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François Jacob
François Jacob
17 June 1920 (age 89)
Born
Nancy, France
Citizenship
French
Known for
operon
Notable awards 1965 Nobel Prize in Medicine
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François Jacob (born 17 June 1920 in Nancy, France) is a French biologist
who, together with Jacques Monod, originated the idea that control of
enzyme levels in all cells occurs through feedback on transcription. He
shared the 1965 Nobel Prize in Medicine with Jacques Monod and André Lwoff.
Childhood and education
François Jacob is the only child of Simon and Thérèse Jacob. An inquisitive
child, he learned to read at a young age. At seven he entered the Lycée
Carnot, where he was schooled for the next ten years; in his autobiography
he describes his impression of it: "a cage". He describes his father as
a "conformist in religion", while his mother and other family members
important in his childhood were secular Jews; shortly after his bar
mitzvah he became an atheist.[1]
Though interested (and talented) in physics and mathematics, Jacob was
horrified at the prospect of spending two additional years in "an even
more draconian regime" to prepare for higher study at the Polytechnique.
Instead, after observing a surgical operation that cemented his "slight
interest" in medicine, he entered medical school.[2]
During the German occupation of France—and on the heels of his mother's
death—Jacob left France for Great Britain to join the war effort. Jacob,
who had only completed his second year of medical studies, joined the
medical company of the French 2nd Armored Division; he did not return to
France until 1 August 1944, after four years in service in North Africa.
He was injured in a German air attack, and was sent to now-liberated Paris
to recover.[3] For his wartime service, he was awarded France's WWII highest
decoration for valor, the Cross of Liberation, as well as Légion d'honneur
and croix de guerre.
After his recovery, Jacob returned to medical school and began researching
penicillin, which had been developed for mass production during the
war—and learning the methods of bacteriology in the process. He completed
a thesis he described as "replicating American work" on the effectiveness
of the antibiotic against local infections, and became a medical doctor
in 1947. Though attracted to research as a career, he was discouraged by
his own perceived ignorance after attending a microbiology congress that
summer. Instead he took a position at the Cabanel Center, where he had
done his thesis research; his new work entailed the manufacture of another
antibiotic, tyrothricin. Later, the center was contracted to convert
gunpowder factories for penicillin production (though this proved
impossible).[4]
Also in this period, he met and began courting his future wife, Lise.[5]
Research
In 1961 Jacob and Monod explored the idea that the control of enzyme
expression levels in cells is a result of feedback on the transcription
of DNA sequences. Their experiments and ideas gave impetus to the emerging
field of molecular developmental biology, and of transcriptional
regulation in particular.
For many years it had been known that bacterial and other cells could
respond to external conditions by regulating levels of their key metabolic
enzymes, and/or the activity of these enzymes. For instance, if a
bacterium finds itself in a broth containing lactose, rather than the
simpler sugar glucose, it must adapt itself to the need to 1) import
lactose, 2) cleave lactose to its constituents glucose and galactose, and
3) convert the galactose to glucose. It was known that cells ramp up their
production of the enzymes that do these steps when exposed to lactose,
rather than wastefully producing these enzymes all the time. Studies of
enzyme activity control were progressing through theories of the
(allosteric) action of small molecules on the enzyme molecule itself
(switching it on or off), but the method of controlling the enzyme
production was not well understood at the time.
With the earlier determination of the structure and central importance
of DNA, it became clear that all proteins were being produced in some way
from its genetic code, and that this step might form a key control point.
Jacob and Monod made key experimental and theoretical discoveries that
demonstrated that in the case of the lactose system outlined above (in
the bacterium E. coli), there are specific proteins that are devoted to
repressing the transcription of the DNA to its product (RNA, which in turn
is decoded into protein).
This repressor (the lac repressor) is made in all cells, binding directly
to DNA at the genes it controls, and physically preventing the
transcription apparatus from gaining access to the DNA. In the presence
of lactose, this repressor binds lactose, making it no longer able to bind
to DNA, and the transcriptional repression is lifted. In this way, a robust
feedback loop is constructed that allows the set of lactose-digesting
proteins products to be made only when they are needed.
Jacob and Monod extended this repressor model to all genes in all organisms
in their initial exuberance. The regulation of gene activity has developed
into a very large sub-discipline of molecular biology, and in truth
exhibits enormous variety in mechanism and many levels of complexity.
Current researchers find regulatory events at every conceivable level of
the processes that express genetic information. In the relatively simple
genome of baker's yeast, (saccharomyces cerevisiae), 405 of its 6,419
protein-encoding genes are directly involved in transcriptional control,
compared to 1,938 that are enzymes.
Awards and recognition
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François Jacob was awarded the Gran Prix Charles-Leopold Mayer by
the Académie des Sciences in 1962
François Jacob was awarded, together with André Lwoff and Jacques
Monod, the 1965 Nobel Prize in Physiology or Medicine.
François Jacob received the Lewis Thomas Prize for Writing about
Science for 1996.
François Jacob was elected a member of the Académie française in
1996.
Books
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Sexuality and the Genetics of Bacteria by E.H. Wollmann and François
Jacob, published by Academic Press, 1961
The Possible & The Actual by François Jacob, published in the United
States by Pantheon Books, and in Canada by Random House of Canada,
1982
The Statue Within: An Autobiography by François Jacob, translated
from the 1987 French edition by Franklin Philip. Basic Books, 1988.
