[Seminar] "Optogenetics for manipulating cellular functions" by Prof. Kazuhiro Aoki, Exploratory Research Center on Life and Living Systems (ExCELLS)

Abstract: Cells respond to a variety of stimuli, and process the input information through an intracellular signaling network comprised of biochemical reactions. It is essential to understand the molecular mechanisms underlying intracellular signal transduction to clarify not only physiological cellular functions but also pathological processes such as tumorigenesis. Fluorescent proteins have revolutionized the field of life science. Much effort has been devoted to developing genetically encoded fluorescent biosensors based on fluorescent proteins, which enable us to visualize the spatio-temporal dynamics of cell signaling. In addition, optogenetic techniques for controlling intracellular signal transduction systems have been developed and applied in recent years by regulating intracellular signaling in a light-dependent manner.

The Ras-ERK MAPK signaling cascade has been highly conserved throughout evolution and plays a key role in many cellular processes, including proliferation, differentiation, survival, and tumorigenesis. Although the Ras-ERK signaling pathway has been extensively studied for decades, it is still unclear how the Ras-ERK signaling controls such diverse cellular processes. To address this issue, we have developed tools to visualize and manipulate ERK signaling with live cell imaging.

Here, I will show two topics in our recent studies about collective cell migration driven by the intercellular propagation of ERK activation, and a genetically-encoded optogenetic tool for manipulation of cell signaling and functions.

References

Aoki, K., Kondo, Y., Naoki, H., Hiratsuka, T., Itoh, R. E., and Matsuda, M. (2017) Propagating Wave of ERK Activation Orients Collective Cell Migration. Dev. Cell. 43, 305–317.e5

Uda, Y., Goto, Y., Oda, S., Kohchi, T., Matsuda, M., and Aoki, K. (2017) Efficient synthesis of phycocyanobilin in mammalian cells for optogenetic control of cell signaling. Proceedings of the National Academy of Sciences. 114, 11962–11967