Hitoshi Okamura

After training as a pediatrician at the Children's Medical Center of the Okayama National Hospital (1979-1981), he worked on neuroanatomy at the Kyoto Prefectural University of Medicine (1981-1995).

Okamura began his study of circadian rhythms in 1982 with the peptide work in the suprachiasmatic nucleus (SCN) using the technique of histochemistry in Yasuhiko Ibata's laboratory in the Kyoto Prefectural University of Medicine.

[9] Okamura's team discovered that mammalian PER proteins made in the cytoplasm translocate into the nucleus of the cell and form a complex composed of CRY1, CRY2, PER1, PER2, PER3, and TIM.

His team discovered that in mice, both types of cells showed temporal expression of profiles of all known clock genes,[13] the phases of various mRNA rhythms, the delay between maximum mRNA levels and appearance of nuclear PER1 and PER2 protein, the inability to produce circadian oscillations in the absence of functional Cry genes, and the control of period length by CRY proteins.

Okamura collaborated with Gijsbertus T.J. van der Horst and found that both peripheral and central clocks are stopped in Cry deficient mice.

This work was achieved by combining the SCN slice-culture technique, transgenic mice carrying the luciferase gene driven by the Per1 promoter (Per1-luc), and the cryogenic high resolution CCD camera.

Tetrodotoxin, which blocks action potentials, not only desynchronizes the cell population, but also suppresses the level of clock gene expression, demonstrating that neuronal networks play a dominant role in oscillation of rhythms in the SCN.

Okamura discovered that flashing NMDA, which is analogous to light stimuli, instantly altered the phase of the core clock oscillation of a slice of SCN.

They performed DNA arrays and Northern blots to characterize the molecular differences in M-phase entry and found that cyclin B1 and cdc2 were positively correlated.

[24][25] Now, Okamura continues investigations of biological clocks, fascinated with the integrational characteristics of "time" in a vertical arrangement, providing a bridge between single genes and the living organism as a whole.