Laboratory for Systems Biology
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circadian transcription circuits

Toward the realization of experimental systems biology at the organism level

With our members from different backgrounds, we would like to realize experimental systems biology at the organism level. To this end, we are using the mammalian circadian clock as a model system, and planning multi-scale research activities covering a series of length scales; molecule-to-cell, cell-to-tissue, and tissue-to-organism. On each layer, we would like to solve at least one fundamental question.
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What's New

2022/4/30 Our team leader Hiroki R. Ueda has been elected as a candidate board member of SRBR (Society for Research on Biological Rhythms).
2022/3/18 Using our analysis method ACCEL, which determines sleep-wake patterns based on the differential acceleration of arm movements, we estimated sleep-wake rhythms of approximately 100,000 people registered in the UKbiobank. As a result, we succeeded in classifying people's sleep patterns into 16 types according to their characteristics, and published the results in the journal PNAS. The report was also highlighted in Nature.
[PDF]   [Press release]   [Nature]  
2022/2/9 A review article introducing the next generation of genetics that our laboratory has been working on in the context of the biological clock was published in the Journal of Biological Rhythms, an international research journal on biological time.
2022/2/5 We published a paper discussing the formation mechanism of spindle waves (spindles), which characteristically appear in EEG during sleep, based on a mathematical model of neuronal firing patterns.
[PDF]   [Press release]  
2022/1/21 Our paper on ACCEL for accurate classification of sleep–wake states using arm acceleration was just published in iScience. ACCEL achieved achieved an accurate sleep–wake classification with a high sensitivity (>90%) and specificity (>80%).
2021/6/22 We have developed "CUBIC-Cloud," an infrastructure technology that promotes data-driven neuroscience by storing and analyzing vast amounts of 3D data on the cloud, including gene function and network structure of the entire brain.
[Press release]   [CUBIC-Cloud]  
2021/1/11 Our theoretical paper "A design principle for posttranslational chaoticoscillators" was published. It may underlie spontaneous activity of cells. It completes our biochemical trilogy over 8yrs (oscillator in 2012, Turing in 2017, chaos).
2020/10/2 Phosphorylation Hypothesis of Sleep Review Paper Published.
2020/10/1 As part of the JST’s Strategic Basic Research Programs, the "Biological timing" project was launched under the supervision of Team Leader Ueda as an ERATO project.
[Press release]  
2020/9/4 Nature Reviews Neuroscience published the viewpoint by 18 experts to overview the past and future of neuroscience. I introduced organism-level systems biology based on whole-organ cell profiling & next-generation genetics, and future human systems biology.
2020/5/11 Our review on whole-brain profiling of cells and circuits was published on Neuron.
2020/5/1 Our new paper on CUBIC-HistoVIsion, a versatile whole-organ/body tissue staining and imaging methods are now published on Nature Communciation.
2020/1/2 Our review "tissue clearing and its applications" has been published in Nature Reviews Neuroscience.
2019/11/20 Our new paper on whole-organ profiling of cells was just published in Nature protocols. We also developed "MOVIE" method to speed up the imaging by LSFM.
2019/4/17 “A period without PER," a review article discussing the design principles of biological time from the viewpoint of phosphorylation control, was published.
2019/4/11 A review article discussing new approaches to human genetics based on next-generation mouse genetics was published.
2018/12/14 Our tissue clearing (TC) reagents CUBICs were featured in Nature by Eisenstein.
2018/10/01 Ms. Harada was awarded a poster prize in RIKEN summer school 2018
2018/9/19 Mathematical model analysis of neurons during sleep predicted that leaky potassium channels are involved in sleep regulation, and confirmed that sleep duration is reduced in knockout mice.
2018/08/29 Publishing research results concerning "Two genes that regulate how much we dream"
The preview by Dr. Hayashi and Kashiwagi of International Institute for Integrative Sleep Medicine (WPI-IIIS) is here.
2018/08/21 Our paper on chemical principle on tissue clearing was published.
2018/03/26 Dr. Shinohara was awarded an encouraging prize in the 18th annual meeting of the protein science society of Japan
2018/03/6 Using a new tissue transparency technique named CUBIC-X, we have completed a map of all cells in the whole mouse brain (CUBIC-Altas).
[Press release]  
2017/12/4 A review article focusing on the relationship between calcium signaling-dependent hyperpolarization pathways and sleep regulation and psychiatric disorders was published.
2017/11/16 New paper with Hideki Ukai (RIKEN QBiC) and Hiroshi Kiyonari (RIKEN CLST) on "production of knock-in mice in a single generation from ES cells" was published in Nature Protocols. Next-generation mammalian genetics w/o crossing has been published.
2017/10/30 Dr. Shinohara was awarded an outstanding poster prize at the 24th annual meeting of Japanese Society for Chronobiology
2017/09/07 Our new paper on molecular mechanisms for temperature compensation of circadian clocks is published in Mol Cell
2017/08/30 A new article on CUBIC pathology was out. We applied tissue-clearing and imaging to clinical pathology.
