个人简介

Ignacio Tinoco received a Bachelor's degree from the University of New Mexico in 1951, and a Ph.D. in Physical Chemistry at the University of Wisconsin, Madison in 1954. He was a postdoctoral fellow with John Kirkwood at Yale University from 1954-56. He joined the University of California, Berkeley as a faculty member in 1956, where he is presently a Professor in the Graduate School. He was Chairman of the Chemistry Department (1979-82). His honors and awards include: Guggenheim Fellow, Medical Research Council Laboratory, Cambridge (1964); California Section Award, American Chemical Society (1965); D.Sc. University of New Mexico (1972); Member, National Academy of Sciences (1985); Elisabeth R. Cole Award, Biophysical Society (1996); Berkeley Citation, University of California (1996); Member, American Academy of Arts and Sciences (2001); Founders Award, Biophysical Society (2006); Fellow: American Physical Society, Biophysical Society.

研究领域

Biophysical Chemistry, Nucleic Acids, Single Molecules — Physical methods are used to determine the structures of nucleic acids and illuminate the biological functions they control. The sequence of nucleotides in a nucleic acid determines its structure and function; Professor Tinoco and his students want to deduce these fundamental properties from the sequence. Important questions are: What folded, base-paired structure of an RNA is specified by the sequence? How do RNA loops interact with each other, or with double-stranded regions to form compact three-dimensional structures? What proteins, drugs, and ions do these structures bind? How do the sequence and structure affect the functions of ribosomal RNA's, the sites of processing of RNA, the translation of messenger RNA's, the replication of RNA viruses, and the catalytic abilities of RNA enzymes? Our main emphasis is single-molecule measurements. A single RNA is held between beads and force is applied to unfold it in any chosen condition. The work done in unfolding the RNA provides the free energy of the reaction in the chosen environment. The kinetics of the reaction can also be obtained. We have recently started studies of protein translation by individual ribosomes. Translation occurs by a series of steps with translocations of approximately 0.1 s followed by pauses of order 1 s. We are learning the effects of messenger RNA sequence and structure, and of antibiotics, on translation, in particular on the mechanism of frameshifting.

(Professor Tinoco no longer accepts students) Biophysical Chemistry, Nucleic Acids, Single Molecules — Physical methods are used to determine the structures of nucleic acids and illuminate the biological functions they control. The sequence of nucleotides in a nucleic acid determines its structure and function; Professor Tinoco and his students want to deduce these fundamental properties from the sequence. Important questions are: What folded, base-paired structure of an RNA is specified by the sequence? How do RNA loops interact with each other, or with double-stranded regions to form compact three-dimensional structures? What proteins, drugs, and ions do these structures bind? How do the sequence and structure affect the functions of ribosomal RNA's, the sites of processing of RNA, the translation of messenger RNA's, the replication of RNA viruses, and the catalytic abilities of RNA enzymes? Our main emphasis is single-molecule measurements. A single RNA is held between beads and force is applied to unfold it in any chosen condition. The work done in unfolding the RNA provides the free energy of the reaction in the chosen environment. The kinetics of the reaction can also be obtained. We have recently started studies of protein translation by individual ribosomes. Translation occurs by a series of steps with translocations of approximately 0.1 s followed by pauses of order 1 s. We are learning the effects of messenger RNA sequence and structure, and of antibiotics, on translation, in particular on the mechanism of frameshifting.

