My research is focused on pushing the limits of single-molecule detection methods to study complex biological systems. His group develops state-of-the-art biophysical techniques (e.g., multicolor fluorescence, super-resolution imaging, combined force and fluorescence spectroscopy, vesicular encapsulation, single-molecule pull-down) and applies them to study diverse protein–nucleic acid and protein-protein complexes, and mechanical perturbation and response of these systems both in vitro and in vivo.
For more details, visit http://www.hhmi.org/research/single-molecule-studies-genomic-maintenance.
Figure: Reaction in a nonocontainer. Solution exchange allows controlled catalysis of protein-DNA interaction inside porous vesicles. The pores in a nanocontainer let small molecules, such as ions and other chemicals, pass through but keep large molecules, such as proteins and DNA, inside.
Illustration courtesy of Ibrahim Cisse and Taekjip Ha. Modified from Cisse I, Okumus B, Joo C and Ha T. 2007 Proceedings of the National Academy of Sciences USA 104: 12646.12650.
- T. Ha, Th. Enderle, D.F. Ogletree, D.S. Chemla, P. Selvin, and S. Weiss, “Probing the interaction between two single molecules: Fluorescence resonance energy transfer between a single donor and a single acceptor ,” Proc. Natl. Acad. Sci. U.S.A. 93, 6264 (1996).
- S. Myong, I. Rasnik, C. Joo, T.M. Lohman and T. Ha, “Repetitive shuttling of a motor protein on DNA,”Nature 437, 1321-1325 (2005).
- C. Joo, S.A. McKinney, M. Nakamura, I. Rasnik, S. Myong and T. Ha, “Real time observation of RecA filament dynamics with single monomer resolution,” Cell 126, 515-528 (2006).
- 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).
- 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).
- R. Roy, A. Kozlov, T. M. Lohman and T. Ha, “SSB protein diffusion on single stranded DNA stimulates RecA filament formation,” Nature 461(7267), 1092-1097 (2009).
- J. Park, S. Myong, A. Niedziela-Majka, K.S. Lee, J. Yu, T. M. Lohman and T. Ha, “PcrA dismantles RecA filaments by reeling in DNA in uniform steps”, Cell 142, 544-555 (2010).
- A. Jain, R. Liu, B. Ramani, E. Arauz, Y. Ishitsuka, K. Ragunathan, J. Park, J. Chen, Y. K. Xiang and T. Ha, “Probing cellular protein complexes using single-molecule pull-down”, Nature 473, 484-488 (2011).
- R. Zhou, A. G. Kozlov, R. Roy, J. Zhang, S. Korolev, T. M. Lohman and T. Ha, “SSB functions as a sliding platform that migrates on DNA via reptation”, Cell 146, 222-232 (2011).
- G. Lee, M. Bratkowski, F. Ding, A. Ke and T. Ha, “Elastic coupling between RNA degradation and unwinding by an exoribonuclease”, Science, 336, 1726-1729 (2012).
- R. Vafabakhsh and T. Ha, “Extreme bendability of DNA less than 100 base pairs long revealed by single molecule cyclization”, Science, 337, 1097-1101 (2012).
- X. Wang and T. Ha, “Defining Single Molecular Forces Required to Activate Integrin and Notch Signaling”,Science 340, 991-994 (2013).
- T. Ngo, Q. Zhang, R. Zhou, J. G. Yodh and T. Ha, “Asymmetric unwrapping of nucleosomes under tension directed by DNA local flexibility”, Cell 160, 1135-1144 (2015).
- J. Fei, D. Singh, Q. Zhang, S. Park, D. Balasubramanian, I. Golding, C. K. Vanderpool and T. Ha, “Determination of in vivo target search kinetics of regulatory noncoding RNA”, Science 347, 1371-1374 (2015).
- S. Arslan, R. Khafizov, C. D. Thomas, Y. R. Chemla and T. Ha, “Engineering of a superhelicase through conformational control”, Science 348, 344-347 (2015).