PAUL BERG & WALTER GILBERT & FREDERICK SANGER

• They were awarded to Nobel Prize in chemistry in 1980 for his fundamental studies of the biochemistry of nucleic
acids, with particular regard to recombinant-DNA (Paul Berg), for their contributions concerning the
determination of base sequences in nucleic acids (Walter Gilbert & Frederick Sanger).

2
 PAUL BERG & WALTER GILBERT & FREDERICK SANGER

• Paul Berg was born on June 30, 1926 in NY City, US.

• BS degree in biochemistry from Penn State in 1948; Ph.D. in biochemistry from Case Western
Reserve University in 1952.
• He worked in Copenhagen, Denmark and Washington State University till 1959. After 1959,
he became faculty at Stanford University.
• He studied metabolism in his Ph.D.
• Berg is arguably most famous for his pioneering work involving gene splicing of
recombinant DNA.
• First scientist to generate a molecule containing DNA from two different species by inserting
DNA from another species into a molecule.
• Fundamental step in the development of modern genetic engineering field.

• He won many prizes; Nobel Prize (1980), AAAS Award for Scientific Freedom and
Responsibility (1982), National Medal of Science (1983) 3
 PAUL BERG & WALTER GILBERT & FREDERICK SANGER

• Walter Gilbert was born on March 21, 1932 in Massachusetts, US.

• BS degree in chemistry and physics from Harvard U in 1953; master’s degree in physics in
1954; got Ph.D. in physics in 1957 from University of Cambridge (supervised by Abdus
Salam).
• Through 1960s he met and worked with James Watson.
• Gilbert was an early proponent of sequencing the human genome.
• He worked at Harvard University in some part of his life he left the university and returned.
• Together with Allan Maxam (his Ph.D. student), Gilbert developed a new DNA sequencing
method, Maxam–Gilbert sequencing.
• Proposed the existence of introns and exons (1978) ; In 1986, Gilbert proposed the RNA
world hypothesis for the origin of life.

• Their 1977 paper "A new method for sequencing DNA" was honored by a Citation for Chemical Breakthrough
Award from the Division of History of Chemistry of the American Chemical Society for 2017.
• He got many awards and honours. 4
 PAUL BERG & WALTER GILBERT & FREDERICK SANGER

• Frederick Sanger was born on August 13, 1918 in UK, died 19 November 2013 in Cambridge.
• In 1936 he went to St John's College, Cambridge to study natural sciences. He started his
Ph.D. in 1940 and completed in 1943 with thesis titled as “The metabolism of the amino acid
lysine in the animal body”
• Sanger's first triumph was to determine the complete amino acid sequence of the two
polypeptide chains of bovine insulin, A and B, in 1952 and 1951, respectively by further
developing partition chromatography method.
• Sanger used a chemical reagent 1-fluoro-2,4-dinitrobenzene (now, also known as Sanger's
reagent, fluorodinitrobenzene, FDNB or DNFB) which effectively labels the N-terminal amino
group at one end of the polypeptide chain.

• It was this achievement that earned him his first Nobel prize in Chemistry in 1958. This discovery was crucial
for the later sequence hypothesis of Crick for developing ideas of how DNA codes for proteins.

5
 PAUL BERG & WALTER GILBERT & FREDERICK SANGER

• In 1975, together with Alan Coulson, he published a sequencing procedure using DNA
polymerase with radiolabelled nucleotides that he called the "Plus and Minus" technique.
• His group were able to sequence most of the 5,386 nucleotides of the single-stranded
bacteriophage φX174.
• In 1977 Sanger and colleagues introduced the "dideoxy" chain-termination method for
sequencing DNA molecules, also known as the "Sanger method"
• This was a major breakthrough and allowed long stretches of DNA to be rapidly and
accurately sequenced; earned him his second Nobel prize in Chemistry in 1980.

• Sanger supervised more than ten PhD students, two of whom went on to also win Nobel
Prizes.

• He got many awards and honours.

