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Marc Kirschner

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Marc Kirschner
Born
Marc Wallace Kirschner

(1945-02-28) February 28, 1945 (age 79)
Chicago, Illinois, U.S.
Alma materUniversity of California, Berkeley (PhD)
Northwestern University (BA)
Known forcell cycle, embryonic development, facilitated evolution
Scientific career
FieldsSystems biology
InstitutionsHarvard Medical School
University of California, San Francisco
Princeton University
ThesisConformational changes in aspartate transcarbamylase (1971)
Doctoral advisorHoward Schachman
Other academic advisorsJohn Gerhart
John Gurdon[citation needed]
Doctoral studentsTim Stearns
Tim Mitchison[1][2]
Websitekirschner.hms.harvard.edu

Marc Wallace Kirschner (born February 28, 1945) 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.[3] He is a leader in applying mathematical approaches to biology.[4] He is the John Franklin Enders University Professor at Harvard University.[5] In 1989 he was elected to the National Academy of Sciences[6]. In 2021 he was elected to the American Philosophical Society.[7]

Early life and education

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Kirschner was born in Chicago, Illinois, on February 28, 1945. He graduated from Northwestern University with a B.A. in chemistry in 1966. He participated in the NSF Graduate Research Fellowship Program at the National Science Foundation in 1966, and earned a doctorate in biochemistry from the University of California, Berkeley in 1971.[8]

Career

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He held postdoctoral positions at University of California, Berkeley and at the University of Oxford in England. He became assistant professor at Princeton University in 1972. In 1978 he was made professor at the University of California, San Francisco. In 1993, he moved to Harvard Medical School, where he served as the chair of the new Department of Cell Biology for a decade. He became the founding chair of the HMS Department of Systems Biology in 2003. He was named the John Franklin Enders University Professor in 2009.[5] In 2018, he was succeeded as Chair of the Department of Systems Biology by Galit Lahav.[9]

Kirschner studies how cells divide, how they generate their shape, how they control their size, and how embryos develop. In his eclectic lab, developmental work on the frog coexists with biochemical work on mechanism of ubiquitination, cytoskeleton assembly or signal transduction.

At Princeton, his early work on microtubules established their unusual molecular assembly from tubulin proteins and identified the first microtubule-stabilizing protein tau,[10] later shown to be a major component of the neurofibrillary tangles in Alzheimer's disease. In studies at UC San Francisco of the frog embryo as a model system of cell development, Kirschner identified the first inducer of embryonic differentiation, fibroblast growth factor (FGF),[11] an early finding in the field of signal transduction.

Kirschner's lab is also known for uncovering basic mechanisms of the cell cycle in eukaryotic cells. Working in Xenopus (frog) egg extracts, Kirschner and Andrew Murray showed that cyclin synthesis drives the cell cycle [12] and, later, that ubiquitin regulates levels of cyclin by marking the cell-cycle molecule for destruction.[13] His lab discovered and purified many of the components involved in cell cycle progression, including anaphase promoting complex (APC), the complex that ubiquitinates cyclin B.[14]

A second noted[15] finding was his discovery, with Tim Mitchison, of the dynamic instability of microtubules,[16][17] In mitosis, for example, microtubules form the spindle that separates the chromosomes. The first step in spindle formation is the nucleation of microtubules by microtubule-organizing centers, which then grow in all directions. Microtubules that attach to a chromosome are stabilized and are therefore retained to form part of the spindle. Because of dynamic instability, some individual microtubules that are not stabilized are at risk of collapse (or “catastrophe” as Kirschner named it), allowing re-use of the tubulin monomers. This recognition of self-organization in biological systems has been highly influential, and helped shape the view of the cytoplasm as a collection of dynamic molecular machines.[18]

Kirschner is also interested in the evolutionary origins of the vertebrate body plan. Together with John Gerhart, he was instrumental in developing the acorn worm Saccoglossus kowalevskii into a model system[19] that could be used to study the divergence between hemichordates and chordates, and the evolution of the chordate nervous system.[20][21]

Kirschner is a pioneer in using mathematical approaches to learn about central biological questions. For example, a model of the Wnt pathway he developed in collaboration with the late Reinhart Heinrich showed that new properties and constraints emerge when the individual biochemical steps are combined into a complete pathway.[22][23] A talk he gave on mathematics and the future of medicine at a retreat for Department Chairs at Harvard Medical School in 2003 inspired the Dean, Joseph B. Martin, to found a new Department, the Department of Systems Biology, with Kirschner as founding chair.[3] Since then, Kirschner's lab has attracted many students and post-docs from theoretical backgrounds who wish to make the transition into biology. His lab is now a leader in using mathematical tools to analyze signaling pathways,[24] cell size control,[25] and the selectivity of drugs.[26]

In two books co-authored with John Gerhart, Kirschner has described the cellular and developmental underpinnings of the evolution of organisms, and the concept of "evolvability".[27] In the most recent book, Kirschner and Gerhart proposed a new theory of "facilitated variation" that aims to answer the question: How can small, random genetic changes be converted into useful changes in complex body parts? [28]

