William G. Kaelin Jr., a member of the American Association for the Advancement of Science, was jointly awarded the 2019 Nobel Prize in Physiology or Medicine along with Gregg L. Semenza and Peter J. Ratcliffe for their research unveiling how cells “sense and adapt” to oxygen levels.
The discovery identified by the three scientists, all medical doctors, revealed “molecular machinery that regulates the activity of genes in response to varying levels of oxygen,” the Nobel committee said in its announcement on Monday.
“The seminal discoveries by this year’s Nobel Laureates revealed the mechanism for one of life’s most essential adaptive processes. They established the basis for our understanding of how oxygen levels affect cellular metabolism and physiological function,” the announcement said. “Their discoveries have also paved the way for promising new strategies to fight anemia, cancer and many other diseases.”
Each of the three laureate’s research was responsible for showing how cells adapt to different oxygen levels and control the molecular machinery driving responses, the Nobel committee said. The awards were announced at the Karolinska Institute in Stockholm.
Jeremy Berg, editor-in-chief of the Science family of journals, said the key to the process “is modification of a protein that controls the expression of particular genes by an oxygen-dependent reaction. When oxygen is plentiful, this modification marks the protein for degradation; when oxygen is scarce, the protein is not modified and it is available to regulate specific genes by binding specific DNA sequences.”
Kaelin, who has been a AAAS member since 1987, established his own laboratory at the Dana-Farber Cancer Institute in Boston and has been a professor at Harvard Medical School since 2002. He also is a Howard Hughes Medical Institute investigator, a position he has held since 1998.
Semenza is director of the Vascular Research Programs at the Johns Hopkins Institute for Cell Engineering in Baltimore. Ratcliffe is director of clinical research at the Francis Crick Institute in London, director of the Target Discovery Institute in Oxford and a member of the Ludwig Institute for Cancer Research. As is customary, each laureate was contacted by telephone before the prizes were announced.
“Thanks to the groundbreaking work of these Nobel Laureates, we know much more about how different oxygen levels regulate fundamental physiological processes,” the announcement said. “Oxygen sensing allows cells to adapt their metabolism to low oxygen levels: for example, in our muscles during intense exercise.”
The oxygen-sensing process also allows cells to make new blood vessels and produce red blood cells. In addition, the process has been found to be pivotal to fetal development, human metabolism and immune response and central to many diseases.
“Changing cellular metabolism and gene expression in response to changes in oxygen availability is clearly a truly fundamental process for oxygen-consuming organisms such as ourselves,” said Berg. “This year’s Nobel Prize is for elucidating the major mechanism by which this occurs. Such pathways are of great importance for normal physiological adaptation as well as in cancer where adjustment of tumors to low availability of oxygen can be essential.”
[Associated Image: Niklas Elmehed/ © Nobel Media]