Michael S. Levine
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Michael Levine is an American developmental and cell biologist at
Princeton University Princeton University is a private university, private research university in Princeton, New Jersey. Founded in 1746 in Elizabeth, New Jersey, Elizabeth as the College of New Jersey, Princeton is the List of Colonial Colleges, fourth-oldest ins ...
, where he is the Director of the Lewis-Sigler Institute for Integrative Genomics and a Professor of Molecular Biology. Levine previously held appointments at the
University of California, Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public land-grant research university in Berkeley, California. Established in 1868 as the University of California, it is the state's first land-grant u ...
, the
University of California, San Diego The University of California, San Diego (UC San Diego or colloquially, UCSD) is a public university, public Land-grant university, land-grant research university in San Diego, California. Established in 1960 near the pre-existing Scripps Insti ...
, and
Columbia University Columbia University (also known as Columbia, and officially as Columbia University in the City of New York) is a private research university in New York City. Established in 1754 as King's College on the grounds of Trinity Church in Manhatt ...
. He is notable for co-discovering the
Homeobox A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. For instance, mutations in a homeobox may change large-scale anatomical features of the full- ...
in 1983 and for discovering the organization of the regulatory regions of developmental genes.


Biography

Levine was born in
West Hollywood West Hollywood is a city in Los Angeles County, California, United States. Incorporated in 1984, it is home to the Sunset Strip. As of the 2020 United States Census, 2020 U.S. Census, its population was 35,757. It is considered one of the most ...
and raised in
Los Angeles Los Angeles ( ; es, Los Ángeles, link=no , ), often referred to by its initials L.A., is the largest city in the state of California and the second most populous city in the United States after New York City, as well as one of the world' ...
. Levine studied biology as an undergraduate at
UC Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public university, public land-grant university, land-grant research university in Berkeley, California. Established in 1868 as the University of Californi ...
, studying biology with Allan Wilson and graduating in 1976.UCSD Press Release
April 30, 1996.
He went on to graduate studies at
Yale Yale University is a private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and among the most prestigious in the wor ...
, where he studied with Alan Garen and in 1981 received a Ph.D. in
molecular biophysics Molecular biophysics is a rapidly evolving interdisciplinary area of research that combines concepts in physics, chemistry, engineering, mathematics and biology. It seeks to understand biomolecular systems and explain biological function in terms ...
and
biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
. Levine joined the Princeton faculty in 2015, and had been a professor at
UC Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public university, public land-grant university, land-grant research university in Berkeley, California. Established in 1868 as the University of Californi ...
after leaving UCSD in 1996.Wilbur Cross Medal 2009 Winners Bios
Yale University Yale University is a private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and among the most prestigious in the wo ...
(last visited 2012 July 29) ("The
Wilbur Lucius Cross Medal The Wilbur Cross Medal, or Wilbur Lucius Cross Medal for Alumni Achievement, is an award by the Yale University Graduate School Alumni Association to recognize "...distinguished achievements in scholarship, teaching, academic administration, and p ...
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.")


Discoveries


Homeobox discovery

Levine was a post-doc with Walter Gehring in Switzerland from 1982 to 1983."What have you got in common with a fly?"
Science Museum, South Kensington, UK (last visited July 29, 2012).
There, he co-discovered the
homeobox A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. For instance, mutations in a homeobox may change large-scale anatomical features of the full- ...
with Ernst Hafen and fellow post-doc William McGinnis:
After learning that
Ultrabithorax Ultrabithorax (Ubx) is a homeobox gene found in insects, and is used in the regulation of patterning in morphogenesis. There are many possible products of this gene, which function as transcription factors. Ubx is used in the specification of se ...
, a gene that specifies the development of wings, showed a localized pattern of expression similar to that of
Antennapedia ''Antennapedia'' (abbreviated ''Antp'') is a Hox gene first discovered in ''Drosophila'' which controls the formation of insect leg, legs during development. Loss-of-function mutations in the regulatory region of this gene result in the devel ...
, they decided to revisit the classic papers of
Ed Lewis Edward Lewis may refer to: Politicians *Edward Lewis (Devizes MP) (1650–1674), British MP for Devizes, 1669–1674 *Edward Lewis (Radnor MP), British MP for Radnor, 1761–1768, 1769–1774 and 1775–1790 *Edward Parke Custis Lewis (1837–1892 ...
. 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 The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public university, public land-grant university, land-grant research university in Berkeley, California. Established in 1868 as the University of Californi ...
as a postdoctoral fellow with Gerry Rubin.Mike Levine (Abstract)
''
Current Biology ''Current Biology'' is a biweekly peer-reviewed scientific journal that covers all areas of biology, especially molecular biology, cell biology, genetics, neurobiology, ecology, and evolutionary biology. The journal includes research articles, var ...
'', v.13, n.14, R545 (July 15, 2003).
He then joined the faculty of
Columbia University Columbia University (also known as Columbia, and officially as Columbia University in the City of New York) is a private research university in New York City. Established in 1754 as King's College on the grounds of Trinity Church in Manhatt ...
, 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 In molecular genetics, a repressor is a DNA-binding protein, DNA- or RNA-binding protein that inhibits the Gene expression, expression of one or more genes by binding to the Operator (biology), operator or associated Silencer (DNA), silencers. ...
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 The University of California, San Diego (UC San Diego or colloquially, UCSD) is a public university, public Land-grant university, land-grant research university in San Diego, California. Established in 1960 near the pre-existing Scripps Insti ...
in 1991, where he added the sea squirt, ''
Ciona intestinalis ''Ciona intestinalis'' (sometimes known by the common name of vase tunicate) is an ascidian (sea squirt), a tunicate with very soft tunic. Its Latin name literally means "pillar of intestines", referring to the fact that its body is a soft, trans ...
'', to his repertoire. Although much of Levine's work, including his homeobox studies, has been done in ''
Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...
'' Levine's team is also prominent in work with the sea squirt, ''
Ciona intestinalis ''Ciona intestinalis'' (sometimes known by the common name of vase tunicate) is an ascidian (sea squirt), a tunicate with very soft tunic. Its Latin name literally means "pillar of intestines", referring to the fact that its body is a soft, trans ...
'', an invertebrate that facilitates study of development. For example, this work included insights into classical myodeterminants and the composition of the
notochord In anatomy, the notochord is a flexible rod which is similar in structure to the stiffer cartilage. If a species has a notochord at any stage of its life cycle (along with 4 other features), it is, by definition, a chordate. The notochord consis ...
, the defining tissue of the chordate phylum.


