Office: JSCBB B421
Lab: JSCBB B455
Lab Phone: 303-492-8304
Ph.D.: University of California, Berkeley, 1975
National Medal of Science, 1995; Nobel Prize in Chemistry, 1989; Heineken Prize, 1988; Member, National Academy of Sciences, 1987; U.S. Steel Award in Molecular Biology, 1987; American Cancer Society Lifetime Research Professor, 1986; Guggenheim Fellow, 1985; Pfizer Award in Enzyme Chemistry, 1985; USPHS Research Career Development Award, 1980
After their discovery of self-splicing RNA and RNA catalysis (1982), the Cech Lab studied the mechanism of catalytic RNAs (ribozymes) at both the chemical and the biological levels. This work integrated enzymology, biophysics, chemical synthesis, molecular biology and genetics, and culminated with the determination of crystal structures of a large ribozyme domain and of entire active ribozymes. As a result of this and other work, we now have a reasonable understanding of how ribonucleotides can form active sites for biological catalysis.
Starting in 1997 with the discovery of TERT (Telomerase Reverse Transcriptase), the Cech Lab has increasingly turned its attention to the RNP (ribonucleoprotein) world. They defined functions for different domains of the TERT protein and of the telomerase RNA subunit in budding yeast, fission yeast, and Tetrahymena, and they investigated the functions of additional regulatory subunits. At the same time, their finding of the telomere end-binding protein POT1 (protection of telomeres 1) led to determination of the molecular structure of the human telomere: protein bound to single-stranded telomeric DNA. The research then addressed the question of how telomeric DNA-binding proteins also recruit telomerase and activate its enzymatic processivity in the human system.
Vast numbers of lncRNAs (long non-coding RNAs) have been identified by genome-wide analysis in mammals, some of which are involved in recruiting histone-modifying proteins and regulating transcription. The Cech Lab is taking a mechanistic and biophysical approach to two proteins that bind these lncRNAs, FUS (fused in sarcoma) and PRC2 (polycomb repressive complex 2). They are combining protein purification and rigorous binding analyses with genome-wide experiments to interrogate the mechanism of these abundant RNPs.
Baumann, P. and Cech, T. R. Pot1, the Putative Telomere End-binding Protein in Fission Yeast and Humans. Science 292, 1171-1175 (2001).
Lei, M., Podell, E. R., Baumann, P. and Cech, T. R. DNA Self-recognition in the Structure of Pot1 Bound to Telomeric Single-stranded DNA. Nature 426, 198-203 (2003).
Pfingsten, J.S., Goodrich, K.J., Taabazuing, C., Ouenzar, F., Chartrand, P., Cech, T.R. Mutually Exclusive Binding of Telomerase RNA and DNA by Ku Alters telomerase recruitment Model. Cell, 148, 922-932 (2012).
Nandakumar, J., Bell, C.F., Weidenfeld, I., Zaug, A.J., Leinwand, L.A., Cech, T.R. The TEL patch of telomere protein TPP1 mediates telomerase recruitment and processivity. Nature, 492: 285-289 (2012).
Schwartz, J.C., Ebmeier, C.C., Podell, E.R., Heimiller, J., Taatjes, D.J., Cech, T.R. FUS binds the CTD of RNA polymerase II and regulates its phosphorylation at Ser2. Genes Dev. 26: 2690-95 (2012).