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Institute for Quantum Life Science

Biological Clock Team

Update：2025年10月9日更新
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The Biological Clock: A Gateway to Understanding Life as Matter

​Circadian clock is a basic cellular function from humans to
bacteria.細菌や様々な動植物 Although transcriptional feedback loops have been used to explain its oscillation mechanism, there is accumulating evidence showing an existenceof unidentified oscillator independent of the loops.

Recently, we found Na⁺/Ca²⁺ exchanger (NCX) as a universally conserved clock factor in all kingdoms of life. The finding suggests circadian Ca²⁺ oscillation, “calcium clock”, is an ancestral clock upstream of the transcriptional loops. Understanding the calcium clock could lead to treatments for sleep and mood disorders, and offer insights into the origin of life. We are exploring this frontier using advanced quantum and cellular biology technologies.)                                                                                                                                                          『Clock of Life』by Nazme Nagasawa (Space-Time Inc.)

​黒いジャケットを着た男性 Team Leader, Naohiro Kon

Selected Publications

  1. Ryosuke Enoki, Naohiro Kon, Kimiko Shimizu, Kenta Kobayashi, Yoshifumi Yamaguchi, Tomomi Nemoto. Cold-induced Suspension and Resetting of Ca2+ and Transcriptional Rhythms in the Suprachiasmatic Nucleus Neurons.
    iScience 26, 108390 (2023).

  2. Kosaku Masuda, Naohiro Kon, Kosuke Iizuka, Yoshitaka Fukada, Takeshi Sakurai, Arisa Hirano. Singularity response reveals entrainment properties in mammalian circadian clock.
    Nature Communications 14, 2819 (2023).

  3. Daisuke Ono, Huan Wang, Chi Jung Hung, Hsin-Tzu Wang, Naohiro Kon, Akihiro Yamanaka, Yulong Li, Takashi Sugiyama. Network-driven intracellular cAMP coordinates circadian rhythm in the suprachiasmatic nucleus.
    Science Advances 9, eabq7032 (2023).

  4. Hsin-tzu Wang, Shiori Miyairi, Miho Kitamura, Kosuke Iizuka, Yoshimasa Asano, Takashi Yoshimura, Naohiro Kon*. Real time monitoring of cold Ca2+ dependent transcription and its modulation by NCX inhibitors.
    Scientific Reports 12, 17325 (2022). *Corresponding author

  5. Naohiro Kon, Hsin-Tzu Wang, Yoshiaki S Kato, Kyouhei Uemoto, Naohiro Kawamoto, Koji Kawasaki, Ryosuke Enoki, Gen Kurosawa, Tatsuto Nakane, Yasunori Sugiyama, Hideaki Tagashira, Motomu Endo, Hideo Iwasaki, Takahiro Iwamoto, Kazuhiko Kume, Yoshitaka Fukada. Na+/Ca2+ exchanger mediates cold Ca2+ signaling conserved for temperature-compensated circadian rhythms. 
    Science Advances 7, 8132 (2021).

  6. Naohiro Kon*, Michiko Murakoshi, Aya Isobe, Katsuji Kagechika, Naoki Miyoshi, Takahiro Nagayama. DS16570511 is a small-molecule inhibitor of the mitochondrial calcium uniporter.
    Cell Death Discovery, 3, 17045 (2017). *Corresponding author

  7. Naohiro Kon*, Atsushi Satoh, Naoki Miyoshi. A small-molecule DS44170716 inhibits Ca2+-induced mitochondrial permeability transition.
    Scientific Reports, 7, 3864 (2017). *Corresponding author

  8. Naohiro Kon, Yasunori Sugiyama, Hikari Yoshitane, Isamu Kameshita, Yoshitaka Fukada. Cell-based inhibitor screening identifies multiple protein kinases important for circadian clock oscillations. 
    Communicative and Integrative Biology, 8, e982405 (2015).

  9. Naohiro Kon, Tomoko Yoshikawa, Sato Honma, Yoko Yamagata, Hikari Yoshitane, Kimiko Shimizu, Yasunori Sugiyama, Chihiro Hara, Isamu Kameshita, Ken-ichi Honma, Yoshitaka Fukada. CaMKII is essential for the cellular clock and coupling between morning and evening behavioral rhythms.
    Genes and Development, 28, 1101-1110 (2014).

  10. Naohiro Kon, Tsuyoshi Hirota, Takeshi Kawamoto, Yukio Kato, Tadashi Tsubota, Yoshitaka Fukada. Activation of TGF-beta/activin signalling resets the circadian clock through rapid induction of Dec1 transcripts.
    Nature Cell Biology, 10, 1463-1469 (2008). 

 

Institute for Quantum Life Science