Project Grant R35GM165678

The National Institute of General Medical Sciences awarded the University of Southern California $456,500 on September 1, 2026, through the Biomedical Research and Research Training program (CFDA 93.859) to decode and remotely reprogram cellular signaling networks. Work will extend through August 31, 2031, performed in Los Angeles, California.

The recipient will develop multiplexed single-fluorophore biosensors to simultaneously visualize multiple signaling activities—including tyrosine kinase activity (SRC and FYN) and histone modifications (H3K4ME3)—at single-cell resolution in live systems, enabling real-time imaging of signal coordination in cell-fate determination. In parallel, the research will advance ultrasound-controllable sonogenetic circuits for multiplexed, reversible gene silencing, permitting spatiotemporally precise and noninvasive perturbation of signaling nodes within deep tissues. The program employs a high-throughput mammalian evolution pipeline to generate ultrasensitive, spectrally diverse biosensors over the five-year performance period. This dual platform addresses the limitation of existing tools, which can monitor only one or two signals and lack capacity for remote, controlled, reversible network perturbation. Unlike chemical inducers or optogenetic tools, ultrasound-based control offers deep-tissue accessibility, supporting both research and therapeutic applications.