Description:

DNA Mechanics And Nucleosome Condensability As Biophysical Backdrop Of Genome Functions

Taekjip Ha, PhD

Mutations primarily function through changing amino acids encoded and altering transcription factor binding. Likewise, epigenetic modifications function through changing interactions with readers, writers, and erasers of epigenetic marks. However, it has been recognized that mutations may act through changes in DNA mechanics, and histone modifications may also directly modify nucleosome biophysical properties. Here, I will present our own line of research using single molecule methods and genome-scale sequencing-based analysis to quantify the roles and magnitudes of DNA mechanics and nucleosome condensation in genome and chromatin functions.

About Taekjip Ha

Dr. Taekjip Ha is George D. Yancopoulos Professor of Pediatrics in honor of Frederick W. Alt at Harvard Medical School and Director and Senior Investigator of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital. He has been an investigator with the Howard Hughes Medical Institute since 2005. He received a bachelor’s degree in Physics from Seoul National University in 1990 and a PhD in Physics from University of California at Berkeley in 1996. After postdoctoral training at Stanford, he was a Physics professor at University of Illinois at Urbana-Champaign (2000-2015), where he co-directed an NSF Physics Frontier Center, and Bloomberg Distinguished Professor at Johns Hopkins University (2015-2023). He is a member of the National Academy of Sciences and the National Academy of Medicine, and a fellow of the American Academy of Arts and Sciences. He received the Ho-Am Prize in Science (2011), Kazuhito Kinosita Award in single molecule biophysics (2018) and Barany Award for young investigators (2007). He was named a Searle Scholar (2001) and Sloan Fellow (2003). He has served on Editorial Boards for Science (2011-present), Cell (2009-2020) and eLife (2014-2020). He co-chaired the National Academies committee Toward Sequencing and Mapping of RNA Modifications (2022-2024). He served as President of the Biophysical Society (2023-2024). Dr. Ha’s current research theme is “genome maintenance at higher resolution”. “Higher resolution” here refers to advances his team pioneered in multiple axes, including time resolution, spatial resolution, single molecule and single cell resolution, and single base pair resolution. His biological focus is genome maintenance, i.e. how the genome is accurately duplicated and repaired for preserving genomic integrity. He advanced CRISPR-based tools in terms of time and space resolution as well as multiplexing and obtained novel insights about repair of CRISPR-generated DNA damage. Because genome maintenance occurs in the context of chromatin and 3D genome, and in the presence of ongoing nuclear processes such as transcription and epigenetic regulation, his team has also been studying how DNA sequences and modifications as well as histone modifications can act directly through changes in biophysical properties of DNA and chromatin such as DNA flexibility and nucleosome stability and condensability. Finally, he used biophysical properties of DNA to develop single molecule force sensors and determined the single molecule force loading rate in cells.