Tim Mitchison

Last updated

Tim Mitchison

FRS
Born
Timothy John Mitchison

1958 (age 64–65) [1]
Edinburgh
Education Haberdashers' Aske's Boys' School
Alma mater University of Oxford (BA)
University of California, San Francisco (PhD)
SpouseChristine M. Field [2]
Awards Haldane Lecture (2002)
Keith R. Porter Lecture (2013)
Scientific career
Fields Systems biology
Institutions Harvard Medical School
National Institute for Medical Research
Marine Biological Laboratory [3]
Thesis Structure and Dynamics of Organized Microtubule Arrays  (1984)
Doctoral advisor Marc Kirschner [4] [5]
Notable students Tony Hyman
Julie Theriot
Jason Swedlow
Inke Nathke
Katharina Ribbeck
Website mitchison.hms.harvard.edu/people/timothy-mitchison

Timothy John Mitchison FRS is a cell biologist and systems biologist and Hasib Sabbagh Professor of Systems Biology at Harvard Medical School in the United States. [6] [7] [8] He is known for his discovery, with Marc Kirschner, of dynamic instability in microtubules, [9] [10] for studies of the mechanism of cell division, and for contributions to chemical biology. [11]

Contents

Education and early life

Mitchison was educated at Haberdashers' Aske's Boys' School and completed his Bachelor of Arts degree in Biochemistry at the University of Oxford where he was an undergraduate student of Merton College, Oxford, from 1976 to 1979. He moved to the University of California, San Francisco (UCSF) in 1979 for his PhD which was supervised by Marc Kirschner [12] and investigated the dynamic instability of microtubules. [12] [13]

Career and research

Mitchison returned to the UK for postdoctoral research at the National Institute for Medical Research (NIMR) in London.[ when? ] In 1988 he returned to San Francisco where he was appointed assistant professor at UCSF. [14] In 1994 he wrote an opinion piece for the journal Chemistry & Biology titled "Towards a pharmacological genetics" which helped to launch the field of chemical genetics. [11] In 1997 he moved to Harvard University to become co-director of the Institute for Chemistry and Cell Biology at Harvard Medical School, [14] where he pioneered phenotype-based screening, [15] discovering the small molecule monastrol – the first small-molecule inhibitor of mitosis that does not target tubulin. Monastrol was shown to inhibit kinesin-5, a motor protein. In 2003 he became Deputy Chair of the newly formed Department of Systems Biology, chaired by Marc Kirschner. [16] [17] He works on aspects of mesoscale biology [18] including the self-organization of the cytoskeleton [19] [20] and of cytoplasm. [21] [22] He collaborates extensively with Christine Field on the mechanism of cytokinesis. [23] [24] [25]

Awards and honors

Mitchison was elected Fellow of the Royal Society (FRS) in 1997 for “substantial contributions to the improvement of natural knowledge” [26] and served as president of the American Society for Cell Biology (ASCB) in 2010. [27] He was elected a member of the National Academy of Sciences of the United States in 2014 [14] and delivered the Keith R. Porter Lecture in 2013.

Personal life

Mitchison is married to scientist Christine M. Field with whom he has two children. [7] Mitchison comes from a family of distinguished biologists; his father is Avrion Mitchison, [6] his uncles are Denis Mitchison [ citation needed ] and Murdoch Mitchison, [6] his great uncle was J.B.S. Haldane [6] and his great-grandfather John Scott Haldane. His grandparents were the politician Dick Mitchison [28] and the writer Naomi Mitchison (née Haldane). [28] His younger sister Hannah M. Mitchison is also a biologist. [29]

Related Research Articles

<span class="mw-page-title-main">Microtubule</span> Polymer of tubulin that forms part of the cytoskeleton

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

<span class="mw-page-title-main">Cell division</span> Process by which living cells divide