The Logic of Life by François Jacob, translated from the 1976 French
edition by Princeton University Press 1993
Of Flies, Mice and Men by François Jacob, translated from the French
edition and published by Harvard University Press, 1998
Publications
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Jacob, F; Perrin, D; Sánchez, C; Monod, J; Edelstein, S (Jun 2005).
"The operon: a group of genes with expression coordinated by an
operator. C.R.Acad. Sci. Paris 250 (1960) 1727-1729". Comptes
rendus biologies 328 (6): 514–20. doi:10.1016/j.crvi.2005.04.005.
ISSN 1631-0691. PMID 15999435.
Ullmann, A; Jacob, F; Monod, J (Feb 1968). "On the subunit structure
of wild-type versus complemented beta-galactosidase of Escherichia
coli". Journal of molecular biology 32 (1): 1–13.
doi:10.1016/0022-2836(68)90140-X. ISSN 0022-2836. PMID 4868117.
Ullmann, A; Jacob, F; Monod, J (Mar 1967). "Characterization by in
vitro complementation of a peptide corresponding to an
operator-proximal segment of the beta-galactosidase structural
gene of Escherichia coli". Journal of molecular biology 24 (2):
339–43. doi:10.1016/0022-2836(67)90341-5. ISSN 0022-2836. PMID
5339877.
Ullmann, A; Perrin, D; Jacob, F; Monod, J (Jul 1965).
"Identification, by in vitro complementation and purification, of
a peptide fraction of Escherichia coli beta-galactosidase".
Journal of molecular biology 12 (3): 918–23.
doi:10.1016/S0022-2836(65)80338-2. ISSN 0022-2836. PMID 4285628.
Willson, C; Perrin; Cohn; Jacob; Monod (Apr 1964). "Non-Inducible
Mutants of the Regulator Gene in the "lactose" System of Escherichia
Coli". Journal of molecular biology 8: 582–92.
doi:10.1016/S0022-2836(64)80013-9. ISSN 0022-2836. PMID 14153528.
Jacob, F; Ullman; Monod (Mar 1964). "The Promotor, A Genetic Element
Necessary to the Expression of an Operon". Comptes rendus
hebdomadaires des seances de l'Academie des sciences 258: 3125–8.
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ISSN 0001-4036. PMID 14143651.
Jacob, F; Monod (1964). "Biochemical and Genetic Mechanisms of
Regulation in the Bacterial Cell". Bulletin de la Societe de chimie
biologique 46: 1499–532. ISSN 0037-9042. PMID 14270538.
Monod, J; Changeux; Jacob (Apr 1963). "Allosteric proteins and
cellular control systems" (Free full text). Journal of molecular
biology 6: 306–29. doi:10.1016/S0022-2836(63)80091-1. ISSN
0022-2836. PMID 13936070.
http://www.scholaruniverse.com/ncbi-linkout?id=13936070.
Jacob, F; Sussman; Monod (Jun 1962). "On the nature of the repressor
ensuring the immunity of lysogenic bacteria". Comptes rendus
hebdomadaires des seances de l'Academie des sciences 254: 4214–6.
ISSN 0001-4036. PMID 14036499.
Jacob, F; Monod (Jun 1961). "Genetic regulatory mechanisms in the
synthesis of proteins" (Free full text). Journal of molecular
biology 3: 318–56. doi:10.1016/S0022-2836(61)80072-7. ISSN
0022-2836. PMID 13718526.
http://www.scholaruniverse.com/ncbi-linkout?id=13718526.
Monod, J; Jacob (1961). "Teleonomic mechanisms in cellular
metabolism, growth, and differentiation". Cold Spring Harbor
symposia on quantitative biology 26: 389–401. ISSN 0091-7451. PMID
14475415.
Perrin, D; Jacob; Monod (Jul 1960). "Induced biosynthesis of a
genetically modified protein not presenting affinity for the
inductor". Comptes rendus hebdomadaires des seances de l'Academie
des sciences 251: 155–7. ISSN 0001-4036. PMID 13734531.
Buttin, G; Jacob; Monod (Mar 1960). "Constituent synthesis of
galactokinase following the development of lambda bacteriophages
in Escherichia coli K 12". Comptes rendus hebdomadaires des seances
de l'Academie des sciences 250: 2471–3. ISSN 0001-4036. PMID
13806544.
Jacob, F; Perrin; Sanchez; Monod (Feb 1960). "Operon: a group of
genes with the expression coordinated by an operator". Comptes
rendus hebdomadaires des seances de l'Academie des sciences 250:
1727–9. ISSN 0001-4036. PMID 14406329.
Jacob, F; Monod (Oct 1959). "Genes of structure and genes of
regulation in the biosynthesis of proteins". Comptes rendus
hebdomadaires des seances de l'Academie des sciences 249: 1282–4.
ISSN 0001-4036. PMID 14406327.
Pardee, Ab; Jacob, F; Monod, J (May 1958). "The role of the inducible
alleles and the constrtutive alleles in the synthesis of
beta-galactosidase in zygotes of Escherichia coli". Comptes rendus
hebdomadaires des seances de l'Academie des sciences 246 (21):
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3125–8. ISSN 0001-4036. PMID 13547552.
Jacob, F; Torriani, Am; Monod, J (Nov 1951). "Effect of ultraviolet
rays on the biosynthesis of galactosidase and on the multiplication
of T2 bacteriophage in Escherichia coli". Comptes rendus
hebdomadaires des seances de l'Academie des sciences 233 (20):
1230–2. ISSN 0001-4036. PMID 14905606.