University of California, Santa Cruz

This project will establish an Adaptive Optical (AO) Microscopy Center to develop enabling technologies and critical procedures to overcome long-standing barriers and vastly improve deep tissue biological imaging.  The approach is inspired by the highly successful use of AO in the W. M. Keck Telescopes, which allows astronomers to see much more clearly and deeply into space.  Members of the team have been at the forefront of these innovations in astronomy and are now working with biologists to apply the same principles to overcome similar barriers that inhibit deep-tissue light microscopy.  A critical aspect of the method involves direct wavefront sensing of biological “guide-stars,” coupled with the use of deformable mirrors, to adjust the optical system to correct for optical distortions that occur as light passes through the inhomogeneous specimen.  The team will create these guide-stars using genetically modified, fluorescently tagged proteins and develop the AO two-photon optical and sensing systems needed to take advantage of them, then test this technology in a mouse model system.  This project may enable dramatic improvements in imaging of the cellular universe, enabling biologists to examine crucial living processes deep within tissues and organs at a scale previously impossible, and lead to new biomedical interventions, such as stem cell therapies.