The Yandong Group is focusing on innovating biophysical technologies in Super-Resolution Imaging, Image Deep Mining, and live-cell Single-Molecule Tracking. The major interest is to understand the biological physics at single-molecule level by integrating the state-of-the-art techniques in optical imaging, data mining, and chemical biology.

I. High-Content Super-Resolution Image Analysis

The multi-color Super-Resolution Microscopy enabled visualization of molecular complex at a scale of 5-15 nm, it is however yet widely applied due to the challenges in deriving quantitative information from the complex image data. Dr. Yandong Yin developed new Stochastic Co-localization modeling and Triple-Correlation (TC) based image mining method that provides higher order statistical information on the spatial organization of biomolecular complexes. In addition, Dr. Yandong Yin also developed fast computational method addressing the expensive TC analysis, enabling high-throughput high-content super-resolution image analysis (Nat. Commun., 2019).

Utilizing these quantitative microscopy methods, Dr. Yandong Yin investigated 1) the molecular mechanism of ATR modulating FANCI’s activity in responding to different level of DNA replication stress (Mol. Cell, 2015), and 2) quantified the spatial organization of individual replisome at single-fork resolution, revealing the physical link between the ATR-mediated surveillance of individual replication fork and stress response (Mol. Cell, 2021).

II. Diffusion-Decelerated Fluorescence Correlation Spectroscopy

Single-molecule techniques could be ideal in probing subtle conformational dynamics, but existing single-molecule techniques had yet cover full temporal window for kinetic studies. Dr. Yandong Yin developed the diffusion-decelerated FCS (ddFCS), enabling a much wider time window for measurements of the dynamic of subtle conformational changes at single-molecule level. As such, Dr. Yandong Yin mapped the panorama of the folding kinetics of the DNA hairpin structure (Chem. Commun., 2012), and probed, for the first time, the dynamics of a single mismatched base spontaneously flipping out of its duplex structure (PNAS, 2014).

Figure 1. High-Content Super-Resolution Image Mining

(A) Multi-Color Super-Resolution imaging provides nanoscale spatial information. (B) The Triple-Correlation Function (TCF) quantifies the spatial organization of the molecular complex: (i) The TCF plots the relative probability density as a function of the pairwise distances of the three examined species; (ii) The most probable configuration obtained from the TCF profile; (iii) Quantification of the spatial organization of the molecular complex.

KE Coleman#, Y Yin#, SKL Lui, S Keegan, D Fenyo, DJ Smith, E Rothenberg, TT Huang, USP1-trapping lesions as a source of DNA replication stress and genomic instability. Nat. Communs. 2022, 13, 1740

Y Yin*, WTC Lee, D Gupta, H Xue, P Tonzi, JA Borowiec, TT Huang, M Modesti, E Rothenberg*, A basal-level activity of ATR links replication fork surveillance and stress response. Mol. Cell 2021, 81, 4243-4257

WTC Lee, Y Yin, M Morton, P Tonzi, PP Gwo, D Odermatt, M Modesti, S Cantor, K Gari, T Huang, E Rothenberg, Single-molecule imaging reveals replication fork coupled formation of G-quadruplex structures hinders local replication stress signaling. Nat. Commun. 2021, 12, 2525

Y Yin*, WTC Lee, E Rothenberg*, Ultrafast Data Mining of Molecular Assemblies in Multiplexed High-Density Super-Resolution Images. Nat. Commun. 2019, 10, 119

Y Yin#, L Yang#, G Zheng, C Gu, C Yi, C He, Y Gao, XS Zhao, Dynamics of spontaneous flipping of a mismatched base in DNA duplex. Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 8043-8048