A microscope design, reported this week in Nature Methods, uses a microscopic mirror placed next to a single human tumor cell to reflect the illumination light into the cell from the side and visualize the dynamics of single transcription factors binding to the genome. By turning microscope illumination on its side, this microscope provides a clearer view of the inner workings of single cells.

Sunney Xie and colleagues constructed the microscope by attaching a tipless mirrored cantilever normally used for atomic force microscopy to a standard fluorescence microscope. This allowed them to reflect a sheet of light through the side of the cell and into the nucleus, where they were able to observe glucocorticoid and estrogen receptors binding to the genome and to other transcription factors that regulate gene expression.

By turning microscope illumination on its side, this microscope provides a clearer view of the inner workings of single cells, particularly in the nucleus where genes are turned on and off by the binding of single proteins to the genome.