6
EDUCATION
▪ Sanger enrolled in a preparatory school in 1927.
At the age of 14, he enrolled at Dorset's
Bryanston School. This school was
implementing the Dalton system, a more liberal
program that Sanger favored.
▪ He wanted to be a problem solver because he
wanted a science career. He studied the
metabolism of amino acids. He received a degree
in biochemistry from St. John's College in 1943.
 Sanger proved by chemical
sequencing of insulin that
proteins have a defined
Sanger received the first composition. And 22 years later,
Nobel Prize in Chemistry in applying various new sequencing
1958 for his work on the methods that he had developed to
sequencing of insulin. DNA, he also won the second
Nobel Prize in Chemistry in
1980, which he shared with Paul
Berg and Walter Gilbert.
The sequence of bases in nucleic
acids determined the physical
arrangement of thymine (T),
adenine (A), cytosine (C) and
guanine (G) in the DNA
molecule, and this discovery by
Frederick Sanger made it
possible to perform sequencing
of the human genome.
 DNA Sequencing
Basing his research on the enzyme
duplication approach used by Swiss
DNA sequencing studies were not chemist Charles Weissmann in his studies DNA polymerase required a primer
developed due to the size of DNA of bacteriophage RNA, Sanger began
molecules and the lack of suitable using the enzyme DNA polymerase to do that could bind to a specific region
enzymes to break DNA into small pieces. DNA sequencing using single-stranded of the template chain.
templates and added radioactive
nucleotides to the new DNA.

Sanger and his British colleague This method produced a series of

Alan R. Coulson developed the DNA molecules of various lengths
"plus and minus" method for rapid that could be separated using
DNA sequencing. polyacrylamide gel electrophoresis.
 Paul Berg has worked as professör Case
Western Reserve Universityas a professor at
the Washington University School of Medicine
and at the Stanford University School of
Medicine in biochemistry in 1952.

Apart from the Nobel Prize, Berg was

presented with the National Medal of Science
in 1983 and 1986 Berg Medal of Medicine
Member of the Board of Sponsors of the
National Library Bulletin of Atomic Scientists.

He has a reputation as a nucleic acid

researcher.
In Berg's theory, he claimed that amino acids are not directly affected by RNA, but are linked together by special molecules
called linkers or receptors in a chain.

In 1956, Berg demonstrated such a molecule that is specific only to the amino acid methionine.

Each amino acid had its own type of linkers, now called a transfer RNA.

He helped organize the Asilomar Conference, an international forum on advances in DNA technology, in February 1975.
• The possibility of recombinant
DNA has emerged from a series
of advances in biochemistry,
particularly from the discoveries
of new enzymes.
• Ligases are enzymes that form
covalent bonds.
• The discovery of dna ligase
provided a kind of chemical bond
that could restore dna after
insertion into a foreign gene.
• These enzymes were used as
tools in genetic engineering.
During Berg's studies, genes taken from an
organism such as a bacterium, virus or yeast cell
could be introduced into another simple
organism with the same technique, thus giving
rise to the idea of new functions to the organism.

•In occuring hybrid DNA molecules, Berg used

the well-studied SV40 monkey virus and the
bacteriophage virus known as bacteriophage.

•The SV40 virus has several genes. It was

convenient for study because it did not have a
protein coat.
Moreover, the ability to
recombine DNA fragments and
transfer them into cells forms the
basis of an important new
medical approach to treating
diseases with a technique called
gene therapy.

