Taekjip Ha

Professor

Ph.D., Physics, Univ. of California, Berkeley, 1996

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.

Other Activities

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.

Additional Information

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:

Ha Group home page

Honors and awards:

• 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
• Searle Scholars Award
• Research Innovation Award, Research Corporation
• Outstanding Young Researcher Award, AKPA

Selected Publications:

• 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).
• R. Roy, A. Kozlov, T. M. Lohman and T. Ha, Dynamic structural rearrangements between DNA binding modes of E. coli SSB protein, J. Mol. Biol. 369, 1244–1257 (2007).
• T. Ha, Need for speed: Mechanical regulation of a replicative helicase, Cell, 129, 1249-1250 (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).