Tim Hunt

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Tim Hunt
Tim Hunt at UCSF 05 2009 (4).jpg
Hunt at UCSF in 2009
Richard Timothy Hunt

(1943-02-19) 19 February 1943 (age 81) [1]
Neston, Cheshire, England
Alma mater University of Cambridge (BA, PhD)
Known for Cell cycle regulation
(m. 1995)
ChildrenTwo daughters [1]
Scientific career
Fields Cell cycle [5] (Biochemistry)
Thesis The synthesis of haemoglobin  (1969)
Doctoral advisor Asher Korner [6]
Doctoral students

Sir Richard Timothy Hunt, FRS FMedSci FRSE MAE (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.


Early life and education

Hunt was born on 19 February 1943 [1] in Neston, Cheshire, to Richard William Hunt, a lecturer in palaeography in Liverpool, and Kit Rowland, daughter of a timber merchant. [12] 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. [12] 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, [1] where he first developed an interest in biology thanks to his science teacher, the German educator Gerd Sommerhoff. [12] 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. [12]

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. [12] There, he worked with scientists such as Louis Reichardt and Tony Hunter. [12] 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. [12] His PhD was supervised by Asher Korner [6] and focused on haemoglobin synthesis in intact rabbit reticulocytes (immature red blood cells), and was awarded in 1968. [6] [13] [14]

Career and research

Early career

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. [12]

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. [15]

Discovery of cyclins

It was at Woods Hole around July 1982, using Arbacia sea urchin eggs as his model organism, that he discovered cyclin proteins. [12] Cyclins play a key role in regulating the cell-division cycle. [16] Hunt was observing the eggs undergo cell division after fertilization. [17] 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. [15] Hunt named the protein "cyclin" based on his observation of the cyclical changes in its levels. [18] It was later discovered that cyclins are continuously synthesised, but are specifically targeted for proteolysis during mitosis. [15] The discovery of cyclins was reported in a study published in Cell in 1983. [19] Hunt later demonstrated that cyclins were also present in another sea urchin, Lytechinus pictus , as well as in Spisula clams. [15]

Hunt was aware that the discovery of cyclins was significant, but was initially unsure of how cyclins functioned in regard to cell division. [17] 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. [17] [15]

Later career

with Cherry A. Murray, Jerome Isaac Friedman, Torsten Wiesel, Koji Omi, Akito Arima, Jonathan M. Dorfan and Robert Baughman OIST BOG Members After Meeting Prime Minister Shinzo Abe 4 October 2013 20131004.jpg
with Cherry A. Murray, Jerome Isaac Friedman, Torsten Wiesel, Kōji Omi, Akito Arima, Jonathan M. Dorfan and Robert Baughman

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. [20] That same year, Hunt defined the concept of short linear motifs, parts of protein sequences that mediate interactions with other proteins. [21] In 1993, the book The Cell Cycle: An Introduction, which Hunt co-authored along with Andrew Murray, was published by Oxford University Press. [22] 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. [23] [24] He is a member of the Advisory Council for the Campaign for Science and Engineering. [25] He has served on the Selection Committee for the Shaw Prize in Life Science and Medicine. [26] In 2010, Hunt joined the Academic Advisory Board of the Austrian think tank Academia Superior, Institute for Future Studies. [27]

Hunt is a highly regarded colleague and mentor in the research community. [28] [29] During his career he has supervised numerous PhD students including Hugh Pelham [7] and Jonathon Pines. [9]

Science advocacy

In addition to his scientific contributions, Hunt is a lifelong advocate for scientific research. After winning the Nobel Prize in 2001, he spent much of his time traveling the world, talking to both popular and specialist audiences. In these talks he offered his characteristic perspective on inquiry, which emphasizes the importance of having fun and being lucky. [30] He also believes that science benefits when power is given to young people, himself having been given full autonomy and authority at age 27. [31]

2015 controversy

At the World Conference of Science Journalists in Seoul in June 2015, Hunt gave a impromptu toast at a lunch for female journalists and scientists. As recounted by an EU official, Hunt said: [32]

It's strange that such a chauvinist monster like me has been asked to speak to women scientists. Let me tell you about my trouble with girls. Three things happen when they are in the lab: you fall in love with them, they fall in love with you, and when you criticise them they cry. Perhaps we should make separate labs for boys and girls? Now, seriously, I'm impressed by the economic development of Korea. And women scientists played, without a doubt, an important role in it. Science needs women, and you should do science, despite all the obstacles, and despite monsters like me.

Parts of the remarks were widely publicised on social media due to their perceived sexist nature, resulting in an intense online backlash, which some described as an act of public shaming. [33] Hunt resigned from his honorary professorship at University College London after the university told him to; he also resigned from several other research positions. [34] Hunt apologised and stated that the remarks were in jest. He said that they had been taken out of context, as the remarks had originally been reported without the words "now seriously". [35] Hunt also stated he "did mean the part about having trouble with girls". [36] Some public figures and scientists, including some who had worked with Hunt, suggested that the backlash against him was disproportionate. [37] [38] [39] [40]

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. [2] He was elected a Fellow of the Royal Society (FRS) in 1991, [3] his certificate of election reads: [41]

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.

