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Division of Biophotonics

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Quantitative analysis and elucidation of underlying mechanism of physiological functions by innovative bioimaging utilizing cutting-edge technologies of photonics

By utilizing such advanced optical technologies as near-infrared ultrashort light pulse lasers, adaptive optics, nanomaterials, we have advanced innovative imaging methods based on nonlinear optical processes. We also have driven applications of these methods to the life- and medical sciences. By facilitating our original world-leading ultra-deep, super-resolution, and ultra-high-speed imaging methods with a combination of genetic engineering and nanoparticles, we aim to realize less-invasive "in vivo" observation and manipulation for living organisms and tissues to establish a quantitative visualization analysis method for physiological functions. Through visualization analysis of neural circuits, activities, and exocytosis, we will elucidate the mechanism of the emergence of neural functions, including biological rhythms, and their molecular basis.
 Recently, we successfully developed multiphoton microscopy to realize cross-sectional fluorescence imaging at the deepest layer in the world. As a result, we visualized neurons in the dentate gyrus of the hippocampus at 1.6 mm depth from the brain surface under anesthesia. Noticeably, we here observed the activity of hippocampal CA1 neurons at a video rate (Fig. A). On the other hand, in order to enable ultra-micromorphology for molecular dynamics in living cells, we are also pursuing super-resolution microscopy by utilizing new laser technology, including vector beams (Fig. B). Utilizing long-term imaging technology for living cell functions, we are promoting research on the generation and the function of ultradian and circadian rhythms (Fig. C). In local neural circuits, endocrine or exocrine glands, and model animals and plants, high-speed three-dimensional "in vivo" imaging is unlocking the principles underlying the emergence of physiological functions and is also exploring the molecular basis of the pathogenic mechanism of diseases such as cancer and diabetes (Fig. D).
  In this research department, these methods collaborate widely with various laboratories covering not only life sciences but also applied physics, chemistry, medicine, and pharmaceutical sciences. Now, we are weaving a new tapestry of interdisciplinary areas applicable to medical science by pursuing cell physiology of neural and secretion activities and by advancing imaging methodology, which can visualize physiological phenomena in vivo "as they are." We are looking for graduate students or young researchers who can share our passion for pioneering new academic fields. We are looking for graduate students or young researchers who can share our passion for pioneering new academic fields.

nemoto2020.jpgFig. (A) “in vivo” video-rate imaging of neural activities of mouse CA1 neurons. (B) Two-photon nanoscopy –breaking the limit of the spatial resolution < 100 nm. (C) Visualizing neuronal circuits controlling circadian and ultradian rhythms. (D) Fast “in vivo” imaging of molecular orientation using second harmonic generation.

Typical paper information

*M. Inoue et al., Cell 177,1346-1360.e24 (2019).
*H. Ishii et al., Biomed. Opt. Express, 10, 3104-3113 (2019).
*Y. Wu et al., Proc. Natl. Acad. Sci. USA, 115, E9469-E9478 (2018).
*A. Goto et al., Front. Phys., 7, 56-1–56-9 (2019).
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