Michael Levine (biologist)
|Prof. Michael S. Levine|
|Institutions||University of California, Berkeley|
|Alma mater||University of California, Berkeley (1976) and Yale University (Ph.D., 1981)|
|Doctoral advisor||Alan Garen|
|Doctoral students||Albert Erives (Iowa)
Others w/ academic appts.
|Known for||Homeobox, eve stripe-2, ascidian developmental biology|
|Notable awards||NAS Award in Molecular Biology (1996)|
Member of the National Academy of Sciences (1998)
Mike Levine (b. circa 1955, West Hollywood, California) is an American developmental biologist at the University of California, Berkeley, notable for co-discovering the Homeobox in 1983 and for discovering the organization of the regulatory regions of developmental genes. Fellow biologist Sean Carroll said of Levine, "Mike's work has done for animal development what the work on the lac operon and phage lambda did for understanding gene regulation in simpler organisms ... [Those] two big discoveries had a very large conceptual significance for developmental biology and by extension for evolutionary biology."
- 1 Biography
- 2 Training
- 3 Notable papers
- 4 Notes
- 5 External links
Levine was born in West Hollywood and raised in Los Angeles. Levine studied biology as an undergraduate at UC Berkeley, studying biology with Allan Wilson and graduating in 1976. Although he described some family pressure to become a doctor ("Coming from a modest background, particularly a Jewish family, the pressure to become a doctor was intense"), he went on to graduate studies at Yale, studying with Alan Garen and receiving in 1981 a Ph.D. in molecular biophysics and biochemistry.
After learning that Ultrabithorax, a gene that specifies the development of wings, showed a localized pattern of expression similar to that of Antennapedia, they decided to revisit the classic papers of Ed Lewis. In 1978, Lewis had proposed that all these homeotic genes (the ones that tell animals where to put a wing and where to put a leg and so on) arose from a common ancestral gene. So McGinnis carved up the Antennapedia gene and, using those pieces as probes, the trio identified eight genes, which turned out to be the eight homeotic genes in flies. "That pissed off a lot of people," says Levine. "The homeotic genes were the trophies of the Drosophila genome. And we got 'em all. I mean, we got 'em all!" Far from being humble, Levine says, "We were like, 'We kicked your ass pretty good, didn't we, baby!' Those were the days."
Discovery of the eve stripe 2 enhancer
Levine briefly returned to UC Berkeley as a postdoctoral fellow with Gerry Rubin. He then joined the faculty of Columbia University, where he "led the discovery of the modular organization of the regulatory regions of developmental genes." After isolating the even-skipped (eve) gene, Levine's team determined that each of the seven stripes was produced by separate enhancers. With further study they discovered that both a set of activators and a set of repressors worked together to shape the expression of eve in the second stripe, and determined that the repressors shut down only their binding enhancers, leaving other enhancers free of repression. Joseph Corbo said of the work,
"Before Levine's studies of even-skipped stripe 2, it wasn't clear how you generated spatially restricted patterns of gene expression from initially broad crude gradients of morphogens. I think that the even-skipped stripe 2 studies were the defining studies that showed how an organism can interpret those gradients and turn them into specific patterns of gene expression. To me that's Mike's crowning achievement."
Discoveries in the ascidian Ciona
After earning tenure in only four years at Columbia, Levine moved to UCSD in 1991, where he added the sea squirt, Ciona intestinalis, to his repertoire. Although much of Levine's work, including his homeobox studies, has been done in Drosophila Levine's team is also prominent in work with the sea squirt, Ciona intestinalis, an invertebrate that facilitates study of development. For example, this work included insights into classical myodeterminants and the composition of the notochord, the defining tissue of the chordate phylum.
- 1982 - Jane Coffin Childs Postdoctoral Fellowship
- 1985 - Searle Scholars Research Fellowship
- 1985 - Alfred P. Sloan Fellowship
- 1996 - NAS Award in Molecular Biology - "For his insightful contributions to our understanding of gene regulation networks and molecular mechanisms governing the development of organisms with a segmented body plan."
- 1998 - Elected to United States National Academy of Sciences in "Cellular and Developmental Biology" section: "Utilizing an elegant blend of in vitro and in vivo studies, Levine carried out insightful and complete analysis of regulatory events that govern segmentation and dorsal-ventral polarity in Drosophila. His work provided a dramatic example of combinatorial regulation at a complex enhancer and established new paradigms for transcriptional control."
- 2009 - Wilbur Cross Medal (Yale Alumni Association)
Levine cites as a significant influence his instructor Fred Wilt (taking his developmental biology class "was probably the single most galvanizing experience I had in terms of defining my future goals"), and cites fellow scientists Eric Davidson, Peter Lawrence and Christiane Nusslein-Volhard as "mentors [and] friends ... over the years".
