Life by Understanding Proteins
By Jennifer Fisher Wilson
photo: Mike Lovett
summer before her senior year at Bryn Mawr College,
Carolyn Cohen 50 was serving breakfast at
a resort located in Pennsylvanias Pocono
Mountains. Recalling the isolated location, the
demanding vacationers, the required hairnet and
the paltry tips, "it was awful," she
says. A friend from Bryn Mawr who was working
at the Marine Biological Laboratory at Woods Hole,
Mass., heard how miserable she was and found her
a job there instead. Cohens
new job still required her to work in food service,
but Woods Hole turned out to be "heaven,
Cohen says. In addition to being surrounded by
scientists every day, she was free to do some
laboratory work in the afternoon and attend scientific
talks in the evening. And at one of the talks,
Cohen found the inspiration for what would become
her long and successful career in science.
talk was given by Dr. Dorothy Wrinch, a British-trained
mathematician, who presented striking diagrams
of her ideas about how proteins are constructed.
Wrinch was convinced that protein structure held
the secret of life. It was 1949, still a few years
before Linus Pauling deciphered one of the key
patterns for protein folding called the "alpha
helix" in 1952, and before James Watson and
Francis Crick discovered the double helical structure
of DNA in 1953.
was intrigued with the idea that in seeing protein
structure, we were seeing the details of the inner
workings of the cell," Cohen explains. She
was hooked. After graduating from Bryn Mawr in
1950, she pursued graduate studies in biophysics
at MIT, focusing on the analysis of the structure
of proteins, and thats what shes been
working on ever since.
research has helped to establish the basic structures
and functions of certain proteins and to clarify
in what ways they can indeed be considered key
to "the secret of life", as Wrinch observed
all those years ago. Her early work focused on
the X-ray diffraction of fibrous proteins, first
collagen and then muscle. She later carried out
electron microscopy studies of various muscle
proteins, such as myosin and paramyosin, to learn
how they are designed to form highly ordered fibers
in the cell. More recently, Cohens focus
has been higher-resolution X-ray crystallography
of these muscle proteins.
did much of her early work with a small group
of colleagues over two decades at the Jimmy Fund
(or the Childrens Cancer Research Foundation)
in Boston. Together, they formed one of the earliest
structural biology laboratories. During that time,
she was also a lecturer in biophysics at Harvard
Medical School. In 1972, the laboratory moved
to Brandeis University in Waltham, Mass., where
Cohen has been a professor of biology for 30 years.
been blessed by the help of marvelous colleagues,
postdoctoral fellows and students over the years,"
Cohen notes. Findings from Cohens laboratory
have earned her some of the highest honors in
science, including memberships in the prestigious
National Academy of Sciences and the American
Academy of Arts and Sciences.
order to appreciate Cohens work, its
necessary to understand that proteins are the
fundamental functional units of every living organism.
Knowledge of protein structure is essential for
understanding life at its most basic level. Genes
in the nucleus of the cell encode the information
required for the linear amino acid sequences that
make up proteins, which then fold into specific
with her postdoctoral work, Cohen has focused
for the most part on the architecture of muscle
proteins, which have both dynamic and structural
roles in the cell. Among other advances, she and
her co-workers have discovered assembly and regulatory
properties of the muscle proteins that control
movement in the thin filaments (actin) and thick
filaments (myosin) that make up muscle tissue.
Cohens current research attempts to obtain
atomic images of the complex motor portion of
myosin, the myosin "head", as it moves
through different stages of contraction.
want to visualize how myosin moves the actin filaments,"
Cohen explains. "By visualizing these large
structures in precise detail, we are beginning
to understand how these molecular machines work."
Related research focuses on visualizing the protein
interactions that lead to the assembly of a fibrin
blood clot at the site of a wound.
focus of Cohens laboratory is on protein
folding. Many proteins, including those involved
in muscle and blood clotting, fold into extended
three-dimensional shapes in which two alpha helices
wind around one another. This simple "coiled
coil" structure reveals features of protein
design in a far more accessible way than does
the structure of complicated globular proteins.
Cohen and her colleagues have shown how certain
amino acid sequences affect a proteins shape
and, in so doing, they have established some of
the principles of protein folding.
work in Cohens laboratory employs X-ray
crystallography to capture atomic-level images
of proteins. This method uses the X-rays diffracted
by crystals to determine where atoms are located
in the protein structure.
Cohen began her doctoral work, X-ray crystallography
was very arduous for example, it could
take many years to determine the structure of
a protein, such as hemoglobin. Today, advances
in practical and theoretical techniques and the
use of computers have allowed scientists to produce
increasingly complex and detailed images. They
can now visualize the structure of certain large
protein molecules all the way down to the atoms
that make up their amino acid sequences. From
this work, they can make beautiful, colorful,
three-dimensional computer diagrams that reveal
how atoms interact to determine the molecular
a great reductionist," Cohen says, noting
the paradox that as we learn more precise information
about the structure of individual proteins we
become better able to generalize about how they
function. For example, protein research is beginning
to provide clues about a wide variety of diseases
such as cancer, cystic fibrosis and Alzheimers
disease, which may arise from malfunctioning proteins.
Cohens work has special relevance to various
neuromuscular and cardiovascular diseases. Increased
knowledge of protein structure may lead to the
development of new therapeutic agents and drugs.
and her colleagues have made much progress in
understanding protein structure and protein folding,
but many questions still remain. After 50 years
in research, she finds that her work is "endlessly
interesting." Cohen paraphrases Albert Einsteins
description of his own devotion to science: it
is her driving force, the pivot of her emotional
life, with her efforts coming straight from the
Cohens work has taken her to London and
Paris and throughout the United States, she says
that she prefers to spend most of her days in
her laboratory at Brandeis University, working
with fellow researchers. From the age of 12, when
Cohen built her first small lab in her bedroom,
and including her years at Bryn Mawr majoring
in biology and physics, this is how it has always
been for her. And this is how she intends to continue,
although at 73, Cohen has passed the usual age
people think that science is a grim business,
but it is neither grim nor a business," Cohen
says. "There can be enormous playfulness,
terrific imagination and wonderful human interactions
in the laboratory. In fact, one of the great pleasures
now in science is the connectedness of the scientific
community ones colleagues are truly
About the Author
Jennifer Fisher Wilson is
a contributing editor for The Scientist.
She writes frequently about science and medicine
for various publications, including Lancet
Neurology, Science and UCLA Magazine.