2017/07/05 Our new paper with Miyazono lab on whole-body clearing and imaging of cancer metastasis is just out.
2017/06/05 A review article on "Next Generation Mouse Genetics," a fast and parallel approach to mouse genetics, was published summarizing the concept and the latest technological developments.
2017/05/31 A review article on calcium signaling-dependent regulation of sleep, focusing on the time constants under which the relevant group of factors function, and discussing the relationship between ion channels and phosphatases, was published.
2017/04/25 We modeled reversible phosphorylation and reported that autonomous spatial pattern formation can occur.
[PDF]   [Press release]  
2017/04/21 A review article discussing the involvement of calcium-dependent hyperpolarization of neuronal membrane potentials and mammalian sleep time regulation was published.
2017/03/22 Ms. Shoko Harada received a student presentation prize at 90th annual meeting of the Japanese pharmacological society
2016/12/27 Our ms "KO-Rescue ES Mouse Reveals Circadian-Period Control by Quality and Quantity of CRY1" came out in Mol Cell. Surprisingly, we could double circadian period of mammalian cells from 19 h to 38 h with the change of only two amino acids in CRY1 protein.
2016/06/17 Mass spectrometry-based absolute quantification of mouse circadian clock proteins is now online.
2016/03/23 We know calcium is good for our bones, but it might also be the key to a good night sleep. Our research group have unveiled a new theory for how sleep works. Published in the journal Neuron, the work shows how slow-wave sleep depends on the activity of calcium inside neurons.
2016/01/23 Cell Chemical Biology has launched with our review on whole-body cell analysis for organism-level systems biology.
2016/01/12 Publishing research results concerning“Snappy Sleep Stager system identifies gene related to shorter sleep”
[PDF]   [Supplemental 1] [Supplemental 2] [Supplemental 3] [Supplemental 4]
2015/10/10 The advanced CUBIC protocols for clearing/imaging/informatics are now on line.  [PDF]   [Supplement movie (nature protocol)]
2015/09/29 Dr.Hiroki R. Ueda was awarded 15th (2015) Yamazaki-Teiichi Prize.
2015/02/24 Dr.Hiroki R. Ueda was elected as Young Academy (1st term), Chair of SCIENCE COUNCIL OF JAPAN.
2014/12/30 Dr. Hiroki R. Ueda talked on his hopes in 2015 on Nature.
2014/12/30 Tissue-clearing techniques such as CUBIC were selected as Methods of the year 2014 ("Methods to watch") by Nature Method.
The interview of Dr. Hiroki R. Ueda was here.
The article on Methods of the year 2014 was here.
2014/12/17 “Transparent mouse” by CUBIC technology from our lab (published on Cell, November 6th) was selected as “Images of the year 2014”.
2014/11/7 Publishing research results concerning“Whole-body imaging with single-cell resolution by tissue-decolorization”
2014/09/16 Publishing research results concerning“A Mammalian Circadian Clock Model Incorporating Daytime Expression Elements”
2014/08/21 ALS Ice Bucket Challenge
2014/08/8 “Tokyo Translational Therapeutics Meeting: Homeodynamics in Clocks, Sleep and Metabolism” will be held on September 24, 2014.”
2014/04/18 Publishing research results concerning“Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis”
2014/03/20 Publishing research results concerning“Non-Enzymatic DNA Cleavage Reaction Induced by 5-Ethynyluracil in Methylamine Aqueous Solution and Application to DNA Concatenation”
2013/07/04 Publishing research results concerning a robust and reproducible approach for surveying the mRNA content of individual cells.
2012/10/19 Publishing research results concerning a generic mathematical model for post-translational biochemical oscillations.
2012/08/28 Publishing research results concerning a convenient, non-invasive method for calculating body time in humans
2011/08/12 Publishing research results concerning comprehensive gene expression data of the adult mouse brain
2011/08/05 Publishing research results concerning perturbation analyses of intermolecular interactions
2011/05/10 Project Leader Hiroki R. Ueda has recently published a review in Nature Reviews Genetics.
2011/03/10 Rikuhiro Yamada (Special Postdoctoral Researcher) and Maki Ukai-Tadenuma (Technical Staff) are awarded RIKEN Research and Technology Incentive Awards respectively for their achievement in elucidation of a design principle in the circadian transcriptional network.
2011/02/04 Project Leader Hiroki R. Ueda wins JSPS Prize
2009/11/10 Team Leader Wins The 23rd Japan IBM Science Prize.
2009/10/28 Dr. Yoichi Minami Wins poster awards for the 16th Annual Meeting of Japanese Society for Chronobiology.
2009/09/01 Announcement of research results concerning “Central gears of the mammalian circadian clock exposed ”
2008/10/25 Announcement of research results concerning “PEPCA”
2008/09/30 Announcement of research results concerning “Principles proven: Transcriptional logic of the mammalian biological clock”
2008/09/24 Announcement of research results concerning “New-found control principles for biological clocks”
2008/06/25 The 17th CDB Meeting “Towards Synthesis of Cells”
2008/04/30 Notification of FPR Recruitment
2008/03/26 Announcement of research results concerning “spring hormone”
2007/12/11 Our laboratory is introduced by the TV program of NHK in 11th December.
2007/11/07 Team Leader Wins Chronobiology Prize
2007/10/21 Announcement of research results concerning ”singularity behavior”
Center for Developmental Biology Laboratory for Systems Biology 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan Tel: 078-306-3195 / Fax: 078-306-3194 E-mail: Osaka University Mammalian Promoter Enhancer Database
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