Biochemistry, Structural Biology
University of Colorado Boulder
Dr. Cech is also Distinguished Professor, Department of Chemistry and Biochemistry, at the University of Colorado Boulder and director, University of Colorado BioFrontiers Institute. Dr. Cech was an HHMI investigator from 1988 to 2000. In 2000 he became president of HHMI, and in April 2009 he stepped down as head of HHMI to conduct research on a full-time basis.
Tom Cech and his research group are studying the structure and mechanism of long noncoding RNAs and RNA-protein complexes, including telomerase and complexes that regulate transcription. Their research also focuses on the telomeric DNA-protein complexes that cap the ends of human chromosomes and help regulate telomerase. The overarching goal is to understand the detailed mechanism of these systems and how their misregulation contributes to diseases, including cancer and amyotrophic lateral sclerosis (ALS).
Growing up in Iowa City, Iowa, a young Tom Cech found rocks more interesting than RNA.
By junior high, he was so enamored with crystals and fossils and meteor showers that he would knock on the doors of geology professors at the nearby University of Iowa and quiz them about the structure of minerals and how they arose.
This obsession with the physical sciences may seem strange for someone who eventually became famous for his groundbreaking studies of biologic molecules. But that interest in structure and function started Cech down a path that eventually led to the Nobel Prize in Chemistry in 1989. He and fellow Nobel laureate Sidney Altman of Yale University independently discovered that RNA is not just a passive information carrier; it can also stimulate chemical reactions in living cells, a shocking finding at the time.
"I found that being able to apply the principles of chemistry to understanding something that was alive was particularly exciting to me personally," Cech says. Cech's parents were the first to stir this interest in science, especially his father, a physician and amateur physicist. It was "impossible in my family to ever take a family walk without him asking why the trees were turning color or something about the hydrodynamics of the water flow in the river running through town, always stimulating an inquiry of nature," he remembers.
That interest in physics and chemistry continued through elementary and high school, spurred by inspiring teachers and encounters with scientists. At Grinnell College in Iowa, Cech loved studying Homer's Odyssey, Dante's Inferno, and constitutional historybut he avoided biology. Cech majored in chemistry at Grinnell, and then chose to go to graduate school in chemistry at the University of California, Berkeley.
But by the time he left college, Cech had discovered that traditional physical chemistry research wasn't for him. "The pace of the work just didn't suit my own personality, which is quite impatient," he explains. "Of course, that is the very definition of graduate work, doing the research, so being a physical chemistry grad student represented a bit of a conundrum." Luckily, Cech came upon John E. Hearst, a professor of chemistry at Berkeley who was using his own physical chemistry background to study chromosomes. Cech knew nothing about chromosomes, but Hearst "was bouncing off the walls with excitement about it," Cech says. "I thought I would give it a try. And I just loved it."
Cech received quick feedback from his experiments with chromosomes—sometimes even the same day—and he found that he loved constantly revising his thinking. "There was this constant interplay between ideas and experiments, which would then generate the next set of ideas. That much better fit my personality."
After receiving his Ph.D. at Berkeley, Cech expanded his knowledge of biology with a postdoctoral fellowship in the lab of Mary Lou Pardue at the Massachusetts Institute of Technology. In 1978, Cech and his wife Carol, a fellow Grinnell graduate and biochemist, both joined the faculty of the University of Colorado Boulder. There, he settled into the work that would eventually overturn conventional wisdom about RNA.
Prior to Cech's research, most scientists believed that proteins were the only catalysts in living cells. In 1982, his research group showed that an RNA molecule from Tetrahymena, a single-celled pond organism, cut and rejoined chemical bonds in the complete absence of proteins. This discovery of self-splicing RNA provided the first exception to the long-held belief that biological reactions are always catalyzed by proteins.
In 1989, Cech was awarded the Nobel Prize in Chemistry. As the Nobel committee wrote, "This discovery, which came as a complete surprise to scientists, concerns fundamental aspects of the molecular basis of life. Many chapters in our textbooks have to be revised."
Cech, who was named a Howard Hughes Medical Institute investigator in 1988, later branched into an entirely different area of research—studying the structure and replication of telomeres, the ends of chromosomes. Research by different teams had shown that aging of human cells is linked to a cell's failure to maintain the length of its telomeres. The enzyme responsible for elongating telomeres, telomerase, has been the subject of intense scrutiny because it may be a useful target for cancer therapeutics or diagnostics. Cech's team cloned and sequenced the gene for the catalytic subunit of human telomerase and, later, the gene for the protein that caps off the telomeric ends of human chromosomes. They continue to study telomere function with the long-term goal of better understanding the mechanism of telomere replication.
In January 2000, Cech was named president of HHMI, the nation's largest science philanthropy. His tenure as president was marked by innovation and significant programmatic expansion. Under his leadership, HHMI opened its first freestanding research facility—the Janelia Farm Research Campus in Ashburn, Virginia—as a new model for conducting interdisciplinary research. Cech also introduced focused competitions to identify exceptional physician-scientists engaged in patient-oriented research, broadened the HHMI investigator competitions to embrace more interdisciplinary research, and initiated the Institute's first ever competition for early career scientists.
Throughout his tenure as president, Cech maintained his lab in Boulder, visiting once a month to keep his research going and his mind engaged in science. In April 2009, Cech stepped down as head of HHMI to return to his lab in Boulder on a full-time basis. There, he hopes to continue making the occasional discovery—and return to the classroom to engage the next generation of potential scientists.