RNA Expert Awarded Sloan Fellowship

April 27, 2006

Biochemist David Mathews, M.D., Ph.D.

Biochemist David Mathews, M.D., Ph.D., has been awarded an Alfred P. Sloan Fellowship to continue his research on RNA, a molecule that is crucial to life and is a target of growing importance for pharmaceutical companies developing new drugs to treat disease. The award,

designed to identify young investigators like Mathews who “who show the most outstanding promise of making fundamental contributions to new knowledge,” brings Mathews $45,000 to build his research program during the next two years.

Mathews, a professor of Biochemistry and Biophysics at the University of Rochester Medical Center, is an expert on the computational biology of RNA, focusing on ways to use today’s powerful computers to learn more about one of life’s most complex and versatile molecules. Since Mathews joined the University as an undergraduate student in 1990, a great deal has changed both in the world of computers – which are so much more powerful than before – and in the world of RNA, which had been considered mainly a molecule that translates the genetic code into proteins. Recently scientists have discovered that RNA does a great many things, such as helping to build proteins. The new discoveries offer opportunity to RNA experts like Mathews and other University researchers, who together make up one of the strongest RNA groups in the world.

Before joining the faculty, Mathews played a key role in an effort that has become one of Rochester’s most successful exports, a computerized method to predict the structure of RNA molecules, which commonly have loops, twists, and turns and are much more complex in shape than any roller coaster imaginable. RNA molecules change shape instantly and often, remarkably transforming themselves to accomplish some bodily task. Understanding the shape of such molecules, and the rules they go by to shift their shapes and keep the body going, is crucial to developing new drugs that interfere with RNA or proteins that cause harm in the body. If scientists understand the shape of a “bad” RNA, they’re more likely to be able to target that RNA with drugs to prevent or treat disease.

For 20 years Mathews’ graduate adviser, Douglas Turner, Ph.D., professor of chemistry, has worked closely with mathematician Michael Zuker, now at Rensselaer Polytechnic Institute, to understand RNA and then develop computer programs to predict the structure of RNA molecules; the team’s methods are widely recognized as among the best in the world. In 1999 Mathews was first author on the team’s publication, cited subsequently more than 1,100 times by other scientists, that brought together much of the team’s work into an extensive computer algorithm for predicting RNA structure. Such knowledge is crucial in budding areas of drug development known as antisense molecule development and in RNA interference.

Mathews is continuing that work to learn more about RNA structure and shape. In contrast to the substantial progress scientists have made identifying thousands of human genes, fewer scientists are trying to tackle the parallel problem of identifying useful portions of RNA code. Mathews is coupling the work of Turner, Zuker and others with today’s powerful computers to develop new ways to identify the most useful snippets of RNA, in a field known as computational biology.

A native of Syracuse, Mathews earned his bachelor’s degree in physics, as well as his medical and doctoral degrees, from the University. As an undergraduate he took advantage of the opportunities the University offers to students to work closely with faculty members who are known internationally for their research. Mathews worked on the structure of atoms in the physics department and with Turner on the structure of RNA. Another former University undergraduate, Martin T. Zanni, a close friend of Mathews’ at Rochester, this year also was awarded a Sloan fellowship to study protein structure at the University of Wisconsin.

A member of Phi Beta Kappa, Mathews joined the faculty in 2004. He is also on the faculty of the Department of Biostatistics and Computational Biology.

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