|Sir Tim Hunt
FRS FRSE FMedSci
Tim Hunt at UCSF in May 2009
|Born||Richard Timothy Hunt
19 February 1943 
Neston, Cheshire, England
|Thesis||The synthesis of haemoglobin (1969)|
|Doctoral advisor||Asher Korner|
|Known for||Cell cycle regulation|
|Spouse||Mary Collins (m. 1995)|
Sir Richard Timothy Hunt, FRS FMedSci FRSE (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. In particular, Hunt discovered what he called cyclin: a protein in fertilised sea urchin eggs which cyclically aggregates and is depleted during cell division cycles.
Early life and education
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 German teacher, Gerd Sommerhoff. When he was fourteen, he moved to Magdalen College School, Oxford, where the science prizes now bear his name, 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 hematologist 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.
Career and research
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 and sea urchins 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 there at Woods Hole in the Summer of 1982 using the sea urchin (Arbacia punctulata) egg as his model organism, he discovered the cyclin molecule. Hunt was a keen cyclist and named the protein based on his observation of the cyclical changes in its levels.
Cyclins are proteins that play a key role in regulating the cell-division cycle. Hunt found that cyclins begin to be synthesised after the eggs are fertilised and increase in levels during interphase, until they drop very quickly in the middle of mitosis in each cell division. He also found that cyclins are present in vertebrate cells, where they also regulate the cell cycle. He and others subsequently showed that cyclins bind and activate a family of protein kinases, now called the cyclin-dependent kinases, one of which had been identified as a crucial cell cycle regulator by Paul Nurse. The cyclin mechanism of cell division is fundamental to all living organisms (excluding bacteria) and thus the study of the process in simple organisms helps shed light on the growth of tumours in humans.
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. 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 also sits on the Selection Committee for Life Science and Medicine, which chooses winners of the Shaw Prize.
Awards and honours
Hunt was elected a member of the European Molecular Biology Organization (EMBO) in 1978, serving as a member of the organisation's Fellowship Committee 1990–1993, its Meeting Committee 2008–2009, and its governing body, the Council, 2004–2009. He was elected a Fellow of the Royal Society (FRS) in 1991, his certificate of election reads:
Distinguished for his studies of the control of protein synthesis in animal cells and for the discovery of cyclin, a protein which regulates the eukaryotic cell cycle. Together with Jackson and their students, he defined steps in formation of the initiation complex in protein synthesis, showing that the 40S ribosomal subunit binds initiator tRNA before it binds mRNA, and that this step was the target of inhibitors such as double-stranded RNA or haem deficiency. They showed that inhibition of protein synthesis is mediated by reversible phosphorylation of initiation factor eIF-2 by two distinct protein kinases and they elucidated the unexpected roles of thioredoxin and thioredoxin reductase in protein synthesis. With Ruderman and Rosenthal, he demonstrated selective translational control of mRNA in early clam embryos. This led to Hunt's discovery of cyclin as a protein which is selectively destroyed in mitosis. He subsequently cloned and sequenced cyclin cDNA from sea urchins and frogs and showed by elegant mRNA ablation experiments that cyclin translation is necessary for mitosis in frog embryos. He has also shown that cyclin is a subunit of the mitosis-promoting factor which regulates entry into mitosis. His discovery and characterization of cyclin are major contributions to our knowledge of cell cycle regulation in eukaryotic cells.
In 2001, he was awarded the Nobel Prize in Physiology or Medicine with Leland Hartwell and Paul Nurse for their discoveries regarding cell cycle regulation by cyclin and cyclin-dependent kinases. The three laureates are cited "for their discoveries of key regulators of the cell cycle," while Hunt in particular
is awarded for his discovery of cyclins, proteins that regulate the CDK function. He showed that cyclins are degraded periodically at each cell division, a mechanism proved to be of general importance for cell cycle control.
