Programmable genetic sensors for deep-tissue imaging

Innovations in protein engineering have revolutionized fluorescent proteins, transforming them into versatile, genetically encoded biosensors that can be easily adapted to monitor a wide range of user-defined biological events with molecular specificity. However, many critical biological processes, such as cancer metastasis, brain function, and the efficacy of cell- and gene-based therapies, still require study within the intact physiological context of experimental animal models, as opposed to cultured cells. This creates a fundamental scientific impasse: sensors based on fluorescent proteins are ineffective at depth, while gold-standard clinical modalities like MRI excel at deep-tissue penetration but lack sensitivity to molecular-level events. To break this impasse, my research explores the convergence of synthetic biology and advanced biomedical imaging. In this talk, I will discuss our recent efforts in this domain, focusing on the development of modular aquaporin-based protease-activatable probes for enhanced reporting (MAPPER) — an all-genetic platform to create modular and easily programmable sensors for MRI. By harnessing the clinical capabilities of MRI for noninvasive, molecular-level reporting within deep, optically opaque tissues, MAPPER provides the crucial link between cellular events and whole-organism physiology.