Public service

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Kirschner has been an advocate for federal biomedical research funding and served as first chair of the Joint Steering Committee for Public Policy, a coalition of scientific societies he helped create in 1993 to educate the U.S. Congress on biomedical research and lobby for public funding of it.[29] In 2014, Kirschner (together with Bruce Alberts, Shirley Tilghman and Harold Varmus) called for a number of changes to the system of US biomedical science, with the intention of reducing "hypercompetition"[30] This publication led to the formation of an organization, Rescuing Biomedical Research, that aims to collect community input and propose changes to the structure of academic science in the USA.[31]

Kirschner helped launch the monthly, peer-reviewed journal PLoS Biology in October 2003 as a member of the editorial board and senior author of a paper in the inaugural issue. The journal was the first publishing venture from the San Francisco-based Public Library of Science (PLoS), which had begun three years previously as a grassroots organization of scientists advocating free and unrestricted access to the scientific literature[32]

Books

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  • with John Gerhart, Cells, Embryos, and Evolution: Toward a Cellular and Developmental Understanding of Phenotypic Variation and Evolutionary Adaptability (Blackwell's, 1997) ISBN 0-86542-574-4
  • with John Gerhart, The Plausibility of Life: Resolving Darwin's Dilemma ([1]Yale University Press 2005) ISBN 0-300-10865-6