近期论文

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Yan, S., J.-D. Wen, C. Bustamante & I. Tinoco, Jr. 2015. Ribosome excursions during mRNA translocation mediate broad branching of frameshift pathways. Cell DOI:10.1016/j.cell.2015.02.003 Tinoco, I., Jr. 2014. The ethical scientist: an old-fashioned view. Biopolymers DOI: 10.1002/bip.22568 Kim, H.-K., F. Liu, J. Fei, C. Bustamante, R. L. Gonzalez, Jr. & I. Tinoco, Jr. 2014. A frameshifting atimulatory stem loop destabilizes the hybrid state and impedes ribosomal translocation. Proc. Natl. Acad. Sci. 111: 5538-43 Kaiser, C. M., I. Tinoco, Jr. 2014. Probing the mechanisms of translation with force. Chem. Rev. 114:3266-80 Tinoco, I., Jr. 2014. Fun and games in Berkeley: the early years (1956-2013). Annu. Rev. Biophys. 43:1-17 Tinoco, I., Jr., H.-K. Kim & S. Yan 2013. Frameshifting dynamics. Biopolymers 99:1147-66 Qu, X.H., L. Lancaster, H. F. Noller, C. Bustamante & I. Tinoco, Jr. 2012. Ribosomal protein S1 unwinds double-stranded RNA in multiple steps. Proc. Natl. Acad. Sci. 109: 14458-63 Kaiser, C. M., D. H. Goldman, J. D. Chodera, I. Tinoco, Jr. & C. Bustamante 2011. The ribosome modulates nascent protein folding. Science 334:1723-7 Cheng, W., S. G. Arunajadai, J. R. Moffitt, I. Tinoco Jr., and C. Bustamante. 2011. Single Base Pair Unwinding and Asynchronous RNA Release by the HCV NS3 Helicase. Science 333: 1746-1749. Qu, X.H., J.-D. Wen, L. Lancaster, H. F. Noller, C. Bustamante & I. Tinoco, Jr. 2011. The ribosome uses two active mechanisms to unwind messenger RNA during translation. Nature 475: 118-121 Tinoco, I., Jr. and R. L. Gonzalez, Jr. 2011. Biological mechanisms, one molecule at a time. Genes Dev. 25: 1205-1231 Tinoco, I., Jr., Chen, G., Qu, X. 2010. RNA Reactions One Molecule at a Time. COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY Volume: 2, Issue: 11, Article Number: a003624 Chen, G., Chang, K.Y., Chou, M.Y., Bustamante, C., Tinoco, I., Jr. 2009. Triplex structures in an RNA pseudoknot enhance mechanical stability and increase efficiency of-1 ribosomal frameshifting. Proc. Natl. Acad. Sci. 106: 12706-11 Tinoco, I., Jr., Wen, J.D. 2009. Simulation and analysis of single-ribosome translation. Phys. Biol. 6: 025006. Li P.T.X., Tinoco I., Jr. 2009. Thermodynamics and Kinetics of RNA Unfolding and Refolding. Page 49-72 in Non-Protein Coding RNAs (SPRINGER SERIES IN BIOPHYSICS: 13). Li P.T.X., Tinoco I., Jr. 2009. Mechanical Unfolding of Two DIS RNA Kissing Complexes from HIV-1. J. Mol. Biol. 386: 1343-56. Li P.T.X., Vieregg J., Tinoco I., Jr. 2008. How RNA Unfolds and Refolds. Annu. Rev. Biochem. 77: 77-100. Wen, J.D., Lancaster, L., Hodges, C., Zeri, A.C., Yoshimura, S.H., Noller, H.F., Bustamante, C., Tinoco, I., Jr. 2008. Following translation by single ribosomes one codon at a time. Nature 452: 598-603 Chen G., Wen J.D., Tinoco I., Jr. 2007. Single-molecule mechanical unfolding and folding of a pseudoknot in human telomerase RNA. RNA 13: 2175-88 Vieregg J., Cheng W., Bustamante C., Tinoco I., Jr. 2007. Measurement of the Effect of Monovalent Cations on RNA Hairpin Stability. J. Am. Chem. Soc. 129: 14966-73 Green L., Kim C.H., Bustamante C., Tinoco I., Jr. 2008. Characterization of the Mechanical Unfolding of RNA Pseudoknots. J. Mol. Biol. 375: 511-28 Cheng W., Dumont S., Tinoco I., Jr., Bustamante C. 2007. NS3 helicase actively separates RNA strands and senses sequence barriers ahead of the opening fork. Proc. Natl. Acad. Sci. 104: 13954-9 Li P.T.X., Bustamante C., Tinoco I., Jr. 2007. Real-time control of the energy landscape by force directs the folding of RNA molecules. Proc. Natl. Acad. Sci. 104: 7039-44 Manosas M., Wen J.D., Li P.T.X., Smith S.B., Bustamante C., Tinoco I., Jr., Ritort F. 2007. Force unfolding kinetics of RNA using optical tweezers. II. Modeling experiments. Biophys. J. 92: 3010-21 Wen J.D., Manosas M., Li P.T.X., Smith S.B., Bustamante C., Ritort F., Tinoco I., Jr. 2007. Force unfolding kinetics of RNA using optical tweezers. I. Effects of experimental variables on measured results. Biophys. J. 92: 2996-3009