Taekjip “TJ” Ha, incoming Biophysical Society president, grew up in Seoul, South Korea. His parents worked in early childhood education, in classroom teaching and administration. As a young person, he was fascinated with early 20th century physicists and wanted to become a theoretical physicist. He studied physics as an undergraduate at Seoul National University, and then traveled to the United States to pursue his PhD in physics at the University of California, Berkeley with advisers Shimon Weiss and Daniel Chemla. “It was only after joining a physics PhD program that I realized that there was experimental physics that had enough theory—at least for me,” Ha shares. “My interest shifted from semiconductor physics to chemical physics and eventually to biophysics, largely through a series of accidental meetings with scientists and their work.”
During his PhD study, Ha built a near-field scanning optical microscope that enabled high time and spatial resolution. Weiss saw the potential for the techniques Ha was developing to be used in single-molecule research and encouraged him. The two regularly had long discussions, pitching and poking holes in ideas for research directions.
After completing his PhD, Ha worked as a postdoctoral fellow—first for a year in Weiss and Chemla’s lab at Lawrence Berkeley National Laboratory and then for two and a half years with Steven Chu at Stanford University. In both labs, he worked on single-molecule fluorescence studies of biomolecules.
“As a postdoc, I was looking for a biological system to study using single-molecule FRET when I read a review paper on helicases and kinesin written by Tim Lohman and Ron Vale,” Ha says. “I contacted Tim to start our helicase collaboration and that led me to my current and long-running interest in proteins that function in the maintenance of our genome integrity.”
Following his second postdoctoral position, in August 2000 he was hired as an assistant professor in the Department of Physics and Center for Biophysics and Computational Biology at the University of Illinois at Urbana-Champaign (UIUC). He remained there until 2015, during which time he became a full professor and served as co-director of the Center for Physics of Living Cells (2008–2015) and director of the Center for Biophysics and Quantitative Biology (2013–2014).
Zaida “Zan” Luthey-Schulten met Ha when his family moved into the house across from her home in Urbana, Illinois. “Later in the Physics Department at the UIUC, he and my husband, Klaus Schulten, were the first director (Ha) and co-director (Schulten) of our NSF Physics Frontier Center in Biological Physics: Center for the Physics of Living Cells (CPLC),” Luthey-Schulten recalls. “Part of the success of CPLC was the emphasis on joint experimental and theoretical/computational biological physics starting with the directors and in our summer school and center projects.”
Luthey-Schulten and Ha began a collaboration, publishing together for the first time in Nature in 2014. “Then again in 2021 (Nature Communications) and 2020 (Frontiers in Molecular Biosciences) on stochastic simulations and experimental measurements using super-resolution single-molecule imaging of small RNA (SgrS) interacting/regulating mRNA of ptsG, the main sugar transporter in bacteria. More recently, we are working on imaging and analyzing cell division in the living minimal cell JCVI-syn3A and comparisons to some of its precursors. Taekjip’s lab has also measured the location of key proteins in the minimal cell involved in sugar transport and cell division,” she explains. “As I have been focusing the efforts of my lab to build a complete 4DWCM of the minimal cell over the complete cell cycle, this is extremely exciting work for me. Taekjip’s lab is so talented and work on major problems in nuclear dynamics of eukaryotic cells—a new direction where hopefully Taekjip and I will have equally successful collaborations in the future.”
In August 2015, Ha started a position as Bloomberg Distinguished Professor of Biophysics & Biophysical Chemistry at Johns Hopkins University.
His colleague at Johns Hopkins, Sarah Woodson, first met Ha during his second postdoc, when he interviewed for a junior faculty position in her department. “I really wanted to hire him—it was obvious he was brilliant and going to be very successful. Unfortunately, we could not hire him at that time, but we were able to hire both he and his wife Sua Myong later,” she reports. “I have really enjoyed having TJ as a colleague.”
Woodson and Ha began collaborating during Ha’s time at UIUC, first on a project to understand how ribosomal protein S4 recognizes its binding site in the ribosomal RNA, using the single-molecule FRET approaches worked out in his lab. “The collaboration was suggested by Zan Luthey-Schulten, who had been doing computer simulations of S4-rRNA interactions. I was thrilled by this opportunity, because my group had been performing a number of biochemical studies of S4 binding, and we knew that the protein S4-RNA recognition process was very complicated. TJ’s single-molecule methods were clearly one of the best ways to sort out this complexity,” Woodson states. “Although this project was technically challenging, it returned a direct view of the kinetic path of binding, showing how protein S4 reshaped the RNA motions.” Those results were published in Nature in 2014.
They next collaborated to develop a method for vectorial RNA folding, using a “super helicase” designed in Ha’s lab. “This method mimics the 5’ to 3’ direction of RNA folding during transcription. The results unexpectedly showed that the first attempt at 5’ to 3’ folding was actually more likely to go wrong than subsequent attempts,” she adds. “This unexpected result helped us understand some later findings that RNAs do not necessarily fold correctly immediately after they are transcribed by RNA polymerase. Sometimes it takes a long time for a newly made RNA to achieve its proper 3D shape.”
As incoming president of the Biophysical Society, Ha looks forward to giving back to the biophysics community in his new role. “What makes the Biophysical Society great is its members. Our members define what biophysics is by their action, by unlocking fundamental answers in biology using quantitative methods,” he declares. “We witnessed biophysicists rising to the challenge of the pandemic. The value of rigorous science and scientific methods to humanity has rarely been as self-evident as in the last few years. The Biophysical Society’s role is to help its members to become heroes of their own scientific endeavors.”