Michael Levine (biologist)

Michael Levine is an American developmental and

cell biologist at Princeton University, where he is the Michael S. Levine
Director of the Lewis-Sigler Institute for Integrative Nationality American
Genomics and a Professor of Molecular Biology.[1][2] Alma mater University of California,
Berkeley (BA)
Levine previously held appointments at the University Yale University (PhD)
of California, Berkeley, the University of California,
Known for Homeobox, eve stripe-2,
San Diego, and Columbia University. He is notable for
ascidian developmental
co-discovering the Homeobox in 1983 and for
biology
discovering the organization of the regulatory regions
of developmental genes.[3] Awards NAS Award in Molecular
Biology (1996)
Scientific career
Biography Fields Developmental biology
Institutions Princeton University
Levine was born in West Hollywood and raised in Los
University of California,
Angeles.[3] Levine studied biology as an undergraduate
Berkeley
at UC Berkeley, studying biology with Allan Wilson[3]
University of California, San
and graduating in 1976.[4] He went on to graduate Diego
studies at Yale, where he studied with Alan Garen and
Columbia University
in 1981 received a Ph.D. in molecular biophysics and
Doctoral Alan Garen
biochemistry.[4]
advisor
Levine joined the Princeton faculty in 2015, and had Doctoral Albert Erives
been a professor at UC Berkeley after leaving UCSD students
in 1996.[5] Notes
Member of the National Academy of Sciences
Discoveries (1998)

Homeobox discovery
Levine was a post-doc with Walter Gehring in Switzerland from 1982 to 1983.[6] There, he co-discovered
the homeobox with Ernst Hafen and fellow post-doc William McGinnis:[7]

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."[3]

Discovery of the eve stripe 2 enhancer

Levine briefly returned to UC Berkeley as a postdoctoral fellow[4] with Gerry Rubin.[8] He then joined
the faculty of Columbia University, where he "led the discovery of the modular organization of the
regulatory regions of developmental genes."[9] After isolating the even-skipped (eve) gene, Levine's team
determined that each of the seven stripes was produced by separate enhancers.[3] 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.[3] 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."[3]

Discoveries in the ascidian Ciona

After earning tenure in only four years at Columbia,[3] Levine moved to UCSD in 1991,[4] 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[6] Levine's team is also prominent in work with the sea
squirt, Ciona intestinalis, an invertebrate that facilitates study of development.[3] For example, this work
included insights into classical myodeterminants[10][11][12] and the composition of the notochord, the
defining tissue of the chordate phylum.[13]

Awards
1982 - Jane Coffin Childs Postdoctoral Fellowship[8]
1985 - Searle Scholars Research Fellowship[14]
1985 - Alfred P. Sloan Fellowship[15]
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."[16]
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."[17]
 2009 - Wilbur Cross Medal (Yale Alumni Association)[5]

Professional relations
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"),[8] and
cites fellow scientists Eric Davidson, Peter Lawrence and Christiane Nusslein-Volhard as "mentors [and]
friends ... over the years".[8]

On choosing to become a research biologist, 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"),[3]

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."[9]