Cell division is the process by which a parent cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there are two distinct types of cell division: a vegetative division (mitosis), producing daughter cells genetically identical to the parent cell, and a cell division that produces haploid gametes for sexual reproduction (meiosis), reducing the number of chromosomes from two of each type in the diploid parent cell to one of each type in the daughter cells. In cell biology, mitosis (/maɪˈtoʊsɪs/) is a part of the cell cycle, in which, replicated chromosomes are separated into two new nuclei. Cell division gives rise to genetically identical cells in which the total number of chromosomes is maintained. In general, mitosis is preceded by the S stage of interphase and is often followed by telophase and cytokinesis; which divides the cytoplasm, organelles, and cell membrane of one cell into two new cells containing roughly equal shares of these cellular components. The different stages of mitosis all together define the mitotic (M) phase of animal cell cycle—the division of the mother cell into two genetically identical daughter cells. Meiosis results in four haploid daughter cells by undergoing one round of DNA replication followed by two divisions. Homologous chromosomes are separated in the first division, and sister chromatids are separated in the second division. Both of these cell division cycles are used in the process of sexual reproduction at some point in their life cycle. Both are believed to be present in the last eukaryotic common ancestor.

<span class="mw-page-title-main">Centrosome</span> Cell organelle in animal cell helping in cell division

In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center (MTOC) of the animal cell, as well as a regulator of cell-cycle progression. The centrosome provides structure for the cell. The centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi and plants lack centrosomes and therefore use other structures to organize their microtubules. Although the centrosome has a key role in efficient mitosis in animal cells, it is not essential in certain fly and flatworm species.

<span class="mw-page-title-main">Cytoskeleton</span> Network of filamentous proteins that forms the internal framework of cells

The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components, microfilaments, intermediate filaments and microtubules, and these are all capable of rapid growth or disassembly dependent on the cell's requirements.

<span class="mw-page-title-main">Cytokinesis</span> Part of the cell division process

Cytokinesis is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meiosis. During cytokinesis the spindle apparatus partitions and transports duplicated chromatids into the cytoplasm of the separating daughter cells. It thereby ensures that chromosome number and complement are maintained from one generation to the next and that, except in special cases, the daughter cells will be functional copies of the parent cell. After the completion of the telophase and cytokinesis, each daughter cell enters the interphase of the cell cycle.

<span class="mw-page-title-main">FtsZ</span> Protein encoded by the ftsZ gene

FtsZ is a protein encoded by the ftsZ gene that assembles into a ring at the future site of bacterial cell division. FtsZ is a prokaryotic homologue of the eukaryotic protein tubulin. The initials FtsZ mean "Filamenting temperature-sensitive mutant Z." The hypothesis was that cell division mutants of E. coli would grow as filaments due to the inability of the daughter cells to separate from one another. FtsZ is found in almost all bacteria, many archaea, all chloroplasts and some mitochondria, where it is essential for cell division. FtsZ assembles the cytoskeletal scaffold of the Z ring that, along with additional proteins, constricts to divide the cell in two.

<span class="mw-page-title-main">Nocodazole</span> Chemical compound

Nocodazole is an antineoplastic agent which exerts its effect in cells by interfering with the polymerization of microtubules. Microtubules are one type of fibre which constitutes the cytoskeleton, and the dynamic microtubule network has several important roles in the cell, including vesicular transport, forming the mitotic spindle and in cytokinesis. Several drugs including vincristine and colcemid are similar to nocodazole in that they interfere with microtubule polymerization.

<span class="mw-page-title-main">Phragmoplast</span> Structure in dividing plant cells that builds the daughter cell wall

The phragmoplast is a plant cell specific structure that forms during late cytokinesis. It serves as a scaffold for cell plate assembly and subsequent formation of a new cell wall separating the two daughter cells. The phragmoplast can only be observed in Phragmoplastophyta, a clade that includes the Coleochaetophyceae, Zygnematophyceae, Mesotaeniaceae, and Embryophyta. Some algae use another type of microtubule array, a phycoplast, during cytokinesis.

