UMass, Harvard professors share Nobel Prize

Victor Ambros at UMass Chan Medical School and Gary Ruvkun of Mass. General and Harvard Medical School woke up this morning to learn they'd been awarded the Nobel Prize for medicine for their discovery of microRNA:

When Ambros and his lab discovered microRNA, also known as miRNA, in the nematode C. elegans in 1993 [when Ambros was at Dartmouth], its broad implications for human biology weren’t immediately apparent. However, scientists now know the ability of these tiny RNA molecules to regulate or silence gene expression has a profound and far-reaching impact on most biological processes governing health and disease, including development, aging, cancer, diabetes, heart disease, Alzheimer’s disease, schizophrenia and many others.

Surprisingly abundant in human cells, these molecules escaped notice by scientists because of their small size (approximately 22 nucleotides-long compared to protein coding genes that contain thousands of nucleotides). Researchers have now identified more than 1,000 unique human miRNAs that are responsible for regulating more than half of all human genes.

As often happens, their discovery stemmed from one of those "huh?" moments: Ambros was looking for one thing, then found another:

Looking to explain developmental abnormalities in worms caused by a mutation to the lin-4 gene, Ambros knew from his previous work that this gene somehow controlled the output of the lin-14 protein. Worms with mutant lin-4 had persistently high levels of lin-14, which affected their development, causing them to remain stuck in a juvenile state.

Expecting to find that the lin-4 gene coded for a regulatory protein that would stop production of the lin-14 protein, Ambros and colleagues found something altogether different. Instead, lin-4 encoded for a very short, single-stranded RNA molecule that scientists now know is miRNA. This miRNA was responsible for putting the brakes on the machinery necessary for creating the lin-14 protein. As a result, worms with a mutated lin-4 gene were unable to produce the miRNA necessary for shutting off the lin-14 gene that would allow the worm to mature normally.

The discovery, however, seemed more an oddity than a breakthrough at the time, in part because the lin-4 gene existed only in the worm. In 2000, Dr. Ruvkun discovered a second miRNA in C. elegans and reported evidence that miRNAs are evolutionarily ancient. By 2001, Ambros and other scientists had identified multiple miRNAs in worms, flies and humans.

Harvard notes Ambros started out as a professor there - and that he and Ruvkun first met as postdoctoral students at MIT in the 1980s - where they studied the lin-14 gene and another one, called lin-4, that together controlled nematode development.

In June 1992, Ambros called Ruvkun and said he didn’t think it was a protein [that stopped lin-14's generation of proteins], but it might be a tiny piece of RNA. If it was, the two realized, it could block lin-14 from working by binding to the messenger RNA that carried instructions to the cell’s protein-making machinery.