Tim Hunt

Sir Richard Timothy Hunt (born 19 February 1943) is a British biochemist and molecular physiologist. He was awarded the 2001 Nobel Prize in Physiology or Medicine with Paul Nurse and Leland H. Hartwell for their discoveries of protein molecules that control the division of cells. While studying fertilized sea urchin eggs in the early 1980s, Hunt discovered cyclin, a protein that cyclically aggregates and is depleted during cell division cycles.

Hunt was born on 19 February 1943 in Neston, Cheshire, to Richard William Hunt, a lecturer in palaeography in Liverpool, and Kit Rowland, daughter of a timber merchant. After the death of both his parents, Hunt found his father had worked at Bush House, then the headquarters of BBC World Service radio, most likely in intelligence, although it is not known what he actually did. In 1945, Richard became Keeper of the Western Manuscripts at the Bodleian Library, and the family relocated to Oxford. At the age of eight, Hunt was accepted into the Dragon School, where he first developed an interest in biology thanks to his science teacher, the German educator Gerd Sommerhoff. When he was fourteen, he moved to Magdalen College School, Oxford, becoming even more interested in science and studying subjects such as chemistry and zoology.

In 1961, he was accepted into Clare College, Cambridge to study Natural Sciences, graduating in 1964 and immediately beginning work in the university Department of Biochemistry under Asher Korner. There, he worked with scientists such as Louis Reichardt and Tony Hunter. A 1965 talk by Vernon Ingram interested him in haemoglobin synthesis, and at a Greek conference in 1966 on the subject, he persuaded the haematologist and geneticist Irving London to allow him to work in his laboratory at Albert Einstein College of Medicine in New York, staying from July to October 1966. His PhD was supervised by Asher Korner and focused on haemoglobin synthesis in intact rabbit reticulocytes (immature red blood cells), and was awarded in 1968.

Following his PhD, Hunt returned to New York to work with London, in collaboration with Nechama Kosower, her husband Edward Kosower, and Ellie Ehrenfeld. While there, they discovered that tiny amounts of glutathione inhibited protein synthesis in reticulocytes and that tiny amounts of RNA killed the synthesis altogether. After returning to Cambridge, he again began work with Tony Hunter and Richard Jackson, who had discovered the RNA strand used to start haemoglobin synthesis. After 3–4 years, the team discovered at least two other chemicals acting as inhibitors.

Hunt regularly spent summers working at the Marine Biological Laboratory at Woods Hole, Massachusetts, which was popular with scientists for its advanced summer courses, and in particular, with those interested in the study of mitosis. The location provided a ready supply of surf clams (Spisula solidissima) and sea urchins (Arbacia punctulata) amongst the reefs and fishing docks, and it was these invertebrates that were particularly useful for the study of the synthesis of proteins in embryogenesis, as the embryos were simply generated with the application of filtered sea water, and the transparency of the embryo cells was well suited to microscopic study.

It was at Woods Hole around July 1982, using Arbacia sea urchin eggs as his model organism, that he discovered cyclin proteins. Cyclins play a key role in regulating the cell-division cycle. Hunt was observing the eggs undergo cell division after fertilization. The study also included a control group where the eggs had been activated without fertilization by a calcium ionophore. The eggs were incubated with the amino acid methionine in which some of the atoms were radioactive isotopes (radiolabelled), with samples being taken from the eggs at 10 minute intervals. During the egg development, the radioactive methionine was uptaken into the cells and used to make proteins. From the samples, proteins were precipitated and then separated by mass into distinct bands on a resolving gel mat, which were then observed by photographic film that could detect the radioactivity emitted by the proteins. Observing the changes in the bands across the samples, Hunt noticed that one of the proteins rose in abundance before disappearing during the mitosis phase of cell division. Hunt named the protein "cyclin" based on his observation of the cyclical changes in its levels. It was later discovered that cyclins are continuously synthesised, but are specifically targeted for proteolysis during mitosis. The discovery of cyclins was reported in a study published in Cell in 1983. Hunt later demonstrated that cyclins were also present in another sea urchin, Lytechinus pictus, as well as in Spisula clams.

Hunt was aware that the discovery of cyclins was significant, but was initially unsure of how cyclins functioned in regard to cell division. This was clarified in later papers in the 1980s and 1990s, some of which Hunt co-authored. These again utilized sea urchin eggs as well as eggs of the frog Xenopus, and demonstrated that cyclins were present in the cells of most organisms, and combine with kinase enzymes (specifically cyclin-dependent kinases) to form maturation-promoting factor (MPF). MPF has previously been identified in 1971 by Yoshio Masui and Clement Markert from Xenopus eggs. MPF induces mitosis, with the cyclic activation and inactivation of MPF being a key element in regulating and progressing the cell cycle.

In 1990, he began work at Imperial Cancer Research Fund, later known as the Cancer Research UK London Research Institute, in the United Kingdom, where his work focused on understanding on what makes cell go cancerous, that is: proliferate uncontrollably, with the ordinary inhibitory signals switched off. That same year, Hunt defined the concept of short linear motifs, parts of protein sequences that mediate interactions with other proteins. In 1993, the book The Cell Cycle: An Introduction, which Hunt co-authored along with Andrew Murray, was published by Oxford University Press. Hunt had his own laboratory at the Clare Hall Laboratories until the end of 2010, and remains an Emeritus Group Leader at the Francis Crick Institute. He is a member of the Advisory Council for the Campaign for Science and Engineering. He has served on the Selection Committee for the Shaw Prize in Life Science and Medicine. In 2010, Hunt joined the Academic Advisory Board of the Austrian think tank Academia Superior, Institute for Future Studies.