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Taekjip Ha

Taekjip Ha's profile

Taekjip  Ha
Taekjip Ha

Professor

Professor Taekjip Ha received his Ph.D. in Physics in 1996, from the University of California, Berkeley. Prior to joining the Physics faculty at the University of Illinois in August 2000, he was a postdoctoral fellow at Lawrence Berkeley National Laboratory (1997) and a postdoctoral research associate in Steven Chu's laboratory in the Department of Physics at Stanford University (1998-2000). He was named 2001 Searle scholar. In 2005, Dr. Ha was named an investigator of the Howard Hughes Medical Institute. In 2008, Dr. Ha was selected by the National Science Foundation to receive a grant to establish and co-direct the Center for the Physics of Living Cells at the University of Illinois.

Professor Ha has achieved many "firsts" in experimental biological physics--the first dectection of dipole-dipole interaction (fluorescence resonance energy transfer, or FRET) between two single molecules; the first observation of "quantum jumps" of single molecules at room temperature; the first detection of the rotation of single molecules; and the first detection of enzyme conformational changes via single-molecule FRET. His most recent work, using single-molecule measurements to understand protein-DNA interactions and enzyme dynamics, has led him to develop novel optical techniques, fluid-handling systems, and surface preparations.

Description of Current Research

My interest is in using physical concepts and experimental techniques to study fundamental questions in molecular biology. The biological systems under study include helicases that unzip DNA, DNA recombination intermediate called 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.

News About Our Research

A main branch of my research is the study of biological processes on vesicle-encapsulated single molecules. Compared to surface immobilization, this unconventional method provides some advantages and new controls. The obvious advantage is complete isolation of the molecule of study from the surface. In addition, effective concentration of one or a few molecules inside a vesicle is in the micromolar range, much larger than other single-molecule essays that are typically performed at picomolar concentration. Such high effective concentrations enable single-molecule fluorescence studies of very weak interactions. We also use porous vesicles so that the reaction buffer can be quickly exchanged while keeping the biomolecule inside the vesicle. We have used our expertise in this area to study the membrane fusion induced by SNARE proteins at the single-vesicle level. SSB protein is another system that serves a crucial role in maintaining the unwound single strands of the DNA open during cellular processes such as DNA replication or repair. We used sm-FRET to study the two main SSB-binding modes and their interconversion rate as a function of monovalent and divalent ion concentration of the media. Beyond these fundamental binding modes, we also observed diffusion of SSB on DNA, which could have important implications for the function of this protein. We are also developing next-generation hybrid microscopes that combine single-molecule imaging with single-molecule manipulation. As a first step, we have built an apparatus combining sm-FRET with optical tweezers and measured force dependence of conformational changes in a Holliday junction. This study generated a two-dimensional reaction landscape of a Holliday junction and provided a detailed structure of the transient states populated by the Holliday junction during its conformational changes.

For more information

  • Single Molecule Nanometry Group (Ha Group)

Honors and awards

  • University Scholar, University of Illinos
  • National Science Foundation Award, Center for the Physics of Living Cells
  • Michael and Kate Bárány Award for Young Investigators, Biophysical Society
  • Fellow, American Physical Society
  • Howard Hughes Medical Institute Investigator
  • Alfred P. Sloan Fellow
  • Xerox Faculty Research Award, UIUC
  • Beckman Fellow at Center for Advanced Studies, UIUC
  • Cottrell Scholar, Research Corporation
  • Fluorescence Young Investigator Award, Biophysical Society
  • NSF CAREER Award

Teaching

The faculty of the Center for the Physics of Living Cells specifically target undergraduates (in addition to graduates) to introduce modern biophysical examples to the teaching of mechanics (bending and torsional elasticity and buckling instability of DNA, etc.), statistical physics (energy conversion efficiency of motor proteins, etc.) and other courses. A special focus will be on our department’s two-semester general physics course without calculus, taken largely by pre-medical students (>500 students). We will add biological examples to the lectures that appeal to the biology majors so that they leave Illinois with a lasting impression that physics is highly relevant to their life and career. Success will be measured via online student surveys and the outcome will be published in The American Journal of Physics. We also have added biophysical laboratory components (optical trap, total internal reflection fluorescence, etc.) to the existing optics and advanced undergraduate labs.

Selected Publications

  • R. Roy, A. G. Kozlov, T. M. Lohman and T. Ha, SSB protein diffusion on single-stranded DNA stimulates RecA filament formation, Nature 461(7267), 1092-1097 (2009).
  • M. Pandey, M., S. Syed, I. Donmez, G. Patel, T. Ha and S. S. Patel, Coordinating DNA replication by means of priming loop and differential synthesis rate, Nature 462, 940-943 (2009).
  • 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 323(5917):1070-1074 (2009).
  • 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).
  • P. V. Cornish, D. N. Ermolenko, H. F. Noller and T. Ha, Spontaneous Intersubunit Rotation in Single Ribosomes, Molecular Cell 30, 578-588 (2008).
  • 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).
  • P. S. Shirude, B. Okumus, L. Ying, T. Ha and S. Balasubramanian, Single-Molecule Conformational Analysis of G-Quadruplex Formation in the Promoter DNA Duplex of the Proto-Oncogene C-kit, JACS 129, 7484-7485 (2007).
  • S. Myong, M. M. Bruno, A. M. Pyle and T. Ha, Spring-loaded mechanism of DNA unwinding by Hepatitis C Virus NS3 helicase, Science 317, 513-516 (2007).
  • P. Cornish and T. Ha, A survey of single molecule techniques in chemical biology. ACS Chemical Biology 2(1), 53-61 (2007).
  • I. Rasnik, S. A. McKinney and T. Ha, Non-blinking and long-lasting single molecule fluorescence imaging. Nature Methods 3, 891-893 (2006).
  • 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).
  • C. Buranachai, S.A. McKinney, and T. Ha, Single molecule nanometronome. Nano Letters 6, 496-500 (2006).
  • 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).

Contact Information

Office
133 Loomis Laboratory

Phone
217.265.0717

Fax
217.244.7187

Email
halab_admin@physics.illinois.edu

Areas of Research

  • Biological Physics (experimental)

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