Today, insulin and factor VIII are

two common drugs produced
by recombinant organisms that
help treat diabetes and
hemophilia, respectively. Oil-fed
bacteria are designed to assist
in cleaning up oil spills.
Early life and Education
• He went to Harvard for
undergraduate and graduate
• He majored in chemistry and
physics
• In college, he focused on
theoretical physics
• As a graduate student, he studied
the theory of elementary particles
and the quantum theory of fields
• After one year graduate in Harvard,
he went to University of Cambridge
for two years, his supervisior is
Abdus Salam
Career and Research
• He joined the Harvard faculty as a lecturer in physics in 1958
• As his interests changed, advanced to assistant professor of
physics in 1959
• Associate professor of biophysics in 1964
• Professor of biochemistry in 1968.
• In 1974, he became American Cancer Society Professor of
Molecular Biology at Harvard.
Career and Research
• In the summer of 1960, J. Watson, F. Gros and Gilbert were
trying to identify mRNA, a short-lived RNA copy of a DNA gene,
which serves as a carrier of information from the genome to
ribosomes, the factories that make proteins.
• After each messenger is used a few times to dictate the structure
of protein, it is broken down and recycled to make other mRNA
molecules. The experiments sought a fleeting new component
that they managed to pin down.
Career and Research
• In the late 1960, Gilbert confirmed the theory of Jacques Monod
and Franƈois Jacob that “repressor proteins” control the genes
responsible for beginning and ending protein synthesis in the
cell. He was able to demonstrate the existence of a repressor in
the bacterium Escherichia coli that prevents a gene from
manufacturing a certain enzyme except when lactose is present.
• In the 1970s, he developed a widely used technique of using gel
electrophoresis to read the nucleotide sequences of DNA
segments. The same method was developed independently by
Sanger.
Career and Research
• In 1979 Gilbert, while retaining his affiliation with Harvard,
joined a group of other scientists and businessmen to form
Biogen, a commercial genetic-engineering research corporation.
Gilbert resigned from Biogen in 1985 and, while continuing to
teach at Harvard, became a chief proponent of the Human
Genome Project, a government-funded effort to compile a
complete map of the gene sequences in human DNA.
• He became retired from Harvard in 1987.
 AZIZ SANCAR & TOMAS LINDAHL & PAUL L. MODRICH

• They were awarded to Nobel Prize in chemistry in 2015 for mechanistic studies of DNA repair..

2
 AZIZ SANCAR & TOMAS LINDHAL & PAUL L. MODRICH

• Aziz Sancar was born on September 8, 1946 in Mardin, Turkey.

• MD degree from İstanbul University in 1969; Ph.D. in molecular biology from University of
Texas in 1977.
• Worked with Claud Stan Rupert, called him as father of DNA repair studies.
• Discovered genes repairing thymine dimers in his Ph.D.
• Elucidated the nucleotide excision repair in bacteria in his post-doctoral studies.
• Then elucidated the excision repair mechanism in humans.

• Tubitak Science Award (1995)

• Vehbi Koç award (2007)
• Aziz Sancar was elected to the National Academy of Sciences in 2005 as the first Turkish-
American member.
• Nobel Prize in Chemistry in 2015
3
 AZIZ SANCAR & TOMAS LINDHAL & PAUL L. MODRICH

• Tomas Lindhal was born on January 28, 1938 in Stockholm, Sweden.

• Lindahl graduated with a Ph.D. from the Karolinska Institute in Stockholm, Sweden, in 1967,
completed M.D. in 1970 in the same institute.
• He worked as faculty at Karolinska Institute and University Gothenborg 1969 – mid 1980s
served as a professor of medical and physiological chemistry; worked at the Imperial
Cancer Research Fund (later Cancer Research UK) in London as principal scientist, 1984 -
2005.

• Initially focused, the Epstein-Barr virus (EBV) and spontaneous DNA damage within cells
• By the late 1970s he had begun to identify key components of the base excision repair pathway discovered
multiple DNA excision repair enzymes, in both bacterial and mammalian cells and deduced the steps of
base excision repair.
• Lindahl received the Royal Society's Royal Medal in 2007, Copley Medal in 2010, member of Norwegian
Academy of Science and Letters, elected foreign associate of the National Academy of Science in 2018. 4
 AZIZ SANCAR & TOMAS LINDHAL & PAUL L. MODRICH
• Paul Modrich was born on June 13, 1946 in Raton, New Mexico.
• Obtained his BS Biology degree from MIT in 1968
• Get his Ph.D. in biochemistry from Stanford University in 1973. Conducted 1-year post-
doctorate research at Harvard University.
• In 1976 he joined Duke University as an Assistant Prof in Biochemistry.

