Under the Microscope:
Professor Janet Smith

Getting to "Aha"

Starting out as a political science major seemed to be a good choice for a high school graduate who wasn't excited by math and science. But in college, Janet Smith gave it another go—she took chemistry, liked it, and decided to stick with it.

"Chemistry was fun, and I could do it, but biochem really excited me," said Smith, LSI structural biologist, who represented the first generation of her family to attend college.

A professor from her undergrad science studies at Indiana University of Pennsylvania encouraged her to go to the best graduate school she could get into, so she pursued a PhD at the University of Wisconsin-Madison and chose to study molecular structures in a field then called crystallography.

"I wanted to see what was happening in the structure of a molecule so I could understand its function."

Again receiving important and excellent advice, Smith joined the lab of Wayne Hendrickson at the Naval Research Laboratory in Washington, DC as a National Research Council Research Fellow.

"I learned an unbelievable amount from one of the leading minds in crystallography while we each solved a protein structure using the rather obscure method called anomalous scattering," Smith said.

Smith assisted Hendrickson in developing a method to solve protein crystal structures called MAD—multiwavelength anomalous diffraction—that gives crystallographers the power to decipher structures far more easily and rapidly than previous methods.

Smith followed her postdoc with research scientist positions at Columbia, and then established a research program in structural biology at Purdue in 1987 where she had a tenure filled with dynamic and productive collaborations.

The MAD method requires a special shared research facility called a synchrotron. Smith has been a leader in using these large facilities and making them available for structural biologists. She currently directs a national facility for structural biology at the Advanced Photon Source, a synchrotron at Argonne National Laboratory near Chicago.

Smith's research passion is to uncover nature's secrets for using proteins as biological tools.

"How does nature do it?" Smith said. "Nature knows, but we don't know, how the sequence of how amino acids codes for the beautiful protein structures we discover. And it's the 3-D structures that are nature's tools."

When all the pieces of a protein puzzle come together, "aha moments" she calls them, Smith demonstrates that seeing IS believing in structural biology.

"Now we get it! The protein makes a tunnel! It's a two-part reaction, and the first product goes through a tunnel and reacts over here!" Smith recounted her team solving the structure of glutamine PRPP amidotransferase, which formed a tunnel to connect two active sites and also regulate enzyme activity. "Now we understand the funky biochemistry from this and a host of other two-step enzymes!"

She was also part of a team that completed the molecular scale picture of how plants convert sunlight to chemical energy, solving mysteries of photosynthesis and metabolism.

When she got a call from UM Structural Biologist Martha Ludwig to do a presentation here, Smith was not considering a move.

"But the biomedical environment and bread and depth of high quality science across the UM campus, combined with the LSI resources, gave me the nudge to make a move to join LSI," Smith said.

"Scientists are so lucky, we do what we like, pursue our passion, it's fantastic," she said.