AI-Designed Proteins Could Transform Fluorescent Cell Imaging

Key Points:

• A team led by HHMI Investigator David Baker and Janelia Senior Group Leader Luke Lavis is using AI to design NovoTags, a new class of fluorescent imaging probes that bind directly to Janelia Fluor (JF) dyes, enabling multi-color protein imaging inside cells.
• The AI model RFdiffusion, developed by the Baker Lab, allows creation of novel small proteins that tightly bind specific fluorescent dyes without needing traditional chemical connectors, overcoming current limitations that restrict imaging to one or two proteins at a time.
• NovoTags enable simultaneous visualization of multiple proteins with different colors, potentially allowing researchers to study complex cellular processes and signaling pathways in ways not possible with existing probes like HaloTag or SNAP-tag.
• The team has successfully generated proteins binding three different JF dyes and plans to expand the toolkit to a dozen dyes, including probes for dyes that change color or blink, as well as sensors for physiological signals such as calcium or metabolites.
• This project is part of AI@HHMI, a $500 million initiative to integrate AI into scientific research, and the NovoTags will be made available to the global scientific community to accelerate biological discovery.