Nanobiology Laboratories

Laboratory of Single Molecule Biology

Prof. UEDA Masahiro Prof. UEDA Masahiro


Single-molecule imaging, Mathematical modeling, Dictyostelium discoideum, Signal transduction, Fluctuation

Understanding molecular stochastic computation in intracellular signaling systems

We are interested in cellular functions such as intracellular signaling and cellular motility. In particular, we focus on questions such as “how do these cellular properties arise from reaction networks composed of stochastically-operating biomolecules?” and “what are the mechanisms that enable the intracellular signaling system to be robust to molecular noise, and sometimes utilize that noise to express its functions?”. Our research group develops and utilizes cutting-edge measurement techniques such as single-molecule imaging and mathematical modeling. We aim to understand the design principles underlying the remarkable signal processing capability of living cells with single-molecule resolution.

(Left) Chemotaxis of the cellular slime mold Dictyostelium discoideum. (Middle) TIRFM for single-molecule imaging in living cells. (Right) Single-molecules of PTEN.


UEDA Masahiro (Professor) masahiroueda[at]
TACHIBANAKI Shuji (Associate Professor) banaki[at]
MATSUOKA Satomi (Assistant Professor) matsuoka[at]

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What is your hot research topic?
We are interested in cellular functions, such as intracellular information processing and cell motility. In particular, we focus on questions such as "how do these cellular properties spontaneously arise from biomolecules and reaction networks composed of biomolecules?", and "what are the mechanisms that enable the information processing system to be robust to intrinsic noise, and sometimes utilize that noise to express its functions while also receiving severe stochastic fluctuations from the external environment?" As a typical example of such a stochastic calculation process, we focus on concentration gradient sensing and the taxis of Dictyostelium discoideum. Our research group utilizes cutting-edge measurement techniques, such as single-molecule imaging; theoretical approaches, including mathematical modeling with the aid of high-performance computers; and in vitro reconstitutions of minimal molecular reaction systems. We aim to understand the design principles underlying the remarkable information processing capability of cells.
What is your breakthrough or research progress in the last 5 years?
To understand how molecules act in cells, it would be ideal to be able to track individual molecules, including where in the cell they are located and what modifications they undergo when conditions in the cell change. However, this ideal situation is difficult to actualize with existing technologies, and a huge amount of time would be required to perform such sensitive monitoring. Recently, we developed a system that can overcome these difficulties by automatically searching for, focusing on, imaging, and tracking single molecules within living cells. Using this system, we were able to analyze hundreds of thousands of single molecules in hundreds of cells in a short period, thereby providing reliable data about the status and dynamics of molecules of interest.
What kind of background do your lab members have?
Biology, engineering, physics, chemistry, mathematics, information science, and so on.
Do you collaborate with other institutions and universities?
We have been collaborating with the RIKEN Center for Life Sciences since 2011. Overseas, we have collaborated with Peter N. Devreotes, Miho Iijima (Johns Hopkins University), Tian Jin (NIH), Peter van Haastert (University of Groningen) and others.
The research includes imaging analysis of intracellular signal transduction systems and development of single-molecule imaging methods.
What kind of careers do your Lab's alumni go on to?
Academia researchers, pharmaceutical company researchers, venture company entrepreneurs, and others.
How do you develop your research?
Since our research is extremely basic, it is difficult to foresee. Hopefully, we would like to be able to understand cellular function mechanisms as the spatiotemporal dynamics of the interaction of individual biomolecules.

Research Highlights

Publications (Research Articles, Reviews, Books)


Daisuke Yoshioka, Seiya Fukushima, Hiroyasu Koteishi, Daichi Okuno, Toru Ide, Satomi Matsuoka, Masahiro Ueda

Single-molecule imaging of PI(4,5)P 2 and PTEN in vitro reveals a positive feedback mechanism for PTEN membrane binding

Communications Biology 3(1):92  2020 PMID:32111929 DOI:10.1038/s42003-020-0818-3

Haruka Hiraoka, Tadashi Nakano, Satoshi Kuwana, Masashi Fukuzawa, Yasuhiro Hirano, Masahiro Ueda, Tokuko Haraguchi, Yasushi Hiraoka

Intracellular ATP levels influence cell fates in Dictyostelium discoideum differentiation

Genes Cells 25(5):312-326  2020 PMID:32125743 DOI:10.1111/gtc.12763

Shinichi Yamazaki, Hidenori Hashimura, Yusuke V. Morimoto, Yukihiro Miyanaga, Satomi Matsuoka, Yoichiro Kamimura and Masahiro Ueda

Talin B regulates collective cell migration via PI3K signaling in Dictyostelium discoideum mounds

Biochem. Biophys. Res. Commun. 525(2):372-377  2020 PMID:32098673 DOI:10.1016/j.bbrc.2020.02.060

Michio Hiroshima, Masato Yasui, and Masahiro Ueda

Large scale single-molecule imaging aided by artificial intelligence

Microscopy 69(2):69-78  2020 PMID:32090254 DOI:10.1093/jmicro/dfz116


Asano T., Kawamura S., Tachibanaki, S.

