Laboratory of Single Molecule Biology
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]fbs.osaka-u.ac.jp|
|TACHIBANAKI Shuji (Associate Professor)||banaki[at]fbs.osaka-u.ac.jp|
|MATSUOKA Satomi (Assistant Professor)||matsuoka[at]fbs.osaka-u.ac.jp|
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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.
Publications (Research Articles, Reviews, Books)
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
Intracellular ATP levels influence cell fates in Dictyostelium discoideum differentiation
Genes Cells 25(5):312-326 2020
Talin B regulates collective cell migration via PI3K signaling in Dictyostelium discoideum mounds
Biochem. Biophys. Res. Commun. 525(2):372-377 2020
Large scale single-molecule imaging aided by artificial intelligence
Microscopy 69(2):69-78 2020
Transducin activates cGMP phosphodiesterase by trapping inhibitory γ subunit freed reversibly from the catalytic subunit in solution.
Sci Rep 5.40625 2019
Excitable dynamics of Ras triggers spontaneous symmetry breaking of PIP3 signaling in motile cells
J. Cell Sci. 132:jcs.224121 2019
Collective cell migration of Dictyostelium without cAMP oscillations at multicellular stages
Communications Biology 2:34 2019
Chemoattractant receptors activate, recruit and capture G proteins for wide range chemotaxis
Biochem. Biophys. Res. Commun. 507:304-310 2018
Parallel signaling pathways regulate excitable dynamics differently to mediate pseudopod formation during eukaryotic chemotaxis
J. Cell Sci. 131:jcs214775 2018
Structural basis of Gip1 for cytosolic sequestration of G-protein in wide range chemotaxis
Nat. Commun. in press 2018
Mutual inhibition between PTEN and PIP3 generates bistability for polarity in motile cells
Nat. Commun. 3.486805556 2018
Single-molecule diffusion-based estimation of ligand effects on G protein-coupled receptors
Sci. Signal. 11(548):eaao1917 2018
Automated single-molecule imaging in living cells
Nat. Commun. 2.500694444 2018
A study of wound repair in Dictyostelium cells by using novel laserporation
Sci Rep 8(1):7969 2018
Transient acceleration of epidermal growth factor receptor dynamics produces higher order signaling clusters
J. Mol. Biol. 430:1381-1396 2018
Intracellular protein-labeling probes for multicolor single-molecule imaging of immune receptor-adaptor molecular dynamics
J. Am. Chem. Soc. 139:17397-17404 2017
Multi-State Transition Kinetics of Intracellular Signaling Molecules by Single-Molecule Imaging Analysis
Methods in Molecular Biology 1407:361-379 2016
Heterotrimeric G-protein shuttling via Gip1 extends the dynamic range of eukaryotic chemotaxis.
Proc. Natl. Acad. Sci. U. S. A. 113:4356-4361 2016
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.
E-mail: masahiroueda[at]fbs.osaka-u.ac.jp (Prof. Masahiro Ueda)
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