Biography
Chen Liangyi is a Boya Distinguished Professor and a New Cornerstone Investigator at Peking University. He has received funding from the National Natural Science Foundation of China's Distinguished Young Scholars and is the Chief Scientist for major research projects funded by the Ministry of Science and Technology and the National Natural Science Foundation. He has invented a series of high spatiotemporal resolution biomedical imaging visualization techniques to study insulin secretion regulation related to diabetes at different spatiotemporal scales. These inventions include high-resolution miniaturized two-photon microscopy, Hessian structured illumination super-resolution microscopy, live-cell dual-mode super-resolution microscopy, and sparse deconvolution super-resolution imaging algorithms based on new mathematical principles. His work has achieved the highest resolution (60nm), fastest speed (564Hz), and longest imaging time (>1 hour) in live-cell imaging, also enabling cross-scale multi-modal super-resolution enhancement. His work was recognized as one of the "Top Ten Social Impact Events in China's Optical Field (Light10) in 2021," and his commercialized super-resolution microscopes and miniaturized two-photon microscopes have been sold to top domestic research institutions, addressing critical issues in high-end microscopy.
Main Contributions:
1. New Principles of Live-Cell Super-Resolution Imaging:He proposed integrating spatiotemporal continuity prior knowledge for super-resolution reconstruction, invented Hessian structured illumination super-resolution microscopy, reduced phototoxicity by three orders of magnitude, enabling long-term live-cell super-resolution imaging, and observed the dynamic structure of mitochondrial cristae for the first time. He further proposed a general mathematical super-resolution method, breaking the physical resolution limit of microscopes, and achieving the highest current resolution (60nm), fastest speed (564Hz), and longest imaging time (>1 hour) for live-cell super-resolution imaging. His work has been recognized and applied by international peers, including Nobel laureate Stefan Hell from the Max Planck Institute. He also invented fluorescence-phase dual-mode super-resolution microscopy, providing the first panoramic view of organelle interactions in live cells, revealing a novel black vesicle body involved in cellular aging.
2. Miniaturized Multi-Photon Microscopy:He invented a 2.2g miniaturized two-photon microscope that can be carried by mice, extended its capabilities to larger fields of view and three-dimensional free-behavior mouse imaging, and collaborated to achieve miniaturized three-photon microscopy, enabling full cortical and hippocampal neuron functional imaging in freely behaving mice. His work was selected as one of the "Top Ten Scientific Progresses in China" in 2017 and Nature Methods' Method of the Year in 2018.
3. Cross-Scale Regulation of Insulin Secretion:Using live-cell super-resolution imaging, he discovered mechanisms of rapid endocytosis mediated by clathrin-coated pits on β-cells' plasma membranes and how glucose toxicity affects insulin secretion channels. Addressing the core question of how glucose stimulates biphasic insulin secretion, he identified major flaws in traditional molecular and cellular data models. His imaging at the whole-islet level demonstrated that paracrine regulation activates only a few β-cells, with their synchronized and asynchronous secretion regulating biphasic secretion, significantly contributing to understanding how defects in the first phase of insulin secretion lead to type 2 diabetes.
Reprensentative Achievement
1.Peng X, Ren H, Yang L, Tong S, Zhou R, Long H, Wu Y, Wang L, Wu Y, Zhang Y, Shen J, Zhang J, Qiu G, Wang J, Han C, Zhang Y, Zhou M, Zhao Y, Xu T, Tang C, Chen Z, Liu H*,Chen L*. Readily releasable β cells with tight Ca2+-exocytosis coupling dictate biphasic glucose-stimulated insulin secretion.Nat Metab. 2024 6(2):238-253.
2.Zhao W, Zhao S, Han Z, Ding X, Hu G, Qu L, Huang Y, Wang X, Mao H, Jiu Y, Hu Y, Tan J, Ding X*,Chen L*, Guo C* & Li H*. Enhanced detection of fluorescence fluctuations for high-throughput super-resolution imaging.Nat Photonics.2023 17(9), pp.806-813.
3.Zhao W, Zhao S, Li L, Huang H, Xing S, Zhang Y, Qiu G, Han Z, Shang Y, Sun D, Shan C, Wu R, Gu L, Zhang S, Chen R, Xiao J, Mo Y, Wang J, Ji W, Chen X, Ding B, Liu Y, Mao H, Song B, Tan J, Liu J, Li H*,Chen L*. Sparse deconvolution improves the resolution of live-cell super-resolution fluorescence microscopy,Nat Biotech., 2022 Apr;40(4):606-617.
4.Huang X, Fan J, Li L, Liu H, Wu R, Wu Y, Wei L, Mao H, Lal A, Xi P, Tang L, Zhang Y, Liu Y, Tan S*,Chen L*. Fast, long-term super-resolution imaging with Hessian structured illumination microscopy,Nat Biotech., 2018 Jun;36(5):451-459. doi: 10.1038/nbt.4115.
5.Zong W, Wu R, Li M, Hu Y, Li Y, Li J, Rong H, Wu H, Xu Y, Lu Y, Jia H, Fan M, Zhou Z, Zhang Y*, Wang A*, Chen L*, Cheng H. Fast High-resolution Miniature Two-photon Microscopy for Brain Imaging in Freely-behaving Mice. Nat Methods. 2017 Jul;14(7):713-719.
