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    Area of Science:

    • Biotechnology
    • Molecular Biology
    • Biophysics

    Background:

    • Protein kinases regulate crucial cellular functions, and their dysregulation is linked to diseases like cancer.
    • Current fluorescent biosensors struggle to penetrate opaque tissues, limiting kinase activity studies.
    • Investigating kinase activity in vivo is essential for understanding disease mechanisms.

    Purpose of the Study:

    • To introduce the first ultrasonic reporter of kinase activity (UReKA).
    • To enable kinase activity monitoring in opaque biological samples.
    • To overcome the limitations of light-based biosensors in deep tissue imaging.

    Main Methods:

    • Engineered gas vesicle shell proteins to be responsive to protein kinase A (PKA).
    • Developed UReKA to alter ultrasound scattering based on PKA activity.
    • Validated UReKA functionality in purified protein and mammalian cell systems.

    Main Results:

    • Demonstrated UReKA's ability to detect PKA activity in vitro and in cells.
    • Showcased UReKA's capacity to monitor PKA signaling changes.
    • Confirmed UReKA's responsiveness to pharmacological and genetic modulations of PKA.

    Conclusions:

    • UReKA provides a novel method for visualizing cellular activity in opaque media using ultrasound.
    • This technology has broad potential for applications in cancer biology, developmental biology, and drug discovery.
    • UReKA represents a significant advancement in non-invasive kinase activity monitoring.