Cincinnati--Faculty from the University of Cincinnati and the
University of Pittsburgh have recently been awarded a $5 million grant
from the U.S. Department of Defense (DoD) Multidisciplinary Research
Program of the University Research Initiative (MURI/URI). John
Cuppoletti, PhD, professor of molecular and cellular physiology at the
UC College of Medicine, is the principal investigator.
working with Dr. Cuppoletti are F. James Boerio, PhD, Herman Schneider
Professor of Materials Science in the UC Department of Materials
Science and Engineering; Jerry Y.S. Lin, PhD, professor of chemical
engineering; Thomas Beck, PhD, professor of chemistry; Paul Rosevear,
PhD, associate professor of molecular genetics and Rob Coalson, PhD,
professor of chemistry at the University of Pittsburgh.
of the research will be on the structure and function of native and
engineered membrane transport proteins in synthetic membranes. The
goals of the research are to figure out how these proteins accomplish
the task of transporting substances; to make proteins that will
transport new substances; and to make new materials and devices that
contain biological proteins.
"This is a new, very sophisticated
scientific effort to understand how it is that transport proteins work
and how their structure allows function to be carried out," Dr.
It has far reaching implications in medicine and technology.
opportunities this research will provide for development and discovery
are enormous," Dr. Cuppoletti explained. "Many diseases involve defects
in transport proteins. Through this new research, my colleagues and I
hope to understand how these proteins work and apply it to numerous
applications, including understanding diseases such as cystic fibrosis,
cardiac disease, secretory diseases and neurological disorders. Once we
know the structure and function we can begin to make predictions and
find new drugs. This will improve the overall quality of life."
Cuppoletti says the structure of many transport proteins is already
known. With this grant, the researchers are attempting to understand
the structural changes that occur over short and long time intervals by
using supercomputers and mathematical modeling.
"Once we know how
the structure of the transporters changes with time during the
transport process, and how each amino acid within the protein interacts
with the transported substances, we can use computational chemistry to
predict how the transported substances will interact with the native
protein over time, and how, for example, to change the protein to
transport new substances. Thus, we will attempt to use computational
chemistry to change and improve upon nature. We are also attempting to
incorporate these proteins into synthetic membranes to produce
materials with new properties, including energy production and
utilization and devices for drug delivery, purification systems and
sensors. These advances will have numerous applications in medicine and
Dr. Cuppoletti hopes to train at least 12
postdoctoral fellows or graduate students each year through the grant.
The training will be done in a multidisciplinary approach involving
chemists, biologists and engineers. In addition, Dr. Cuppoletti and his
colleagues will be working with and learning from scientists in the DoD
"We are currently looking for the best and brightest
to join our team and effort," Dr. Cuppoletti said. "An important aspect
of this grant is that we're going to be training many young people to
think in a new way. This is really going to catalyze a great deal of
new research and training in Cincinnati and beyond."