• In his Ph.D, worked on ligase enzyme and found that the ligase is essential for DNA synthesis

• Then in 1970s, focused on DNA lesions and the process of DNA replication, began to examine base-pair
mismatches in E. coli. 1980s, developed an assay to analyze mismatched base pairs.
• In 1990s, described the excision repair mechanism by which mismatched DNA is targeted and eliminated in
E. coli cells. Then elucidated the mechanism of mismatch repair in human cells.
• Pfizer Award in Enzyme Chemistry in 1983, National Academy of Science member in 1993, a fellow of the
American Academy of Arts and Sciences from 2004, American Cancer Society Medal of Honor in 2005
5
 Graduate school and postdoctoral work
● As a graduate student at Stanford, Modrich investigated an
enzyme called ligase and its ability to catalyze the joining
together of nucleotides in the DNA of the bacterium
Escherichia coli. He found that ligase enzymes are
essential to normal DNA synthesis in E. coli and hence are
fundamental to the bacterium’s survival. Modrich became
an assistant professor at the chemistry department of
University of California, Berkeley in 1974.

● In 1976, following postdoctoral studies at Duke University

and has been a Howard Hughes Investigator sin 1995.
 Researches

● DNA, however, is not entirely stable - it can be damaged

and decay with age or even through the natural process
of cell division and replication.

● The 2015 Nobel Prize in Chemistry was awarded to Paul

Modrich, along with Tomas Lindahl and Aziz Sancar, for
their independent work into how cells repair damaged
DNA and preserve the genetic information. Their work has
not only expanded our knowledge of cell functions and
genetics, but also has implications for cancer treatment.
● It was Lindahl who demonstrated that DNA is unstable and discovered base excision repair, a
molecular process which constantly rebuilds and repairs damaged or decayed DNA. Aziz Sancar
mapped nucleotide excision repair, which repairs UV damage to DNA and corrects defects
caused by mutagenic substances. Paul Modrich established the nature of mismatch repair, the
mechanism by which cells correct errors that occur when DNA is replicated during cell division.
Such defects can cause a hereditary variant of colon cancer. Efficient mismatch repair
dramatically reduces this risk.
◦ He known for his discovery of base excision repair, a major
mechanism of DNA repair, by which cells maintain their
genetic integrity. Base excision repair corrects damage sustained
by individual DNA bases (adenine, cytosine, guanine, and
thymine), which frequently occurs as a result of spontaneous DNA
decay, a process suspected of contributing to aging ,mutation,
and the development of cancer.
Career
Diagram of both the TC-NER and GG-NER
pathways. The two pathways differ only in
initial DNA damage recognition
Following his mechanistic elucidations of
nucleotide exchange repair, he was
accepted as a lecturer at the University of
North Carolina, the only university that he
got a positive response from out of the 50
he applied to. He has stated that his
accent of English was detrimental to his
career as a lecturer. At Chapel Hill, Sancar
discovered the following steps of
nucleotide excision repair in bacteria and
worked on the more complex version of
this repair mechanism in humans. His
longest-running study has involved
photolyase and the mechanisms of photo-
reactivation. In his inaugural article in the
PNAS, Sancar captured the photolyase
radicals he has chased for nearly 20 years,
thus providing direct observation of the
photocycle for thymine dimer repair.
All His Work

• PhD studies: cloning the photolyase

gene

• Post-doctoral work: maxicells; dual

incision I

• Transcription-coupled repair

• Excision repair in humans; Dual

incision II

• Brief map of the human genome

• DNA damage checkpoints
• Cryptochrome and the Circadian
clock
(A) Mammalian molecular clock model of the transcription-translation
feedback loop (TTFL). (B) PER2 removes CRY1 from the
CRY1:CLOCK:BMAL1:E-box complex. (C) New model for the mammalian
circadian clock. The figure shows a semiquantitative heat map
representation of CRY1 and PER2 protein expression as well as the ChIP
data for CLOCK:BMAL1 and CRY1 over a circadian cycle and its
consequences with regard to interactions of core clock proteins with the E-
box and the effects of these interactions on transcription of genes (Nr1d1
and Dbp) regulated exclusively by the core TTFL.
 EMMANUELLE CHARPENTIER & JENNIFER DOUDNA

• They were awarded to Nobel Prize in

chemistry in 2020 for the development of a

method for genome editing.

2
 EMMANUELLE CHARPENTIER & JENNIFER DOUDNA

• Emmanuelle Charpentier was born on December 11, 1968 in Juvisy-sur-Orge, France.