In 2003, Hunt was made an honorary Fellow of the Royal Society of Edinburgh (HonFRSE). In 2006, he was awarded the Royal Society's Royal Medal, two of which are presented annually for "the most important contributions to the advancement of natural knowledge", in his case for "discovering a key aspect of cell cycle control, the protein cyclin which is a component of cyclin dependent kinases, demonstrating his ability to grasp the significance of the result outside his immediate sphere of interest".
Collins is a professor of immunology. In the summer 2016, she was appointed director of research at the newly founded Okinawa Institute of Science and Technology, and the couple moved to Japan for an extended stay expected to last five years.
Controversy at WCSJ
In 2015, Hunt was involved in a highly publicised controversy at the World Conference of Science Journalists (WCSJ) in Seoul.
- Mochida, Satoru; Maslen, Sarah L; Skehel, Mark; Hunt, Tim (2010). "Greatwall phosphorylates an inhibitor of protein phosphatase 2Α that is essential for mitosis". Science. 330 (6011): 1670–1673. PMID 21164013. doi:10.1126/science.1195689.
- Mochida, Satoru; Hunt, Tim (2007). "Calcineurin is required to release Xenopus egg extracts from meiotic M phase". Nature. 449: 336–340. PMID 17882219. doi:10.1038/nature06121.
- Rouse, John; Cohen, Philip; Trigon, Sylviane; Morange, Michel; Alonso-Llamazares, Ana; Zamanillo, Daniel; Hunt, Tim; Nebreda, Angel R. (1994). "A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins". Cell. 78 (6): 1027–1037. ISSN 0092-8674. PMID 7923353. doi:10.1016/0092-8674(94)90277-1.
- Evans, Tom; Rosenthal, Eric T.; Youngblom, Jim; Distel, Dan; Hunt, Tim (1983). "Cyclin: A protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division". Cell. 33 (2): 389–396. ISSN 0092-8674. PMID 6134587. doi:10.1016/0092-8674(83)90420-8.
- Farrell, Paul J.; Balkow, Ken; Hunt, Tim; Jackson, Richard J.; Trachsel, Hans (1977). "Phosphorylation of initiation factor eIF-2 and the control of reticulocyte protein synthesis". Cell. 11 (1): 187–200. ISSN 0092-8674. PMID 559547. doi:10.1016/0092-8674(77)90330-0.
- Poon, R. Y.; Yamashita, K.; Adamczewski, J. P.; Hunt, T.; Shuttleworth, J. (1993). "The cdc2-related protein p40MO15 is the catalytic subunit of a protein kinase that can activate p33cdk2 and p34cdc2". EMBO Journal. 12: 3123–3132. PMC . PMID 8393783.
- Nebreda, A.R.; Hunt, T. (1993). "The c-mos proto-oncogene protein kinase turns on and maintains the activity of MAP kinase, but not MPF, in cell-free extracts of Xenopus oocytes and eggs". EMBO J. 12: 1979–1986. PMC . PMID 8387916.
- Craig, D.; Howell, M.T.; Gibbs, C.L.; Hunt, T.; Jackson, R.J. (1992). "Plasmid cDNA-directed protein synthesis in a couple eukaryotic in vitro transcription-translation system". Nucl. Acid. Res. 20: 4987–4995. PMC . PMID 1383935. doi:10.1093/nar/20.19.4987.
- Standart, N.; Dale, M.; Stewart, E.; Hunt, T. (1990). "Maternal mRNA from clam oocytes can be specifically unmasked in vitro by antisense RNA complementary to the 3’ untranslated region". Genes Dev. 4: 2157–2168. PMID 2148535. doi:10.1101/gad.4.12a.2157.
- Gautier, J.; Minshull, J.; Lohka, M.; Glotzer, M.; Hunt, T.; Maller, J.L. (1990). "Cyclin is a component of MPF from Xenopus". Cell. 60: 487–494. PMID 1967981. doi:10.1016/0092-8674(90)90599-a.
- Standart, N.; Minshull, J.; Pines, J.; Hunt, T. (1987). "Cyclin synthesis, modification and destruction during meiotic maturation of the starfish oocyte". Dev. Biol. 124: 248–258. PMID 15669148. doi:10.1016/0012-1606(87)90476-3.
