Taekjip Ha

Research

We are interested in using physical concepts and experimental techniques to study fundamental questions in molecular biology. The biological systems under study include helicases that unzip DNA, a DNA recombination intermediate called a Holliday junction and its associated enzymes, folding and catalysis of hairpin and VS ribozymes, DNA replication machinery, and chromatin remodeling complexes.

Our main experimental tool is single-molecule fluorescence spectroscopy and microscopy, supported by nano-mechanical tools such as magnetic and optical tweezers. We use modern molecular biology techniques to engineer the molecules with fluorescence tags and tether them to a bio-friendly surface. Then, we shine laser light on each molecule to watch it do its thing. A clever design of such experiments can yield new insights to fundamental biological problems. We also use computational tools extensively, not only to acquire and analyze data, but also to model the problems mathematically, to exploit the genomic databases, and to simulate molecular motions and reactions.

Publications

T. Ha, "Need for speed: Mechanical regulation of a replicative helicase," Cell 129, 1249-1250 (2007).

S. Myong, M. M. Bruno, A. M. Pyle and T. Ha, "Spring-loaded mechanism of DNA unwinding by HCV NS3 helicase," Science 317, 513-516 (2007).

I. Cisse, B. Okumus, C. Joo and T. Ha, "Fueling DNA-protein interactions inside porous nanocontainers," PNAS 104, 12646-12650 (2007).

J. Yu, T. Ha and K. Schulten, "How Directional Translocation is Regulated in a DNA Helicase Motor," Biophys. J. 93(11), 3783-97(2007).

S. Hohng, R. Zhou, M. K. Nahas, J. Yu, K. Schulten, D. M. J. Lilley and T. Ha, "Fluorescence-force spectroscopy maps two-dimensional reaction landscape of the Holliday junction," Science 318, 279-283 (2007).

E. Rothenberg, M. A. Trakselis, S. D. Bell and T. Ha, "MCM fork substrate specificity involves dynamic interaction with the 5’ tail," J. Biol. Chem. 282, 34229-34234 (2007).

H. Kim, I. Rasnik, J. Liu, T. Ha and Y. Lu, "Dissecting metal ion dependent folding and catalysis of single DNAzyme," Nature Chemical Biology 3, 763-768 (2007).

P. R. Selvin and T. Ha, editors, Single Molecule Techniques: A Laboratory Manual, Cold Spring Harbor Laboratory Press, 507 pp., ISBN 978-087969775-4 (2008).

C. Joo, H. Balci, Y. Ishisuka, C. Buranachai and T. Ha, "Advances in Single-Molecule Fluorescence Methods for Molecular Biology," Annual Review of Biochemistry 77, 18.1-18.26 (2008).

I. Rasnik, Y. Jeong, S.A. McKinney, V. Rajagopal, S.S. Patel and T. Ha, "Branch migration enzyme as a Brownian Ratchet," The EMBO J. 27, 1727-1735 (2008).

R. Roy, S. Hohng and T. Ha, "A practical guide to single molecule FRET," Nature Methods 6, 507-516 (2008).

G. Q. Tang,  R. Roy, T. Ha, S. S. Patel, "Initial transcription in a single-subunit RNA Polymerase Proceeds through DNA Scrunching and Rotation of the N-terminal Subdomains," Molecular Cell 30, 567-577 (2008).

P. V. Cornish, D. N. Ermolenko, H. F. Noller and T. Ha, "Spontaneous Intersubunit Rotation in Single Ribosomes," Molecular Cell 30, 578-588 (2008).

T. Y. Yoon, X. Lu, J. J. Diao, S. M. Lee, T. Ha and Y. K. Shin, "Single-vesicle analysis reveals strong stimulation of SNARE-mediated membrane fusion by complexin and Ca2+," Nature Structural & Molecular Biology 15, 707-713 (2008).

Z. Su, Y. Ishitsuka, T. Ha and Y.K. Shin, "The SNARE complex from yeast is partially unstructured on the membrane," Structure 16, 1138-1146 (2008).

A. Iqbal, S. Arslan, B. Okumus, T. J. Wilson, G. Giraud, D. G. Norman, T. Ha and D. M. Lilly, "Orientation dependence in fluorescent energy transfer between Cy3 and Cy5 terminally attached to double-stranded nucleic acids," Proc Natl Acad Sci, USA, 105(32), 11176-11181 (2008).

Y. Lin, L.-J. Lin, P. Sriratana, K. Coleman, T. Ha, M. Spies and I. K. O. Cann, "Engineering of functional replication protein A homologs based on insights in evolution of oligonucleotide/oligosaccharide binding (OB) folds", J. Bacteriology 190(17), 5766-5780 (2008).

M. U. Gack, A. Kirchhofer, Y. C. Shin, K. S. Inn, C. Liang, S. Cui, S. Myong, T. Ha, K. P. Hopfner and J. U. Jung, "Roles of RIG-I N-terminal tandem CARD and splice variant in TRIM25-mediated anti-viral signal transduction," Proc Natl Acad Sci, USA 105(43):16743-16748 (2008).

E. Rothenberg, J. M. Grimme, M. Spies and T. Ha, "Human Rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes." PNAS 205(51), 20274-20279 (2008).

Heller, D., H. Jin, B. Martinez, D. Patel, B. Miller, T.-K. Yeung, P. Jena, C. Hobartner, T. Ha, S. Silverman, M. Strano, "Multimodal optical sensing and analyte specificity using single-walled carbon nanotubes," Nature Nanotechnology, doi: 10.1038/nnano.2008.369 (2008) .

S. Myong, S. Cui, P. V. Cornish, A. Kirchhofer, M. U. Gack, J. U. Jung, K. P. Hopfner and T. Ha, "Cytosolic viral sensor RIG-I is a 5'-triphosphate-dependent translocase on double-stranded RNA," Science, 10.1126/science.1168352 (2009).

J. G. Yodh, B.C. Stevens, K. Radhakrishnan, P. Janscak and T. Ha, "BLM helicase measures DNA unwound before switching strands and hRPA promotes unwinding reinitiation," The EMBO J, doi:10.1038/emboj.2008.298, 1-12, (2009).

P. V. Cornish, D. N. Ermolenko, D.W. Staple, L. Hoang, R.P. Hickerson, H.F. Noller and T. Ha, "Following movement of the L1 stalk between three functional states in single ribosomes." PNAS in press, (2009).

Awards

• Howard Hughes Medical Institute Investigator, 2005
• Alfred P. Sloan Fellowship, 2003
• Beckman Fellow, UIUC Center for Advanced Studies, 2003
• Xerox Faculty Research Award, UIUC, 2003
• Cottrell Scholar Award, 2003
• NSF CAREER Award, 2002
• Fluorescence Young Investigator Award, 2002
• Searle Scholar Award, 2001
• Research Innovation Award, 2001
• Outstanding Young Researcher Award, AKPA, 2001

Highlights