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University of Cincinnati Academic Health Center
Publish Date: 05/08/02
Media Contact: AHC Public Relations, (513) 558-4553
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Membrane Transport Proteins Focus of $5 Million Department of Defense Grant

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.

Others 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.

The focus 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. Cuppoletti said.

It has far reaching implications in medicine and technology.

"The 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."

Dr. 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 technology."

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 community.

"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."



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