Rhobo6: A Breakthrough In Live Imaging Of The ECM

Physicist Antonio Fiore, previously focused on the physics of optical instrument design, transitioned to biological applications at Janelia three years ago.  Seeking a different impact, he joined the Pedram Lab to develop tools for unexplored areas of biology, maintaining his connection to light microscopy.  This shift has proven fruitful in developing Rhobo6, a novel light microscopy probe.

Rhobo6 offers an unprecedented view of the extracellular matrix (ECM), the intricate network of molecules filling the spaces between cells.  The ECM provides structural support, influences tissue mechanics, and guides cell movement.  Understanding its role is crucial for comprehending tissue biology, akin to understanding a city by examining its infrastructure.

Rhobo6 overcomes previous limitations in ECM research.  Unlike existing methods, it remains extracellular, reversibly binding to glycans, and has abundant ECM biomolecules.  This binding enhances its fluorescence, allowing visualization of ECM structure in live tissues and animals without disrupting native processes.

Beyond fundamental research, Rhobo6 holds promise for studying ECM-related diseases and diagnostic imaging.  Collaborating with the Weaver lab at UCSF, the team used Rhobo6 in live animal surgical imaging of breast tumors, revealing significant differences in the ECM surrounding cancerous versus healthy tissue.

Janelia’s collaborative environment was crucial for Rhobo6’s development.  Contributions from multiple labs, including Wang, Lavis, Rubin, Shroff, and Ahrens, facilitated testing across various model organisms.  Scaling up Rhobo6 synthesis by Guoqiang Yu ensures its availability to the wider scientific community.  The researchers anticipate Rhobo6 will enable the capture of stunning ECM images and facilitate answering previously inaccessible biological questions.

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