Project Summary:
Our understanding of fundamental cell biological processes is both driven by and limited by our ability to
visualize the organization of structures and molecules within cells and tissues. The development of super-
resolution fluorescence imaging methods that circumvent the resolution limits of conventional light microscopy,
achieving lateral resolution of <100 nm, have transformed cell biological research. Access to super-resolution
fluorescence imaging technology is now essential for scientists wishing to push the frontiers of cell biological
research. This proposal requests funds to replace Stanford University’s Cell Sciences Imaging Facility’s
11-year-old, obsolete OMX structured illumination, super resolution microscope with an Elyra 7 lattice-
SIM2 super-resolution imaging system (Zeiss, Inc.). This state-of-the-art, super-resolution microscope can
achieve both lateral and axial resolution at greater than twice the diffraction limit of conventional light
microscopy and is capable of multichannel super-resolution far beyond the cover glass. The fast-imaging
capability of Elyra 7 lattice SIM2 is also designed to overcome speed limitations enabling 3D live-cell super
resolution imaging. This advanced imaging system will be a shared resource, located in a well-established,
multi-user microscopy facility at Stanford: The Cell Sciences Imaging Facility. The requested Elyra 7 lattice
SIM2 imaging system will support research projects from eight researchers, all of which are NIH funded. These
projects investigate a wide range of topics, including: meiotic chromosome segregation and genetic
recombination (Villeneuve); signaling and vesicular transport in primary cilia (Jackson), molecular mechanisms
of myelin wrapping in neurons (Zuchero); maintenance and regulation of genomic stability (Cimprich and
Chistol), spatial organization of cell-cell junctions (Dunn); the role of the extra cellular matrix in cell invasion
and migration (Chaudhuri); and the role human calcineurin signaling pathways in cellular processes (Cyert).
These studies investigate critical functional and structural questions regarding fundamental cell biological
processes and cover NIH research areas with implications for diverse aspects of human health and disease,
including cancer, birth defects, obesity, immunity, as well as neurodegenerative disease. All these projects
require multi-channel super-resolution imaging and simultaneous multi-channel fast imaging; this combination
of capabilities is most effectively provided by the requested Elyra 7 lattice SIM2 instrument.