We engineer fluorescent proteins to enable new biological insights. Our work includes the creation of a series of fluorescent proteins with improved brightness or red-shifted spectra, including mClover1-mClover3, mRuby2-mRuby3, CyOFP, mCyRFP1, mCyRFP3, mCardinal, mMaroon1, and mMaroon2.
By creating a new reporter of S-phase exit and by performing four-color imaging with mMaroon1, we developed the FUCCI4 system for reporting all four cell cycle phases (below).
Unlike fluorescent proteins, luciferases do not require excitation light, making them useful for noninvasive reporting from deep locations in scattering tissue. Improving per-molecule photon yield in vivo is the major challenge in luciferase research. We take an integrated approach to improve both protein and small-molecule substrates simultaneously. We also develop general designs for luciferase-based reporters of biochemical activities, exploring new uses for bioluminescence in tracking pathogenesis and treatment. For example, we developed Calcium-Modulated Bioluminescent Indicators (CaMBIs) to visualize neuronal activity without requiring excitation light (right).