The "D5 Medical & Life Science Seminar" course will be offered by International Research Center for Medical Sciences (IRCMS). It will run from May 2025 to March 2026, with lectures given by scientists who are affiliated with IRCMS or in collaboration with researchers at IRCMS. The lectures will be given once a month, in English, and by leading scientists in the relevant research field. Students will be taught: 1) how normal physiological functions are maintained in the human body; 2) how these systems become abnormal under certain pathophysiologic conditions; 3) why stem cells are important in animal development and homeostasis; 4) how stem cell-based approaches can help us understand disease mechanisms and find potential cure for diseases related to stem cell malfunction (e.g., cancer, aging).

Anyone who wants to join is welcome.
For students who have registered for the course, please check your attendance in Moodle.

Date      : August 22nd, 2025 (Friday)
               

Format  : Hybrid

Time      : 16:00 - 17:00 (JST)
               

Speaker : Dr. Yusuke Nasu (Academia Sinica/National Taiwan University)
               

Title       : Next-generation fluorescent biosensors for unraveling of lactate metabolism and signaling

Abstract  :

Cells across diverse organisms use sugars as fundamental fuel sources to drive essential metabolic processes. In the core pathway of glycolysis, lactate (lactic acid) has been traditionally considered a "waste" byproduct. However, there is increasing recognition that lactate plays an important role as an intercellular energy source and signaling molecule in a range of tissues.

Deeper mechanistic insights into the mechanisms by which lactate integrates metabolic and signaling pathways to influence cell physiology and pathology will require technologies capable of monitoring lactate dynamics in living cells with high spatiotemporal precision. Unfortunately, existing methodologies such as mass spectroscopy lack these abilities, thus hampering comprehensive understanding of lactate's multifaceted functions.

Herein, I present that directed protein evolution can enable the engineering of fluorescent protein-based biosensors, designated the LACCO biosensor series, for a versatile metabolite lactate with high sensitivity, brightness, specificity, and spatiotemporal resolution in living cultured cells and in vivo. We used these state-of-the-art biosensors to achieve a visualization of the lactate dynamics across cellular compartments, revealing an unprecedented lactate shuttle in a spatiotemporal manner. The LACCO series represents a major technological leap towards understanding of the central roles of lactate in both metabolism and signaling.

2-3 Major Papers

1. Nasu Y.*, Aggarwal A., Le G.N.T., Vo C.T., Kambe Y., Wang X., Beinlich F.R.M., Lee A.B., Ram T.R., Wang F., Gorzo K.A., Kamijo Y., Boisvert M., Nishinami S., Kawamura G., Ozawa T., Toda H., Gordon G.R., Ge S., Hirase H., Nedergaard M., Paquet M.-E., Drobizhev M., Podgorski K., Campbell R. E.*, "Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging", Nature Communications, 14, 6598 (2023)

2.  Nasu Y., Murphy-Royal C., Wen Y., Haidey J., Molina R. S., Aggarwal A., Zhang S., Kamijo Y., Paquet M., Podgorski K., Drobizhev M., Bains J. S., Lemieux M. J., Gordon G. R., Campbell R. E.*, "A genetically encoded fluorescent biosensor for extracellular L-lactate", Nature Communications, 12, 7058 (2021)

 3. Nasu Y.^#, Shen Y.^#, Kramer L., Campbell R. E.*, "Structure- and mechanism-guided design of single fluorescent protein-based biosensors", Nature Chemical Biology, 17, 509−518 (2021)

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