University of Rochester

NIH Awards Two Chemists $3.3 Million to Study Basics of Life

May 1, 2007

Two chemists at the University of Rochester have received more than $3 million from the National Institutes of Health (NIH) to study some of the most basic properties of how key molecules behave in organisms.

"It is indeed a great pleasure to see two outstanding young scientists receive the much needed support that their research so richly deserves," says Robert K. Boeckman, Jr., chair of the Department of Chemistry. "Their success is particularly noteworthy in this era of extremely tight federal funding, and a vote of confidence in the quality and innovation of their research programs."

Kara Bren, associate professor in the Department of Chemistry, received $1.5 million to investigate how proteins called cytochromes transport energy throughout the body. These cytochromes are of intense interest to the health industry because they are involved in all metabolism, from respiration to aging.

"To develop a complete understanding of events contributing to aging and cell death, and to the development and progression of a range of diseases, the fundamentals of this chemistry in the cell must be understood," says Bren. "Understanding the basic mechanisms controlling this chemistry is of fundamental importance to biomedical sciences and human health."

Cytochromes move energy between protein complexes by distorting their shape—a flat cytochrome can pick up an electron more easily than a distorted one, and a distorted cytochrome can release an electron more easily than a flat one. Chemists have long known that transporting electrons within a cell is critically important to the cell's health, but Bren is taking the next step and looking into how the cytochrome undergoes its distortion/flattening act to make efficient electron transport possible.

Bren joined the University in 1997 after earning her doctorate in chemistry from the California Institute of Technology, and was named an Alfred P. Sloan Research Fellow in 2003.

Alison Frontier, assistant professor in the Department of Chemistry, has received $1.8 million to synthesize two unusual and complex molecules that could eventually provide medical researchers with tools to combat cancer and inflammation, as well as methods to synthesize other molecules that will impact diseases important to public health.

"Synthesis of these structurally interesting compounds will allow us to explore unique chemical transformations and improve our ability to study the bioactivity of these molecules," says Frontier. "The research will contribute potential strategies for the creation of these and other natural products, enabling chemists to prepare and study various pharmacological agents for medical applications."

Often these kinds of molecules are found only in small fungi or in deep-sea organisms, and so are in short supply. Frontier will build these two molecules "carbon-by-carbon," essentially following a convoluted recipe of mixing, heating, and testing in small, measured steps. One of the molecules she is looking to synthesize is an inhibitor of lipoxygenase, an enzyme relevant to a surprisingly wide range of human disease states, including cancer, heart disease, asthma and other inflammations. She is already working with neuroscientists at the University of Rochester Medical Center to test the potential of the second molecule, which shows signs of helping nerve cells regrow—a very rare and sought-after attribute.

Frontier earned her doctorate in chemistry from Columbia University in 1999, did postdoctoral research at Stanford, and came to the University's Department of Chemistry in 2002.




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