Event

Dr. Kai Chen
University of California, Berkeley
 
Friday, January 31, 2025
10:30 AM
Carolyn Hoff Lynch Lecture Hall
Chemistry Complex
231 South 34th Street
 
 
Exploring and repurposing nature’s molecular machinery for applications in chemistry and biology  

Proteins function as nature’s molecular machinery, driving the biological processes essential for life’s adaptation to diverse environments. Directed evolution, inspired by natural principles of mutation and selection, has emerged as a powerful strategy to optimize and repurpose these biomolecules for human needs. During my Ph.D. research, I employed directed evolution to engineer heme-dependent enzymes into efficient carbene transferases, unlocking new biocatalytic approaches for forming carbon-carbon/heteroatom bonds. These engineered enzymes enabled the synthesis of complex molecular structures, including strained carbocycles and heterocyclic compounds, expanding the catalytic repertoire of natural enzymes and providing versatile tools for synthetic purposes.
        Beyond its impact on chemistry, directed evolution plays a transformative role in optimizing biomolecules for biological applications. CRISPR-Cas technology, derived from bacterial adaptive immune systems, has revolutionized genome editing with its programmability and precision in modifying DNA. However, its clinical and research applications face critical challenges, such as limited editing efficiency, off-target effects, immunogenicity, and delivery constraints. During my postdoc research, I harnessed directed evolution to improve the efficiency, specificity, and stability of CRISPR-Cas9 and Cas12 proteins while uncovering mechanistic insights into their function as robust genome editors. These advancements further enabled the development of new delivery platforms based on cell-penetrating peptides and lipid nanoparticles to deliver gene editors in their ribonucleoprotein form, which allows for targeted in vivo genome editing in the brain, liver, and lungs.
        In this seminar, I will highlight how protein engineering integrated with molecular understanding and emerging biotechnologies addresses fundamental challenges at the intersection of chemistry and biology. These approaches offer transformative solutions for applications ranging from synthetic chemistry and biology to therapeutic genome editing.

Bio: Dr. Kai Chen’s research work bridges synthetic chemistry, biomolecular engineering, and genome editing. He earned his undergraduate degree in Chemistry from Zhejiang University in China, laying a strong foundation for his future research in molecular sciences. In 2015, he began his Ph.D. at Caltech under the guidance of Nobel Laureate Prof. Frances Arnold, a pioneer in directed evolution. During his Ph.D. studies, Kai focused on the directed evolution of cytochrome P450 monooxygenases to expand their functional capabilities, repurposing these enzymes to catalyze new-to-nature functions, such as transferring carbon- and nitrogen-based moieties. His work unlocked new strategies for synthetic chemistry and broadened the horizons of enzyme engineering. In 2020, Kai transitioned to postdoctoral research at UC Berkeley in the lab of another Nobel Laureate, Prof. Jennifer Doudna, a pioneer in CRISPR genome editing. His postdoctoral work has centered on addressing key challenges in therapeutic genome editing, developing new CRISPR tools with enhanced capabilities, and shedding light on their mechanisms of editing functions. Furthermore, Kai has spearheaded efforts to create new delivery platforms, such as lipid nanoparticles, to enable the targeted and safe delivery of these genome editors for therapeutic applications. Dr. Chen’s career exemplifies the seamless integration of chemistry, biology, and engineering, addressing pressing challenges in science and medicine.