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In my Janelia lab we conceive, develop, and implement new microscopy techniques for biology. This exploration covers both optical and electron microscopy innovations. On the optical side we are focusing on applications of a super-resolution microscope called iPALM that can resolve locations to ~10 nm of up to millions of specially fluorescent labeled proteins. These positions can be rendered in three dimensions to give architectural and structural insight to protein organization in cells. In the case of electrons, commercial scanning electron microscopes are optimized for high throughput and 3D capability that is required for neural circuit reconstruction. Two approaches have been implemented. Scanning transmission electron microscope images of thousands of thin sections are acquired directly and optionally with tilt to reassemble neural wiring diagrams. A complementary approach is to alternate with an electron image and an ion beam polish cycle to acquire such three-dimensional pictures.