Awards

* 1982 - Jane Coffin Childs Postdoctoral Fellowship * 1985 - Searle Scholars Research Fellowship * 1985 - Alfred P. Sloan Fellowship * 1996 -
NAS Award in Molecular Biology The NAS Award in Molecular Biology is awarded by the U.S. National Academy of Sciences "for recent notable discovery in molecular biology by a young scientist who is a citizen of the United States." It has been awarded annually since its inceptio ...
- "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 The National Academy of Sciences (NAS) is a United States nonprofit, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the Nati ...
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.""Michael S. Levine"
National Academy of Sciences Member Directory (last visited 2012 July 29).
* 2009 -
Wilbur Cross Medal The Wilbur Cross Medal, or Wilbur Lucius Cross Medal for Alumni Achievement, is an award by the Yale University Graduate School Alumni Association to recognize "...distinguished achievements in scholarship, teaching, academic administration, and p ...
(Yale Alumni Association)


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"), and cites fellow scientists Eric Davidson, Peter Lawrence and Christiane Nusslein-Volhard as "mentors ndfriends ... over the years". 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"), 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 ''Enterobacteria phage λ'' (lambda phage, coliphage λ, officially ''Escherichia virus Lambda'') is a bacterial virus, or bacteriophage, that infects the bacterial species ''Escherichia coli'' (''E. coli''). It was discovered by Esther Lederb ...
did for understanding
gene regulation Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are wide ...
in simpler organisms ...
hose A hose is a flexible hollow tube designed to carry fluids from one location to another. Hoses are also sometimes called ''pipes'' (the word ''pipe'' usually refers to a rigid tube, whereas a hose is usually a flexible one), or more generally '' ...
two big discoveries had a very large conceptual significance for
developmental biology Developmental biology is the study of the process by which animals and plants grow and develop. Developmental biology also encompasses the biology of Regeneration (biology), regeneration, asexual reproduction, metamorphosis, and the growth and di ...
and by extension for
evolutionary biology Evolutionary biology is the subfield of biology that studies the evolutionary processes (natural selection, common descent, speciation) that produced the diversity of life on Earth. It is also defined as the study of the history of life fo ...
." Sean B. Carroll, quoted in


Notable papers

* (the
homeobox A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. For instance, mutations in a homeobox may change large-scale anatomical features of the full- ...
paper) * * * * * * * * * * * *


Notes


External links


Levine Lab website
* ; Seminars and Talks
Michael Levine's Seminar Series: "Transcriptional Precision in the Drosophila Embryo"
; Interviews (print and video)

"Evolution: 'Great Transformations'" (
WGBH WGBH may refer to: * WGBH Educational Foundation, based in Boston, Massachusetts, United States ** WGBH (FM), a public radio station at Boston, Massachusetts on 89.7 MHz owned by the WGBH Educational Foundation ** WGBH-TV WGBH-TV (channel 2), ...
2001).
Levine interviewed in "What Darwin Never Knew"
PBS Nova ''Nova'' (stylized as ''NOVΛ'') is an American popular science television program produced by WGBH in Boston, Massachusetts, since 1974. It is broadcast on PBS in the United States, and in more than 100 other countries. The program has won man ...
, Dec. 21, 2011
Video Interview with Levine by Andrea Anderson
"The Biology of Genomes (2008)", ''
SciVee SciVee http://www.scivee.tv scivee.tv was a science video sharing website where researchers could upload, view and share science video clips and connect them to scientific literature, posters and slides from 2007 to 2015. The SciVee website is par ...
'' (April 8, 2009) * ; Profiles *
"25 Years of Homeodomain / Homeobox discovery"
''Evo devo, HOX'', May 10, 2008. * {{DEFAULTSORT:Levine, Michael 21st-century American biologists Developmental biologists University of California, Berkeley faculty Members of the United States National Academy of Sciences Jewish American scientists Year of birth missing (living people) Living people 21st-century American Jews