<span class="mw-page-title-main">Marc Kirschner</span>

Marc Wallace Kirschner is an American cell biologist and biochemist and the founding chair of the Department of Systems Biology at Harvard Medical School. He is known for major discoveries in cell and developmental biology related to the dynamics and function of the cytoskeleton, the regulation of the cell cycle, and the process of signaling in embryos, as well as the evolution of the vertebrate body plan. He is a leader in applying mathematical approaches to biology. He is the John Franklin Enders University Professor at Harvard University. In 2021 he was elected to the American Philosophical Society.

<span class="mw-page-title-main">Stathmin</span> Protein in Eukaryotes

Stathmin, also known as metablastin and oncoprotein 18 is a protein that in humans is encoded by the STMN1 gene.

<span class="mw-page-title-main">Treadmilling</span> Simultaneous growth and breakdown on opposite ends of a protein filament

In molecular biology, treadmilling is a phenomenon observed within protein filaments of the cytoskeletons of many cells, especially in actin filaments and microtubules. It occurs when one end of a filament grows in length while the other end shrinks, resulting in a section of filament seemingly "moving" across a stratum or the cytosol. This is due to the constant removal of the protein subunits from these filaments at one end of the filament, while protein subunits are constantly added at the other end. Treadmilling was discovered by Wegner, who defined the thermodynamic and kinetic constraints. Wegner recognized that: “The equilibrium constant (K) for association of a monomer with a polymer is the same at both ends, since the addition of a monomer to each end leads to the same polymer.”; a simple reversible polymer can’t treadmill; ATP hydrolysis is required. GTP is hydrolyzed for microtubule treadmilling.

In cell biology, microtubule nucleation is the event that initiates de novo formation of microtubules (MTs). These filaments of the cytoskeleton typically form through polymerization of α- and β-tubulin dimers, the basic building blocks of the microtubule, which initially interact to nucleate a seed from which the filament elongates.

<span class="mw-page-title-main">TPX2</span> Protein-coding gene in the species Homo sapiens

Targeting protein for Xklp2 is a protein that in humans is encoded by the TPX2 gene. It is one of the many spindle assembly factors that play a key role in inducing microtubule assembly and growth during M phase.

<span class="mw-page-title-main">Citron kinase</span> Protein-coding gene in the species Homo sapiens

Citron Rho-interacting kinase is an enzyme that in humans is encoded by the CIT gene.

<span class="mw-page-title-main">ANLN</span> Mammalian protein found in Homo sapiens

Anillin is a conserved protein implicated in cytoskeletal dynamics during cellularization and cytokinesis. The ANLN gene in humans and the scraps gene in Drosophila encode Anillin. In 1989, anillin was first isolated in embryos of Drosophila melanogaster. It was identified as an F-actin binding protein. Six years later, the anillin gene was cloned from cDNA originating from a Drosophila ovary. Staining with anti-anillin antibody showed the anillin localizes to the nucleus during interphase and to the contractile ring during cytokinesis. These observations agree with further research that found anillin in high concentrations near the cleavage furrow coinciding with RhoA, a key regulator of contractile ring formation.

Shinya Inoué was a Japanese American biophysicist and cell biologist, a member of the National Academy of Sciences. His research field was the visualization of dynamic processes within living cells using light microscopy.

<span class="mw-page-title-main">Anthony A. Hyman</span> British biologist

Anthony Arie Hyman is a British scientist and director at the Max Planck Institute of Molecular Cell Biology and Genetics.

<span class="mw-page-title-main">Rong Li</span> American cell biologist (born 1967)

Rong Li is the Director of Mechanobiology Institute, a Singapore Research Center of Excellence, at the National University of Singapore. She is a Distinguished Professor at the National University of Singapore's Department of Biological Sciences and Bloomberg Distinguished Professor of Cell Biology and Chemical & Biomolecular Engineering at the Johns Hopkins School of Medicine and Whiting School of Engineering. She previously served as Director of Center for Cell Dynamics in the Johns Hopkins School of Medicine’s Institute for Basic Biomedical Sciences. She is a leader in understanding cellular asymmetry, division and evolution, and specifically, in how eukaryotic cells establish their distinct morphology and organization in order to carry out their specialized functions.