• Charpentier studied biochemistry, microbiology and genetics at the Pierre and Marie
Curie University (today the Faculty of Science of Sorbonne University) in Paris.
• Graduate student at Institut Pasteur, Paris (1992-1995) and University Teaching Assistant at
UPMC, Paris (1993-1995).
• Charpentier's PhD project investigated molecular mechanisms involved in antibiotic
resistance.
• She worked as researcher in Rockefeller University (NY), NY University Medical Center,
Skirball Institute of Biomolecular Medicine (1996-2002), University of Vienna Department of
Microbiology, Immunobiology & Genetics (2002-09), Laboratory for Molecular Infection
Medicine Sweden (MIMS), Umeå University (2009-13), Hannover University Medical School
(2013-15), Director at the Max Planck Institute for Infection Biology, Berlin (2015-2018)

3
 EMMANUELLE CHARPENTIER & JENNIFER DOUDNA

• She tried to understanding the fundamental mechanisms of diseases, with a particular

interest in infections caused by Gram-positive pathogenic bacteria such as Listeria,
staphylococci and streptococci.
• Explored the regulation of hair growth in mice (in US)
• Discovered an RNA molecule involved in the regulation of virulence-factor synthesis in
Streptococcus pyogenes (in Europe).
• is best known for her and her lab’s research on the CRISPR-Cas9 adaptive immune system in
the human pathogen Streptococcus pyogenes.
• Her research laid the foundation for the development of a highly versatile and specific
genome editing and engineering technology.

4
 EMMANUELLE CHARPENTIER & JENNIFER DOUDNA

• Jennifer Doudna was born on February 19, 1964 in Washington D. C., US.
• She obtained BA degree in Biochemistry in 1985 in Pomona College in Claremont,
California.
• She obtained her PhD in Biological Chemistry and Molecular Pharmacology in 1989
from Harvard University.
• She studied system that increased the efficiency of a self-replicating catalytic RNA in her PhD
• Doudna worked to uncover the structure and biological function of RNA enzymes or
ribozymes

• She wanted to crystallize and determine the three-dimensional structure of a ribozyme

started this project at the Cech lab in 1991 and finished it at Yale University in 1996.
• 1994-2001 worked at Yale University crystallized ribozymes from different viruses.

5
 EMMANUELLE CHARPENTIER & JENNIFER DOUDNA

• In 2002 she joined University of Berkeley as professor of biochemistry and molecular

biology.
• Doudna’s laboratory entered into a long-distance collaboration with Emmanuelle
Charpentier, in 20111, a French biochemist who was working in Sweden at the time.
• Together, they were investigating the function of Cas9, a protein found in the immune system
of Streptococcus bacteria

• CRISPR-Cas9 system led scientists to manipulate and change genes/chromosomes.

• Evaluated as a new tool for genetic diseases.

6
At Yale, Doudna's group was able to crystallize and solve
the three-dimensional structure of the catalytic core of the
Tetrahymena Group I ribozyme. They showed that a core of
five magnesium ions clustered in one region of the P4-P6
domain of the ribozyme, forming a hydrophobic core
around which the rest of the structure could fold. This is
analogous, but chemically distinct from, the way proteins
typically have a core of hydrophobic amino acids. Her group
has crystallized other ribozymes, including the Hepatitis
Delta Virus ribozyme. This initial work to solve large RNA
structures led to further structural studies on an internal
ribosome entry site(IRES) and protein-RNA complexes such
as the Signal Recognition Particle.
In 2012, Doudna and her colleagues made a new discovery that
reduces the time and work needed to edit genomic DNA. Their
discovery relies on a protein named Cas9 found in the Streptococcus
bacterial "CRISPR" immune system that cooperates with guide RNA
and works like scissors. The protein attacks its prey, the DNA of
viruses, and slices it up, preventing it from infecting the bacterium.
This system was first discovered by Yoshizumi Ishino and colleagues in
1987 and later characterized by Francisco Mojica, but Doudna and
Emmanuelle Charpentier showed for the first time that they could use
different RNAs to program it to cut and edit different DNAs.
A POWERFUL TOOL THAT AFFECTS EVERYONE

