Engineering Next-Generation Intrabodies for Monitoring the Dynamics of Histone Modification in Living Cells

Intrabodies are engineered antibodies that work inside living cells, enabling a wide range of therapeutic, diagnostic, and imaging applications. In my lab, we use intrabodies to visualize the dynamics of post-translational modifications and mRNA translation – two processes that are notoriously difficult to capture by other means. In the first part of the talk, I'll describe a new AI-driven pipeline that integrates AlphaFold2, ProteinMPNN, and live-cell screening to dramatically accelerate intrabody design. This approach has yielded dozens of functional scFv intrabodies targeting synthetic, viral, and histone modifications for live imaging. In the second part, I'll showcase how we're applying these tools to monitor the dynamics of residue-specific histone modifications in the context of transcription and mechanotransduction.