Marc Kirschner

Marc Kirschner
Born Marc Wallace Kirschner
(1945-02-28) February 28, 1945
Chicago, Illinois
Residence Massachusetts
Nationality United States
Alma mater University of California, Berkeley (PhD)
Northwestern University (BA)
Known for cell cycle, embryonic development, facilitated evolution
Scientific career
Fields Systems biology
Institutions Harvard Medical School
University of California, San Francisco
Princeton University
Thesis Conformational changes in aspartate transcarbamylase (1971)
Doctoral advisor Howard Schachman
Other academic advisors John Gerhart
John Gurdon
Doctoral students Tim Mitchison[1][2]
Website kirschner.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. His research involves problems in cell and developmental biology, such as 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, and applying mathematical approaches to biology.

Education and early life

Kirschner was born in Chicago, Illinois, on February 28, 1945. He graduated from Northwestern University with a B.A. in chemistry in 1966. In 1971, he received his doctorate in biochemistry from the University of California, Berkeley.[3]

Career and research

He held postdoctoral positions at UC 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.[4] In 2018, he was succeeded as Chair of the Department of Systems Biology by Galit Lahav.[5]

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,[6] 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),[7] 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 [8] and, later, that ubiquitin regulates levels of cyclin by marking the cell-cycle molecule for destruction.[9] 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.[10]

A second noted[11] finding was his discovery, with Tim Mitchison, of the dynamic instability of microtubules,[12][13] 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.[14]

In addition to these contributions, Kirschner has interests in the evolutionary origins of the vertebrate body plan, and in particular the origins of the chordate nervous system. He has been involved 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.[15]

Since founding the Department of Systems Biology at Harvard Medical School, 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,[16] cell size control,[17] and the selectivity of drugs.[18]

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".[19] 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? [20]

Public service

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.[21] 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"[22] 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.

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[23]

Books

  • 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 (Yale University Press 2005) ISBN 0-300-10865-6

Awards and associations

References

  1. ↑ Mitchison, Timothy John (1984). Structure and Dynamics of Organized Microtubule Arrays. proquest.com (PhD thesis). University of California, San Francisco. OCLC 1020493513.
  2. ↑ Mitchison, Tim; Kirschner, Marc (1984). "Dynamic instability of microtubule growth". Nature. 312 (5991): 237–242. doi:10.1038/312237a0. ISSN 0028-0836. PMID 6504138.
  3. ↑ https://kirschner.hms.harvard.edu/people/marc-kirschner
  4. ↑ Ireland C "Kirschner and King named University Professors" Harvard Gazette, 23 July 2009 (retrieved 16 May 2012)
  5. ↑ Jiang K "New Systems Bio Chair named" Harvard Medical School News, April 16, 2018 (retrieved 6 June 2018)
  6. ↑ 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. doi:10.1073/pnas.72.5.1858. PMC 432646. PMID 1057175.
  7. ↑ 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. PMID 3194757.
  8. ↑ Pulverer, Bernd "Milestones in cell division (12): Surfing the cyclin wave" Nature Publishing Group (retrieved 16 May 2012)
  9. ↑ Brooksbank, Cath "Milestones in cell division (20): Disappearing Act" Nature Publishing Group (retrieved 16 May 2012)
  10. ↑ 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. PMID 7736580.
  11. ↑ Lewin, B "Great experiments: Dynamic instability of microtubules - Marc Kirschner and Tim Mitchison", CELLS! The web site accompanying the Cells textbook (Jones and Bartlett Publishers (2007)
  12. ↑ Le Bot, Nathalie "Milestones in cytoskeleton (14) (1984): Microtubule dynamic instability" doi:10.1038/nrm2584 Nature Publishing Group, 1 December 2008 (retrieved 16 May 2012)
  13. ↑ 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. doi:10.1073/pnas.91.12.5682. PMC 44060. PMID 8202548.
  14. ↑ "Kirschner Wins Gairdner International Award", Focus, Harvard University, April 20, 2001, retrieved 16 May 2012 |chapter= ignored (help)
  15. ↑ Kirschner, Marc W. (2006). "Obituary: Reinhart Heinrich (1946–2006)". Nature. 444 (7120): 700. doi:10.1038/444700a. PMID 17151654.
  16. ↑ 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. doi:10.1126/science.1228734. PMID 23138978. Retrieved 2014-08-25.
  17. ↑ 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. doi:10.1038/nature11897. PMC 3730528. PMID 23446419.
  18. ↑ 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. doi:10.1073/pnas.1403080111. PMC 3977247. PMID 24707051. Retrieved 2014-08-24.
  19. ↑ 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.
  20. ↑ 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. doi:10.1371/journal.pcbi.1000206. PMC 2563028. PMID 18989390.
  21. ↑ 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).
  22. ↑ 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. doi:10.1073/pnas.1404402111. PMC 4000813. PMID 24733905. Retrieved 2014-08-24.
  23. ↑ Reynolds, Tom (24 October 2003), "Publishing: Online Journal Opens Access to Scientific Literature", Focus, Harvard University, retrieved 16 May 2012
  24. ↑ AAAS member lists in PDF
  25. ↑ Archived award citation
  26. ↑ "CMU press release, 3 March 2004". Archived from the original on 2016-03-03. Retrieved 2012-05-24.
  27. ↑ Harvey Prize 2015
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