Hunt was elected a fellow of the UK's Academy of Medical Sciences (FMedSci) in 1998, [42] and a foreign associate of the US National Academy of Sciences in 1999. [43]

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. [44]

In 2003, Hunt was made an honorary Fellow of the Royal Society of Edinburgh (HonFRSE). [4] 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". [45]

Hunt was knighted in the 2006 Birthday Honours for his service to science. [46]

Personal life

Hunt is married to the immunologist Mary Collins, who was provost of the Okinawa Institute of Science and Technology in Japan, and is now Director of the Blizard Institute Queen Mary University of London. The couple have two daughters. [1]


Related Research Articles

Cell biology is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and functioning of organisms. Cell biology is the study of the structural and functional units of cells. Cell biology encompasses both prokaryotic and eukaryotic cells and has many subtopics which may include the study of cell metabolism, cell communication, cell cycle, biochemistry, and cell composition. The study of cells is performed using several microscopy techniques, cell culture, and cell fractionation. These have allowed for and are currently being used for discoveries and research pertaining to how cells function, ultimately giving insight into understanding larger organisms. Knowing the components of cells and how cells work is fundamental to all biological sciences while also being essential for research in biomedical fields such as cancer, and other diseases. Research in cell biology is interconnected to other fields such as genetics, molecular genetics, molecular biology, medical microbiology, immunology, and cytochemistry.

<span class="mw-page-title-main">Cell cycle</span> Series of events and stages that result in cell division

The cell cycle, or cell-division cycle, is the series of events that take place in a cell that causes it to divide into two daughter cells. These events include the duplication of its DNA and some of its organelles, and subsequently the partitioning of its cytoplasm, chromosomes and other components into two daughter cells in a process called cell division.

<span class="mw-page-title-main">Marine Biological Laboratory</span> Research institution in Woods Hole, Massachusetts, United States

The Marine Biological Laboratory (MBL) is an international center for research and education in biological and environmental science. Founded in Woods Hole, Massachusetts, in 1888, the MBL is a private, nonprofit institution that was independent for most of its history, but became officially affiliated with the University of Chicago on July 1, 2013. It also collaborates with numerous other institutions.

G<sub>1</sub> phase First growth phase in the eukaryotic cell cycle

The G1 phase, gap 1 phase, or growth 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. In this part of interphase, the cell synthesizes mRNA and proteins in preparation for subsequent steps leading to mitosis. G1 phase ends when the cell moves into the S phase of interphase. Around 30 to 40 percent of cell cycle time is spent in the G1 phase.

Leland Harrison (Lee) Hartwell is former president and director of the Fred Hutchinson Cancer Research Center in Seattle, Washington. He shared the 2001 Nobel Prize in Physiology or Medicine with Paul Nurse and Tim Hunt, for their discoveries of protein molecules that control the division (duplication) of cells.

<span class="mw-page-title-main">Cyclin</span> Group of proteins

Cyclins are proteins that control the progression of a cell through the cell cycle by activating cyclin-dependent kinases (CDK).

<span class="mw-page-title-main">Cyclin-dependent kinase</span> Class of enzymes

Cyclin-dependent kinases (CDKs) are a predominant group of serine/threonine protein kinases involved in the regulation of the cell cycle and its progression, ensuring the integrity and functionality of cellular machinery. These regulatory enzymes play a crucial role in the regulation of eukaryotic cell cycle and transcription, as well as DNA repair, metabolism, and epigenetic regulation, in response to several extracellular and intracellular signals. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. The catalytic activities of CDKs are regulated by interactions with CDK inhibitors (CKIs) and regulatory subunits known as cyclins. Cyclins have no enzymatic activity themselves, but they become active once they bind to CDKs. Without cyclin, CDK is less active than in the cyclin-CDK heterodimer complex. CDKs phosphorylate proteins on serine (S) or threonine (T) residues. The specificity of CDKs for their substrates is defined by the S/T-P-X-K/R sequence, where S/T is the phosphorylation site, P is proline, X is any amino acid, and the sequence ends with lysine (K) or arginine (R). This motif ensures CDKs accurately target and modify proteins, crucial for regulating cell cycle and other functions. Deregulation of the CDK activity is linked to various pathologies, including cancer, neurodegenerative diseases, and stroke.

G<sub>2</sub> phase Second growth phase in the eukaryotic cell cycle, prior to mitosis

G2 phase, Gap 2 phase, or Growth 2 phase, is the third subphase of interphase in the cell cycle directly preceding mitosis. It follows the successful completion of S phase, during which the cell’s DNA is replicated. G2 phase ends with the onset of prophase, the first phase of mitosis in which the cell’s chromatin condenses into chromosomes.

