Super Resolution, Light Sheet, and Smart Microscopy:

Conventional microscopes are too slow, too phototoxic, or lack the spatial resolution to capture many complex cellular processes.  We are developing novel light sheet fluorescence microscopes for rapid three-dimensional imaging with minimal phototoxicity.  Current work incorporates three focus areas – applying adaptive optics to see clearly deep into living organisms, super-resolution single molecule and structured illumination microscopy to enhance spatial resolution, and novel computational algorithms to pull insight from vast quantities of dynamic three-dimensional data.  These advances will improve current observations of living systems and enable fundamentally new investigations in cell biology. Relevant publications: Shi et al. 2024, Shi et al. 2022, Legant et al. 2016, Chen et al. 2014

Chromatin Biology and Transcription:

Dozens of biological processes occur simultaneously within the nucleus of every cell. To understand how these processes are accomplished in the absence of partitioning membranes, we use single molecule tracking and super-resolution imaging to visualize single proteins as they diffuse through the dynamic mesh work of nucleic acid polymers. We combine these datasets with physical models and statistical analysis to understand how nuclear functions are regulated in normal and disease conditions.

Relevant publications: Rahman et al. 2024, Daugird et al. 2024, Ahn et al. 2021, Chen et al. 2014

Cell Migration and Mechanobiology:

Cell migration is critical both in development and in physiological and disease settings such as wound healing and cancer metastasis. Importantly, the movement of cells through three-dimensional space is driven by physical forces exerted by cells on the surrounding matrix.  We have developed quantitative tools to precisely map the location of these forces with subcellular precision.  We are applying these methods to build biophysical models of how cancer cells migrate away from the primary tumor and invade the surrounding tissue.  This work may provide novel insight into the physical mechanisms of tumor metastasis and suggest new strategies to treat cancer. Relevant publications: Hockenberry et al. 2024, Legant et al. 2013, Miller et al. 2010, Legant et al. 2010