Levine is well-known within academic biologist circles for his unconventional sense of humor, including an incident in which he lit a ring of fire around a postdoc:
"The most famous thing I ever did is I torched one of my postdocs," says Levine. [Joseph] Corbo was there at the time. "Mike got a squirt bottle of ethanol, unbeknownst to this hapless postdoc who was sitting at his bench minding his own business," says Corbo. Levine shot a ring of ethanol around the young man's seat and trailed a wick into the hallway. Then he lit it. "So this tongue of flame snaked into the lab and encircled this postdoc," says Corbo. "My technique was a little off and I put a little too much ethanol around his bench. So it's true, he was temporarily enveloped in a curtain of fire," says Levine. "But the fire receded and he was ok."
Levine has trained a number of people in developmental biology and molecular biology. Many of these people are chairs, directors, and principal investigators of labs across the world (U.S., Europe, Japan, China, and Singapore).
Postdocs with academic appointments
- Stephen Small, Professor, Chair of Biology, New York University
- Y. Tony Ip, Professor, University of Massachusetts Medical School
- Christine Rushlow, Professor of Biology, New York University
- Manfred Frasch, Professor, Chair, Department of Biology, University of Erlangen-Nuremberg
- John Reinitz, Professor, Department of Statistics, University of Chicago
- Haini Cai, Assoc. Professor, Dept. of Cellular Biology, University of Georgia
- David Arnosti, Professor, Director, Dept. of Biochemistry & Molecular Biology, Michigan State University
- Ju-min Zhou, Professor, Kunming Institute of Zoology, Chinese Academy of Sciences, China
- Hilary Ashe, University of Manchester, UK
- Angelike Stathopoulos, Professor, Division of Biology, California Institute of Technology.
- Anna Di Gregorio, Associate Professor of Cell and Developmental Biology, Weill Cornell Medical College
- Yutaka Nibu, Adjunct Assistant Research Professor, Weill Cornell Medical College
- Sumio Ohtsuki, Associate Professor of Tohoku University, Japan
- Lionel Christiaen, Assistant Professor of Biology, New York University
- Robert Zeller, Professor, San Diego State University
- Matthew Ronshaugen, University of Manchester, UK
- David Hendrix, Assistant Professor, Oregon State University
PhD students with academic appointments
- Jin Jiang, Professor, University of Texas, Southwestern
- Joseph Corbo, Asst. Professor, Div. of Biology and Biomedical Sciences, Washington University in St. Louis
- Scott Barolo, Associate Professor, Dept. of Cell & Developmental Biology, University of Michigan
- Albert Erives, Associate Professor, Dept. of Biology, University of Iowa
- Michele Markstein, Assistant Professor, Biology Department, University of Massachusetts, Amherst
- Rachel Susan Kraut, Associate Professor, Division of Molecular Genetics & Cell Biology, Nanyang Technological University, Singapore
- Robert Zinzen, Group Leader, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany
- McGinnis, W.; Levine, M. S.; Hafen, E.; Kuroiwa, A.; Gehring, W. J. (1984). "A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes". Nature 308 (5958): 428–33. Bibcode:1984Natur.308..428M. doi:10.1038/308428a0. PMID 6323992. (the homeobox paper)
- Han, Kyuhyung; Levine, Michael S.; Manley, James L. (1989). "Synergistic activation and repression of transcription by Drosophila homeobox proteins". Cell 56 (4): 573–83. doi:10.1016/0092-8674(89)90580-1. PMID 2563673.
- Small, S; Blair, A; Levine, M (1992). "Regulation of even-skipped stripe 2 in the Drosophila embryo". The EMBO Journal 11 (11): 4047–57. PMC 556915. PMID 1327756.
- Arora, K; Levine, M S; O'Connor, M B (1994). "The screw gene encodes a ubiquitously expressed member of the TGF-beta family required for specification of dorsal cell fates in the Drosophila embryo". Genes & Development 8 (21): 2588. doi:10.1101/gad.8.21.2588.
- Cai, Haini; Levine, Michael (1995). "Modulation of enhancer-promoter interactions by insulators in the Drosophila embryo". Nature 376 (6540): 533–6. Bibcode:1995Natur.376..533C. doi:10.1038/376533a0. PMID 7637789.
- Arnosti, DN; Barolo, S; Levine, M; Small, S (1996). "The eve stripe 2 enhancer employs multiple modes of transcriptional synergy". Development 122 (1): 205–14. PMID 8565831.
- Zhou, J; Barolo, S; Szymanski, P; Levine, M (1996). "The Fab-7 element of the bithorax complex attenuates enhancer-promoter interactions in the Drosophila embryo". Genes & Development 10 (24): 3195. doi:10.1101/gad.10.24.3195.
- Nibu, Yutaka; Zhang, Hailan; Bajor, Ewa; Barolo, Scott; Small, Stephen; Levine, Michael (1998). "DCtBP mediates transcriptional repression by Knirps, Krüppel and Snail in the Drosophila embryo". The EMBO Journal 17 (23): 7009–20. doi:10.1093/emboj/17.23.7009. PMC 1171049. PMID 9843507.