Just eight years after their discovery, these genetic scissors have reshaped the life
sciences. Biochemists and cell biologists can now easily investigate the functions
of different genes and their possible role in the progression of disease. In plant
breeding, researchers can give plants specific characteristics, such as the ability to
withstand drought in a warmer climate. In medicine, this gene editor is
contributing to new cancer therapies and the first studies attempting
to cure inherited diseases.
These arrays of repeated sequences are called clustered regularly
interspaced short palindromic repeats, abbreviated as CRISPR. The
interesting thing is that the unique, non-repetitive sequences in
CRISPR appear to match the genetic code of various viruses, so the
current thinking is that this is one part of an ancient immune
system that protects bacteria and archaea from viruses. The
hypothesis is that if a bacterium has succeeded in surviving a virus
infection, it adds a piece of the virus’ genetic code into its genome
as a memory of the infection.
Doudna Maps A Complex Machinery

In addition to the CRISPR sequences, researchers have

discovered special genes that they have called CRISPR-
associated, abbreviated as cas. What Doudna finds interesting is
that these genes are very similar to genes that code for already
known proteins that specialise in unwinding and cutting up
DNA. So do the Cas proteins have the same function? Do they
cleave virus DNA?
She puts her research group to work and, after a few years,
they have succeeded in revealing the function of several
different Cas proteins. In parallel, a handful of other
research groups at other universities are studying the
newly discovered CRISPR/Cas system. Their mapping shows
that bacteria’s immune systems can take very different
forms. The CRISPR/Cas system studied by Doudna belongs
to class 1; it is a complex machinery that requires many
different Cas proteins to disarm a virus. The class 2 systems
are significantly simpler because they need fewer proteins.
In another part of the world, Emmanuelle Charpentier has
just come across such a system.
Charpentier had never worked with CRISPR, but
her research group initiates some thorough
microbiological detective work to map the
CRISPR system in S. pyogenes. This system, which
belongs to class 2, was already known to only
require a single Cas protein, Cas9, to cleave virus
DNA. Charpentier shows that the unknown RNA
molecule, which is named trans-activating crispr
RNA (tracrRNA), also has a decisive function; it is
necessary for the long RNA that is created from
the CRISPR sequence in the genome to mature
into its active form.
 JEFFREY C. HALL & MICHAEL ROSBASH & MICHAEL YOUNG

• They were awarded to Nobel Prize in physiology or

medicine in 2017 “for their discoveries of molecular

mechanisms controlling the circadian rhythm”.

2
 JEFFREY C. HALL & MICHAEL ROSBASH & MICHAEL YOUNG
• Jeffery Hall was born on May 3, 1945, Brooklyn NY.
• He studied at Amherst College for his BA degree; obtained his Ph.D. degree from
University of Washington in 1971 (genetic mechanisms in Drosophila).
• As post-doctoral researcher worked Prof. Seymour Benzer at California Institute of
Technology who was first person discovered the period gene from Drosophila. Studied
neuroanatomy and neurochemistry.

• Became faculty at Brandeis University, MA investigated the nervous system function and
behaviour in Drosophila.
• He met and collaborated with Michael Rosbash at Brandies University and focused on the
circadian rhythm mechanism in Drosophila.

3
 JEFFREY C. HALL & MICHAEL ROSBASH & MICHAEL YOUNG
• Michael Rosbash was born on March 7, 1944, Kansas City, Missouri.
• He studied chemistry at Caltech and graduated in 1965. Obtained his Ph.D. in biophysics
from MIT in 1970. Worked as post-doctoral researcher at the University of Edinburgh (1 y).
• Joined Brandeis University as faculty in 1974.
• In his Ph.D. and post-doc years studied metabolism and process of mRNA. Revealed
enzymes, proteins, and subcellular organelles and their convergence upon mRNA in a
specific order in order to translate mRNA into proteins in Saccharomyces cerevisiae .
• Then he met and collaborate with Jeffrey Hall to study genetic influences on circadian
rhythms of the internal biological clock.

