Michelle S. Frei

A chemigenetic fluorescence lifetime-based biosensor for imaging of ERK activity

Extracellular signal-regulated kinase (ERK) governs many cellular processes, and its spatiotemporal activity dynamics are important for downstream signaling specificity. Existing fluorescent ERK activity biosensors, however, fall short in enabling spectrally multiplexed, spatially resolved, or deep tissue measurements....

Nanobodies Equipped with HaloTag Enable Scalable Fluorescence-Lifetime Multiplexing

Fluorescence lifetime (FL) is a robust strategy for multiplexed imaging; however, variability in fluorophores’ local microenvironment when used on affinity probes broadens lifetime distributions, limiting its practical applicability. We create a modular platform for FL encoding with nanobody–HaloTag variants, enabling...

A chemigenetic endogenous Ras activity biosensor for live-cell pharmacology

Protein engineering: status report

Protein engineering appears to be entering a golden age, defined by a rapidly accelerating pace of progress, even as significant challenges in design, screening, and real-world application remain.