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Nat L. Sternberg (August 2, 1942 – September 26, 1995) was an American
molecular biologist Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...
and
bacteriophage A bacteriophage (), also known informally as a phage (), is a virus that infects and replicates within bacteria. The term is derived . Bacteriophages are composed of proteins that Capsid, encapsulate a DNA or RNA genome, and may have structu ...
researcher, particularly known for his work on
DNA recombination Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be found ...
and the phage P1.


Early life and education

Born in 1942 in
Brooklyn Brooklyn is a Boroughs of New York City, borough of New York City located at the westernmost end of Long Island in the New York (state), State of New York. Formerly an independent city, the borough is coextensive with Kings County, one of twelv ...
,
New York New York most commonly refers to: * New York (state), a state in the northeastern United States * New York City, the most populous city in the United States, located in the state of New York New York may also refer to: Places United Kingdom * ...
, Sternberg gained a BSc at
Brooklyn College Brooklyn College is a public university in Brooklyn in New York City, United States. It is part of the City University of New York system and enrolls nearly 14,000 students on a campus in the Midwood and Flatbush sections of Brooklyn as of fall ...
, followed by a master's at
Long Island University Long Island University (LIU) is a private university in Brooklyn and Brookville, New York, United States. The university enrolls over 16,000 students and offers over 500 academic programs at its main campuses, LIU Brooklyn and LIU Post on Long I ...
. In 1969, he received a PhD from
Purdue University Purdue University is a Public university#United States, public Land-grant university, land-grant research university in West Lafayette, Indiana, United States, and the flagship campus of the Purdue University system. The university was founded ...
,
Indiana Indiana ( ) is a U.S. state, state in the Midwestern United States, Midwestern region of the United States. It borders Lake Michigan to the northwest, Michigan to the north and northeast, Ohio to the east, the Ohio River and Kentucky to the s ...
, researching T-even phage head proteins under the supervision of Sewell Champe.


Career

In 1970–72, Sternberg held a postdoctoral fellowship at the Laboratory of Molecular Biology of the
Centre national de la recherche scientifique The French National Centre for Scientific Research (, , CNRS) is the French state research organisation and is the largest fundamental science agency in Europe. In 2016, it employed 31,637 staff, including 11,137 tenured researchers, 13,415 eng ...
(CNRS) in
Paris Paris () is the Capital city, capital and List of communes in France with over 20,000 inhabitants, largest city of France. With an estimated population of 2,048,472 residents in January 2025 in an area of more than , Paris is the List of ci ...
, under the direction of François Gros, where he researched the head proteins of phage λ. He then returned to the US, taking up the position of staff fellow in the laboratory of Robert Weisberg at the
National Institutes of Health The National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. It was founded in 1887 and is part of the United States Department of Health and Human Service ...
(NIH) in Bethesda,
Maryland Maryland ( ) is a U.S. state, state in the Mid-Atlantic (United States), Mid-Atlantic region of the United States. It borders the states of Virginia to its south, West Virginia to its west, Pennsylvania to its north, and Delaware to its east ...
, where he continued to study λ, in collaboration with
Lynn W. Enquist Lynn William Enquist is professor ''emeritus'' in molecular biology at Princeton University, as well as founding editor of the journal ''Annual Review of Virology''. His research focuses on neuroinvasive alpha-herpesviridae, herpesviruses. Ed ...
and others. In 1976, Sternberg joined the group being established by Michael Yarmolinsky in the Laboratory of Molecular Biology of the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
's Frederick Cancer Research Center at
Fort Detrick Fort Detrick () is a United States Army Futures Command installation located in Frederick, Maryland. Fort Detrick was the center of the U.S. biological weapons program from 1943 to 1969. Since the discontinuation of that program, it has hosted m ...
,
Frederick, Maryland Frederick is a city in, and the county seat of, Frederick County, Maryland, United States. Frederick's population was 78,171 people as of the 2020 United States census, 2020 census, making it the List of municipalities in Maryland, second-largest ...
, where he started to study the phage P1. From 1981 he directed his own group, continuing to research the P1 phage, as well as branching out to study
DNA recombination Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be found ...
in mammalian cells. In 1984, his group moved to the Central Research and Development Department of
DuPont Dupont, DuPont, Du Pont, duPont, or du Pont may refer to: People * Dupont (surname) Dupont, also spelled as DuPont, duPont, Du Pont, or du Pont is a French surname meaning "of the bridge", historically indicating that the holder of the surname re ...
, in Wilmington,
Delaware Delaware ( ) is a U.S. state, state in the Mid-Atlantic (United States), Mid-Atlantic and South Atlantic states, South Atlantic regions of the United States. It borders Maryland to its south and west, Pennsylvania to its north, New Jersey ...
, and Sternberg was a senior research fellow at DuPont Merck at the time of his death. Sternberg advised the NIH on
human genome The human genome is a complete set of nucleic acid sequences for humans, encoded as the DNA within each of the 23 distinct chromosomes in the cell nucleus. A small DNA molecule is found within individual Mitochondrial DNA, mitochondria. These ar ...
research. He served on the editorial board of the academic journal, ''
Journal of Molecular Biology The ''Journal of Molecular Biology'' is a biweekly peer-reviewed scientific journal covering all aspects of molecular biology. It was established in 1959 by Academic Press in London. It is currently published by Elsevier. The editor-in-chief was P ...
.''


