When she arrived on campus as the newest faculty member in a rejuvenated Biophysics Department, one of the first things Sarah Woodson did, besides setting up her lab on the fourth floor of Jenkins Hall, was to meet with the first-year graduate students.
As one of the leading scientists in the study of RNA, Woodson recently joined the faculty after spending eight fruitful years at the University of Maryland at College Park. She had been looking forward to this introduction with the students because it offered one way to generate skilled staff for her lab when she takes up permanent residence there in March.
Her pitch to attract labor, discretely packaged as a high-order lecture with a small assortment of color transparencies, took place during the lunch hour in a small classroom on the first floor of Jenkins.
The graduate students listened quietly. But was their silence reverential, polite or skeptical?
"So what I thought I would do is give you an overview of some of the problems we're interested in working on," she said, flipping through a pile of transparencies. The grad students, about 20 in all, sat stoney-faced.
Except for the neatness and relative formality of her dress, it might have been difficult to distinguish Woodson from the students in the classroom. Only 10 years ago, she had joined the prestigious labs of Thomas Cech as a postdoctoral fellow at the University of Colorado. That was in 1988, the year before Cech and Sidney Altman of Yale University won the Nobel Prize for pioneering discoveries about RNA.
Since Cech's "revolutionary" discoveries, Woodson said, the study of RNA has taken on greater significance. Advances in understanding its molecular structure are coming quickly. Because it is now known that RNA can actually catalyze chemical reactions, thanks to Cech and Altman's research, the old paradigm of RNA as the traveling blueprint of DNA has changed dramatically. No longer restricted simply to its role as genetic messenger, it is understood now that RNA actively participates in directing the body's cellular biochemistry. As a catalyst, RNA has assumed a more central role in theories about the origin of life.
"There has been a huge burst of interest both from the viewpoint of molecular genetics and cell biology," she said. "The structures in RNA are clearly important in a number of the steps that are critical for regulating genes in human cells and pathogens. The problem is we have only a primitive understanding of the very complex structure of RNA and how it relates to biological function."
She displayed a number of colored cartoons and diagrams of simplified RNA structures that looked like a complex interconnection of mangled pipes and circuits. Some people grimace the first time they see a complete RNA model, she said, adding that RNA molecules actually look nothing like the simple, squiggly lines published in most biology textbooks.
Some of the most important interactions in an RNA molecule take place within the first second of synthesis, as the RNA begins to fold. One challenge for Woodson has been to look carefully at what happens during that first second. With the help of collaborators at the Albert Einstein College of Medicine at Yeshiva University, she has developed a method to analyze the process that begins RNA folding at millisecond intervals. A paper about this process was published in Science in March last year.
She talked about a variety of experiments under way in her lab and explained one, in particular, being conducted by her postdoctoral fellow. "He needs some help," she concluded slyly, with a gentle laugh. "He could use a few more hands."
She had tried to tone down the rhetoric for the presentation, but when she invited questions, it was quickly apparent that the students knew quite a bit about RNA structure already.
"Is it understood whether this folded state represents one meta-stable structure or an ensemble of independent equally meta-stable structures?..."
"Are you using potassium chloride or sodium sulphate or different salts to slow down the reaction?..."
"Have you done any transition state traps on the RNA folding?..."
After a rapid flurry of questions, which Woodson answered thoroughly without a moment's hesitation, most of the students disappeared quickly in search of pizza across the hall. But then a few came back to find out more about how they could help in her new lab.
"Good graduate students!" she muttered.
Woodson looked delighted.