Inke Näthke is a German-British cell biologist. She is Professor of Epithelial Biology at the Department of Cell & Developmental Biology, Interim Dean and Associate Dean for Professional Culture at the School of Life Sciences at the University of Dundee in Scotland. She is known for her work on the role of the adenomatous polyposis coli (APC) protein in colorectal cancer.

<span class="mw-page-title-main">David G. Drubin</span> American biologist, academic, and researcher

David G. Drubin is an American biologist, academic, and researcher. He is a Distinguished Professor of Cell and Developmental Biology at the University of California, Berkeley where he holds the Ernette Comby Chair in Microbiology.

References

  1. ↑ "Profile" (PDF). ascb.org.
  2. ↑ "Timothy Mitchison". Harvard Magazine. 1 November 2003. Retrieved 9 February 2019.
  3. ↑ "Tim Mitchison (Harvard) Part 1: Self-organization of microtubule assemblies". Archived from the original on 13 December 2021 – via YouTube.
  4. ↑ "Cell Biology Tree - Timothy J. Mitchison". academictree.org.
  5. ↑ Mitchison, T. J. (2013). "A question of taste". Molecular Biology of the Cell. 24 (21): 3278–3280. doi:10.1091/mbc.e13-07-0410. ISSN   1059-1524. PMC   3814136 . PMID   24174461.
  6. 1 2 3 4 Wells, William (1997). "Tim Mitchison: Dynamic productivity". Current Biology. 7 (11): R666–R667. doi: 10.1016/S0960-9822(06)00346-0 . PMID   9382812.
  7. 1 2 "Timothy Mitchison". November 2003.
  8. ↑ Ishihara, K.; Nguyen, P. A.; Wuhr, M.; Groen, A. C.; Field, C. M.; Mitchison, T. J. (2014). "Organization of early frog embryos by chemical waves emanating from centrosomes". Philosophical Transactions of the Royal Society B: Biological Sciences. 369 (1650): 20130454. doi:10.1098/rstb.2013.0454. ISSN   0962-8436. PMC   4113098 . PMID   25047608.
  9. ↑ Lewin, Ben (2007). "Great Experiments: Dynamic Instability of Microtubules - Marc Kirschner and Tim Mitchison". Archived from the original on 17 October 2013. Retrieved 9 February 2019.
  10. ↑ "Milestone 14 : Nature Milestones in Cytoskeleton". Nature. Retrieved 9 February 2019.
  11. 1 2 Mitchison, T. J. (1994). "Towards a pharmacological genetics". Chemistry & Biology. 1 (1): 3–6. doi:10.1016/1074-5521(94)90034-5. ISSN   1074-5521. PMID   9383364.
  12. 1 2 Mitchison, Timothy John (1984). Structure and Dynamics of Organized Microtubule Arrays (PhD thesis). University of California, San Francisco. OCLC   1020493513. ProQuest   303337748. Closed Access logo transparent.svg
  13. ↑ Mitchison, Tim; Kirschner, Marc (1984). "Dynamic instability of microtubule growth". Nature. 312 (5991): 237–242. Bibcode:1984Natur.312..237M. doi:10.1038/312237a0. ISSN   0028-0836. PMID   6504138. S2CID   30079133.
  14. 1 2 3 "Timothy Mitchison". nasonline.org.
  15. ↑ Mayer, T. U.; Kapoor, T. M.; Haggarty, S. J.; King, R. W.; Schreiber, S. L.; Mitchison, T. J. (29 October 1999). "Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen" (PDF). Science. 286 (5441): 971–974. doi:10.1126/science.286.5441.971. ISSN   0036-8075. PMID   10542155.
  16. ↑ "HMS launches new department to study systems biology". Harvard Gazette. 25 September 2003. Retrieved 9 February 2019.