Notable papers
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 (https://ui.adsabs.h
arvard.edu/abs/1984Natur.308..428M). doi:10.1038/308428a0 (https://doi.org/10.1038%2F3
08428a0). PMID 6323992 (https://pubmed.ncbi.nlm.nih.gov/6323992). S2CID 4235713 (http
s://api.semanticscholar.org/CorpusID:4235713). (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 (https://doi.org/10.1016%2F0092-8674%2889%299058
0-1). PMID 2563673 (https://pubmed.ncbi.nlm.nih.gov/2563673). S2CID 41210570 (https://a
pi.semanticscholar.org/CorpusID:41210570).
Small, S; Blair, A; Levine, M (1992). "Regulation of even-skipped stripe 2 in the Drosophila
embryo" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC556915). The EMBO Journal. 11
(11): 4047–57. doi:10.1002/j.1460-2075.1992.tb05498.x (https://doi.org/10.1002%2Fj.1460-
2075.1992.tb05498.x). PMC 556915 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC55691
5). PMID 1327756 (https://pubmed.ncbi.nlm.nih.gov/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" (https://doi.org/10.1101%2Fgad.8.21.2588). Genes & Development.
8 (21): 2588–601. doi:10.1101/gad.8.21.2588 (https://doi.org/10.1101%2Fgad.8.21.2588).
PMID 7958918 (https://pubmed.ncbi.nlm.nih.gov/7958918).
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 (https://ui.adsabs.harvard.edu/abs/1995Natur.376..533C).
doi:10.1038/376533a0 (https://doi.org/10.1038%2F376533a0). PMID 7637789 (https://pubm
ed.ncbi.nlm.nih.gov/7637789). S2CID 4267876 (https://api.semanticscholar.org/CorpusID:42
67876).
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.
 doi:10.1242/dev.122.1.205 (https://doi.org/10.1242%2Fdev.122.1.205). PMID 8565831 (http
s://pubmed.ncbi.nlm.nih.gov/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" (https://doi.or
g/10.1101%2Fgad.10.24.3195). Genes & Development. 10 (24): 3195–201.
doi:10.1101/gad.10.24.3195 (https://doi.org/10.1101%2Fgad.10.24.3195). PMID 8985187 (h
ttps://pubmed.ncbi.nlm.nih.gov/8985187).
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" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171049). The EMBO
Journal. 17 (23): 7009–20. doi:10.1093/emboj/17.23.7009 (https://doi.org/10.1093%2Fembo
j%2F17.23.7009). PMC 1171049 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171049).
PMID 9843507 (https://pubmed.ncbi.nlm.nih.gov/9843507).
Ohtsuki, S; Levine, M; Cai, HN (1998). "Different core promoters possess distinct regulatory
activities in the Drosophila embryo" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC31652
5). Genes & Development. 12 (4): 547–56. doi:10.1101/gad.12.4.547 (https://doi.org/10.110
1%2Fgad.12.4.547). PMC 316525 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC316525).
PMID 9472023 (https://pubmed.ncbi.nlm.nih.gov/9472023).
Mannervik, M.; Nibu, Y; Zhang, H; Levine, M (1999). "Transcriptional Coregulators in
Development". Science. 284 (5414): 606–9. Bibcode:1999Sci...284..606. (https://ui.adsabs.
harvard.edu/abs/1999Sci...284..606.). doi:10.1126/science.284.5414.606 (https://doi.org/10.
1126%2Fscience.284.5414.606). PMID 10213677 (https://pubmed.ncbi.nlm.nih.gov/102136
77).
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" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC117379).
Proceedings of the National Academy of Sciences. 99 (2): 763–8.
Bibcode:2002PNAS...99..763M (https://ui.adsabs.harvard.edu/abs/2002PNAS...99..763M).
doi:10.1073/pnas.012591199 (https://doi.org/10.1073%2Fpnas.012591199).
JSTOR 3057639 (https://www.jstor.org/stable/3057639). PMC 117379 (https://www.ncbi.nlm.
nih.gov/pmc/articles/PMC117379). PMID 11752406 (https://pubmed.ncbi.nlm.nih.gov/11752
406).
Stathopoulos, Angelike; Levine, Michael (2002). "Dorsal Gradient Networks in the
Drosophila Embryo" (https://doi.org/10.1006%2Fdbio.2002.0652). Developmental Biology.
246 (1): 57–67. doi:10.1006/dbio.2002.0652 (https://doi.org/10.1006%2Fdbio.2002.0652).
PMID 12027434 (https://pubmed.ncbi.nlm.nih.gov/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" (https://www.ncbi.nl
m.nih.gov/pmc/articles/PMC2824921). Nature Genetics. 39 (12): 1512–6.
doi:10.1038/ng.2007.26 (https://doi.org/10.1038%2Fng.2007.26). PMC 2824921 (https://ww
w.ncbi.nlm.nih.gov/pmc/articles/PMC2824921). PMID 17994019 (https://pubmed.ncbi.nlm.ni
h.gov/17994019).

