Cyclins at the MBL - Tim Hunt and His Discovery of Cyclin

In the 1970s and 1980s, Tim Hunt worked with protein synthesis in reticulocytes (immature red blood cells). In 1976, Hunt invited Tom Humphreys to Cambridge for a European Molecular Biology Organization workshop on translational controls in the cell (Hunt, 2004: S63). Tom Humphreys was a researcher at the University of Hawaii and spent many summers at the MBL helping to teach the Embryology course. During his time in Cambridge, Humphreys befriended Hunt, and invited him to the MBL in the summer of 1977. Hunt spent his first summer at the MBL studying sea urchin (Arbacia punctulata) eggs and their fertilization (Hunt, 2004: S63). He returned in 1979 to work with Ruderman on her work with cyclin in clam embryos and for several subsequent summers to continue his work with Ruderman.

In 1982, Hunt returned to the MBL to teach the annual Physiology course (Hunt, 2004: S63). He brought with him medical student, Tom Evans, and Ruderman’s former student, Eric Rosenthal, also attended the course. Over the course of that summer, Hunt and his team within the Physiology course discovered and described the actions of the protein they named cyclin. Hunt began by determining whether sea urchin eggs and embryos underwent protein synthesis changes similar to the clam eggs and embryos. Clam eggs are arrested in Gap 2 and mitosis begins after the egg is fertilized. Sea urchin eggs, though, are laid during the resting phase (G0) of the cell cycle. At that point the cells have grown in size, but have not gone through any other steps of the cell cycle. The eggs do not enter mitosis until after they are fertilized, which is often after a significant period of time.

Hunt and his team looked at fertilized sea urchin eggs, labeling the proteins apparent at the beginning of fertilization and tracking their existence as the eggs underwent cell division. They found that one protein synthesized by the cell in high levels at the early time after fertilization disappeared abruptly around the time that the fertilized eggs divided (Evans, 1983).  Similarly, other proteins which were prevalent in the unfertilized sea urchin eggs could often not be detected in fertilized eggs (Evans, 1983: 390). Those results mirrored the results of Ruderman and Hunt in clam embryos.

Going further, Hunt and his team tracked the synthesis and disappearance of particular proteins over the course of fertilization and cell division. They found that the disappearance and reappearance of one particular protein corresponded to particular points in the cell cycle (Evans, 1983: 391). They named that protein cyclin, some claim due to the cyclical nature of its presence in the cell and others claim due to Hunt’s love of cycling (Hunt, Nobel Prize speech, 2001).

The next step for the researchers was to determine why cyclin was disappearing. Within the sea urchin eggs, Hunt and his team noted that cyclin was continuously synthesized by the cell, meaning that cyclin was always being produced. Because they knew that cyclin disappeared from the cell even while it was being produced, Hunt and his team concluded that cyclin is continuously produced and periodically destroyed via proteolysis (the breakdown of proteins) (Evans, 1983: 391).

Evans, Hunt, Rosenthal, and two other students - Jim Youngblom and Dan Distel - went on to identify two different cyclin proteins in the sea urchin species Lytechinus pictus. They also went back to the proteins A and B found by Ruderman and Hunt in their experiments with clams and identified them as cyclin proteins as well. From that, researchers hypothesized that many organisms have differing numbers of cyclins, something that would later be confirmed by researchers around the world.