Ludwig Oxford’s Sir Peter Ratcliffe received the 2019 Nobel Prize for Physiology or Medicine in October. He was recognized by the Nobel Committee for his landmark discoveries on the mechanisms by which mammalian cells sense and respond to the availability of oxygen. Peter shared the prize with U.S. researchers William Kaelin of the Dana-Farber Cancer Institute and Gregg Semenza of Johns Hopkins University. Their discoveries, which were made independently through the 1990s and early 2000s, have had a profound influence on our understanding of biological processes and disorders ranging from heart disease to wound-healing to cancer. Peter and his two co-winners built sequentially on discoveries made in each of their labs to identify a cellular oxygen sensor. The gene expression driven by oxygen starvation was reported by Gregg Semenza’s lab to be governed by proteins known as hypoxia-inducible factors (HIFs), though how they were controlled remained a mystery. Peter and his team discovered how that control occurs and described the elegant mechanism by which a set of enzymes directly link the availability of molecular oxygen to HIF activity. Those findings were simultaneously made by William Kaelin and his colleagues. Some variation of the oxygen-sensing system Peter discovered has since been found in all animals, and he has over the years fleshed out the molecular biology and genetic regulation of hypoxic signaling in a variety of biological processes, most notably cancer: oxygen starvation at the core of solid tumors is known to contribute significantly to drug resistance and metastasis. Just this summer, he and his colleagues reported in Science their discovery of an entirely novel cellular oxygen sensor—one so ancient in its evolutionary origins that it is shared by plants (see page 12). For more on Peter Ratcliffe and his research career, see this profile in the Ludwig 2019 Research Highlights report. Congratulations, Peter!
This article appeared in the November 2019 issue of Ludwig Link. Click here to download a PDF (1 MB).