FIP Seminar: Multi-molecular Super Resolution Metabolic Imaging in Aging and Diseases

Understanding the dynamics of metabolism in a multicellular organism is essential to unraveling the mechanistic basis of many biological processes in physiological and pathological conditions. There has been an urgent need of high spatial resolution, non-invasive in situ imaging techniques for visualizing metabolic activities of various biomolecules in cells and tissues. In the present work, we transformed SRS microscopy into a super resolution (~52nm) multiplex metabolic imaging platform by developing Adam optimization-based Pointillism Deconvolution (A-PoD) and penalized reference matching (PRM) algorithms, and further integrated it with deuterium probed Stimulated Raman scattering (DO-SRS), multiphoton fluorescence (MPF), and second harmonic generation (SHG) into a multimodal imaging system. Using this imaging system, we detected various molecules' metabolic activities in the same region of interest in situ at subcellular scale. Within the broad vibrational spectra, we established a Raman spectra library with more than 25 standard molecules including lipid subtypes, proteins, and RNA/DNA. We quantitatively imaged the lipid and protein turnover rate and the metabolic heterogeneity in cells, animal models, and human tissues. This Multi-Molecular super resolution optical imaging platform is non-invasive, universal applicable, and it can be adapted into a broad range of biological studies such as aging, homeostasis, and diseases including neurodegeneration & tumor progression, etc. Dr. Lingyan Shi is currently an Assistant Professor in the Department of Bioengineering at UCSD. Her research focuses on developing high resolution optical spectroscopy and imaging platform, and its applications for studying metabolic dynamics in cells and animals during aging and disease processes. She discovered "Golden Window" for deep tissue imaging and developed metabolic imaging platforms that combines deuterium probing and stimulated Raman scattering (DO-SRS using heavy water and STRIDE with D-glucose) to visualize metabolic activities in situ. Her group at UCSD transformed SRS into a super resolution multiplex metabolic imaging platform by developing Adam optimization-based Pointillism Deconvolution (A-PoD) and penalized reference matching (PRM) algorithms. Dr. Shi holds six awarded patents. She received Blavatnik Regional Award for Young Scientist in Physical Sciences & Engineering in 2018; Hell