- Minshull, J.; Hunt, T. (1986). "The use of single-stranded DNA and RNase H to promote quantitative ‘hybrid arrest of translation’ of mRNA/DNA hybrids in reticulocyte lysate cell-free translations". Nucleic Acids Res. 14: 6433–6451. PMC . PMID 3018671. doi:10.1093/nar/14.16.6433.
- Hunt, T.; Herbert, P.; Campbell, E.A.; Delidakis, C.; Jackson, R.J. (1983). "The use of affinity chromatography on 2'-5'ADP- Sepharose reveals a requirement for NADPH, thioredoxin and thioredoxin reductase for the maintenance of high protein synthesis activity in rabbit reticulocyte lysates". Eur. J. Biochem. 131: 303–311. PMID 6299735. doi:10.1111/j.1432-1033.1983.tb07263.x.
- Rosenthal, E.T.; Hunt, T.; Ruderman, J.V. (1980). "Selective translation of mRNA controls the pattern of protein synthesis during early development of the surf clam, Spisula solidissima". Cell. 20: 487–494. PMID 7190072. doi:10.1016/0092-8674(80)90635-2.
- Hunter, A.R.; Hunt, T.; Knowland, J.S.; Zimmern, D. (1976). "Messenger RNA for the coat protein of tobacco mosaic virus". Nature. 260: 759–764. PMID 1264250. doi:10.1038/260759a0.
- Darnbrough, C.H.; Legon, S.; Hunt, T.; Jackson, R.J. (1973). "Initiation of protein synthesis: evidence for messenger RNA- independent binding of methionyl transfer RNA to the 40S ribosomal subunit". J. Mol. Biol. 76: 379–403. PMID 4732074. doi:10.1016/0022-2836(73)90511-1.
- Kosower, N.S.; Vanderhoff, G.A.; Benerofe, B.; Hunt, T.; Kosower, E.M. (1971). "Inhibition of protein synthesis by glutathione disulfide in the presence of glutathione". Biochem. Biophys. Res. Comm. 45: 816–821. PMID 5128185. doi:10.1016/0006-291x(71)90490-6.
- Ehrenfeld, E.; Hunt, T. (1971). "Double-stranded poliovirus RNA inhibits initiation of protein synthesis by reticulocyte lysates". Proc. Natl. Acad. Sci. USA. 68: 1075–1078. PMC . PMID 4325000. doi:10.1073/pnas.68.5.1075.
- Hunt, T.; Hunter, A.R.; Munro, A.J. (1968). "Control of haemoglobin synthesis: distribution of ribosomes on the messenger RNA for a and b chains". J. Mol. Biol. 36: 31–45. PMID 5760537. doi:10.1016/0022-2836(68)90217-9.
- Murray, Andrew; Hunt, Tim (1993). The Cell Cycle: An Introduction. Oxford: Oxford University Press. ISBN 978-0195095296.
- Wilson, John; Hunt, Tim (2014). Molecular Biology of the Cell: The Problems Book (6th ed.). Taylor & Francis Ltd. ISBN 978-0815344537.
- HUNT, Sir Tim. ukwhoswho.com. Who's Who. 2015 (online Oxford University Press ed.). A & C Black, an imprint of Bloomsbury Publishing plc. (subscription required)
- Tim Hunt's publications indexed by Google Scholar
- Hunt, Richard Timothy (1969). The synthesis of haemoglobin (PhD thesis). University of Cambridge. OCLC 885437139.
- Cockerill, Matthew James (1996). D-type cyclins in Xenopus laevis (PhD thesis). University of Cambridge. OCLC 557383637.
- Pelham, Hugh R. B. (1978). Transcription and Translation in Reticulocyte Lysates. (PhD thesis). University of Cambridge. OCLC 500538683.
- "Sir Hugh Pelham FMedSci FRS". London: Royal Society. Archived from the original on 17 November 2015.
- Pines, Jonathon Noe Joseph (1987). Cyclin : a major maternal message in sea urchin eggs (PhD thesis). University of Cambridge. OCLC 499166627.
