Abstract

Efforts to repurpose CRISPR-Cas systems have produced a suite of genome editing tools, including programmable nucleases, base editors, and prime editors. These tools have greatly enabled the study of genomes and gene function, and their advancement to therapeutic development has demonstrated promise for addressing a host of unmet medical needs. Our understanding of how endogenous cellular processes influence the activity of these tools, however, lags behind their application and, due to the rapid pace of technology development, behind efforts to build new approaches. Our work focuses on identifying cellular determinants of genome editing tools to better understand how they work. In pursuit of this goal, we consider that to introduce sequence changes, genome editing tools must damage DNA. Development of genome-editing tools therefore requires a basic understanding of the cellular systems that sense and respond to DNA damage and presents new opportunities to study those basic cellular systems. Our results provide key insights into how genome editing tools interact with the cellular environment and suggest general strategies for improvement of these important technologies.

Biography

Britt Adamson is an Assistant Professor in the Department of Molecular Biology and the Lewis-Sigler Institute for Integrative Genomics. Dr. Adamson started her training in 2004 at the Massachusetts Institute of Technology in the laboratory of Angelika Amon. She graduated in 2005 and moved to Harvard Medical School for her graduate work. There, advised by Stephen Elledge, Dr. Adamson leveraged cutting-edge functional genomics technologies to systematically investigate mechanisms of genome integrity maintenance in human cells. She earned her PhD in 2012. Following graduate school, Dr. Adamson joined the laboratory of Jonathan Weissman at the University of California, San Francisco, where she received a postdoctoral fellowship from the Damon Runyon Cancer Research Foundation. Her postdoctoral work pioneered new approaches for functional genomics in human cells, technologies that now enable comprehensive dissection of cellular pathways and delineation of cell behaviors with unprecedented resolution. Dr. Adamson’s research interests center on how cells respond to stress, how such responses are regulated, and how they are altered in disease states.