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Dr.
Abby Parrill (center) and her team of researchers, including
graduate students Charlie Singer (left) and Hongbin Yuan
(right), use computers to simplify and study the chemical
receptors of molecules, like the one pictured here. |
The human body is made up of a complicated system of amino
acid chains, molecules and chemical receptors, among other
things. Making sense of it can often lead to frustration and
bewilderment. But a U of M assistant professor of chemistry
has discovered the perfect way to analyze these biological
systems, and she is using it to make significant strides in
research that could help save others from deadly diseases.
Since arriving at the University in 1996, Dr. Abby Parrill
has been "simplifying" the study of molecules and
chemical receptors to find ways these particles can be synthetically
modified to produce better prescription drugs. Specifically,
she and her research team use computers to study biologicalmolecules,
and how these molecules, or growth factors, interact with
proteins in the body.
"The growth factors that we are studying affect wound
healing, cell migration and vascular, or blood vessel, development,"
Parrill says. "Synthetic molecules could be designed
to mimic the natural ones. These natural molecules don't make
good drugs, but the synthetic molecules could. The modification
of these molecules could lead to improvements in the treatments
of certain types of cancer and tumors. It could also aid neonatal
development, the healing time of burn victims and increase
the viability of organ transplants."
Parrill's work begins with reports from other research groups
on "interesting" proteins. Proteins, made up of
amino acid chains, are classified into specific types. One
kind of protein is a set of receptors embedded in the membrane
surrounding a human cell. These receptors that intercept chemical
signals from outside the cell and inform the cell about the
signal are the focus of Parrill's research.
"Receptors are useful biological systems that we might
want to influence," Parrill says. "Sixty percent
of known drugs interact with the receptors we are studying
in order to take effect."
To analyze these interactions, Parrill's team builds computer-generated
models of the receptors and simplifies them even further to
the individual amino acids that make up each receptor's structure.
Biologists and molecular biologists then test the hypotheses
generated from these models in test tubes.
The results provide useful information to synthetic chemists
regarding chemical modifications that can be made to the signal
molecules in order to produce the desired response from the
receptor.
The path from pure research to clinically useful drugs takes
many years and many additional researchers. If desired results
are achieved by Parrill's team, and subsequent animal testing
indicates the modified molecules are safe, clinical testing
then begins on small groups of healthy humans. Once proven
safe in humans, the effect must be demonstrated on a sample
of people with a health problem targeted by the studied disease.
Final tests are then conducted on larger populations. If all
procedures prove favorable, the molecules can be produced
for medicinal use.
"The whole process from start to finish takes 10 years
or more before it reaches the clinic where it can be used
for therapeutic treatments," Parrill says.
Parrill's crew has already made a significant stride toward
its overall goal of understanding how the receptors recognize
the signaling molecules. "The protein has 400 amino acids,"
she says. "We identified one position out of the 400
that, when changed, could make a receptor recognize a different
molecule, or growth factor."
The finding was verified and put the group one step closer
to identifying what can be done to synthetically duplicate
the effect of the natural growth factors.
Parrill is not the only one who believes in the power of
this work. The American Heart Association has committed $70,000
to her research in collaboration with the University of Tennessee
Health Science Center-Memphis every year between 1999 and
2001. The National Science Foundation has granted her $150,000
in support of summer research programs. The National Institutes
of Health is also funding Parrill's research with a three-year,
$75,000 grant.
Yet, for this researcher bestowed with many accolades, including
an Early Career Research Award from the College of Arts and
Sciences, the rewards of her work extend beyond personal honors
and pharmaceutical benefits.
"I really get a lot of enjoyment out of seeing my students
learn to do and enjoy research," Parrill says.
Her current team of 10 student researchers seems to be doing
just that. In the Smith Hall labs on campus that make up the
Computational Research on Materials Institute (CROMIUM), they
continue simplifying biological complexities, receiving occasional
help from UT, the University of Alberta, Georgetown, Ohio
State and other U of M faculty.
"It's fascinating to understand how the simple principles
of chemistry work in very complex systems," Parrill says.
"When you focus tightly on small parts of large protein
structures, they're as easy to understand as basic chemistry."
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