Dr. Cech's Research Background

Thomas R. Cech

CHEVY CHASE, Md, March 25, 1999— Thomas R. Cech's research on ribonucleic acid, or RNA, has revolutionized the understanding of the biological role of this genetic material. Prior to Cech's research on RNA, most scientists believed that proteins were the only catalysts in living cells. A series of experiments done independently by Cech and Sidney Altman at Yale University ultimately revealed that RNA can also act as a biologic catalyst, a "ribozyme."

Cech's and Altman's discoveries overturned the notion that RNA is merely a genetic messenger—an intermediate in the synthesis of proteins from DNA. In 1989, Cech and Altman received the Nobel Prize in chemistry for discovering the catalytic properties of RNA.

Since becoming an HHMI investigator at the University of Colorado at Boulder in 1988, Cech has probed the mechanisms of RNA catalysis. Many of these studies involved the ribozyme originally found in the ciliated protozoan Tetrahymena thermophila. Such ribozymes may one day be used as therapeutic agents to treat a variety of human diseases.

More recently, Cech's research group has tackled the problem of discerning the shape of the Tetrahymena ribozyme. Cech's team, as well as other research groups, has made great strides in overcoming a number of hurdles that have prevented scientists from obtaining precise molecular snapshots of ribozymes. Recent breakthroughs in X-ray crystallography of RNA have made it possible for Cech and colleagues to determine that the active site of a Tetrahymena ribozyme is largely preorganized for catalysis, much like protein enzymes.

A small group within Cech's laboratory has branched into an entirely different area of research—studying the structure and replication of telomeres, the ends of chromosomes. In recent years, several research teams have provided evidence that senescence 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.

Cloning the gene for telomerase eluded many research teams because the gene product was present in nearly undetectable amounts in most eukaryotic cells. Cech's team cloned and isolated the gene for the catalytic center of human telomerase largely because they had already found a similar catalytic protein in the ciliated single-celled pond organism Euplotes aediculatus and in a fission yeast.

Cech and colleagues showed that the enzymatically active part of the proteins produced by genes from the two organisms contained reverse transcriptase motifs, which bore striking similarity to motifs found in retroviruses and retrotransposons (mobile DNA sequences). The discovery led to the identification of a new branch of the reverse transcriptase family called TERT, telomerase reverse transcriptase. Cech's group is now studying telomere function in yeast with the long-term goal of better understanding the mechanism of telomere replication.

Photo: Paul Fetters