  17. ↑ Check, Erika (2 October 2003). "Harvard heralds fresh take on systems biology". Nature. 425 (6957): 439. Bibcode:2003Natur.425..439C. doi: 10.1038/425439a . ISSN   1476-4687. PMID   14523408.
  18. ↑ Sear, Richard P.; Pagonabarraga, Ignacio; Flaus, Andrew (25 February 2015). "Life at the mesoscale: the self-organised cytoplasm and nucleoplasm". BMC Biophysics. 8 (1): 4. doi:10.1186/s13628-015-0018-6. ISSN   2046-1682. PMC   4374369 . PMID   25815164.
  19. ↑ Mitchison, T. J. (29 April 1992). "Self-organization of polymer-motor systems in the cytoskeleton". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 336 (1276): 99–106. Bibcode:1992RSPTB.336...99M. doi:10.1098/rstb.1992.0049. ISSN   0962-8436. PMID   1351302.
  20. ↑ Ishihara, Keisuke; Nguyen, Phuong A.; Wühr, Martin; Groen, Aaron C.; Field, Christine M.; Mitchison, Timothy J. (5 September 2014). "Organization of early frog embryos by chemical waves emanating from centrosomes". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 369 (1650): 20130454. doi:10.1098/rstb.2013.0454. ISSN   1471-2970. PMC   4113098 . PMID   25047608.
  21. ↑ Mitchison, Timothy J. (15 November 2010). "Remaining mysteries of the cytoplasm". Molecular Biology of the Cell. 21 (22): 3811–3812. doi:10.1091/mbc.E10-02-0084. ISSN   1939-4586. PMC   2982103 . PMID   21079024.
  22. ↑ Boke, Elvan; Ruer, Martine; Wühr, Martin; Coughlin, Margaret; Lemaitre, Regis; Gygi, Steven P.; Alberti, Simon; Drechsel, David; Hyman, Anthony A.; Mitchison, Timothy J. (28 July 2016). "Amyloid-like Self-Assembly of a Cellular Compartment". Cell. 166 (3): 637–650. doi:10.1016/j.cell.2016.06.051. ISSN   1097-4172. PMC   5082712 . PMID   27471966.
  23. ↑ Eggert, Ulrike S.; Mitchison, Timothy J.; Field, Christine M. (2006). "Animal Cytokinesis: From Parts List to Mechanisms". Annual Review of Biochemistry. 75 (1): 543–566. doi:10.1146/annurev.biochem.74.082803.133425. PMID   16756502.
  24. ↑ Eggert, Ulrike S.; Kiger, Amy A.; Richter, Constance; Perlman, Zachary E.; Perrimon, Norbert; Mitchison, Timothy J.; Field, Christine M. (2004). "Parallel chemical genetic and genome-wide RNAi screens identify cytokinesis inhibitors and targets". PLOS Biology. 2 (12): e379. doi:10.1371/journal.pbio.0020379. ISSN   1545-7885. PMC   528723 . PMID   15547975.
  25. ↑ Nguyen, Phuong A.; Groen, Aaron C.; Loose, Martin; Ishihara, Keisuke; Wühr, Martin; Field, Christine M.; Mitchison, Timothy J. (10 October 2014). "Spatial organization of cytokinesis signaling reconstituted in a cell-free system". Science. 346 (6206): 244–247. Bibcode:2014Sci...346..244N. doi:10.1126/science.1256773. ISSN   1095-9203. PMC   4281018 . PMID   25301629.
  26. ↑ Anon (1997). "Professor Timothy Mitchison FRS". royalsociety. London: Royal Society. 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 2016-11-11)
  27. ↑ "ASCB Presidents". ASCB. Retrieved 9 February 2019.
  28. 1 2 "Obituary: Naomi Mitchison" . The Independent. 13 January 1999. Archived from the original on 7 May 2022. Retrieved 9 February 2019.
  29. ↑ Elmeshad, Sarah (2018). "Gene mutation identified in PCD, rare disease". Nature Middle East. doi:10.1038/nmiddleeast.2018.62. S2CID   90633419.

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