Next-generation imaging to interrogate biological systems across time and space - PROJECT SUMMARY Our research develops new microscopes that transform our ability to observe biological specimens and applies these microscopes to solve fundamental problems in cell biology. Light microscopes are a cornerstone of biological research. Recent optical, technological, and computational advances have greatly increased the resolution and speed at which we can observe living samples. However, in many cases, the ability of instruments to generate data has greatly outpaced our ability to analyze, interpret, and act upon this information. This is especially true for microscopes that can image across spatiotemporal scales, observing single molecules to whole organisms. Over the next five years, we will combine new optical principles together with computer vision to build autonomous microscopes that can not only capture data more rapidly, but also more efficiently. These instruments will be able to process data in real time and use this information to navigate through and interact with biological specimens based on experimental goals. In parallel projects, we will leverage recent advances in light sheet and single molecule imaging to study a key biological question, namely, how thousands of unique proteins navigate within and accomplish distinct biological functions in the cell nucleus. The overall vision for this research is to develop new microscope capabilities that enable new studies of biological processes and to test key hypotheses about how functional environments are organized in the nucleus of individual cells.