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Tue Oct 29 20:11:09 PDT 2024

NIH Director's Blog Daily Digest (Unofficial)

(https://directorsblog.nih.gov/2024/10/29/recognizing-the-curiosity-driven-discoveries-by-2024-nobel-prize-winners-ambros-ruvkun-and-baker/) Recognizing the Curiosity-Driven Discoveries by 2024 Nobel Prize Winners Ambros, Ruvkun, and Baker
Oct 29th 2024, 09:00

>From left: David Baker (Credit: University of Washington School of Medicine), Victor Ambros (Credit: UMass Chan Medical School), and Gary Ruvkun (Credit: Kris Snibbe/Harvard)

Earlier this month, we were honored to add three names to the (https://www.nih.gov/about-nih/what-we-do/nih-almanac/nobel-laureates) list of Nobel laureates whose work has been supported by NIH. The 2024 Nobel Prize in Physiology or Medicine was jointly awarded to Victor Ambros and Gary Ruvkun for their (https://www.nobelprize.org/prizes/medicine/2024/press-release/) discovery of microRNA and its role in post-transcriptional gene regulation. In addition, David Baker, one of three awardees of the Nobel Prize in Chemistry for his work in (https://www.nobelprize.org/prizes/chemistry/2024/press-release/) designing new computational proteins, is a long-time recipient of NIH support. On behalf of the NIH community, I’d like to congratulate these esteemed researchers for receiving this honor and thank them for their pioneering contributions to biomedical science.

Ambros and Ruvkun began the work that would eventually earn them the Nobel Prize in the late 1980s, when they were postdoctoral fellows studying gene regulation in a minuscule roundworm. Though very small, the worm has many specialized cell types that make it a good model for studying the growth of multicellular organisms. The researchers were especially interested in two mutant strains of worms and how their mutated genes affected the development of certain kinds of cells. Over many years and continued findings, Ambros and Ruvkun made the unexpected discovery of a new form of genetic regulation by a previously unknown type of molecule, microRNAs.1,2,3 They eventually showed through their work that this type of gene regulation is essential for all complex life forms. We now know that cells and tissues cannot develop normally without microRNAs, and abnormalities in microRNAs can lead to congenital hearing loss, eye and skeletal disorders, cancer, and other diseases. These findings have opened up new directions for research into stopping these conditions.

The discovery of microRNAs has led to a new understanding of gene regulation. © The Nobel Committee for Physiology or Medicine. Ill. Mattias Karlén

Curiosity-driven research also enabled the recipients of the 2024 Nobel Prize in Chemistry, who were recognized for cracking the code of protein structures. When Baker started as a student at Harvard University, he originally planned to study philosophy and social science. But when he came across a textbook on the molecular biology of the cell in a biology class, he changed his focus and became fascinated with cell biology and especially protein structures. Proteins are molecules made up of amino acids that drive all the chemical reactions in our bodies and are required for the body to function properly. Through his work exploring how proteins fold, Baker began to develop computer software called Rosetta that could predict protein structures. He then had the idea to use the software to do something long thought impossible: create new proteins that have new functions. In 2003, Baker and his team did just that—they created the first entirely new protein.4 Since then, he and his colleagues have produced multiple new proteins that have a range of purposes, including serving as the basis of new pharmaceuticals and vaccines.

The other half of the Chemistry prize was given jointly to Demis Hassabis and John Jumper of Google DeepMind, for the development of an artificial intelligence (AI) tool that can predict protein structure and has been able to do this for almost all known proteins. Called AlphaFold2, this tool is publicly available and has been used by more than 2 million people around the world for a range of processes, from helping us better understand antibiotic resistance to finding ways to use enzymes to break down plastic. Baker, Hassabis, and Jumper were awarded the prize together because it was their joint discoveries that provided these amazing insights into protein structure.

These Nobel Prizes are a reminder of the importance of basic research and the ways studies that start seemingly small—like investigating the cells of a tiny worm—can lead to breakthroughs that forever change our understanding of human health.

References:

Lee RC, et al. (https://pubmed.ncbi.nlm.nih.gov/8252621/) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. DOI: 10.1016/0092-8674(93)90529-y (1993).

Wightman B, et al. (https://pubmed.ncbi.nlm.nih.gov/8252622/) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. DOI: 10.1016/0092-8674(93)90530-4. PMID: 8252622 (1993).

Pasquinelli AE, et al. (https://pubmed.ncbi.nlm.nih.gov/11081512/) Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature. DOI: 10.1038/35040556 (2000).

Brian Kuhlman, et al. (https://pubmed.ncbi.nlm.nih.gov/14631033/) Design of a novel globular protein fold with atomic-level accuracy. Science. DOI:10.1126/science.1089427 (2003).

NIH Support:

Victor Ambros: National Institute of General Medical Sciences, National Cancer Institute

Gary Ruvkun: National Institute of General Medical Sciences, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases

David Baker: NIH Fogarty International Center, National Cancer Institute, National Institute on Aging, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences

Forwarded by:
Michael Reeder LCPC
Baltimore, MD

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