Awards, Honorary Degrees and Associations

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References

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  1. ^ Mitchison, Timothy John (1984). Structure and Dynamics of Organized Microtubule Arrays (PhD thesis). University of California, San Francisco. OCLC 1020493513. ProQuest 303337748. Closed access icon
  2. ^ 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.
  3. ^ a b "Sprouting Seeds | Harvard Medical School". hms.harvard.edu. 20 November 2018. Retrieved 2019-03-30.
  4. ^ "Harvard teams' studies featured in Science 'Breakthrough of the Year'". Harvard Gazette. 2018-12-21. Retrieved 2019-03-30.
  5. ^ a b Ireland C "Kirschner and King named University Professors" Harvard Gazette, 23 July 2009 (retrieved 16 May 2012)
  6. ^ "Marc W. Kirschner – NAS".
  7. ^ "The American Philosophical Society Welcomes New Members for 2021".
  8. ^ "Marc W. Kirschner Ph.D. | Kirschner Lab".
  9. ^ Jiang K "New Systems Bio Chair named" Harvard Medical School News, April 16, 2018 (retrieved 6 June 2018)
  10. ^ Weingarten, MD; Lockwood, AH; Hwo, SY; Kirschner, MW (1975). "A protein factor essential for microtubule assembly". Proceedings of the National Academy of Sciences of the United States of America. 72 (5): 1858–1862. Bibcode:1975PNAS...72.1858W. doi:10.1073/pnas.72.5.1858. PMC 432646. PMID 1057175.
  11. ^ Kimelman, D; Abraham, J. A; Haaparanta, T; Palisi, T. M; Kirschner, M. W (1988). "The presence of fibroblast growth factor in the frog egg: Its role as a natural mesoderm inducer". Science. 242 (4881): 1053–6. Bibcode:1988Sci...242.1053K. doi:10.1126/science.3194757. PMID 3194757.
  12. ^ Pulverer, Bernd "Milestones in cell division (12): Surfing the cyclin wave" Nature Publishing Group (retrieved 16 May 2012)
  13. ^ Brooksbank, Cath "Milestones in cell division (20): Disappearing Act" Nature Publishing Group (retrieved 16 May 2012)
  14. ^ King, RW; Peters, JM; Tugendreich, S; Rolfe, M; Heiter, P; Kirschner, MW (1995). "A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B". Cell. 81 (2): 279–88. doi:10.1016/0092-8674(95)90338-0. PMID 7736580. S2CID 16958690.
  15. ^ Lewin, B "Great experiments: Dynamic instability of microtubules - Marc Kirschner and Tim Mitchison" Archived 2013-10-17 at the Wayback Machine, CELLS! The web site accompanying the Cells textbook (Jones and Bartlett Publishers (2007)
  16. ^ Le Bot, Nathalie (2010). "Key instability". Nature Reviews Molecular Cell Biology. 9: s14–s15. doi:10.1038/nrm2584.
  17. ^ Holy, TE; Leibler, S (1994). "Dynamic instability of microtubules as an efficient way to search in space". Proceedings of the National Academy of Sciences of the United States of America. 91 (12): 5682–5685. Bibcode:1994PNAS...91.5682H. doi:10.1073/pnas.91.12.5682. PMC 44060. PMID 8202548.
  18. ^ "Achievements". Kirschner Wins Gairdner International Award. Harvard University. April 20, 2001. Archived from the original on 8 July 2012. Retrieved 16 May 2012. {{cite book}}: |periodical= ignored (help)
  19. ^ Lowe, Christopher J.; Tagawa, Kuni; Humphreys, Tom; Kirschner, Marc; Gerhart, John (2004), "Hemichordate Embryos: Procurement, Culture, and Basic Methods", Development of Sea Urchins, Ascidians, and Other Invertebrate Deuterostomes: Experimental Approaches, Methods in Cell Biology, vol. 74, Elsevier, pp. 171–194, doi:10.1016/s0091-679x(04)74008-x, ISBN 9780124802780, PMID 15575607
  20. ^ Tautz, Diethard (2003). "Chordate Evolution in a New Light". Cell. 113 (7): 812–813. doi:10.1016/S0092-8674(03)00472-0. PMID 12837236. S2CID 11562638.
  21. ^ Lowe, Christopher J; Wu, Mike; Salic, Adrian; Evans, Louise; Lander, Eric; Stange-Thomann, Nicole; Gruber, Christian E; Gerhart, John; Kirschner, Marc (2003). "Anteroposterior Patterning in Hemichordates and the Origins of the Chordate Nervous System". Cell. 113 (7): 853–865. doi:10.1016/S0092-8674(03)00469-0. PMID 12837244. S2CID 18009831.
  22. ^ Kirschner, Marc W. (2006). "Obituary: Reinhart Heinrich (1946–2006)". Nature. 444 (7120): 700. Bibcode:2006Natur.444..700K. doi:10.1038/444700a. PMID 17151654.
  23. ^ Lee, Ethan; Salic, Adrian; Krüger, Roland; Heinrich, Reinhart; Kirschner, Marc W (2003-10-13). Roel Nusse (ed.). "The Roles of APC and Axin Derived from Experimental and Theoretical Analysis of the Wnt Pathway". PLOS Biology. 1 (1): e10. doi:10.1371/journal.pbio.0000010. ISSN 1545-7885. PMC 212691. PMID 14551908.
  24. ^ Hernández, AR; Klein, AM; Kirschner, MW (Dec 7, 2012). "Kinetic responses of β-catenin specify the sites of Wnt control". Science. 338 (6112): 1337–1340. Bibcode:2012Sci...338.1337H. doi:10.1126/science.1228734. PMID 23138978. S2CID 3470717.
  25. ^ Kafri, R; Levy, J; Ginzberg, MB; Oh, S; Lahav, G; Kirschner, MW (Feb 28, 2013). "Dynamics extracted from fixed cells reveal feedback linking cell growth to cell cycle". Nature. 494 (7438): 480–483. Bibcode:2013Natur.494..480K. doi:10.1038/nature11897. PMC 3730528. PMID 23446419.
  26. ^ Gujral, TS; Peshkin, L; Kirschner, MW (April 1, 2014). "Exploiting polypharmacology for drug target deconvolution". Proc. Natl. Acad. Sci. U.S.A. 111 (13): 5048–53. Bibcode:2014PNAS..111.5048G. doi:10.1073/pnas.1403080111. PMC 3977247. PMID 24707051.
  27. ^ Kirschner, M (7 November 2013). "Beyond Darwin: Evolvability and the generation of novelty". BMC Biology. 11: 110. doi:10.1186/1741-7007-11-110. PMC 4225857. PMID 24228732.
  28. ^ Parter, Merav; Kashtan, Nadav; Alon, Uri (2008). Stormo, Gary (ed.). "Facilitated Variation: How Evolution Learns from Past Environments to Generalize to New Environments". PLOS Computational Biology. 4 (11): e1000206. Bibcode:2008PLSCB...4E0206P. doi:10.1371/journal.pcbi.1000206. PMC 2563028. PMID 18989390.
  29. ^ Speech for the American Society for Microbiology National Meeting Archived 2012-05-31 at the Wayback Machine by Harold Varmus, director of the National Institutes of Health, New Orleans, 11 December 1993 (retrieved 16 May 2012).
  30. ^ Alberts, B; Kirschner, MW; Tilghman, S; Varmus, H (April 22, 2014). "Rescuing US biomedical research from its systemic flaws". Proc. Natl. Acad. Sci. U.S.A. 111 (16): 5773–5777. Bibcode:2014PNAS..111.5773A. doi:10.1073/pnas.1404402111. PMC 4000813. PMID 24733905.
  31. ^ "Rescuing Biomedical Research (RBR)". UCSF Bruce Alberts, PHD. August 17, 2016.
  32. ^ Reynolds, Tom (24 October 2003), "Publishing: Online Journal Opens Access to Scientific Literature", Focus, Harvard University, archived from the original on 20 January 2012, retrieved 16 May 2012
  33. ^ AAAS member lists in PDF
  34. ^ "Past Honorary Degree Recipients | Convocation | the University of Chicago".
  35. ^ Archived award citation[permanent dead link‍]
  36. ^ "CMU press release, 3 March 2004". Archived from the original on 2016-03-03. Retrieved 2012-05-24.
  37. ^ Harvey Prize 2015
  38. ^ "Marc W. Kirschner, Ph.D."
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