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Near-infrared light (NIR) is favorable over shorter wavelengths for use in mammalian tissues due to its low absorbance by hemoglobin, melanin, and water, reduced tissue autofluorescence, and lower light scattering induced by lipids and fat (so called “NIR tissue transparency window”). We develop new NIR fluorescent proteins, biosensors and optogenetic tools on the base of bacterial phytochromes for non-invasive in vivo imaging and optical manipulation of cellular processes.