Research

P1 phage had been discovered in 1951, but was little understood when Sternberg began to research the virus. He discovered the Cre–''lox''
site-specific recombination Site-specific recombination, also known as conservative site-specific recombination, is a type of genetic recombination in which DNA strand exchange takes place between segments possessing at least a certain degree of sequence homology. Enzymes know ...
system, in which the
Cre recombinase Cre recombinase is a tyrosine recombinase enzyme derived from the P1 bacteriophage. The enzyme uses a topoisomerase I-like mechanism to carry out site specific recombination events. The enzyme (38 kDa) is a member of the integrase family of si ...
enzyme acts at the ''lox'' recombination site to allow P1's double-stranded DNA
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
to circularise after infection. Sternberg, Brian Sauer and others in his group subsequently showed that Cre–''lox'' is a flexible recombination system which also functions in
eukaryotic cells The eukaryotes ( ) constitute the domain of Eukaryota or Eukarya, organisms whose cells have a membrane-bound nucleus. All animals, plants, fungi, seaweeds, and many unicellular organisms are eukaryotes. They constitute a major group of li ...
, and it is now widely used in
genetic engineering Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of Genetic engineering techniques, technologies used to change the genet ...
. Sternberg elucidated multiple other features of the phage and its life cycle, including
lytic The lytic cycle ( ) is one of the two cycles of viral reproduction (referring to bacterial viruses or bacteriophages), the other being the lysogenic cycle. The lytic cycle results in the destruction of the infected cell and its membrane. Bact ...
and
lysogenic Lysogeny, or the lysogenic cycle, is one of two cycles of viral reproduction (the lytic cycle being the other). Lysogeny is characterized by integration of the bacteriophage nucleic acid into the host bacterium's genome or formation of a cir ...
replication cycles,
DNA methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter (genetics), promoter, DNA methylati ...
and viral packaging, as well as immunity to the phage. He and his coworkers also developed P1-derived cloning vectors, enabling the cloning of very long stretches of DNA, which have been used in mapping the human genome.


Personal life and legacy

Sternberg married Ilene Harfenist, also from Brooklyn, in July 1967. The couple had a daughter, Rebecca. He was diagnosed with cancer in 1987, from which he died in 1995 at West Chester,
Pennsylvania Pennsylvania, officially the Commonwealth of Pennsylvania, is a U.S. state, state spanning the Mid-Atlantic (United States), Mid-Atlantic, Northeastern United States, Northeastern, Appalachian, and Great Lakes region, Great Lakes regions o ...
. The Nat L. Sternberg Thesis Prize, an annual award for PhD theses in the field of
prokaryotic A prokaryote (; less commonly spelled procaryote) is a single-celled organism whose cell lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Greek (), meaning 'before', and (), meaning 'nut' ...
molecular biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...
, was founded in his memory by former colleagues
Lynn W. Enquist Lynn William Enquist is professor ''emeritus'' in molecular biology at Princeton University, as well as founding editor of the journal ''Annual Review of Virology''. His research focuses on neuroinvasive alpha-herpesviridae, herpesviruses. Ed ...
and Thomas J. Silhavy.


Selected publications

Book chapters *Michael B. Yarmolinsky, Nat Sternberg. "Bacteriophage P1". In ''The Bacteriophages'', Vol. 1, ed. Richard Calendar, pp. 291–438 (Plenum; 1988) Research papers * * *


References

{{DEFAULTSORT:Sternberg, Nat 1942 births 1995 deaths Scientists from Brooklyn Brooklyn College alumni Long Island University alumni Purdue University alumni Phage workers American molecular biologists American virologists Scientists from New York (state)