Laboratory for Synthetic Biology

Team Leader

Hiroki UedaM.D., Ph.D.

  • Location:Osaka / Osaka University BioSystems Building
  • E-mail:uedah-tky[at]umin.ac.jpPlease replace [at] with @.
  • Lab Website

Science of sleep – from molecules to organisms

Research Summary

A paradigm shift in biological research from reductionistic to synthetic approach has been undertaken in recent years. Even though the synthetic approach has been acknowledged as a central strategy of life science over the next few decades, basic technologies required in the synthetic approach, such like designing, controlling and manipulating biological molecules (DNAs, proteins and lipids) is remained to be established. The main tasks for laboratory for synthetic biology are to develop basic technologies for synthetic biology through close collaborative study within this center and to present pioneer studies in this new field.

In our laboratory, we are developing innovative techniques to answer biological questions through the interdisciplinary efforts of collaborating members from multiple backgrounds. We have achieved several breakthroughs. (Top: Synthesize) Toward understanding biological systems at the organism level, we facilitate genetics by using information technology and developing efficient methods to produce genetically modified mice. Next generation genetics does not require the crossing that conventional methods do and allows researchers to prepare multiple lines of genetically modified mice in parallel within just a couple of months (left). The triple-target CRISPR method can produce whole-body biallelic knockout (KO) mice at high-efficiently (>90%) in a single generation (middle). The ES mouse method is a highly efficient procedure for producing knock-in (KI) mice (right).

(left: Measure) The non-invasive respiration-based automated sleep phenotyping system – snappy sleep stager (SSS) – significantly simplifies and enhances the sleep phenotyping for which conventional methods required intricate and laborious work of a skilled researcher. (middle: See through) The tissue-clearing technique: CUBIC method innovates the way to observe deep inside of intact tissues by making them transparent. Example tissues shown above are brain, heart, liver, and kidney of mouse (from left to right). (right: Observe) The observation of transparent tissues is facilitated by a new technology of microscopy: light-sheet fluorescence microscopy (LSFM).

Research Theme

  • Design of chemicals that can control and create dynamic protein behaviour.
  • Design of molecular interactions in circadian clocks.
  • Development of high-throughput genome engineering system.
  • Gene synthesis for the design and construction of biological systems.
  • Design and measurement of protein network dynamics at a single-cell level

Main Publications List

  • Niwa Y, Kanda GN, Yamada RG, et al.
    Muscarinic acetylcholine receptors Chrm1 and Chrm3 are essential for REM sleep.
    Cell Reports (2018) doi: 10.1016/j.celrep.2018.07.082
  • Tainaka K, Murakami TC, Susaki EA, et al.
    Chemical Landscape for Tissue Clearing based on Hydrophilic Reagents.
    Cell Reports (2018) doi: 10.1016/j.celrep.2018.07.056
  • Ukai H, Kiyonari H, Ueda HR.
    Production of knock-in mice in a single generation from embryonic stem cells
    Nature Protocol 12. 2513-2530 (2017) doi: 10.1038/nprot.2017.110
  • Shinohara Y, Koyama YM, Ukai-Tadenuma M et al.
    Temperature-Sensitive Substrate and Product Binding Underlie Temperature-Compensated Phosphorylation in the Clock
    Molecular Cell 67. 783-798 (2017) doi: 10.1016/j.molcel.2017.08.009
  • Kubota SI, Takahashi K, et al.
    Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution
    Cell Reports 20. 236-250 (2017) doi: 10.1016/j.celrep.2017.06.010
  • Ode KL, Ukai H, Susaki EA, et al.
    Knockout-rescue embryonic stem cell-derived mouse reveals circadian-period control by quality and quantity of CRY1
    Molecular Cell 65. 176-190 (2017) doi: 10.1016/j.molcel.2016.11.022
  • Narumi R, Shimizu Y, et al.
    Mass spectrometry-based absolute quantification reveals rhythmic variation of mouse circadian clock proteins
    Proceedings National Academy of Sciences of the United States of America 133. E3461-E3467 (2016) doi: 10.1073/pnas.1603799113
  • Tatsuki F, Sunagawa GA, Shi S, et al.
    Involvement of Ca2+-Dependent Hyperpolarization in Sleep Duration in Mammals.
    Neuron 90(1). 70-85 (2016) doi: 10.1016/j.neuron.2016.02.032
  • Sunagawa GA.
    Mammalian Reverse Genetics without Crossing Reveals Nr3a as a Short-Sleeper Gene.
    Cell Reports 14(3). 662-677 (2016) doi: 10.1016/j.celrep.2015.12.052
  • Susaki EA, Tainaka K, Perrin D, et al.
    Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging.
    Nature Protocol 10(11). 1709-1727 (2015) doi: 10.1038/nprot.2015.085
  • Tainaka K, Kubota SI, Suyama TQ, et al.
    Whole-Body Imaging with Single-Cell Resolution by Tissue Decolorization.
    Cell 159(4). 911-924 (2014) doi: 10.1016/j.cell.2014.10.034
  • Susaki EA, Tainaka K, Perrin D, et al.
    Whole-Brain Imaging with Single-Cell Resolution Using Chemical Cocktails and Computational Analysis.
    Cell 157(3). 726-739 (2014) doi: 10.1016/j.cell.2014.03.042