Transducin activates cGMP phosphodiesterase by trapping inhibitory γ subunit freed reversibly from the catalytic subunit in solution.

Sci Rep 5.40625  2019 PMID:31076603 DOI:10.1038/s41598-019-43675-9

Fukushima, S., Matsuoka, S., and Ueda, M.

Excitable dynamics of Ras triggers spontaneous symmetry breaking of PIP3 signaling in motile cells

J. Cell Sci. 132:jcs.224121  2019 PMID:30745337 DOI:10.1242/jcs.224121

Hashimura, H., Morimoto, Y. V., Yasui, M. and Ueda, M.

Collective cell migration of Dictyostelium without cAMP oscillations at multicellular stages

Communications Biology 2:34  2019 PMID:30701199 DOI:10.1038/s42003-018-0273-6


Miyanaga, Y., Kamimura, Y., Kuwayama, H., Devreotes, P.N., and Ueda, M.

Chemoattractant receptors activate, recruit and capture G proteins for wide range chemotaxis

Biochem. Biophys. Res. Commun. 507:304-310  2018 PMID:30454895 DOI:10.1016/j.bbrc.2018.11.029

Tanabe, Y., Kamimura, Y., and Ueda, M.

Parallel signaling pathways regulate excitable dynamics differently to mediate pseudopod formation during eukaryotic chemotaxis

J. Cell Sci. 131:jcs214775  2018 PMID:30404836 DOI:10.1242/jcs.214775

Miyagawa, T., Koteishi, H., Kamimura, Y., Miyanaga, Y., Takeshita, K., Nakagawa, A., and Ueda, M.

Structural basis of Gip1 for cytosolic sequestration of G-protein in wide range chemotaxis

Nat. Commun. in press  2018 PMID:30401901 DOI:10.1038/s41467-018-07035-x

Matsuoka, S., and Ueda, M.

Mutual inhibition between PTEN and PIP3 generates bistability for polarity in motile cells

Nat. Commun. 3.486805556  2018 PMID:30367048 DOI:10.1038/s41467-018-06856-0

Yanagawa, M., Hiroshima, M., Togashi, Y., Abe, M., Yamashita, T., Shichida ,Y., Murata, M., Ueda, M. and Sako, Y.

Single-molecule diffusion-based estimation of ligand effects on G protein-coupled receptors

Sci. Signal. 11(548):eaao1917  2018 PMID:30228224 DOI:10.1126/scisignal.aao1917

Yasui M., Hiroshima M., Kozuka J., Sako Y., and Ueda M.

Automated single-molecule imaging in living cells

Nat. Commun. 2.500694444  2018 PMID:30076305 DOI:10.1038/s41467-018-05524-7

Pervin, M.S., Itoh, G., Talukder, M.S.U., Fujimoto, K., Morimoto, Y.V., Tanaka, M., Ueda, M., Yumura, S.

A study of wound repair in Dictyostelium cells by using novel laserporation

Sci Rep 8(1):7969  2018 PMID:29789591 DOI:10.1038/s41598-018-26337-0

Hiroshima M., Pack CG., Kaizu K., Takahashi K., Ueda M., and Sako Y.

Transient acceleration of epidermal growth factor receptor dynamics produces higher order signaling clusters

J. Mol. Biol. 430:1381-1396  2018 PMID:29505756 DOI:10.1016/j.jmb.2018.02.018


Sato R., Kozuka J., Ueda M., Mishima R., Kumagai Y., Yoshimura A., Minoshima M., Mizukami S. and Kikuchi K.

Intracellular protein-labeling probes for multicolor single-molecule imaging of immune receptor-adaptor molecular dynamics

J. Am. Chem. Soc. 139:17397-17404  2017 PMID:29119782 DOI:10.1021/jacs.7b08262


Satomi Matsuoka, Yukihiro Miyanaga, Masahiro Ueda

Multi-State Transition Kinetics of Intracellular Signaling Molecules by Single-Molecule Imaging Analysis

Methods in Molecular Biology 1407:361-379  2016 PMID:27271914 DOI:10.1007/978-1-4939-3480-5_25

Yoichiro Kamimura, Yukihiro Miyanaga, Masahiro Ueda

Heterotrimeric G-protein shuttling via Gip1 extends the dynamic range of eukaryotic chemotaxis.

Proc. Natl. Acad. Sci. U. S. A. 113:4356-4361  2016 PMID:27044073 DOI:10.1073/pnas.1516767113

Our ideal candidate (as a graduate student)

We are looking for a highly motivated person to work on our research topics as our lab member. Our lab welcomes the person who loves taking care of creatures, hand working and handcraft too. Any kind of background (such as your expertise or major) is available.


Laboratory of Single Molecule Biology, Graduate School of Frontier Biosciences, Osaka University,
1-3 Yamadaoka, Suita, Osaka 565-0871 Japan.

TEL: +81-6-6879-4611

E-mail: masahiroueda[at] (Prof. Masahiro Ueda)

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