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Live-Cell Imaging of Secretion activity (LCI-S)

Our bodies are made up of about 37 trillion cells. Each cell properly fulfills the role assigned to itself to maintain a healthy body.For example, muscle cells have a mechanism for expanding and contracting in cells, and by contracting throughout the cell, they become the mobility that moves the body.In addition, nerve cells have a mechanism to generate potential differences inside and outside the cell, and the stimulus is converted into a momentary electrical signal and transmitted to a distant part of the body.

Of course, these special functions limited to certain types of cells are indispensable for maintaining a healthy body, but there is a function that harmonizes them, that is, a function that allows cells to communicate with each other and manage the body appropriately. This is a function called secretion.

Secretion is the function of cells to release message substances outward, and cells that receive message substances behave according to the message. The secreted message substance is, so to speak, a voice from the cell, and the exchange of message substances is a conversation between cells.

When do cells emit a voice and how do they convey their messages?It is in fact, not yet well understood.It has been believed that since it is a conversation that may change the state of the body, the loudness of the voice and the timing of the speech must be strictly controlled. LCI-S (Live-Cell Imaging of Secretion activity) is a technology for secretly eavesdropping on such conversations.

The basic principle of LCI-S is that immunoassays, which are the most commonly used method for detecting message substances, are observed using total internal reflection illumination, a microscopic observation technique used in single-molecule fluorescence imaging. The basic principles (see figure below) were published in a paper in 2014*.

* Shirasaki, Y., Yamagishi, M., Suzuki, N. et al. Real-time single-cell imaging of protein secretion. Sci Rep 44736 (2014). https://doi.org/10.1038/srep04736

With this technology, it has become possible to visualize the released message substances in real time on the spot while culturing cells. Watch this video to see how the moving cells send out messages.

LCI-S Development

The prototype of LCI-S was born from a casual conversation between Dr. Yoshie Harada, then Director of the Clinical Research Institute (currently a professor at the Institute for Protein Research, Osaka University), who was also an advisor to our company, and Dr. Ohara, Deputy Director of the Kazusa DNA Research Institute. There was some trial and error, but the major change to the current form was made after Dr. Yoshitaka ShirasakWe (currently a specially appointed assistant professor at the University of Tokyo) was assigned to Dr. Ohara as a postdoctoral fellow.More about this untold development story will be released at a later date.