Path to the Prize

March 22, 2010
Dr. Thomas Steitz, 2009 Nobel Laureate and former JCC fellow reflects on his postdoctoral experience

Last fall, the Nobel Prize in Chemistry was awarded to Dr. Thomas Steitz for determining the structure and function of the ribosome, which translates RNA into proteins. Steitz’s journey to the Nobel Prize began decades ago, and one crucial step along the way was his postdoctoral fellowship, funded by the Jane Coffin Childs Memorial Fund.

Steitz spent his fellowship at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England with Dr. David Blow. “It was a pivotally important experience to spend three years in the best structural biology lab in the world at that time,” Steitz says.

He landed the position in 1966 after completing his Ph.D. with Dr. William Lipscomb at Harvard University, where his interest in using X-ray crystallog- raphy to study structural biochemistry began. As a graduate student, he met a postdoc who recommended working with Dr. Blow.

“I went to the library, read one of his papers, and wrote him a letter,” Steitz recalls, adding that he didn’t meet his mentor until he arrived in England, quite a difference from today’s jet-setting applicants and in-person interviews.

Funding from the JCC made his postdoc possible, and it came about thanks to a “marvelous accident,” Steitz says. A graduate student from James Watson’s lab happened to have a copy of the JCC application but did not plan to apply. Steitz was unaware of the JCC fellowships until the moment the application was handed to him. The deadline loomed the next day. Luckily, with a project and laboratory already in mind—and minimal bureaucracy in those days—filling out the application was straightforward, according to Steitz.

At the Laboratory of Molecular Biology in England, Steitz shifted his studies from one enzyme, carboxypeptidase A, to another, alpha chymotrypsin, and focused on its mechanism.

Access to great scientists and opportunities to discuss ideas were critical to Steitz’s early career. At the Laboratory of Molecular Biology, people assembled daily for morning tea, lunch, and afternoon coffee, which fostered a conversational culture rich with scientific debates and discussions. “It was quite unlike what happens today,” says Steitz, describing people eating lunch alone at their desks while checking email.

In transitioning to a faculty position, Steitz briefly held a position at the University of California at Berkeley, but plans changed when his grant application was rejected and his wife, Dr. Joan Steitz, was not offered a position there (she is now a Sterling Professor of Molecular Biophysics and Biochemistry and HHMI Investigator at Yale).

So instead, he extended his postdoctoral fellowship for a total of three years, instead of the then-usual two. “The JCC was very helpful in letting me stay,” says Steitz, grateful for the additional funding.

He spent his extra year beginning his study of yeast hexokinase and eventually demonstrated that specific substrate binding induces a large conformational change within it. Accepted understanding of enzyme action was changing at the time. Daniel Koshland’s induced fit theory proposed that enzymes are not as static as bricks, but can instead change shape to bind substrates. Steitz’s studies on yeast hexokinase provided compelling evidence for the concept.

In 1970, Steitz joined the faculty at Yale University, where he has spent the majority of his career using X-ray crystallography to understand the mechanisms of gene expression, from DNA to RNA to proteins. Currently, he is the Sterling Professor of Molecular Biophysics and Biochemistry, Professor of Chemistry, and Howard Hughes Medical Institute Investigator.

Over the past two decades, he chipped away at visualizing the ribosome, the complex structure that translates RNA into proteins. Overcoming one challenge after another, he obtained images of the ribosome’s large subunit with ever-increasing resolution and bound to different substrates, including antibiotics. For his work, he was honored with the 2009 Nobel Prize in Chemistry, which he shares with Ada Yonath and Venkatraman Ramakrishnan.

“My postdoc was an absolutely marvelous time,” Steitz says. With none of the exams, courses, or theses associated with graduate school, and none of the grant applications or teaching assignments required of faculty, he could devote all his energies to research. Today, he hosts about 11 postdocs in his 20-person lab and aims to encourage joint projects and interactive group meetings—in other words, the same sort of scientific discussions that were so valuable during his early career. His advice to current JCC fellows? “Follow your passion. Do that which excites you the most.”