed by Ambros and Ruvkun, has been at work for hundreds of millions of years… We know from genetic research that cells and tissues do not develop normally without microRNAs. Abnormal regulation by microRNA can contribute to cancer, and mutations in genes coding for microRNAs have been found in humans, causing conditions such as congenital hearing loss, eye and skeletal disorders,” the website says.

Who are Victor Ambros and Gary Ruvkun?

Ambros, 70, is the Silverman Professor of Natural Science at the University of Massachusetts Medical School. He has a PhD from Massachusetts Institute of Technology, where he also did postdoctoral research from 1979-1985.

Ruvkun, 72, is Professor of Genetics at Harvard Medical School. He has a PhD from Harvard University. He too was a postdoctoral fellow at Massachusetts Institute of Technology, from 1982-1985.