- Ohtsuki, S; Levine, M; Cai, HN (1998). "Different core promoters possess distinct regulatory activities in the Drosophila embryo". Genes & Development 12 (4): 547–56. doi:10.1101/gad.12.4.547. PMC 316525. PMID 9472023.
- Mannervik, M.; Nibu, Y; Zhang, H; Levine, M (1999). "Transcriptional Coregulators in Development". Science 284 (5414): 606–9. doi:10.1126/science.284.5414.606. PMID 10213677.
- Markstein, Michele; Markstein, Peter; Markstein, Vicky; Levine, Michael S. (2002). "Genome-wide analysis of clustered Dorsal binding sites identifies putative target genes in the Drosophila embryo". Proceedings of the National Academy of Sciences 99 (2): 763–8. Bibcode:2002PNAS...99..763M. doi:10.1073/pnas.012591199. JSTOR 3057639. PMC 117379. PMID 11752406.
- Stathopoulos, Angelike; Levine, Michael (2002). "Dorsal Gradient Networks in the Drosophila Embryo". Developmental Biology 246 (1): 57–67. doi:10.1006/dbio.2002.0652. PMID 12027434.
- Zeitlinger, Julia; Stark, Alexander; Kellis, Manolis; Hong, Joung-Woo; Nechaev, Sergei; Adelman, Karen; Levine, Michael; Young, Richard A (2007). "RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo". Nature Genetics 39 (12): 1512–6. doi:10.1038/ng.2007.26. PMC 2824921. PMID 17994019.
- Hopkin, Karen (March 1, 2007). "Fire Fly". The Scientist 21 (3): 58.
- Sean B. Carroll, quoted in Hopkin, Karen (March 1, 2007). "Fire Fly". The Scientist 21 (3): 58.
- UCSD Press Release, April 30, 1996.
- Wilbur Cross Medal 2009 Winners Bios, Yale University (last visited 2012 July 29) ("The Wilbur Lucius Cross Medal is an honor presented each year by the Graduate School Alumni Association to a small number of outstanding alumni. The medal recognizes distinguished achievements in scholarship, teaching, academic administration, and public service–all areas in which the legendary Dean Cross excelled.")
- "What have you got in common with a fly?", Science Museum, South Kensington, UK (last visited July 29, 2012).
- McGinnis, W.; Levine, M. S.; Hafen, E.; Kuroiwa, A.; Gehring, W. J. (1984). "A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes". Nature 308 (5958): 428–33. Bibcode:1984Natur.308..428M. doi:10.1038/308428a0. PMID 6323992.
- Mike Levine (Abstract), Current Biology, v.13, n.14, R545 (July 15, 2003).
- Erives, Albert; Levine, Michael (2001). "Ci-sna cis-Regulation of Ascidian Tail Muscle Genes". The Biology of Ascidians. pp. 193–201. doi:10.1007/978-4-431-66982-1_30. ISBN 978-4-431-66984-5.
- Erives, Albert; Levine, Michael (2000). "Characterization of a Maternal T-Box Gene in Ciona intestinalis". Developmental Biology 225 (1): 169–78. doi:10.1006/dbio.2000.9815. PMID 10964472.
- Erives, Albert; Corbo, Joseph C.; Levine, Michael (1998). "Lineage-Specific Regulation of the Ciona snail Gene in the Embryonic Mesoderm and Neuroectoderm". Developmental Biology 194 (2): 213–25. doi:10.1006/dbio.1997.8810. PMID 9501022.
- Takahashi, H.; Hotta, K.; Erives, A.; Di Gregorio, A.; Zeller, R. W.; Levine, M.; Satoh, N. (1999). "Brachyury downstream notochord differentiation in the ascidian embryo". Genes & Development 13 (12): 1519–23. doi:10.1101/gad.13.12.1519. PMC 316807. PMID 10385620.
- "Michael Levine", Searle Scholars Program directory. (last visited July 29, 2012).
- "90 Scientists and Economists Win Sloan Research Awards", New York Times, March 10, 1985.
- "NAS Award in Molecular Biology", National Academy of Sciences (Awarded for recent notable discovery in molecular biology by a young scientist age 45 or younger).
- "Michael S. Levine", National Academy of Sciences Member Directory (last visited 2012 July 29).
- Seminars and Talks
- Interviews (print and video)
- Video interview with Levine, "Evolution: 'Great Transformations'" (WGBH 2001).
- Levine interviewed in "What Darwin Never Knew", PBS Nova, Dec. 21, 2011
- Video Interview with Levine by Andrea Anderson, "The Biology of Genomes (2008)", SciVee (April 8, 2009)
- Levine, M (2003). "Mike Levine". Current Biology 13 (14): R545. doi:10.1016/S0960-9822(03)00466-4. PMID 12867042.