The 1 mm worm helped two scientists win the 2024 Nobel Prize in Biomedicine

According to the Nobel Council’s statement, the 2024 Nobel Prize in Biomedicine honors the discovery of important gene regulation mechanisms in cells. The owners of the prestigious award are scientists Victor Ambros and Gary Ruvkun for their work discovering microRNA (micro RNA), a new gene regulation mechanism in the roundworm C. elegans.

Experts explain that genetic information from DNA is transcribed into messenger RNA (mRNA), which is then translated to create proteins according to genetic instructions.

Since the mid-20th century, many basic scientific discoveries have explained how this process works. According to scientists, human organs and tissues consist of many types of cells, all of which have identical genetic information stored in DNA. However, these cells express different groups of proteins.

The question is where does this difference come from? The answer lies in gene regulation, ensuring that only the correct group of genes is active in each specific cell type. This allows cells such as muscle, intestine and different types of nerve cells to carry out their specialized functions. In addition, gene activity must be continuously fine-tuned to adapt to changing conditions in the body and environment.

Malfunctioning gene regulation can lead to serious diseases such as cancer, diabetes or autoimmune diseases. Therefore, understanding the regulation of gene activity has been an important goal for decades. This is also the reason why Ambros and Ruvkun’s contributions received the prestigious Nobel Prize.

It all starts with a small worm

In the 1960s, scientists demonstrated that specialized proteins, called transcription factors, could bind to specific regions in DNA and control the flow of genetic information. Since then, thousands of transcription factors have been identified.

For a long time, scientists believed they understood everything about gene regulation. However, in 1993, Ambros and Ruvkun published unexpected findings, describing four new, highly significant levels of gene regulation that are conserved throughout evolution.

They began their work in the late 1980s, while they were postdoctoral fellows in the lab of 2002 Nobel Prize winner Robert Horvitz.

Here, they studied the 1 mm long roundworm C. elegans. Despite its small size, C. elegans possesses many specialized cell types such as neurons and muscle cells, which are also found in larger, more complex animals. The tiny worm thus becomes a useful model for studying how tissues develop and mature in multicellular organisms.

Ambros and Ruvkun focused on genes that control when different genetic programs are activated, ensuring different cell types develop at the right time. They studied two mutant worm strains, lin-4 and lin-14, with the hope of identifying the mutated genes and understanding their function.

At the end of the postdoctoral research program, Ambros successfully analyzed mutations of lin-4 worms in the laboratory. He created a map that allowed gene cloning, and unexpectedly discovered that the lin-4 worm gene produces an unusually short RNA molecule that lacks the code to make proteins.

At the same time, Ruvkun studied the regulation of the lin-14 gene. He showed that the worm gene lin-4 can inhibit the production of mRNA from lin-14. This was different from the understanding of gene regulation at that time. Thus, Ruvkun discovered a new principle of gene regulation, mediated by a previously unknown type of RNA, microRNA. These results were published in 1993 in two articles in the journal Cell.

Big discovery about micronRNA

Initially, the research went largely unnoticed by the scientific community. Although the results are interesting, many people believe that the unusual gene regulation mechanism is specific to C. elegans worms, and may not be relevant to humans and more complex animals.

However, that view changed in 2000, when Ruvkun and his colleagues discovered another microRNA, present in the entire animal kingdom, including humans. The report created great resonance in the following years. Since then, hundreds of different microRNAs have been identified.

Today, scientists know that there are more than 1,000 genes for different microRNAs in humans and that gene regulation by microRNAs is common in multicellular organisms. This mechanism is the foundation that makes organisms evolve increasingly complex.

Genetic research shows that cells and tissues do not develop normally without microRNA. Abnormalities in microRNA can lead to cancer, congenital hearing loss, and eye and bone disorders.

Thus, Ambros and Ruvkun’s important discovery in the tiny worm C. elegans reveals a new aspect of gene regulation, essential for all complex life forms.