• Hall and Rosbash later found that levels of the period gene product, PER, fluctuated in the fruit fly brain,
• PER building up at night and declining during the day.
• The oscillations, they discovered, were the result of a negative feedback loop, whereby PER was produced until
it reached a specific level, at which point it then turned off its own synthesis.
4
 JEFFREY C. HALL & MICHAEL ROSBASH & MICHAEL YOUNG
• Michael Rosbash was born on March 7, 1944, Kansas City, Missouri.
• He studied chemistry at Caltech and graduated in 1965. Obtained his Ph.D. in biophysics
from MIT in 1970. Worked as post-doctoral researcher at the University of Edinburgh (1 y).
• Joined Brandeis University as faculty in 1974.
• In his Ph.D. and post-doc years studied metabolism and process of mRNA. Revealed
enzymes, proteins, and subcellular organelles and their convergence upon mRNA in a
specific order in order to translate mRNA into proteins in Saccharomyces cerevisiae .
• Then he met and collaborate with Jeffrey Hall to study genetic influences on circadian
rhythms of the internal biological clock.

• About the same time, Michael Young, who was at Rockefeller University in NY,
independently isolated the same gene.

5
 JEFFREY C. HALL & MICHAEL ROSBASH & MICHAEL YOUNG
• Michael Young was born on March 28, 1949, Miami, FL.
• He got his undergraduate degree in biology from University of Texas at Austin in 1971. In
1975 completed his Ph.D. in genetics at UT.
• He has been influenced by Drosophila genome study and learnt about Ron Konopka and
Seymour Benzer’s work on Drosophila circadian gene period.
• Study transposable elements in his post-doctoral studies at Stanford University School of
Medicine and gained experience in the recombinant DNA methods.

• Joined Rockefeller University as faculty in 1978.

• In the 1980s, Young’s research on genetic mechanisms in Drosophila became increasingly
focused on elucidating the molecular basis of circadian rhythm. 1984 cloned period gene.

• He discovered a second key gene, timeless, RNA levels of which oscillate on a 24-hour cycle. TIM and PER
interacting partners in the circadian clock mechanism.
• Started to collaborate with M. Rosbash and F. Hall to elucidate the circadian clock mechanism. 6
• He loved to work with Drosophilia
• He studied about recombination
and translocation in Drosophilia
• Hall pursied at University
Washington in Seatle
• He began to work in Lawrence
Sendler’s laboratory on analysing
age-dependent enzyme change in
Drosophila with concentration on
the genetic control of chromosome
in meiosis.
 What is circadien rhythms?
• Circadian rhythms are generated by endogenous oscillators to allow
organisms to change their behaviors with a period of ∼24 h in
anticipation for the changing environment of day–night cycle
brought about by the Earth's rotation. The term “circadian” (circa, ∼;
dies, a day) is used because in constant conditions (free from
external time cues) the free-running period may be longer or
shorter than, but not exactly, 24 h.
• Hall's research has generally focused on nervous system function
and behavior in Drosophila, particularly the neurogenetics of
courtship and biological rhythms.
• While investigating the regions of the nervous system that help
regulate singing behavior during courtship in Drosophila, he
observed that the fly's chirps occur periodically at regular
intervals.
• Hall and Rosbash found that levels of the related gene product
PER in fruit fly brains fluctuate, increasing at night and decreasing
during the day. In this way, protein production was regulated in a
continuous 24-hour cycle.
• Hall focused on flies with the "fruitless
gene", which he began working with in
his post-doctoral years. The fruitless (fru)
mutant gene was behaviorally infertile.
As a result of research from the cloned
genes, Hall proved that this gene is the
main regulator gene for courtship
behavior.
In 1997, Hall and his team discovered genes that are part of TTFL,
which is expressed throughout the body.
Although these genes were identified as essential genes for the
circadian clock, they also had differential expression at various
cellular levels in various parts of the body.
Hall found in 2003 that the pigment dispersing factor protein (PDF)
helps these genes in cells control circadian rhythms and locomotor
activity. He concluded that PDF allows synchronization between
cells. Thanks to this work, he was awarded the 2017 Nobel Prize in
Medicine and Physiology.
• In 1998, Hall found that CRY is a key
photoreceptor for regulating as well as
regulating locomotor activity. It has
been hypothesized that CRY may play a
role not only as an input to the
circadian system, but also as a
pacemaker. In addition, Hall discovered
that the CLOCK and Cycle (CYC) proteins
form a heterodimer via the PAS domain.