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Research

BDR researchers coming from diverse research fields are working together to achieve higher goals.

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About Us

About Us

Exploring the scientific foundations of life through interdisciplinary approaches to address society’s problems.

Photo of Team leder, Hiroki Ueda

Team Leader
Hiroki Ueda M.D., Ph.D.

Laboratory for Synthetic Biology

LocationOsaka / Osaka University BioSystems Building

E-mailuedah-tky[at]umin.ac.jp

Please replace [at] with @.

Science of sleep – from molecules to organisms

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

Selected Publications

Susaki EA, Shimizu C, Kuno A, et al.
Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues.
Nature Communications 11, 1982 Tue Dec 01 00:00:00 JST 2020 doi: 10.1038/s41467-020-15906-5

Funano SI, Tone D, Ukai H, et al.
Rapid and easy-to-use ES cell manipulation device with a small groove near culturing wells.
BMC research notes 13(1), 453 Mon Oct 05 00:00:00 JST 2020 doi: 10.1186/s13104-020-05294-w

Ota N, Kanda GN, Moriguchi H, et al.
A Microfluidic Platform Based on Robust Gas and Liquid Exchange for Long-term Culturing of Explanted Tissues.
Analytical sciences : the international journal of the Japan Society for Analytical Chemistry 35(10), 1141-1147 Sun Dec 01 00:00:00 JST 2019 doi: 10.2116/analsci.19P099

Matsumoto K, Mitani TT, Horiguchi SA, et al.
Advanced CUBIC tissue clearing for whole-organ cell profiling.
Nature Protocols 14, 3506-3537 Sun Dec 01 00:00:00 JST 2019 doi: 10.1038/s41596-019-0240-9

Niwa Y, Kanda GN, Yamada RG, et al.
Muscarinic Acetylcholine Receptors Chrm1 and Chrm3 Are Essential for REM Sleep.
Cell reports 24(9), 2231-2247 Tue Aug 28 00:00:00 JST 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 24(8), 2196-2210 Tue Aug 21 00:00:00 JST 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 Fri Dec 01 00:00:00 JST 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 Wed Nov 01 00:00:00 JST 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 Sun Oct 01 00:00:00 JST 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 Fri Sep 01 00:00:00 JST 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 Thu Dec 01 00:00:00 JST 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 Tue Nov 01 00:00:00 JST 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 Sat Oct 01 00:00:00 JST 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 Tue Dec 01 00:00:00 JST 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 Mon Dec 01 00:00:00 JST 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 Sat Nov 01 00:00:00 JST 2014 doi: 10.1016/j.cell.2014.03.042

Members

Hiroki Ueda

Team Leader

Rikuhiro Yamada

Senior Scientist

Hideki Ukai

Senior Scientist

Yohei Koyama

Research Scientist

Katsuhiko Matsumoto

Research Scientist

Genki Kanda

Special Postdoctoral Researcher

Hiroko Yukinaga

Special Postdoctoral Researcher

Arthur Robert Millius

Foreign Postdoctoral Researcher

Yuta Shinohara

Postdoctoral Researcher

Daisuke Tone

Postdoctoral Researcher

Maki Ukai

Technical Staff I

Hiroshi Fujishima

Technical Staff I

Chika Shimizu

Technical Staff I

Junko Garcon

Technical Staff I

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