Sir Tim Hunt | |
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![]() Tim Hunt at UCSF in May 2009 | |
Born | Richard Timothy Hunt 19 February 1943 [1] |
Citizenship | United Kingdom |
Education | |
Alma mater | University of Cambridge (BA, PhD) |
Known for | Cell cycle regulation |
Spouse | [1] |
Children | Two daughters [1] |
Awards |
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Scientific career | |
Fields | Cell cycle [5] (Biochemistry) |
Institutions | |
Thesis | The synthesis of haemoglobin (1969) |
Doctoral advisor | Asher Korner [6] |
Doctoral students | |
Influenced | Anne Ridley [12] [13] |
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.
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. [14] 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. [14] 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 German teacher, Gerd Sommerhoff. [14] 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. [14] [15] [16] [17]
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. [14] There, he worked with scientists such as Louis Reichardt and Tony Hunter. [14] 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. [14] 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] [18] [19]
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. [14]
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. [20]
It was at Woods Hole in the Summer of 1982, using the sea urchin (Arbacia punctulata) egg as his model organism, that he discovered the cyclin molecule. [14] Hunt was a keen cyclist and named the protein based on his observation of the cyclical changes in its levels. [21]
Cyclins are proteins that play a key role in regulating the cell-division cycle. [22] 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. [23]
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. [24] 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] [25] He is a member of the Advisory Council for the Campaign for Science and Engineering. [26] He has served on the Selection Committee for the Shaw Prize in Life Science and Medicine. [27] In 2010, Hunt joined the Academic Advisory Board of the Austrian think tank Academia Superior, Institute for Future Studies. [28]
Hunt is a highly regarded colleague and mentor in the research community. [29] [30] During his career he has supervised numerous PhD students including Hugh Pelham [7] and Jonathon Pines. [9]
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. [31] He also believes that science benefits when power is given to young people. [32]
In June 2015, Hunt became the target of an online shaming campaign after remarks he made at a science journalism conference were construed as sexist. [33] The pressure of the controversy forced his resignation from several key research and policy positions, including the European Research Council, and a temporary withdrawal from public life and professional activities. [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44]
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: [45]
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, [46] and a foreign associate of the US National Academy of Sciences in 1999. [47]
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. [48]
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". [49]
Hunt was knighted in the 2006 Birthday Honours for his service to science. [50]
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]
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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.
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.
Cell growth refers to an increase in the total mass of a cell, including both cytoplasmic, nuclear and organelle volume. Cell growth occurs when the overall rate of cellular biosynthesis is greater than the overall rate of cellular degradation.
Cyclin is a family of proteins that controls the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes or group of enzymes required for synthesis of cell cycle.
Cdc25 is a dual-specificity phosphatase first isolated from the yeast Schizosaccharomyces pombe as a cell cycle defective mutant. As with other cell cycle proteins or genes such as Cdc2 and Cdc4, the "cdc" in its name refers to "cell division control". Dual-specificity phosphatases are considered a sub-class of protein tyrosine phosphatases. By removing inhibitory phosphate residues from target cyclin-dependent kinases (Cdks), Cdc25 proteins control entry into and progression through various phases of the cell cycle, including mitosis and S ("Synthesis") phase.
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.
p21Cip1, also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, though is primarily associated with inhibition of CDK2. p21 represents a major target of p53 activity and thus is associated with linking DNA damage to cell cycle arrest. This protein is encoded by the CDKN1A gene located on chromosome 6 (6p21.2) in humans.
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.
Cyclin-dependent kinase 1 also known as CDK1 or cell division cycle protein 2 homolog is a highly conserved protein that functions as a serine/threonine protein kinase, and is a key player in cell cycle regulation. It has been highly studied in the budding yeast S. cerevisiae, and the fission yeast S. pombe, where it is encoded by genes cdc28 and cdc2, respectively. With its cyclin partners, Cdk1 forms complexes that phosphorylate a variety of target substrates ; phosphorylation of these proteins leads to cell cycle progression.
G2/mitotic-specific cyclin-B1 is a protein that in humans is encoded by the CCNB1 gene.
M-phase inducer phosphatase 3 is an enzyme that in humans is encoded by the CDC25C gene.
Cyclin-C is a protein that in humans is encoded by the CCNC gene.
Cyclin-dependent kinase inhibitor 3 is an enzyme that in humans is encoded by the CDKN3 gene.
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.
Maternal to zygotic transition (MZT), also known as embryonic genome activation, is the stage in embryonic development during which development comes under the exclusive control of the zygotic genome rather than the maternal (egg) genome. The egg contains stored maternal genetic material mRNA which controls embryo development until the onset of MZT. After MZT the diploid embryo takes over genetic control. This requires both zygotic genome activation (ZGA), and degradation of maternal products. This process is important because it is the first time that the new embryonic genome is utilized and the paternal and maternal genomes are used in combination. The zygotic genome now drives embryo development.
The G2-M DNA damage checkpoint is an important cell cycle checkpoint in eukaryotic organisms that ensures that cells don't initiate mitosis until damaged or incompletely replicated DNA is sufficiently repaired. Cells with a defective G2-M checkpoint will undergo apoptosis or death after cell division if they enter the M phase before repairing their DNA. The defining biochemical feature of this checkpoint is the activation of M-phase cyclin-CDK complexes, which phosphorylate proteins that promote spindle assembly and bring the cell to metaphase.
Michael Morris Rosbash is an American geneticist and chronobiologist. Rosbash is a professor and researcher at Brandeis University and investigator at the Howard Hughes Medical Institute. Rosbash's research group cloned the Drosophila period gene in 1984 and proposed the Transcription Translation Negative Feedback Loop for circadian clocks in 1990. In 1998, they discovered the cycle gene, clock gene, and cryptochrome photoreceptor in Drosophila through the use of forward genetics, by first identifying the phenotype of a mutant and then determining the genetics behind the mutation. Rosbash was elected to the National Academy of Sciences in 2003. Along with Michael W. Young and Jeffrey C. Hall, he was awarded the 2017 Nobel Prize in Physiology or Medicine "for their discoveries of molecular mechanisms controlling the circadian rhythm".
Anthony Rex Hunter is a British-American biologist who is a professor of biology at the Salk Institute for Biological Studies and the University of California San Diego. His research publications list his name as Tony Hunter.
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.
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.
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