Laboratory of Bioanalytical Chemistry
Graduate School of Pharmaceutical Sciences, The University of Tokyo

Japanese / English

Subject of research

Life is driven by the function of various cells and numerous biomolecules. Elucidation of the molecular mechanisms of biomolecular functions, biomolecular interactions, and cell-cell interactions has become an important theme in life science. To elucidate these molecular mechanisms, we are developing analytical techniques using highly sensitive optical microscopes and micro/nano devices.

Specific research themes are as follows.

Theme 1: Elucidation of the molecular mechanism of biomolecular machines

We study the regulatory mechanism of protein synthesis by ribosomes using single molecule fluorescence imaging and single molecule manipulation with optical tweezers. Understanding the molecular mechanism allows us to theoretically design functional proteins, which will lead to drug discovery in the future.

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Theme 2: Analysis of cellular function using single molecule fluorescence microscopy

2-1. mRNA imaging in living cells

Quantifying the expression levels of specific mRNAs in living cells and imaging their dynamics at the single molecule level are extremely important for understanding the spatio-temporal regulation of gene expression. To this end, we are developing a highly sensitive quantitative imaging method for intracellular mRNA expression and dynamics. This technique is expected to contribute to the elucidation of the intracellular functions of functional RNAs such as siRNA and miRNA.

2-2. Imaging of intracellular temperature in living cells and analysis of cellular functions by local laser heating

Intracellular temperature has recently attracted much attention. We have discovered interesting intracellular temperature fluctuations by imaging the temperature in living cells. Furthermore, we are manipulating cellular functions by artificially heating the inside of cells and analyzing the relationship between local intracellular temperature and cellular functions. This research is expected not only to create a new trend in biology, but also to create medical and pharmaceutical value as a method of manipulating cellular functions by heat generation.

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Theme 3: Analysis of cell-cell interactions by real-time imaging of single-cell secretion

Cells cooperatively regulate biological systems by exchanging information through secretion and acceptance of intercellular message substances such as hormones, cytokines, and extracellular vesicles. Recent advances in microfabrication and microfluidics technologies have made it possible to quantify cellular secretory activity at the single cell level. As a result, it has become clear that the amount of secretion and the rhythms of secretion differ among individual cells, even within the same cell type. We have developed a "single cell secretion real-time imaging platform" that combines fluorescence sandwich immunostaining technology with total internal reflection fluorescence microscopy to visualize the true state of cell secretion. For example, it is possible to observe the active secretion of cytokines that induce inflammation and allergies from activated immune cells. We are trying to apply this platform to visualize the gene expression that regulates cell activation and the sites of cell-cell interactions.

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Theme 4: Development of analytical techniques using micro/nano devices

4-1. Development of on-chip liquid chromatography

In the diagnosis of diseases and health checkups, several mL of blood is analyzed over several hours. We are developing a microanalytical device that can analyze a single drop of blood in a few seconds. We have developed the liquid chromatography separation part of this device and have achieved faster separation and analysis of biomolecules compared to conventional analytical devices. We expect that the development of other parts (pretreatment, detection, etc.) will enable ultra-fast analysis of biomarkers that are indicators of disease.

4-2. Acquisition of novel enzyme genes from microorganisms using microdroplets.

More than 99% of microorganisms in the environment are considered difficult to cultivate. Enzymes produced by these microorganisms have great potential as new enzyme resources. We have developed a method to screen microorganisms in the environment and obtained enzyme genes without cultivation. This technology will contribute to drug discovery and biomass utilization.

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