Dr. Lingyan Shi, University of California, San Diego, will lecture on "Multimodal Metabolic Nanoscopy for Studying Aging and Related Diseases."
Abstract: Understanding the dynamics of metabolism in multicellular organisms is crucial for uncovering the mechanistic foundations of numerous biological processes. Metabolism, defined as the synthesis, transformation, and degradation of biomolecules, executes the genetic blueprint. Traditional imaging methods like MRI, PET, fluorescence, and mass spectrometry have inherent limitations. As an emerging non-linear vibrational imaging microscopy technique, stimulated Raman scattering (SRS) can produce chemically specific images with high resolution, deep penetration, and quantitative capabilities. In this context, we have developed and integrated deuterium-probed picosecond stimulated Raman scattering (DO-SRS), multiphoton fluorescence (MPF), and second harmonic generation (SHG) into a single nanoscopy for studying metabolic changes in aging and diseases. The enzymatic incorporation of deuterium (D) generates carbon-deuterium (C-D) bonds in newly synthesized molecules. These new molecules with C-D bonds can be detected by DO-SRS in the spectral cell-silence region of the Raman spectrum, allowing distinction from pre-existing old molecules. One of our findings unveiled that lipid turnover diminishes more rapidly in aged female Drosophila compared to males. Meanwhile, dietary restriction, downregulation of the insulin/IGF-1 signaling (IIS) pathway, and activation of AMPK notably changed lipid metabolism in aged or Alzheimer’s brains. By developing APoD and PRM algorithms, our current multimodal metabolic nanoscopy provides superresolution with hyperspectral volumetric imaging capability. Combined with deuterated molecules (glucose, amino acids, fatty acids, water molecules, etc.) as bioorthogonal probes, the metabolic heterogeneity of the brain, adipose tissue, liver, muscle, retina, kidney, lung, and ovaries (in human, mouse, and Drosophila tissues) is quantitatively imaged. This platform equips researchers to quantitatively visualize various molecular events within the same region of interest, offering tools for early-stage disease detection, drug delivery/resistance assessment, as well as fostering a deeper mechanistic understanding of the fundamentals of aging biology and related diseases.