Timothy Keiderling, a professor of chemistry at the University of Illinois at Chicago, has won a fellowship from the New York-based John Simon Guggenheim Memorial Foundation. He is one of 184 American and Canadian artists, scholars and scientists selected this year from more than 3,200 applicants for the prestigious awards, announced April 10.
A UIC faculty member since 1976, Keiderling will spend much of 2004 learning new laboratory and computational techniques and applications to further his study of a molecular formation in peptides and proteins called the beta sheet. His work may yield clues to the protein-folding disorders that underlie Alzheimer's, "mad cow" and Creutzfeldt-Jakob diseases.
"I'm trained as a physical chemist. I deal with the principles behind molecular structures, but I apply it to biological problems," Keiderling said.
The most common structure within protein polymers is the corkscrew-shaped alpha helix. It has been thoroughly studied and is well understood. The next most common molecular motif is the beta sheet, which contains stretched out polymer segments that come together to form a flattened formation.
"Alpha helixes are more uniform. When you find one, you know it," said Keiderling. "But when you find a beta sheet, sometimes it's unclear. They tend to twist, and the degree of twist varies."
Keiderling thinks a better understanding how beta sheets are formed will be of interest both to chemists and medical researchers.
Alzheimer's is sometimes called a protein-folding disease, Keiderling said, because a protein in the body gets clipped by an enzyme, leaving the protein shorter. These shortened protein molecules tend to grab on to each other and form structures that resemble beta sheets. "They kill nerve cells," Keiderling said.
Diseases such as mad-cow and Creutzfeldt-Jakob are also the result of mis-folded protein molecules, called prions.
"Prions are also proteins that, for some reason, go amiss and come together to form beta sheet-like structures. We don't know if that's what causes cellular damage, but we think it's an important element," Keiderling said.
"We'd like to understand in detail how beta sheets form, then try to find ways to monitor that, so we can follow these disease functions."
Keiderling studies how infrared light interacts with matter, to learn more about protein structure and properties. Shining infrared light on molecules heats them up and makes the atoms move faster.
"By finding out what wavelength causes that, I learn how heavy the atoms are, or which bond is involved, and the strength of that bond," Keiderling said. "Learning about the bond tells me how things are put together."
Keiderling will consult with scientists at special laboratories in Germany and Switzerland who do time-dependent infrared measurements, hoping he can adapt some of these techniques to study how proteins form beta sheets. He also plans to do research at Cambridge University in England on computational modeling of beta sheets.
"Timothy Keiderling's Guggenheim fellowship recognizes not only the high quality and value of his own scientific research, but underscores the breadth of interdisciplinary work going on among the physical and biological sciences and medicine here at UIC," said Stanley Fish, dean of the College of Liberal Arts and Sciences.
Keiderling earned his bachelor's degree in chemistry from Loras College in Dubuque, Iowa and his master's and Ph.D. from Princeton University. He has been a senior visitor at Oxford University's Centre for Molecular Sciences and a guest professor at the Max Planck Institute in Munich.
Pleased by the professional recognition that goes with winning a Guggenheim Fellowship, Keiderling said it follows some 30 years of doing a job he loves.
"It's discovery. It's knowing how something works. Once you do it, there's a feeling of satisfaction. That's what I do every day. I solve puzzles."
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