<span class="mw-page-title-main">Paul Nurse</span> English geneticist and Nobel laureate

Sir Paul Maxime Nurse is an English geneticist, former President of the Royal Society and Chief Executive and Director of the Francis Crick Institute. He was awarded the 2001 Nobel Prize in Physiology or Medicine, along with Leland Hartwell and Tim Hunt, for their discoveries of protein molecules that control the division of cells in the cell cycle.

<span class="mw-page-title-main">Cell cycle checkpoint</span> Control mechanism in the eukaryotic cell cycle

Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed, with progression through the various phases of the cell cycle occurring only when favorable conditions are met. There are many checkpoints in the cell cycle, but the three major ones are: the G1 checkpoint, also known as the Start or restriction checkpoint or Major Checkpoint; the G2/M checkpoint; and the metaphase-to-anaphase transition, also known as the spindle checkpoint. Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein subunits called cyclins, different forms of which are produced at each stage of the cell cycle to control the specific events that occur therein.

<span class="mw-page-title-main">G1/S transition</span> Stage in cell cycle

The G1/S transition is a stage in the cell cycle at the boundary between the G1 phase, in which the cell grows, and the S phase, during which DNA is replicated. It is governed by cell cycle checkpoints to ensure cell cycle integrity and the subsequent S phase can pause in response to improperly or partially replicated DNA. During this transition the cell makes decisions to become quiescent, differentiate, make DNA repairs, or proliferate based on environmental cues and molecular signaling inputs. The G1/S transition occurs late in G1 and the absence or improper application of this highly regulated checkpoint can lead to cellular transformation and disease states such as cancer.

Cyclin A is a member of the cyclin family, a group of proteins that function in regulating progression through the cell cycle. The stages that a cell passes through that culminate in its division and replication are collectively known as the cell cycle Since the successful division and replication of a cell is essential for its survival, the cell cycle is tightly regulated by several components to ensure the efficient and error-free progression through the cell cycle. One such regulatory component is cyclin A which plays a role in the regulation of two different cell cycle stages.

<span class="mw-page-title-main">Cyclin-dependent kinase inhibitor protein</span> Protein which inhibits cyclin-dependent kinase

A cyclin-dependent kinase inhibitor protein(also known as CKIs, CDIs, or CDKIs) is a protein which inhibits the enzyme cyclin-dependent kinase (CDK) and Cyclin activity by stopping the cell cycle if there are unfavorable conditions, therefore, acting as tumor suppressors. Cell cycle progression is stopped by Cyclin-dependent kinase inhibitor protein at the G1 phase. CKIs are vital proteins within the control system that point out whether the process of DNA synthesis, mitosis, and cytokines control one another. If a malfunction prevents the successful completion of DNA synthesis during the G1 phase, a signal is sent to delay or stop the progression to the S phase. Cyclin-dependent kinase inhibitor proteins are essential in the regulation of the cell cycle. If cell mutations surpass the cell cycle checkpoints during cell cycle regulation, it can result in various types of cancer.

<span class="mw-page-title-main">Outline of cell biology</span> Overview of and topical guide to cell biology

The following outline is provided as an overview of and topical guide to cell biology:

<span class="mw-page-title-main">Wee1</span> Nuclear protein

Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe. Wee1 has a molecular mass of 96 kDa and is a key regulator of cell cycle progression. It influences cell size by inhibiting the entry into mitosis, through inhibiting Cdk1. Wee1 has homologues in many other organisms, including mammals.

Sir Hugh Reginald Brentnall Pelham, is a cell biologist who has contributed to our understanding of the body's response to rises in temperature through the synthesis of heat shock proteins. He served as director of the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB) between 2006 and 2018.

<span class="mw-page-title-main">Jonathon Pines</span> British oncologist (born 1961)

Jonathon Noë Joseph Pines is Head of the Cancer Biology Division at the Institute of Cancer Research in London. He was formerly a senior group leader at the Gurdon Institute at the University of Cambridge.

Calcium plays a crucial role in regulating the events of cellular division. Calcium acts both to modulate intracellular signaling as a secondary messenger and to facilitate structural changes as cells progress through division. Exquisite control of intracellular calcium dynamics are required, as calcium appears to play a role at multiple cell cycle checkpoints.

Induced cell cycle arrest is the use of a chemical or genetic manipulation to artificially halt progression through the cell cycle. Cellular processes like genome duplication and cell division stop. It can be temporary or permanent. It is an artificial activation of naturally occurring cell cycle checkpoints, induced by exogenous stimuli controlled by an experimenter.

Julian Blow is a molecular biologist, Professor of Chromosome Maintenance, and also the Dean of the School of Life Sciences, University of Dundee, Scotland.


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  46. Recorded in The Gazette (London Gazette), issue 58014, 16 June 2006, supplement 1.