Notes
1. "Molecular Biology Faculty Michael Levine" (http://molbio.princeton.edu/faculty/molbio-facult
y/891-levine).
2. "LSI History" (http://lsi.princeton.edu/about/lsi-history).
 3. Hopkin, Karen (March 1, 2007). "Fire Fly" (http://classic.the-scientist.com/article/home/5288
5/). The Scientist. 21 (3): 58.
4. UCSD Press Release (http://libraries.ucsd.edu/historyofucsd/newsreleases/1996/19960430
b.html), April 30, 1996.
5. Wilbur Cross Medal 2009 Winners Bios (http://www.aya.yale.edu/content/2009-winners-bio
s), 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.")
6. "What have you got in common with a fly?" (http://www.sciencemuseum.org.uk/WhoAmI/Fin
dOutMore/Yourbody/Howdoyoubecomeyou/Howdoestheembryodevelop/Howisthebodyshap
ed.aspx), Science Museum, South Kensington, UK (last visited July 29, 2012).
7. 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 (https://ui.adsabs.h
arvard.edu/abs/1984Natur.308..428M). doi:10.1038/308428a0 (https://doi.org/10.1038%2F3
08428a0). PMID 6323992 (https://pubmed.ncbi.nlm.nih.gov/6323992). S2CID 4235713 (http
s://api.semanticscholar.org/CorpusID:4235713).
8. Mike Levine (Abstract) (http://www.cell.com/current-biology/retrieve/pii/S096098220300466
4), Current Biology, v.13, n.14, R545 (July 15, 2003).
9. Sean B. Carroll, quoted in Hopkin, Karen (March 1, 2007). "Fire Fly" (http://classic.the-scient
ist.com/article/home/52885/). The Scientist. 21 (3): 58.
10. 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 (https://
doi.org/10.1007%2F978-4-431-66982-1_30). ISBN 978-4-431-66984-5.
11. Erives, Albert; Levine, Michael (2000). "Characterization of a Maternal T-box Gene in Ciona
intestinalis" (https://doi.org/10.1006%2Fdbio.2000.9815). Developmental Biology. 225 (1):
169–78. doi:10.1006/dbio.2000.9815 (https://doi.org/10.1006%2Fdbio.2000.9815).
PMID 10964472 (https://pubmed.ncbi.nlm.nih.gov/10964472).
12. Erives, Albert; Corbo, Joseph C.; Levine, Michael (1998). "Lineage-Specific Regulation of
the Ciona snail Gene in the Embryonic Mesoderm and Neuroectoderm" (https://doi.org/10.1
006%2Fdbio.1997.8810). Developmental Biology. 194 (2): 213–25.
doi:10.1006/dbio.1997.8810 (https://doi.org/10.1006%2Fdbio.1997.8810). PMID 9501022 (h
ttps://pubmed.ncbi.nlm.nih.gov/9501022).
13. 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" (https://ww
w.ncbi.nlm.nih.gov/pmc/articles/PMC316807). Genes & Development. 13 (12): 1519–23.
doi:10.1101/gad.13.12.1519 (https://doi.org/10.1101%2Fgad.13.12.1519). PMC 316807 (htt
ps://www.ncbi.nlm.nih.gov/pmc/articles/PMC316807). PMID 10385620 (https://pubmed.ncbi.
nlm.nih.gov/10385620).
14. "Michael Levine" (http://www.searlescholars.net/person/375), Searle Scholars Program
directory. (last visited July 29, 2012).
15. "90 Scientists and Economists Win Sloan Research Awards" (https://www.nytimes.com/198
5/03/10/nyregion/90-scientists-and-economists-win-sloan-research-awards.html), New York
Times, March 10, 1985.
16. "NAS Award in Molecular Biology" (http://nas.nasonline.org/site/PageServer?pagename=A
WARDS_molbio) Archived (https://web.archive.org/web/20120722011217/http://nas.nasonli
ne.org/site/PageServer?pagename=AWARDS_molbio) 2012-07-22 at the Wayback
Machine, National Academy of Sciences (Awarded for recent notable discovery in molecular
biology by a young scientist age 45 or younger).
17. "Michael S. Levine" (http://nas.nasonline.org/site/Dir/2083705746?pg=vprof&mbr=1001182
&returl=http%3A%2F%2Fnas.nasonline.org%2Fsite%2FDir%2F2083705746%3Fpg%3Dsrc
h%26view%3Dbasic&retmk=search_again_link), National Academy of Sciences Member
Directory (last visited 2012 July 29).

External links
Levine Lab website (http://flydev.berkeley.edu/cgi-bin/labpage/Levine_Lab/Welcome.html)
Search Results for author Levine M (https://www.ncbi.nlm.nih.gov/pubmed?term=%22Levin
e%20M%22%5BAuthor%5D) on PubMed.

Seminars and Talks

Michael Levine's Seminar Series: "Transcriptional Precision in the Drosophila Embryo" (http
s://www.ibiology.org/development-and-stem-cells/enhancers/)

Interviews (print and video)

Video interview with Levine (https://www.pbs.org/wgbh/evolution/library/04/4/l_044_20.html),

"Evolution: 'Great Transformations'" (WGBH 2001).
Levine interviewed in "What Darwin Never Knew" (https://www.pbs.org/wgbh/nova/evolution/
darwin-never-knew.html), PBS Nova, Dec. 21, 2011
Video Interview with Levine by Andrea Anderson (http://www.scivee.tv/node/10709), "The
Biology of Genomes (2008)", SciVee (April 8, 2009)
Levine, M (2003). "Mike Levine" (https://doi.org/10.1016%2FS0960-9822%2803%2900466-
4). Current Biology. 13 (14): R545. doi:10.1016/S0960-9822(03)00466-4 (https://doi.org/10.
1016%2FS0960-9822%2803%2900466-4). PMID 12867042 (https://pubmed.ncbi.nlm.nih.g
ov/12867042). S2CID 3186289 (https://api.semanticscholar.org/CorpusID:3186289).

Profiles

Hopkin, Karen (March 1, 2007). "Fire Fly" (http://classic.the-scientist.com/article/home/5288

5/). The Scientist. 21 (3): 58.
"25 Years of Homeodomain / Homeobox discovery" (http://www.hoxfulmonsters.com/2008/0
5/25-years-of-homeodomain-discovery/), Evo devo, HOX, May 10, 2008.
"Fly Guy" (http://mcb.berkeley.edu/news-and-events/department-news/levine-fly/). Science
Matters. 1 (7). UC Berkeley. 21 December 2004.

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