- Pines, Jonathon; Hunt, Tim (1987). "Molecular cloning and characterization of the mRNA for cyclin from sea urchin eggs". The EMBO Journal. 6 (10): 2987–2995. PMC . PMID 2826125.
- "Dr Jonathon Pines: Department of Zoology". Cambridge: cam.ac.uk. Archived from the original on 2015-05-15.
- Anon (2016). "Meet the Professors: Anne Ridley". kcl.ac.uk.
- Anon (2006). "Anne Ridley Profile" (PDF). ascb.org. American Society for Cell Biology. Archived from the original (PDF) on 2007-07-13.
- "Tim Hunt". Heidelberg: European Molecular Biology Organization.
- Anon (1991). "Sir Tim Hunt FMedSci FRS". London: Royal Society. Archived from the original on 2015-11-17. One or more of the preceding sentences incorporates text from the royalsociety.org website where:
“All text published under the heading 'Biography' on Fellow profile pages is available under Creative Commons Attribution 4.0 International License.” --Royal Society Terms, conditions and policies at the Wayback Machine (archived 25 September 2015)
- "PDF List of Fellows on the webpages of the RSE" (PDF). 24 November 2015. Retrieved 28 December 2015.
- "Tim Hunt – Autobiography". Nobelprize.org. Nobel Media AB. 2002. Retrieved 13 November 2008.
- Hunt, Tim (8 August 2015). "Pursuing the impossible: an interview with Tim Hunt". BMC Biology. 13: 64. PMC . PMID 26253553. doi:10.1186/s12915-015-0164-y.
- Creative Breakthroughs | Tim Hunt | TEDxLancasterU
- BBC Radio 4 interview with Jim Al-Khalili on The Life Scientific
- Hunt, Tim; Hunter, Tony; Munro, Alan (1968). "Control of haemoglobin synthesis: Distribution of ribosomes on the messenger RNA for α and β chains". Journal of Molecular Biology. 36 (1): 31–45. PMID 5760537. doi:10.1016/0022-2836(68)90217-9.
- Hunt, Tim; Hunter, Tony; Munro, Alan (1968). "Control of haemoglobin synthesis: a difference in the size of the polysomes making alpha and beta chains". Nature. 220: 481–483. PMID 5686164. doi:10.1038/220481a0.
- Jackson, Peter K. (July 2008). "The Hunt for Cyclin". Cell. 134 (2): 199–202. doi:10.1016/j.cell.2008.07.011.
- "Understanding how cells divide – the story of a Nobel prize". Cancer Research UK - Science blog. Retrieved 24 October 2015.
- The Nobel Prize in Physiology or Medicine 2001 Illustrated Lecture
- "Cancer Research UK: Tim Hunt". Archived from the original on 13 October 2008. Retrieved 13 November 2008.
- Liz Hunt (21 December 2010). "Sir Tim Hunt: I am interested in how cells know what they are and how they should behave (Interview)". The Telegraph. Retrieved 26 December 2015.
- "Tim Hunt biography on the web pages of the Francis Crick Institute". Retrieved 26 December 2015.
- "Advisory Council of the Campaign for Science and Engineering". Retrieved 11 February 2011.
- "Shaw Prize Website: Selection Committee". Retrieved 25 December 2015.
- "Certificate of election EC/1991/14: Hunt, Richard Timothy". London: Royal Society. Archived from the original on 9 December 2015.
- "Fellow list entry for Tim Hunt on the Academy web pages". Retrieved 28 December 2015.
- "Tim Hunt entry in the online member directory of the US National Academy of Science". Retrieved 26 December 2015.
- "The Nobel Prize in Physiology or Medicine 2001". nobelprize.org.
- "Royal Medal recent winners". Retrieved 13 November 2008.
- "Interview about knighthoods on BBCR4 PM Show". 15 December 2014. Retrieved 15 December 2014.
- "Collins' profile in the UCL IRIS database". Retrieved 21 June 2015.
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